Obesity

Many adults can achieve remission of type 2 diabetes with a primary intervention consisting of a diet that emphasizes whole, plant-based foods, according to a new publication from the American College of Lifestyle Medicine (ACLM).

The document was developed to assist clinicians treating adults with type 2 diabetes, with the goal of remission using diet as a primary intervention. A panel of 15 experts from seven societies reached consensus on 69 statements.

“A healthy diet is a foundational component of current lifestyle guidelines for treatment of type 2 diabetes, but it is often overlooked because of the lack of physician training and patient awareness,” Felice A. Caldarella, MD, president of the American Association of Clinical Endocrinology (AACE), said in a press release from ACLM.

“The consensus statements produced by this panel of experts are invaluable in bringing awareness to the value of diet for diabetes remission in addition to management,” he summarized.

The initiative was cosponsored by the Endocrine Society, endorsed by AACE, and supported by the Academy of Nutrition and Dietetics. The expert panel also included representatives from the American College of Cardiology, the American Heart Association, and the American Academy of Family Physicians. It was published in the American Journal of Lifestyle Medicine.

“I think many patients would do the challenging work of making lifestyle modifications if it meant remission of [type 2 diabetes] and sparing them the burden and cost of medications or surgery,” said Amy E. Rothberg, MD, PhD, who represented the Endocrine Society on the panel.

“By changing the course of the disease, i.e., if in remission, they are unlikely to get the complications related to [type 2 diabetes],” Dr. Rothberg, professor of nutritional sciences at the University of Michigan, Ann Arbor, told this news organization.
 

Consensus on 69 statements

The panel members used a modified Delphi process to develop the consensus statement. They identified 49 articles from the literature regarding dietary interventions in adults with type 2 diabetes. They reached consensus on 69 statements that cover seven topics: definitions and basic concepts; diet and remission of type 2 diabetes; dietary specifics and types of diets; adjuvant and alternative interventions; support, monitoring, and adherence to therapy; weight loss; and payment and policy.

Dr. Rothberg identified six key areas:

• Definition of remission: Type 2 diabetes remission is defined as A1c < 6.5% for at least 3 months with no surgery, devices, or active pharmacologic therapy for lowering blood glucose, consistent with the diabetes remission timeline published in 2021 by the American Diabetes Association. Remission does not exclude the possibility of recurrence. Remission is a realistic and achievable goal for some adults with type 2 diabetes.
• High-intensity diet, short duration of diabetes: Patients are more likely to attain remission with a high-intensity diet (e.g., high level of restrictions plus frequent patient contact or counseling) accompanied by physical activity and if the patient has had diabetes for 4 years or less. A high-fiber diet is essential.
• Fewer calories, focus on plant-based foods: Calorie reduction could be achieved by reducing food volume, portion sizes, or energy density, or by using liquid meal replacements, or by a combination of these approaches. It should mainly include whole, plant-based foods (whole grains, vegetables, legumes, fruits, nuts, and seeds) and avoid or minimize meat and other animal products, refined foods, ultra-processed foods, and foods with added fats.
• A very low energy diet as initial intervention is optional: There was consensus that this approach can achieve remission, but there was not agreement that low calorie content was essential for achieving remission, Dr. Rothberg noted.
• Beyond type 2 remission: Diet as a primary intervention can also lower the risk of cardiovascular disease and improve lipoprotein profile.
• Self-management, support, and monitoring: The group recognizes the importance of patient education and support. “This can play a vital role and should be part of any comprehensive lifestyle treatment,” said Dr. Rothberg. The diet and lifestyle strategies should be acceptable to most patients, easy to adhere to, accommodate patient preferences and values, and be culturally sensitive.

Intensive lifestyle change can equate to bariatric surgery

Also invited to comment, Yehuda Handelsman, MD, who coauthored a 2020 type 2 diabetes management algorithm by AACE and the American College of Endocrinology, and was not involved with the current initiative, agrees with the importance of lifestyle in the management of type 2 diabetes but takes issue with a few points.

Most clinicians and experts do not believe that diabetes can be reversed, as such, only controlled, noted Dr. Handelsman, medical director of the Metabolic Institute of America, Tarzana, Calif.

“We always have approached type 2 diabetes treatment with lifestyle – diet, exercise, and (as of late) sleep – as the mainstay of therapy,” he said.

However, most patients do not adhere to diet modifications by 6 months and especially by 1 year, which has led to universal recommendations to add medication to lifestyle from inception, he continued.

Most clinicians have not been trained in lifestyle modalities. And many patients with type 2 diabetes are not adherent to medications, which “led to the relative success of bariatric surgery leading to remission (at least for 3-5 years).”

“Remission, which in broad terms implies the disappearance of signs and symptoms, should be a top priority for individuals with type 2 diabetes,” the consensus statement authors wrote.

“While [bariatric surgery] can induce remission in 25% to 80% of targeted patients, it carries risk and its effectiveness wanes as subjects regain lost weight,” and “more dramatic and intensive [lifestyle] change produces remission rates equivalent to bariatric surgery,” they noted.

Need for more randomized trials

Dr. Handelsman also stressed that remission may be temporary. “Three months or 6 months cannot be a measure of success. We must have at least 1 year,” he added. “In fact, there are data to show that remission requires 3 years.”

Nevertheless, the consensus statement does highlight the importance of lifestyle in remission of diabetes, he agreed.

The expert panel also noted that patients can benefit from a healthy lifestyle, even if they do not attain remission, Dr. Rothberg pointed out. 

Moving forward, the statement concludes that “there is ... an ongoing need for additional randomized controlled trials to assess sustainable plant-based dietary interventions with whole or minimally processed foods, as a primary means of treating [type 2 diabetes] with the goal of remission, as well as factors that lead to successful patient adherence and effective dissemination and implementation of such interventions.”

This study was supported by the Lisa Wendel Memorial Foundation. Dr. Rothberg has disclosed being the medical director of  Rewind, a virtual platform created for weight control with the goal to “defeat” type 2 diabetes, and a consultant for a study for which Nestle provides product. Dr. Handelsman has disclosed receiving research grants and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Esperion, Ionis, Mankind, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Regor, Sanofi, and Vertis.

A version of this article first appeared on Medscape.com.

Many adults can achieve remission of type 2 diabetes with a primary intervention consisting of a diet that emphasizes whole, plant-based foods, according to a new publication from the American College of Lifestyle Medicine (ACLM).

The document was developed to assist clinicians treating adults with type 2 diabetes, with the goal of remission using diet as a primary intervention. A panel of 15 experts from seven societies reached consensus on 69 statements.

“A healthy diet is a foundational component of current lifestyle guidelines for treatment of type 2 diabetes, but it is often overlooked because of the lack of physician training and patient awareness,” Felice A. Caldarella, MD, president of the American Association of Clinical Endocrinology (AACE), said in a press release from ACLM.

“The consensus statements produced by this panel of experts are invaluable in bringing awareness to the value of diet for diabetes remission in addition to management,” he summarized.

The initiative was cosponsored by the Endocrine Society, endorsed by AACE, and supported by the Academy of Nutrition and Dietetics. The expert panel also included representatives from the American College of Cardiology, the American Heart Association, and the American Academy of Family Physicians. It was published in the American Journal of Lifestyle Medicine.

“I think many patients would do the challenging work of making lifestyle modifications if it meant remission of [type 2 diabetes] and sparing them the burden and cost of medications or surgery,” said Amy E. Rothberg, MD, PhD, who represented the Endocrine Society on the panel.

“By changing the course of the disease, i.e., if in remission, they are unlikely to get the complications related to [type 2 diabetes],” Dr. Rothberg, professor of nutritional sciences at the University of Michigan, Ann Arbor, told this news organization.
 

Consensus on 69 statements

The panel members used a modified Delphi process to develop the consensus statement. They identified 49 articles from the literature regarding dietary interventions in adults with type 2 diabetes. They reached consensus on 69 statements that cover seven topics: definitions and basic concepts; diet and remission of type 2 diabetes; dietary specifics and types of diets; adjuvant and alternative interventions; support, monitoring, and adherence to therapy; weight loss; and payment and policy.

Dr. Rothberg identified six key areas:

• Definition of remission: Type 2 diabetes remission is defined as A1c < 6.5% for at least 3 months with no surgery, devices, or active pharmacologic therapy for lowering blood glucose, consistent with the diabetes remission timeline published in 2021 by the American Diabetes Association. Remission does not exclude the possibility of recurrence. Remission is a realistic and achievable goal for some adults with type 2 diabetes.
• High-intensity diet, short duration of diabetes: Patients are more likely to attain remission with a high-intensity diet (e.g., high level of restrictions plus frequent patient contact or counseling) accompanied by physical activity and if the patient has had diabetes for 4 years or less. A high-fiber diet is essential.
• Fewer calories, focus on plant-based foods: Calorie reduction could be achieved by reducing food volume, portion sizes, or energy density, or by using liquid meal replacements, or by a combination of these approaches. It should mainly include whole, plant-based foods (whole grains, vegetables, legumes, fruits, nuts, and seeds) and avoid or minimize meat and other animal products, refined foods, ultra-processed foods, and foods with added fats.
• A very low energy diet as initial intervention is optional: There was consensus that this approach can achieve remission, but there was not agreement that low calorie content was essential for achieving remission, Dr. Rothberg noted.
• Beyond type 2 remission: Diet as a primary intervention can also lower the risk of cardiovascular disease and improve lipoprotein profile.
• Self-management, support, and monitoring: The group recognizes the importance of patient education and support. “This can play a vital role and should be part of any comprehensive lifestyle treatment,” said Dr. Rothberg. The diet and lifestyle strategies should be acceptable to most patients, easy to adhere to, accommodate patient preferences and values, and be culturally sensitive.

Intensive lifestyle change can equate to bariatric surgery

Also invited to comment, Yehuda Handelsman, MD, who coauthored a 2020 type 2 diabetes management algorithm by AACE and the American College of Endocrinology, and was not involved with the current initiative, agrees with the importance of lifestyle in the management of type 2 diabetes but takes issue with a few points.

Most clinicians and experts do not believe that diabetes can be reversed, as such, only controlled, noted Dr. Handelsman, medical director of the Metabolic Institute of America, Tarzana, Calif.

“We always have approached type 2 diabetes treatment with lifestyle – diet, exercise, and (as of late) sleep – as the mainstay of therapy,” he said.

However, most patients do not adhere to diet modifications by 6 months and especially by 1 year, which has led to universal recommendations to add medication to lifestyle from inception, he continued.

Most clinicians have not been trained in lifestyle modalities. And many patients with type 2 diabetes are not adherent to medications, which “led to the relative success of bariatric surgery leading to remission (at least for 3-5 years).”

“Remission, which in broad terms implies the disappearance of signs and symptoms, should be a top priority for individuals with type 2 diabetes,” the consensus statement authors wrote.

“While [bariatric surgery] can induce remission in 25% to 80% of targeted patients, it carries risk and its effectiveness wanes as subjects regain lost weight,” and “more dramatic and intensive [lifestyle] change produces remission rates equivalent to bariatric surgery,” they noted.

Need for more randomized trials

Dr. Handelsman also stressed that remission may be temporary. “Three months or 6 months cannot be a measure of success. We must have at least 1 year,” he added. “In fact, there are data to show that remission requires 3 years.”

Nevertheless, the consensus statement does highlight the importance of lifestyle in remission of diabetes, he agreed.

The expert panel also noted that patients can benefit from a healthy lifestyle, even if they do not attain remission, Dr. Rothberg pointed out. 

Moving forward, the statement concludes that “there is ... an ongoing need for additional randomized controlled trials to assess sustainable plant-based dietary interventions with whole or minimally processed foods, as a primary means of treating [type 2 diabetes] with the goal of remission, as well as factors that lead to successful patient adherence and effective dissemination and implementation of such interventions.”

This study was supported by the Lisa Wendel Memorial Foundation. Dr. Rothberg has disclosed being the medical director of  Rewind, a virtual platform created for weight control with the goal to “defeat” type 2 diabetes, and a consultant for a study for which Nestle provides product. Dr. Handelsman has disclosed receiving research grants and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Esperion, Ionis, Mankind, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Regor, Sanofi, and Vertis.

A version of this article first appeared on Medscape.com.

Many adults can achieve remission of type 2 diabetes with a primary intervention consisting of a diet that emphasizes whole, plant-based foods, according to a new publication from the American College of Lifestyle Medicine (ACLM).

The document was developed to assist clinicians treating adults with type 2 diabetes, with the goal of remission using diet as a primary intervention. A panel of 15 experts from seven societies reached consensus on 69 statements.

“A healthy diet is a foundational component of current lifestyle guidelines for treatment of type 2 diabetes, but it is often overlooked because of the lack of physician training and patient awareness,” Felice A. Caldarella, MD, president of the American Association of Clinical Endocrinology (AACE), said in a press release from ACLM.

“The consensus statements produced by this panel of experts are invaluable in bringing awareness to the value of diet for diabetes remission in addition to management,” he summarized.

The initiative was cosponsored by the Endocrine Society, endorsed by AACE, and supported by the Academy of Nutrition and Dietetics. The expert panel also included representatives from the American College of Cardiology, the American Heart Association, and the American Academy of Family Physicians. It was published in the American Journal of Lifestyle Medicine.

“I think many patients would do the challenging work of making lifestyle modifications if it meant remission of [type 2 diabetes] and sparing them the burden and cost of medications or surgery,” said Amy E. Rothberg, MD, PhD, who represented the Endocrine Society on the panel.

“By changing the course of the disease, i.e., if in remission, they are unlikely to get the complications related to [type 2 diabetes],” Dr. Rothberg, professor of nutritional sciences at the University of Michigan, Ann Arbor, told this news organization.
 

Consensus on 69 statements

The panel members used a modified Delphi process to develop the consensus statement. They identified 49 articles from the literature regarding dietary interventions in adults with type 2 diabetes. They reached consensus on 69 statements that cover seven topics: definitions and basic concepts; diet and remission of type 2 diabetes; dietary specifics and types of diets; adjuvant and alternative interventions; support, monitoring, and adherence to therapy; weight loss; and payment and policy.

Dr. Rothberg identified six key areas:

• Definition of remission: Type 2 diabetes remission is defined as A1c < 6.5% for at least 3 months with no surgery, devices, or active pharmacologic therapy for lowering blood glucose, consistent with the diabetes remission timeline published in 2021 by the American Diabetes Association. Remission does not exclude the possibility of recurrence. Remission is a realistic and achievable goal for some adults with type 2 diabetes.
• High-intensity diet, short duration of diabetes: Patients are more likely to attain remission with a high-intensity diet (e.g., high level of restrictions plus frequent patient contact or counseling) accompanied by physical activity and if the patient has had diabetes for 4 years or less. A high-fiber diet is essential.
• Fewer calories, focus on plant-based foods: Calorie reduction could be achieved by reducing food volume, portion sizes, or energy density, or by using liquid meal replacements, or by a combination of these approaches. It should mainly include whole, plant-based foods (whole grains, vegetables, legumes, fruits, nuts, and seeds) and avoid or minimize meat and other animal products, refined foods, ultra-processed foods, and foods with added fats.
• A very low energy diet as initial intervention is optional: There was consensus that this approach can achieve remission, but there was not agreement that low calorie content was essential for achieving remission, Dr. Rothberg noted.
• Beyond type 2 remission: Diet as a primary intervention can also lower the risk of cardiovascular disease and improve lipoprotein profile.
• Self-management, support, and monitoring: The group recognizes the importance of patient education and support. “This can play a vital role and should be part of any comprehensive lifestyle treatment,” said Dr. Rothberg. The diet and lifestyle strategies should be acceptable to most patients, easy to adhere to, accommodate patient preferences and values, and be culturally sensitive.

Intensive lifestyle change can equate to bariatric surgery

Also invited to comment, Yehuda Handelsman, MD, who coauthored a 2020 type 2 diabetes management algorithm by AACE and the American College of Endocrinology, and was not involved with the current initiative, agrees with the importance of lifestyle in the management of type 2 diabetes but takes issue with a few points.

Most clinicians and experts do not believe that diabetes can be reversed, as such, only controlled, noted Dr. Handelsman, medical director of the Metabolic Institute of America, Tarzana, Calif.

“We always have approached type 2 diabetes treatment with lifestyle – diet, exercise, and (as of late) sleep – as the mainstay of therapy,” he said.

However, most patients do not adhere to diet modifications by 6 months and especially by 1 year, which has led to universal recommendations to add medication to lifestyle from inception, he continued.

Most clinicians have not been trained in lifestyle modalities. And many patients with type 2 diabetes are not adherent to medications, which “led to the relative success of bariatric surgery leading to remission (at least for 3-5 years).”

“Remission, which in broad terms implies the disappearance of signs and symptoms, should be a top priority for individuals with type 2 diabetes,” the consensus statement authors wrote.

“While [bariatric surgery] can induce remission in 25% to 80% of targeted patients, it carries risk and its effectiveness wanes as subjects regain lost weight,” and “more dramatic and intensive [lifestyle] change produces remission rates equivalent to bariatric surgery,” they noted.

Need for more randomized trials

Dr. Handelsman also stressed that remission may be temporary. “Three months or 6 months cannot be a measure of success. We must have at least 1 year,” he added. “In fact, there are data to show that remission requires 3 years.”

Nevertheless, the consensus statement does highlight the importance of lifestyle in remission of diabetes, he agreed.

The expert panel also noted that patients can benefit from a healthy lifestyle, even if they do not attain remission, Dr. Rothberg pointed out. 

Moving forward, the statement concludes that “there is ... an ongoing need for additional randomized controlled trials to assess sustainable plant-based dietary interventions with whole or minimally processed foods, as a primary means of treating [type 2 diabetes] with the goal of remission, as well as factors that lead to successful patient adherence and effective dissemination and implementation of such interventions.”

This study was supported by the Lisa Wendel Memorial Foundation. Dr. Rothberg has disclosed being the medical director of  Rewind, a virtual platform created for weight control with the goal to “defeat” type 2 diabetes, and a consultant for a study for which Nestle provides product. Dr. Handelsman has disclosed receiving research grants and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Esperion, Ionis, Mankind, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Regor, Sanofi, and Vertis.

A version of this article first appeared on Medscape.com.

Debra Katz, CNM, has noticed a shift in the number of teenagers coming to the teen obstetrics program at St. Joseph’s Medical Center in Paterson, N.J. A decade ago, about 30 adolescents gave birth in a given month; now, that figure is closer to 20, said Ms. Katz, chief of the nurse midwifery service at the center.

Ms. Katz’s observations mirror a national trend: The rate of teen births is falling in the United States, according to a study published in Obstetrics and Gynecology.

But, there’s a catch. The adolescents who are giving birth are more likely to have obesity, mental health problems, asthma, and other conditions that can complicate their pregnancies, the research shows. Rates of delivery complications have also increased in this age group.

Ms. Katz said that, compared with adult patients, teens tend to require longer medical visits. Most patients have limited knowledge of what prenatal care entails.

“Most of these patients have never even had a female [gynecologic] exam before,” Ms. Katz said. “They come in and they’re not used to the equipment. They’re not used to the terminology.”

Also consistent with the national trends, St. Joseph’s younger patients often have mental health problems or obesity. Many also lack stable housing and adequate food.

“Unfortunately, we are seeing a greater number of patients with morbid obesity; there’s a lot of bipolar disease; here’s a lot of depression; there’s a lot of anxiety,” Ms. Katz said. “And we also have a bit of PTSD [post traumatic stress disorder] as well.”

These factors make clinical practice more complex, according to the authors of the new study. “To optimize adolescent pregnancy outcomes, prenatal care will likely need to provide increasingly complex clinical management in addition to addressing outreach challenges of this population,” the authors of the new study write.

At St. Joseph’s, teens receive prenatal care in a group setting with other patients who are due to deliver in the same month. This model, called CenteringPregnancy, can increase self-esteem, build community, and may improve patient outcomes, Ms. Katz said. The program uses a team approach that includes a dietitian and social worker to address social support needs.
 

Shifting health status

To characterize delivery hospitalization trends for patients aged 11-19 years, Anna P. Staniczenko, MD, with Columbia University Irving Medical Center, New York, and her colleagues conducted a cross-sectional analysis of data from the 2000-2018 National Inpatient Sample.

Of more than 73 million estimated delivery hospitalizations during that period, 88,363 occurred in patients aged 11-14 years, and 6,359,331 were among patients aged 15-19 years.

Deliveries among patients aged 11-14 years decreased from 2.1 per 1,000 to 0.4 per 1,000 during the time frame. Deliveries among patients aged 15-19 years decreased from 11.5% of all deliveries to 4.8% over the study period.

Among patients aged 11-19 years, rates of comorbidities significantly increased from 2000 to 2018, the researchers found. The prevalence of obesity increased from 0.2% to 7.2%, asthma increased from 1.6% to 7%, while mental health conditions increased from 0.5% to 7.1%.

Severe maternal morbidity, defined as a patient having at least one of 20 conditions, including stroke, heart failure, and sepsis, increased from 0.5% to 0.7%. The rate of postpartum hemorrhage increased from 2.9% to 4.7%, the rate of cesarean delivery increased from 15.2% to 19.5%, and that of hypertensive disorders of pregnancy increased from 7.5% to 13.7%.
 

An often overlooked group

Adolescent pregnancies are more common in the United States than in other wealthy nations, and about 80% are unintended. In addition to the growth in comorbid conditions, adolescent mothers are at an increased risk of living under the poverty line, and children born to teen moms may be at increased risk for adverse pediatric outcomes.

Still, these pregnancies “may be planned and desired. ... It is unclear that there is an ‘ideal’ rate of pregnancy for this age group,” the study authors write.

Prior research has shown an increase in rates of chronic conditions among adults giving birth, but, “from what I could tell, this is really the first data” on chronic conditions in the pediatric obstetric population, said Lindsay K. Admon, MD, an ob.gyn. at the University of Michigan, Ann Arbor, who wrote an editorial accompanying the journal article.
 

Behind the decline

That there are fewer teen deliveries may be because the adolescent population is savvier about contraceptive methods. In addition, the Affordable Care Act expanded insurance coverage of contraception, said Stephanie Teal, MD, MPH, chair of obstetrics and gynecology and reproductive biology at University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland.

Dr. Teal was involved in the Colorado Family Planning Initiative, a state effort that showed that long-acting reversible contraception was effective and acceptable to young people.

“We are definitely seeing more adolescents who use birth control the first time they have sex,” Dr. Teal told this news organization. “When I started in practice, it was fairly uncommon that I would see a teenager who was sexually active who was consistently using a birth control method. And now they just look at me, roll their eyes, and are, like, ‘Duh, of course. He uses condoms, and I have an IUD.’ ”

To the extent that these deliveries include unintended pregnancies, the data may point to a need for clinicians to provide contraceptive education to adolescents with chronic conditions, according to Dr. Admon.
 

Abortion shifts

If U.S. Supreme Court rulings and state laws further limit access to contraception or abortion, the result could lead to more teen deliveries, Dr. Admon said.

While the adolescent birth rate has plummeted, the teen abortion rate has not increased, Dr. Teal said.

“Pregnancy is a time of health risk for women, and it’s getting riskier,” she said. “Our concern is that if people are having to go through a pregnancy that they don’t feel physically or financially or emotionally prepared to go through, that we will see an increase in these kinds of adverse health outcomes with birth.”

One study author has a leadership role on an American College of Obstetricians and Gynecologists safe motherhood initiative that has received unrestricted funding from Merck for Mothers. Another author has ties to Delfina Care, and one is on the board of directors of Planned Parenthood of Greater New York. Dr. Admon receives funding from the Agency for Healthcare Research and Quality and the National Institutes of Health. Dr. Teal has received grants from Merck, Bayer Healthcare, Sebela, and Medicines360 and personal fees from Merck and from Bayer Healthcare. Ms. Katz has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Debra Katz, CNM, has noticed a shift in the number of teenagers coming to the teen obstetrics program at St. Joseph’s Medical Center in Paterson, N.J. A decade ago, about 30 adolescents gave birth in a given month; now, that figure is closer to 20, said Ms. Katz, chief of the nurse midwifery service at the center.

Ms. Katz’s observations mirror a national trend: The rate of teen births is falling in the United States, according to a study published in Obstetrics and Gynecology.

But, there’s a catch. The adolescents who are giving birth are more likely to have obesity, mental health problems, asthma, and other conditions that can complicate their pregnancies, the research shows. Rates of delivery complications have also increased in this age group.

Ms. Katz said that, compared with adult patients, teens tend to require longer medical visits. Most patients have limited knowledge of what prenatal care entails.

“Most of these patients have never even had a female [gynecologic] exam before,” Ms. Katz said. “They come in and they’re not used to the equipment. They’re not used to the terminology.”

Also consistent with the national trends, St. Joseph’s younger patients often have mental health problems or obesity. Many also lack stable housing and adequate food.

“Unfortunately, we are seeing a greater number of patients with morbid obesity; there’s a lot of bipolar disease; here’s a lot of depression; there’s a lot of anxiety,” Ms. Katz said. “And we also have a bit of PTSD [post traumatic stress disorder] as well.”

These factors make clinical practice more complex, according to the authors of the new study. “To optimize adolescent pregnancy outcomes, prenatal care will likely need to provide increasingly complex clinical management in addition to addressing outreach challenges of this population,” the authors of the new study write.

At St. Joseph’s, teens receive prenatal care in a group setting with other patients who are due to deliver in the same month. This model, called CenteringPregnancy, can increase self-esteem, build community, and may improve patient outcomes, Ms. Katz said. The program uses a team approach that includes a dietitian and social worker to address social support needs.
 

Shifting health status

To characterize delivery hospitalization trends for patients aged 11-19 years, Anna P. Staniczenko, MD, with Columbia University Irving Medical Center, New York, and her colleagues conducted a cross-sectional analysis of data from the 2000-2018 National Inpatient Sample.

Of more than 73 million estimated delivery hospitalizations during that period, 88,363 occurred in patients aged 11-14 years, and 6,359,331 were among patients aged 15-19 years.

Deliveries among patients aged 11-14 years decreased from 2.1 per 1,000 to 0.4 per 1,000 during the time frame. Deliveries among patients aged 15-19 years decreased from 11.5% of all deliveries to 4.8% over the study period.

Among patients aged 11-19 years, rates of comorbidities significantly increased from 2000 to 2018, the researchers found. The prevalence of obesity increased from 0.2% to 7.2%, asthma increased from 1.6% to 7%, while mental health conditions increased from 0.5% to 7.1%.

Severe maternal morbidity, defined as a patient having at least one of 20 conditions, including stroke, heart failure, and sepsis, increased from 0.5% to 0.7%. The rate of postpartum hemorrhage increased from 2.9% to 4.7%, the rate of cesarean delivery increased from 15.2% to 19.5%, and that of hypertensive disorders of pregnancy increased from 7.5% to 13.7%.
 

An often overlooked group

Adolescent pregnancies are more common in the United States than in other wealthy nations, and about 80% are unintended. In addition to the growth in comorbid conditions, adolescent mothers are at an increased risk of living under the poverty line, and children born to teen moms may be at increased risk for adverse pediatric outcomes.

Still, these pregnancies “may be planned and desired. ... It is unclear that there is an ‘ideal’ rate of pregnancy for this age group,” the study authors write.

Prior research has shown an increase in rates of chronic conditions among adults giving birth, but, “from what I could tell, this is really the first data” on chronic conditions in the pediatric obstetric population, said Lindsay K. Admon, MD, an ob.gyn. at the University of Michigan, Ann Arbor, who wrote an editorial accompanying the journal article.
 

Behind the decline

That there are fewer teen deliveries may be because the adolescent population is savvier about contraceptive methods. In addition, the Affordable Care Act expanded insurance coverage of contraception, said Stephanie Teal, MD, MPH, chair of obstetrics and gynecology and reproductive biology at University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland.

Dr. Teal was involved in the Colorado Family Planning Initiative, a state effort that showed that long-acting reversible contraception was effective and acceptable to young people.

“We are definitely seeing more adolescents who use birth control the first time they have sex,” Dr. Teal told this news organization. “When I started in practice, it was fairly uncommon that I would see a teenager who was sexually active who was consistently using a birth control method. And now they just look at me, roll their eyes, and are, like, ‘Duh, of course. He uses condoms, and I have an IUD.’ ”

To the extent that these deliveries include unintended pregnancies, the data may point to a need for clinicians to provide contraceptive education to adolescents with chronic conditions, according to Dr. Admon.
 

Abortion shifts

If U.S. Supreme Court rulings and state laws further limit access to contraception or abortion, the result could lead to more teen deliveries, Dr. Admon said.

While the adolescent birth rate has plummeted, the teen abortion rate has not increased, Dr. Teal said.

“Pregnancy is a time of health risk for women, and it’s getting riskier,” she said. “Our concern is that if people are having to go through a pregnancy that they don’t feel physically or financially or emotionally prepared to go through, that we will see an increase in these kinds of adverse health outcomes with birth.”

One study author has a leadership role on an American College of Obstetricians and Gynecologists safe motherhood initiative that has received unrestricted funding from Merck for Mothers. Another author has ties to Delfina Care, and one is on the board of directors of Planned Parenthood of Greater New York. Dr. Admon receives funding from the Agency for Healthcare Research and Quality and the National Institutes of Health. Dr. Teal has received grants from Merck, Bayer Healthcare, Sebela, and Medicines360 and personal fees from Merck and from Bayer Healthcare. Ms. Katz has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Debra Katz, CNM, has noticed a shift in the number of teenagers coming to the teen obstetrics program at St. Joseph’s Medical Center in Paterson, N.J. A decade ago, about 30 adolescents gave birth in a given month; now, that figure is closer to 20, said Ms. Katz, chief of the nurse midwifery service at the center.

Ms. Katz’s observations mirror a national trend: The rate of teen births is falling in the United States, according to a study published in Obstetrics and Gynecology.

But, there’s a catch. The adolescents who are giving birth are more likely to have obesity, mental health problems, asthma, and other conditions that can complicate their pregnancies, the research shows. Rates of delivery complications have also increased in this age group.

Ms. Katz said that, compared with adult patients, teens tend to require longer medical visits. Most patients have limited knowledge of what prenatal care entails.

“Most of these patients have never even had a female [gynecologic] exam before,” Ms. Katz said. “They come in and they’re not used to the equipment. They’re not used to the terminology.”

Also consistent with the national trends, St. Joseph’s younger patients often have mental health problems or obesity. Many also lack stable housing and adequate food.

“Unfortunately, we are seeing a greater number of patients with morbid obesity; there’s a lot of bipolar disease; here’s a lot of depression; there’s a lot of anxiety,” Ms. Katz said. “And we also have a bit of PTSD [post traumatic stress disorder] as well.”

These factors make clinical practice more complex, according to the authors of the new study. “To optimize adolescent pregnancy outcomes, prenatal care will likely need to provide increasingly complex clinical management in addition to addressing outreach challenges of this population,” the authors of the new study write.

At St. Joseph’s, teens receive prenatal care in a group setting with other patients who are due to deliver in the same month. This model, called CenteringPregnancy, can increase self-esteem, build community, and may improve patient outcomes, Ms. Katz said. The program uses a team approach that includes a dietitian and social worker to address social support needs.
 

Shifting health status

To characterize delivery hospitalization trends for patients aged 11-19 years, Anna P. Staniczenko, MD, with Columbia University Irving Medical Center, New York, and her colleagues conducted a cross-sectional analysis of data from the 2000-2018 National Inpatient Sample.

Of more than 73 million estimated delivery hospitalizations during that period, 88,363 occurred in patients aged 11-14 years, and 6,359,331 were among patients aged 15-19 years.

Deliveries among patients aged 11-14 years decreased from 2.1 per 1,000 to 0.4 per 1,000 during the time frame. Deliveries among patients aged 15-19 years decreased from 11.5% of all deliveries to 4.8% over the study period.

Among patients aged 11-19 years, rates of comorbidities significantly increased from 2000 to 2018, the researchers found. The prevalence of obesity increased from 0.2% to 7.2%, asthma increased from 1.6% to 7%, while mental health conditions increased from 0.5% to 7.1%.

Severe maternal morbidity, defined as a patient having at least one of 20 conditions, including stroke, heart failure, and sepsis, increased from 0.5% to 0.7%. The rate of postpartum hemorrhage increased from 2.9% to 4.7%, the rate of cesarean delivery increased from 15.2% to 19.5%, and that of hypertensive disorders of pregnancy increased from 7.5% to 13.7%.
 

An often overlooked group

Adolescent pregnancies are more common in the United States than in other wealthy nations, and about 80% are unintended. In addition to the growth in comorbid conditions, adolescent mothers are at an increased risk of living under the poverty line, and children born to teen moms may be at increased risk for adverse pediatric outcomes.

Still, these pregnancies “may be planned and desired. ... It is unclear that there is an ‘ideal’ rate of pregnancy for this age group,” the study authors write.

Prior research has shown an increase in rates of chronic conditions among adults giving birth, but, “from what I could tell, this is really the first data” on chronic conditions in the pediatric obstetric population, said Lindsay K. Admon, MD, an ob.gyn. at the University of Michigan, Ann Arbor, who wrote an editorial accompanying the journal article.
 

Behind the decline

That there are fewer teen deliveries may be because the adolescent population is savvier about contraceptive methods. In addition, the Affordable Care Act expanded insurance coverage of contraception, said Stephanie Teal, MD, MPH, chair of obstetrics and gynecology and reproductive biology at University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland.

Dr. Teal was involved in the Colorado Family Planning Initiative, a state effort that showed that long-acting reversible contraception was effective and acceptable to young people.

“We are definitely seeing more adolescents who use birth control the first time they have sex,” Dr. Teal told this news organization. “When I started in practice, it was fairly uncommon that I would see a teenager who was sexually active who was consistently using a birth control method. And now they just look at me, roll their eyes, and are, like, ‘Duh, of course. He uses condoms, and I have an IUD.’ ”

To the extent that these deliveries include unintended pregnancies, the data may point to a need for clinicians to provide contraceptive education to adolescents with chronic conditions, according to Dr. Admon.
 

Abortion shifts

If U.S. Supreme Court rulings and state laws further limit access to contraception or abortion, the result could lead to more teen deliveries, Dr. Admon said.

While the adolescent birth rate has plummeted, the teen abortion rate has not increased, Dr. Teal said.

“Pregnancy is a time of health risk for women, and it’s getting riskier,” she said. “Our concern is that if people are having to go through a pregnancy that they don’t feel physically or financially or emotionally prepared to go through, that we will see an increase in these kinds of adverse health outcomes with birth.”

One study author has a leadership role on an American College of Obstetricians and Gynecologists safe motherhood initiative that has received unrestricted funding from Merck for Mothers. Another author has ties to Delfina Care, and one is on the board of directors of Planned Parenthood of Greater New York. Dr. Admon receives funding from the Agency for Healthcare Research and Quality and the National Institutes of Health. Dr. Teal has received grants from Merck, Bayer Healthcare, Sebela, and Medicines360 and personal fees from Merck and from Bayer Healthcare. Ms. Katz has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The diverse effects of obesity on lung health and disease are increasingly being teased apart, with researchers honing in on the impact of metabolic dysfunction, circulating inflammatory factors produced by adipose tissue, lipid handling, and other factors – in addition to body mass index – that are associated with the obese state.

“The bird’s eye view is that obesity completely changes lung health. It’s something we’ve only recently begun to appreciate,” said Anne E. Dixon, MA, BM, BCh, director of the Vermont Lung Center at the University of Vermont, Burlington, who is focused on the research field of obesity and lung disease.

OSA and OHS

“With sleep apnea we tend to focus on anatomic considerations, but there may be relationships or interactions between obesity and neuromuscular function and neuroventilatory control,” Susheel P. Patil, MD, PhD, director of the sleep medicine program for University Hospitals and assistant professor at Case Western Reserve University, Cleveland, said in an interview.

Some studies suggest, for instance, that TNF-alpha can increase obstructive sleep apnea (OSA) susceptibility and severity through its neuroventilatory modulating properties during sleep. And the potential for additional proinflammatory cytokines produced by adipose tissue to similarly affect upper airway neuroventilatory control is an “intriguing line” of inquiry for researchers in the sleep apnea space, he said.

Leptin is of interest particularly in obesity hypoventilation syndrome (OHS), which is characterized by chronic daytime hypercapnia. Best known as a satiety hormone, leptin is produced by adipose tissue and suppresses appetite at the central nervous system level. But it has long been known that leptin also affects ventilation and the control of breathing.

When transported across the blood-brain barrier, leptin increases the hypercapnic ventilatory response, Babak Mokhlesi, MD, MSc, codirector of the Rush Lung Center and chief of pulmonary, critical care, and sleep medicine at Rush University Medical Center in Chicago, said in an interview.

Research suggests that patients with OHS may have resistance to leptin at the central nervous system level – with leptin not reaching the sites of ventilatory control. This is a “prevailing theory” and could explain why these patients “do not augment their ventilation to maintain homeostasis, normal levels of CO₂,” Dr. Mokhlesi said.

“Why some patients with severe obesity develop CO₂ retention while others do not is not fully understood,” he said, noting that patients with OHS can normalize their CO₂ quickly when instructed to take deep breaths. “What we know is that the centers in the brain responsible for augmenting ventilation when CO₂ goes up are somehow blunted.”

In a study of obese mice led by Vsevolod Y. Polotsky, MD, PhD, of Johns Hopkins University, Baltimore – and highlighted by Dr. Mokhlesi as an example of important, recent research – leptin delivered intranasally alleviated hypoventilation (and upper-airway obstruction), while intraperitoneally administered leptin did not, seemingly overcoming “central leptin deficiency.” (Am J Respir Crit Care Med. 2019;199[6]:773-83).

“This proved that there is some level of resistance in this animal model ... and has potential for therapeutics in the future,” Dr. Mokhlesi said.

Understanding the role of insulin resistance in OSA is another research focus. Some data suggest that insulin resistance, which is more common in obesity, is more prevalent in populations with OSA, Dr. Patil said. Researchers have discussed a bidirectional relationship for years, but it’s likely that insulin resistance is a precursor, he said.

In a mechanistic study published in 2016, Dr. Patil and his coinvestigators found that obese individuals with insulin resistance but without frank diabetes or sleep apnea demonstrated preclinical elevations in pharyngeal collapsibility during sleep. The findings suggest that insulin resistance could play a causal role in OSA pathogenesis by “generating requisite elevations in pharyngeal collapsibility,” they wrote (Eur. Respir J. 2016;47[6]:1718-26).

More recently, Dr. Patil noted in the interview, there is increasing appreciation in academia that the type of fat may be important to predicting OSA. “Visceral fat has a completely different cytokine-secretion profile than subcutaneous fat ... it is the more metabolically active fat that may secondarily impact upper airway function though a neuroinflammatory mechanism,” he said. “That is one of the working hypotheses today.”
 

Asthma

Research has so roundly suggested that metabolic dysfunction contributes to severe, poorly controlled asthma that there’s recent and growing interest in targeting metabolic dysfunction as part of the treatment of obese asthma, said Dr. Dixon, whose own research in obesity and lung disease has focused on asthma.

Data from animal models and some epidemiologic studies have suggested that drugs used to treat type 2 diabetes mellitus, such as glucagon-like peptide receptor-1 (GLPR-1) agonists and metformin, may help control asthma. In one recent study – cited by Dr. Dixon in a 2022 review of obesity and asthma – people with obesity and asthma who were prescribed GLPR-1 agonists for diabetes had fewer asthma exacerbations compared with those who took other medications for diabetes (Semin Respir Crit Care Med. 2022 Feb 17. doi: 10.1055/s-0042-1742384).

There is also research interest in targeting the pro-inflammatory adipokine interleukin 6 (IL-6), since increased circulating levels of IL-6 correlate with asthma severity, and in addressing oxidative stress in asthma through treatment with a mitochondrially targeted antioxidant, she said. Oxidative stress is increased in the airways of people with obesity, and researchers believe it may contribute to the pathophysiology of obese asthma through effects on airway nitric oxide levels.

(Her own research work at the University of Vermont has found associations between poor asthma control and high levels of leptin, and similar associations involving low levels of adiponectin, an anti-inflammatory adipokine that has been shown to downregulate eosinophil recruitment in the airways.)

Weight loss has been shown in mostly small, single-center studies to improve asthma control, but short of weight loss, researchers are also investigating the role of poor dietary quality. Thus far, data suggest that it’s the composition of the diet, and not just its contribution to weight gain, that could be impactful, Dr. Dixon said.

More basic research questions cited by Dr. Dixon include the extent to which adipose tissue inflammation causes inflammation in the lungs. “It’s a little unclear whether all the metabolic dysfunction associated with poor asthma control is causing inflammation in the lungs,” she said, though “we’ve done some work here that shows mediators produced by the adipose tissue could be impacting production of inflammatory mediators by the airway epithelium.”

Overall, she said, “the big questions [in asthma] are, how does adipose tissue affect the airway? Is it through direct effects? Through effects on the immune system? And obesity is affected by diet and the gut microbiome – how can these be [impacting] the airway?”

Obesity “is associated with so many changes – the gut, the immune system, and metabolic dysfunction, in addition to airway mechanics,” she said, “that I no longer think, as I did when I came to this, that it’s just one thing. It’s probably all of these things together.”

In the meantime, questions about potential shared pathways for the development of obesity and asthma remain. “Obesity is a risk factor for developing asthma, but it’s also entirely possible that asthma is a risk factor for developing obesity,” she said. (Some data from pediatric populations, she noted, suggest that nonobese children with asthma are at increased risk of developing obesity.)

Also important, Dr. Dixon said, is “emerging literature in the last 5-10 years” that suggests that people with obesity are more susceptible to the effects of air pollution. Research involving inner-city schoolchildren with asthma, for instance, has shown that those with obesity had worse symptoms with air pollution exposure than did those who were not obese.
 

Pulmonary arterial hypertension

Some research has looked at adipose tissue–produced substances in PAH, but the most well-established association in obesity and PAH involves insulin resistance.

“I don’t think we’re certain as a community that obesity [in general] is the problem – it’s not itself considered a risk factor for PAH,” Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., said in an interview. She noted that it’s “hard to dissect obesity” apart.

Researchers are “more confident,” she said, “that insulin resistance – one feature of obesity [in some people] – is associated with worse outcomes in PAH.” Metabolic disease resembling insulin resistance is common in PAH and is believed to contribute to pulmonary vascular disease and right ventricular (RV) failure – the main cause of mortality in PAH – at least in part because of increased oxidative stress.

Dr. Hemnes led a mechanistic phase II clinical trial of metformin in PAH in which the drug was associated with improved RV fractional area change and reduced RV lipid deposition (J Am Heart Assoc. 2020;9[22]:e018349), and she’s now leading a National Institutes of Health–funded multicenter trial looking at the impact of metformin and an exercise intervention on 6-minute walk distance and World Health Organization functional class in PAH.

At the Rush Lung Center, in the meantime, Dr. Mokhlesi is utilizing animal models of OSA and OHS to explore the effect of hypoxia and nighttime hypercapnia on the development of PAH. “I think the jury is still out as to whether obesity itself is a major risk factor, but if so, by what mechanism?” he said. “Is it worsening [sleep-disordered breathing], which then worsens PAH?”
 

COPD

The focus in COPD has traditionally been on underweight, but the relationship between obesity and COPD has increasingly been recognized in the last 10-15 years, said Frits M. E. Franssen, MD, PhD, of CIRO, a research institute in Horn, the Netherlands, that treats COPD and other chronic lung diseases, and of the department of respiratory medicine at Maastricht University.

Researchers like Dr. Franssen are trying, for one, to understand obesity’s impact on COPD pathophysiology and to tease apart the impact of both conditions on disease severity and patient-related outcomes such as exercise capacity and exercise-related symptoms.

When Dr. Franssen’s group compared responses to weight-bearing exercise (6-min. walk test) and weight-supported exercise (cycling) in obese and normal weight COPD patients matched for age, gender, and degree of airflow limitation, the researchers found that walking capacity was significantly reduced while cycling capacity was preserved in the obese group (Respirology. 2016;21[3]:483-8).

Exercise-related symptoms (dyspnea and leg fatigue) were largely comparable between the obese and normal-weight COPD patients in both exercise modalities. However, in other studies, dyspnea ratings during cycling – at any given level of ventilation – have been lower in obese patients, indicating that “additional fat mass may have a beneficial effect on lung functioning [in non–weight-bearing exercise],” he said in an interview.

Dr. Franssen’s group also has assessed body composition in overweight and obese patients with COPD and found that a significant number have low muscle mass. These patients had worse lung function, exercise tolerance, and muscle strength compared to patients with comparable BMI and normal muscle mass (Respir Res. 2021 Mar 25. doi: 10.1186/s12931-021-01689-w).

“We’d always thought that obese patients have normal muscle mass ... but now we know it can be dramatically low,” he said. In assessing obesity and formulating any weight loss plans, “we’re now interested not only in weight but in the distribution of fat mass and fat-free mass ... and in maintaining muscle mass in patients who are [prescribed dietary interventions].”

Paradoxically, in patients with severe COPD, obesity is associated with prolonged survival, while in patients with mild to moderate COPD, obesity is associated with increased mortality risk, he noted.

The impact of adipose tissue and the chronic inflammation and metabolic disturbances that characterize obesity are currently largely unexplored, he said. Researchers have not yet studied what optimal weights may be for patients with COPD. “And we’re interested in the questions, are body weight and body composition the result of the disease, or [are they] determining the type of COPD one will get?” Dr. Franssen said.

Patients with COPD who are obese have “more of the phenotype of chronic bronchitis,” he noted, “while typical emphysema patients are normally underweight.”

The diverse effects of obesity on lung health and disease are increasingly being teased apart, with researchers honing in on the impact of metabolic dysfunction, circulating inflammatory factors produced by adipose tissue, lipid handling, and other factors – in addition to body mass index – that are associated with the obese state.

“The bird’s eye view is that obesity completely changes lung health. It’s something we’ve only recently begun to appreciate,” said Anne E. Dixon, MA, BM, BCh, director of the Vermont Lung Center at the University of Vermont, Burlington, who is focused on the research field of obesity and lung disease.

OSA and OHS

“With sleep apnea we tend to focus on anatomic considerations, but there may be relationships or interactions between obesity and neuromuscular function and neuroventilatory control,” Susheel P. Patil, MD, PhD, director of the sleep medicine program for University Hospitals and assistant professor at Case Western Reserve University, Cleveland, said in an interview.

Some studies suggest, for instance, that TNF-alpha can increase obstructive sleep apnea (OSA) susceptibility and severity through its neuroventilatory modulating properties during sleep. And the potential for additional proinflammatory cytokines produced by adipose tissue to similarly affect upper airway neuroventilatory control is an “intriguing line” of inquiry for researchers in the sleep apnea space, he said.

Leptin is of interest particularly in obesity hypoventilation syndrome (OHS), which is characterized by chronic daytime hypercapnia. Best known as a satiety hormone, leptin is produced by adipose tissue and suppresses appetite at the central nervous system level. But it has long been known that leptin also affects ventilation and the control of breathing.

When transported across the blood-brain barrier, leptin increases the hypercapnic ventilatory response, Babak Mokhlesi, MD, MSc, codirector of the Rush Lung Center and chief of pulmonary, critical care, and sleep medicine at Rush University Medical Center in Chicago, said in an interview.

Research suggests that patients with OHS may have resistance to leptin at the central nervous system level – with leptin not reaching the sites of ventilatory control. This is a “prevailing theory” and could explain why these patients “do not augment their ventilation to maintain homeostasis, normal levels of CO₂,” Dr. Mokhlesi said.

“Why some patients with severe obesity develop CO₂ retention while others do not is not fully understood,” he said, noting that patients with OHS can normalize their CO₂ quickly when instructed to take deep breaths. “What we know is that the centers in the brain responsible for augmenting ventilation when CO₂ goes up are somehow blunted.”

In a study of obese mice led by Vsevolod Y. Polotsky, MD, PhD, of Johns Hopkins University, Baltimore – and highlighted by Dr. Mokhlesi as an example of important, recent research – leptin delivered intranasally alleviated hypoventilation (and upper-airway obstruction), while intraperitoneally administered leptin did not, seemingly overcoming “central leptin deficiency.” (Am J Respir Crit Care Med. 2019;199[6]:773-83).

“This proved that there is some level of resistance in this animal model ... and has potential for therapeutics in the future,” Dr. Mokhlesi said.

Understanding the role of insulin resistance in OSA is another research focus. Some data suggest that insulin resistance, which is more common in obesity, is more prevalent in populations with OSA, Dr. Patil said. Researchers have discussed a bidirectional relationship for years, but it’s likely that insulin resistance is a precursor, he said.

In a mechanistic study published in 2016, Dr. Patil and his coinvestigators found that obese individuals with insulin resistance but without frank diabetes or sleep apnea demonstrated preclinical elevations in pharyngeal collapsibility during sleep. The findings suggest that insulin resistance could play a causal role in OSA pathogenesis by “generating requisite elevations in pharyngeal collapsibility,” they wrote (Eur. Respir J. 2016;47[6]:1718-26).

More recently, Dr. Patil noted in the interview, there is increasing appreciation in academia that the type of fat may be important to predicting OSA. “Visceral fat has a completely different cytokine-secretion profile than subcutaneous fat ... it is the more metabolically active fat that may secondarily impact upper airway function though a neuroinflammatory mechanism,” he said. “That is one of the working hypotheses today.”
 

Asthma

Research has so roundly suggested that metabolic dysfunction contributes to severe, poorly controlled asthma that there’s recent and growing interest in targeting metabolic dysfunction as part of the treatment of obese asthma, said Dr. Dixon, whose own research in obesity and lung disease has focused on asthma.

Data from animal models and some epidemiologic studies have suggested that drugs used to treat type 2 diabetes mellitus, such as glucagon-like peptide receptor-1 (GLPR-1) agonists and metformin, may help control asthma. In one recent study – cited by Dr. Dixon in a 2022 review of obesity and asthma – people with obesity and asthma who were prescribed GLPR-1 agonists for diabetes had fewer asthma exacerbations compared with those who took other medications for diabetes (Semin Respir Crit Care Med. 2022 Feb 17. doi: 10.1055/s-0042-1742384).

There is also research interest in targeting the pro-inflammatory adipokine interleukin 6 (IL-6), since increased circulating levels of IL-6 correlate with asthma severity, and in addressing oxidative stress in asthma through treatment with a mitochondrially targeted antioxidant, she said. Oxidative stress is increased in the airways of people with obesity, and researchers believe it may contribute to the pathophysiology of obese asthma through effects on airway nitric oxide levels.

(Her own research work at the University of Vermont has found associations between poor asthma control and high levels of leptin, and similar associations involving low levels of adiponectin, an anti-inflammatory adipokine that has been shown to downregulate eosinophil recruitment in the airways.)

Weight loss has been shown in mostly small, single-center studies to improve asthma control, but short of weight loss, researchers are also investigating the role of poor dietary quality. Thus far, data suggest that it’s the composition of the diet, and not just its contribution to weight gain, that could be impactful, Dr. Dixon said.

More basic research questions cited by Dr. Dixon include the extent to which adipose tissue inflammation causes inflammation in the lungs. “It’s a little unclear whether all the metabolic dysfunction associated with poor asthma control is causing inflammation in the lungs,” she said, though “we’ve done some work here that shows mediators produced by the adipose tissue could be impacting production of inflammatory mediators by the airway epithelium.”

Overall, she said, “the big questions [in asthma] are, how does adipose tissue affect the airway? Is it through direct effects? Through effects on the immune system? And obesity is affected by diet and the gut microbiome – how can these be [impacting] the airway?”

Obesity “is associated with so many changes – the gut, the immune system, and metabolic dysfunction, in addition to airway mechanics,” she said, “that I no longer think, as I did when I came to this, that it’s just one thing. It’s probably all of these things together.”

In the meantime, questions about potential shared pathways for the development of obesity and asthma remain. “Obesity is a risk factor for developing asthma, but it’s also entirely possible that asthma is a risk factor for developing obesity,” she said. (Some data from pediatric populations, she noted, suggest that nonobese children with asthma are at increased risk of developing obesity.)

Also important, Dr. Dixon said, is “emerging literature in the last 5-10 years” that suggests that people with obesity are more susceptible to the effects of air pollution. Research involving inner-city schoolchildren with asthma, for instance, has shown that those with obesity had worse symptoms with air pollution exposure than did those who were not obese.
 

Pulmonary arterial hypertension

Some research has looked at adipose tissue–produced substances in PAH, but the most well-established association in obesity and PAH involves insulin resistance.

“I don’t think we’re certain as a community that obesity [in general] is the problem – it’s not itself considered a risk factor for PAH,” Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., said in an interview. She noted that it’s “hard to dissect obesity” apart.

Researchers are “more confident,” she said, “that insulin resistance – one feature of obesity [in some people] – is associated with worse outcomes in PAH.” Metabolic disease resembling insulin resistance is common in PAH and is believed to contribute to pulmonary vascular disease and right ventricular (RV) failure – the main cause of mortality in PAH – at least in part because of increased oxidative stress.

Dr. Hemnes led a mechanistic phase II clinical trial of metformin in PAH in which the drug was associated with improved RV fractional area change and reduced RV lipid deposition (J Am Heart Assoc. 2020;9[22]:e018349), and she’s now leading a National Institutes of Health–funded multicenter trial looking at the impact of metformin and an exercise intervention on 6-minute walk distance and World Health Organization functional class in PAH.

At the Rush Lung Center, in the meantime, Dr. Mokhlesi is utilizing animal models of OSA and OHS to explore the effect of hypoxia and nighttime hypercapnia on the development of PAH. “I think the jury is still out as to whether obesity itself is a major risk factor, but if so, by what mechanism?” he said. “Is it worsening [sleep-disordered breathing], which then worsens PAH?”
 

COPD

The focus in COPD has traditionally been on underweight, but the relationship between obesity and COPD has increasingly been recognized in the last 10-15 years, said Frits M. E. Franssen, MD, PhD, of CIRO, a research institute in Horn, the Netherlands, that treats COPD and other chronic lung diseases, and of the department of respiratory medicine at Maastricht University.

Researchers like Dr. Franssen are trying, for one, to understand obesity’s impact on COPD pathophysiology and to tease apart the impact of both conditions on disease severity and patient-related outcomes such as exercise capacity and exercise-related symptoms.

When Dr. Franssen’s group compared responses to weight-bearing exercise (6-min. walk test) and weight-supported exercise (cycling) in obese and normal weight COPD patients matched for age, gender, and degree of airflow limitation, the researchers found that walking capacity was significantly reduced while cycling capacity was preserved in the obese group (Respirology. 2016;21[3]:483-8).

Exercise-related symptoms (dyspnea and leg fatigue) were largely comparable between the obese and normal-weight COPD patients in both exercise modalities. However, in other studies, dyspnea ratings during cycling – at any given level of ventilation – have been lower in obese patients, indicating that “additional fat mass may have a beneficial effect on lung functioning [in non–weight-bearing exercise],” he said in an interview.

Dr. Franssen’s group also has assessed body composition in overweight and obese patients with COPD and found that a significant number have low muscle mass. These patients had worse lung function, exercise tolerance, and muscle strength compared to patients with comparable BMI and normal muscle mass (Respir Res. 2021 Mar 25. doi: 10.1186/s12931-021-01689-w).

“We’d always thought that obese patients have normal muscle mass ... but now we know it can be dramatically low,” he said. In assessing obesity and formulating any weight loss plans, “we’re now interested not only in weight but in the distribution of fat mass and fat-free mass ... and in maintaining muscle mass in patients who are [prescribed dietary interventions].”

Paradoxically, in patients with severe COPD, obesity is associated with prolonged survival, while in patients with mild to moderate COPD, obesity is associated with increased mortality risk, he noted.

The impact of adipose tissue and the chronic inflammation and metabolic disturbances that characterize obesity are currently largely unexplored, he said. Researchers have not yet studied what optimal weights may be for patients with COPD. “And we’re interested in the questions, are body weight and body composition the result of the disease, or [are they] determining the type of COPD one will get?” Dr. Franssen said.

Patients with COPD who are obese have “more of the phenotype of chronic bronchitis,” he noted, “while typical emphysema patients are normally underweight.”

The diverse effects of obesity on lung health and disease are increasingly being teased apart, with researchers honing in on the impact of metabolic dysfunction, circulating inflammatory factors produced by adipose tissue, lipid handling, and other factors – in addition to body mass index – that are associated with the obese state.

“The bird’s eye view is that obesity completely changes lung health. It’s something we’ve only recently begun to appreciate,” said Anne E. Dixon, MA, BM, BCh, director of the Vermont Lung Center at the University of Vermont, Burlington, who is focused on the research field of obesity and lung disease.

OSA and OHS

“With sleep apnea we tend to focus on anatomic considerations, but there may be relationships or interactions between obesity and neuromuscular function and neuroventilatory control,” Susheel P. Patil, MD, PhD, director of the sleep medicine program for University Hospitals and assistant professor at Case Western Reserve University, Cleveland, said in an interview.

Some studies suggest, for instance, that TNF-alpha can increase obstructive sleep apnea (OSA) susceptibility and severity through its neuroventilatory modulating properties during sleep. And the potential for additional proinflammatory cytokines produced by adipose tissue to similarly affect upper airway neuroventilatory control is an “intriguing line” of inquiry for researchers in the sleep apnea space, he said.

Leptin is of interest particularly in obesity hypoventilation syndrome (OHS), which is characterized by chronic daytime hypercapnia. Best known as a satiety hormone, leptin is produced by adipose tissue and suppresses appetite at the central nervous system level. But it has long been known that leptin also affects ventilation and the control of breathing.

When transported across the blood-brain barrier, leptin increases the hypercapnic ventilatory response, Babak Mokhlesi, MD, MSc, codirector of the Rush Lung Center and chief of pulmonary, critical care, and sleep medicine at Rush University Medical Center in Chicago, said in an interview.

Research suggests that patients with OHS may have resistance to leptin at the central nervous system level – with leptin not reaching the sites of ventilatory control. This is a “prevailing theory” and could explain why these patients “do not augment their ventilation to maintain homeostasis, normal levels of CO₂,” Dr. Mokhlesi said.

“Why some patients with severe obesity develop CO₂ retention while others do not is not fully understood,” he said, noting that patients with OHS can normalize their CO₂ quickly when instructed to take deep breaths. “What we know is that the centers in the brain responsible for augmenting ventilation when CO₂ goes up are somehow blunted.”

In a study of obese mice led by Vsevolod Y. Polotsky, MD, PhD, of Johns Hopkins University, Baltimore – and highlighted by Dr. Mokhlesi as an example of important, recent research – leptin delivered intranasally alleviated hypoventilation (and upper-airway obstruction), while intraperitoneally administered leptin did not, seemingly overcoming “central leptin deficiency.” (Am J Respir Crit Care Med. 2019;199[6]:773-83).

“This proved that there is some level of resistance in this animal model ... and has potential for therapeutics in the future,” Dr. Mokhlesi said.

Understanding the role of insulin resistance in OSA is another research focus. Some data suggest that insulin resistance, which is more common in obesity, is more prevalent in populations with OSA, Dr. Patil said. Researchers have discussed a bidirectional relationship for years, but it’s likely that insulin resistance is a precursor, he said.

In a mechanistic study published in 2016, Dr. Patil and his coinvestigators found that obese individuals with insulin resistance but without frank diabetes or sleep apnea demonstrated preclinical elevations in pharyngeal collapsibility during sleep. The findings suggest that insulin resistance could play a causal role in OSA pathogenesis by “generating requisite elevations in pharyngeal collapsibility,” they wrote (Eur. Respir J. 2016;47[6]:1718-26).

More recently, Dr. Patil noted in the interview, there is increasing appreciation in academia that the type of fat may be important to predicting OSA. “Visceral fat has a completely different cytokine-secretion profile than subcutaneous fat ... it is the more metabolically active fat that may secondarily impact upper airway function though a neuroinflammatory mechanism,” he said. “That is one of the working hypotheses today.”
 

Asthma

Research has so roundly suggested that metabolic dysfunction contributes to severe, poorly controlled asthma that there’s recent and growing interest in targeting metabolic dysfunction as part of the treatment of obese asthma, said Dr. Dixon, whose own research in obesity and lung disease has focused on asthma.

Data from animal models and some epidemiologic studies have suggested that drugs used to treat type 2 diabetes mellitus, such as glucagon-like peptide receptor-1 (GLPR-1) agonists and metformin, may help control asthma. In one recent study – cited by Dr. Dixon in a 2022 review of obesity and asthma – people with obesity and asthma who were prescribed GLPR-1 agonists for diabetes had fewer asthma exacerbations compared with those who took other medications for diabetes (Semin Respir Crit Care Med. 2022 Feb 17. doi: 10.1055/s-0042-1742384).

There is also research interest in targeting the pro-inflammatory adipokine interleukin 6 (IL-6), since increased circulating levels of IL-6 correlate with asthma severity, and in addressing oxidative stress in asthma through treatment with a mitochondrially targeted antioxidant, she said. Oxidative stress is increased in the airways of people with obesity, and researchers believe it may contribute to the pathophysiology of obese asthma through effects on airway nitric oxide levels.

(Her own research work at the University of Vermont has found associations between poor asthma control and high levels of leptin, and similar associations involving low levels of adiponectin, an anti-inflammatory adipokine that has been shown to downregulate eosinophil recruitment in the airways.)

Weight loss has been shown in mostly small, single-center studies to improve asthma control, but short of weight loss, researchers are also investigating the role of poor dietary quality. Thus far, data suggest that it’s the composition of the diet, and not just its contribution to weight gain, that could be impactful, Dr. Dixon said.

More basic research questions cited by Dr. Dixon include the extent to which adipose tissue inflammation causes inflammation in the lungs. “It’s a little unclear whether all the metabolic dysfunction associated with poor asthma control is causing inflammation in the lungs,” she said, though “we’ve done some work here that shows mediators produced by the adipose tissue could be impacting production of inflammatory mediators by the airway epithelium.”

Overall, she said, “the big questions [in asthma] are, how does adipose tissue affect the airway? Is it through direct effects? Through effects on the immune system? And obesity is affected by diet and the gut microbiome – how can these be [impacting] the airway?”

Obesity “is associated with so many changes – the gut, the immune system, and metabolic dysfunction, in addition to airway mechanics,” she said, “that I no longer think, as I did when I came to this, that it’s just one thing. It’s probably all of these things together.”

In the meantime, questions about potential shared pathways for the development of obesity and asthma remain. “Obesity is a risk factor for developing asthma, but it’s also entirely possible that asthma is a risk factor for developing obesity,” she said. (Some data from pediatric populations, she noted, suggest that nonobese children with asthma are at increased risk of developing obesity.)

Also important, Dr. Dixon said, is “emerging literature in the last 5-10 years” that suggests that people with obesity are more susceptible to the effects of air pollution. Research involving inner-city schoolchildren with asthma, for instance, has shown that those with obesity had worse symptoms with air pollution exposure than did those who were not obese.
 

Pulmonary arterial hypertension

Some research has looked at adipose tissue–produced substances in PAH, but the most well-established association in obesity and PAH involves insulin resistance.

“I don’t think we’re certain as a community that obesity [in general] is the problem – it’s not itself considered a risk factor for PAH,” Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., said in an interview. She noted that it’s “hard to dissect obesity” apart.

Researchers are “more confident,” she said, “that insulin resistance – one feature of obesity [in some people] – is associated with worse outcomes in PAH.” Metabolic disease resembling insulin resistance is common in PAH and is believed to contribute to pulmonary vascular disease and right ventricular (RV) failure – the main cause of mortality in PAH – at least in part because of increased oxidative stress.

Dr. Hemnes led a mechanistic phase II clinical trial of metformin in PAH in which the drug was associated with improved RV fractional area change and reduced RV lipid deposition (J Am Heart Assoc. 2020;9[22]:e018349), and she’s now leading a National Institutes of Health–funded multicenter trial looking at the impact of metformin and an exercise intervention on 6-minute walk distance and World Health Organization functional class in PAH.

At the Rush Lung Center, in the meantime, Dr. Mokhlesi is utilizing animal models of OSA and OHS to explore the effect of hypoxia and nighttime hypercapnia on the development of PAH. “I think the jury is still out as to whether obesity itself is a major risk factor, but if so, by what mechanism?” he said. “Is it worsening [sleep-disordered breathing], which then worsens PAH?”
 

COPD

The focus in COPD has traditionally been on underweight, but the relationship between obesity and COPD has increasingly been recognized in the last 10-15 years, said Frits M. E. Franssen, MD, PhD, of CIRO, a research institute in Horn, the Netherlands, that treats COPD and other chronic lung diseases, and of the department of respiratory medicine at Maastricht University.

Researchers like Dr. Franssen are trying, for one, to understand obesity’s impact on COPD pathophysiology and to tease apart the impact of both conditions on disease severity and patient-related outcomes such as exercise capacity and exercise-related symptoms.

When Dr. Franssen’s group compared responses to weight-bearing exercise (6-min. walk test) and weight-supported exercise (cycling) in obese and normal weight COPD patients matched for age, gender, and degree of airflow limitation, the researchers found that walking capacity was significantly reduced while cycling capacity was preserved in the obese group (Respirology. 2016;21[3]:483-8).

Exercise-related symptoms (dyspnea and leg fatigue) were largely comparable between the obese and normal-weight COPD patients in both exercise modalities. However, in other studies, dyspnea ratings during cycling – at any given level of ventilation – have been lower in obese patients, indicating that “additional fat mass may have a beneficial effect on lung functioning [in non–weight-bearing exercise],” he said in an interview.

Dr. Franssen’s group also has assessed body composition in overweight and obese patients with COPD and found that a significant number have low muscle mass. These patients had worse lung function, exercise tolerance, and muscle strength compared to patients with comparable BMI and normal muscle mass (Respir Res. 2021 Mar 25. doi: 10.1186/s12931-021-01689-w).

“We’d always thought that obese patients have normal muscle mass ... but now we know it can be dramatically low,” he said. In assessing obesity and formulating any weight loss plans, “we’re now interested not only in weight but in the distribution of fat mass and fat-free mass ... and in maintaining muscle mass in patients who are [prescribed dietary interventions].”

Paradoxically, in patients with severe COPD, obesity is associated with prolonged survival, while in patients with mild to moderate COPD, obesity is associated with increased mortality risk, he noted.

The impact of adipose tissue and the chronic inflammation and metabolic disturbances that characterize obesity are currently largely unexplored, he said. Researchers have not yet studied what optimal weights may be for patients with COPD. “And we’re interested in the questions, are body weight and body composition the result of the disease, or [are they] determining the type of COPD one will get?” Dr. Franssen said.

Patients with COPD who are obese have “more of the phenotype of chronic bronchitis,” he noted, “while typical emphysema patients are normally underweight.”

An intensive 1-year behavior therapy program aimed at changing a person’s response to food “cues” might help people with obesity lose a modest amount of weight, a randomized clinical trial suggests.

“Patients who are food-cue sensitive often feel out of control with their eating; they cannot resist food and/or cannot stop thinking about food,” said lead author Kerri N. Boutelle, PhD.

“Behavioral weight loss skills are not sufficient for these individuals,” so they designed this new approach, Dr. Boutelle, of the University of California, San Diego, explained in a press release.

The regulation of cues (ROC) intervention trains individuals to respond to their hunger and to resist eating highly craved foods (internal management), in contrast to behavioral weight loss programs that focus on counting calories (external management), Dr. Boutelle explained in an email.

The results of the Providing Adult Collaborative Interventions for Ideal Changes (PACIFIC) clinical trial, including follow-up out to 2 years, were published  in JAMA Network Open.

Patients in the behavioral weight loss therapy group or the combined ROC and behavioral weight loss therapy group lost more weight at 6 months than patients in the ROC group – but then they slowly regained weight (whereas patients in the ROC group did not).

At 24 months, the three groups had a similar modest weight loss, compared with a control group that did not lose weight.

“We believe these internal management strategies are more durable over time,” said Dr. Boutelle.  

However, two obesity experts, who helped develop the Canadian Adult Obesity Clinical Practice Guidelines, cautioned in emails that the intervention is very labor-intensive with less than 5% weight loss.

Four interventions

The trial was conducted at the Center for Healthy Eating and Activity Research at the University of California, San Diego, from December 2015 to December 2019.

Researchers randomized 271 adults with a mean BMI of 35 kg/m² to one of four interventions:

• Regulation of cues: Patients were not given a prescribed diet but instead were given skills to tolerate cravings and respond better to hunger or satiety cues.
• Behavioral weight loss therapy: Patients were advised to follow a balanced, calorie-deficit diet based on their weight and given related skills.
• Combined regulation of cues plus behavioral weight loss therapy.
• Control: Patients received information about nutrition and stress management plus mindfulness training and were encouraged to find social support.

Therapy was given as 26 group sessions, 90 minutes each, over 12 months, with 16 weekly sessions, four biweekly sessions, and six monthly booster sessions.

Participants were asked to take part in 150 minutes of moderate to high intensity exercise each week and aim for 10,000 steps per day. All patients except those in the control group received a pedometer.

The patients were a mean age of 46 years, 82% were women and 62% were White.

At the end of the 12-month intervention, mean BMI had dropped by –1.18 kg/m² in the ROC group and by –1.58 kg/m² and –1.56 kg/m² in the other two groups, compared with the control group, where BMI was virtually unchanged.

At 24 months follow-up, mean BMI was similar (roughly 33.5 kg/m²) in the ROC, the behavioral weight loss therapy, and the ROC plus behavioral weight loss therapy groups.

There was weight regain from 12 months in the latter two groups but not in the ROC group.
 

‘Nice study, but not practical’

“This is a nice study, but in no way is it practical,” Sean Wharton, MD, summarized.

“I think it may have difficulty finding its way into everyday practice,” said Dr. Wharton, adjunct professor at McMaster University, Hamilton, Ontario.

Also, “it does not compare ROC to pharmacotherapy,” he added, which is “quickly becoming the gold standard for obesity management. We have learned that adding intensive behavioral therapy – more visits and possibly a liquid diet as part of the weight management and some light group counseling – to pharmacotherapy does not add much.”

However, Dr. Wharton conceded that if an individual did not want, or could not take, pharmacotherapy and had access to ROC sessions, this might be a good option.

“The challenge will be offering this labor-intensive tool to 40% of Americans living with obesity,” he said.

The ROC intervention “is very different than a GP’s office that may see a patient two to three times/year max, with limited supports,” Dr. Wharton pointed out.

“It is labor-intensive, not reproducible in most places, and cannot be sustained forever. There is no evidence that the learning remains past the treatment interval. For example, 2 to 3 years later, are patients still adhering to ROC? Is weight still decreased or do they need to come to classes every month forever?”  
 

‘Modest weight loss, doubtful long-term benefits’

Similarly, Arya M. Sharma, MD, said: “While this [ROC] approach may be helpful for some individuals, given the rather modest weight loss achieved (despite considerable efforts and a cash incentive), the long-term clinical benefits remain doubtful.”

The weight loss of less than 5% over 24 months is “in the ballpark of other behavioral weight-loss interventions,” said Dr. Sharma, of the University of Edmonton, Alberta, and past scientific director of Obesity Canada.  

“I’m not convinced” about less weight regain, he added. “The difference between the groups is minimal. While this approach may well help individuals better deal with food cues, it does not change the underlying biology of weight regain.”

“This approach at best may help prevent future weight gain in susceptible individuals,” he speculated. “I would consider this more as a weight-stabilization than a weight-loss strategy.”
 

Next steps

Insurance doesn’t always cover weight loss with a mental health professional, Dr. Boutelle agreed. “However, there are eating disorder categories that also apply to many of our food-cue-sensitive patients, including binge eating,” she noted.

“We believe that ROC is an alternative model for weight loss that could be offered to patients who are interested or for whom behavioral weight loss has not been successful ... who are highly food-cue-responsive.”

The group is writing a manual about the ROC program to disseminate to other behavior therapists. They are also studying ROC in another clinical trial, Solutions for Hunger and Regulating Eating (SHARE). The ROC program is being offered at the UC San Diego Center for Healthy Eating and Activity Research, of which Dr. Boutelle is director.

The study was supported by grants from the National Institutes of Health. The researchers have reported no relevant financial relationships. Dr. Wharton has reported receiving honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has reported receiving speakers bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.

A version of this article first appeared on Medscape.com.

An intensive 1-year behavior therapy program aimed at changing a person’s response to food “cues” might help people with obesity lose a modest amount of weight, a randomized clinical trial suggests.

“Patients who are food-cue sensitive often feel out of control with their eating; they cannot resist food and/or cannot stop thinking about food,” said lead author Kerri N. Boutelle, PhD.

“Behavioral weight loss skills are not sufficient for these individuals,” so they designed this new approach, Dr. Boutelle, of the University of California, San Diego, explained in a press release.

The regulation of cues (ROC) intervention trains individuals to respond to their hunger and to resist eating highly craved foods (internal management), in contrast to behavioral weight loss programs that focus on counting calories (external management), Dr. Boutelle explained in an email.

The results of the Providing Adult Collaborative Interventions for Ideal Changes (PACIFIC) clinical trial, including follow-up out to 2 years, were published  in JAMA Network Open.

Patients in the behavioral weight loss therapy group or the combined ROC and behavioral weight loss therapy group lost more weight at 6 months than patients in the ROC group – but then they slowly regained weight (whereas patients in the ROC group did not).

At 24 months, the three groups had a similar modest weight loss, compared with a control group that did not lose weight.

“We believe these internal management strategies are more durable over time,” said Dr. Boutelle.  

However, two obesity experts, who helped develop the Canadian Adult Obesity Clinical Practice Guidelines, cautioned in emails that the intervention is very labor-intensive with less than 5% weight loss.

Four interventions

The trial was conducted at the Center for Healthy Eating and Activity Research at the University of California, San Diego, from December 2015 to December 2019.

Researchers randomized 271 adults with a mean BMI of 35 kg/m² to one of four interventions:

• Regulation of cues: Patients were not given a prescribed diet but instead were given skills to tolerate cravings and respond better to hunger or satiety cues.
• Behavioral weight loss therapy: Patients were advised to follow a balanced, calorie-deficit diet based on their weight and given related skills.
• Combined regulation of cues plus behavioral weight loss therapy.
• Control: Patients received information about nutrition and stress management plus mindfulness training and were encouraged to find social support.

Therapy was given as 26 group sessions, 90 minutes each, over 12 months, with 16 weekly sessions, four biweekly sessions, and six monthly booster sessions.

Participants were asked to take part in 150 minutes of moderate to high intensity exercise each week and aim for 10,000 steps per day. All patients except those in the control group received a pedometer.

The patients were a mean age of 46 years, 82% were women and 62% were White.

At the end of the 12-month intervention, mean BMI had dropped by –1.18 kg/m² in the ROC group and by –1.58 kg/m² and –1.56 kg/m² in the other two groups, compared with the control group, where BMI was virtually unchanged.

At 24 months follow-up, mean BMI was similar (roughly 33.5 kg/m²) in the ROC, the behavioral weight loss therapy, and the ROC plus behavioral weight loss therapy groups.

There was weight regain from 12 months in the latter two groups but not in the ROC group.
 

‘Nice study, but not practical’

“This is a nice study, but in no way is it practical,” Sean Wharton, MD, summarized.

“I think it may have difficulty finding its way into everyday practice,” said Dr. Wharton, adjunct professor at McMaster University, Hamilton, Ontario.

Also, “it does not compare ROC to pharmacotherapy,” he added, which is “quickly becoming the gold standard for obesity management. We have learned that adding intensive behavioral therapy – more visits and possibly a liquid diet as part of the weight management and some light group counseling – to pharmacotherapy does not add much.”

However, Dr. Wharton conceded that if an individual did not want, or could not take, pharmacotherapy and had access to ROC sessions, this might be a good option.

“The challenge will be offering this labor-intensive tool to 40% of Americans living with obesity,” he said.

The ROC intervention “is very different than a GP’s office that may see a patient two to three times/year max, with limited supports,” Dr. Wharton pointed out.

“It is labor-intensive, not reproducible in most places, and cannot be sustained forever. There is no evidence that the learning remains past the treatment interval. For example, 2 to 3 years later, are patients still adhering to ROC? Is weight still decreased or do they need to come to classes every month forever?”  
 

‘Modest weight loss, doubtful long-term benefits’

Similarly, Arya M. Sharma, MD, said: “While this [ROC] approach may be helpful for some individuals, given the rather modest weight loss achieved (despite considerable efforts and a cash incentive), the long-term clinical benefits remain doubtful.”

The weight loss of less than 5% over 24 months is “in the ballpark of other behavioral weight-loss interventions,” said Dr. Sharma, of the University of Edmonton, Alberta, and past scientific director of Obesity Canada.  

“I’m not convinced” about less weight regain, he added. “The difference between the groups is minimal. While this approach may well help individuals better deal with food cues, it does not change the underlying biology of weight regain.”

“This approach at best may help prevent future weight gain in susceptible individuals,” he speculated. “I would consider this more as a weight-stabilization than a weight-loss strategy.”
 

Next steps

Insurance doesn’t always cover weight loss with a mental health professional, Dr. Boutelle agreed. “However, there are eating disorder categories that also apply to many of our food-cue-sensitive patients, including binge eating,” she noted.

“We believe that ROC is an alternative model for weight loss that could be offered to patients who are interested or for whom behavioral weight loss has not been successful ... who are highly food-cue-responsive.”

The group is writing a manual about the ROC program to disseminate to other behavior therapists. They are also studying ROC in another clinical trial, Solutions for Hunger and Regulating Eating (SHARE). The ROC program is being offered at the UC San Diego Center for Healthy Eating and Activity Research, of which Dr. Boutelle is director.

The study was supported by grants from the National Institutes of Health. The researchers have reported no relevant financial relationships. Dr. Wharton has reported receiving honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has reported receiving speakers bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.

A version of this article first appeared on Medscape.com.

An intensive 1-year behavior therapy program aimed at changing a person’s response to food “cues” might help people with obesity lose a modest amount of weight, a randomized clinical trial suggests.

“Patients who are food-cue sensitive often feel out of control with their eating; they cannot resist food and/or cannot stop thinking about food,” said lead author Kerri N. Boutelle, PhD.

“Behavioral weight loss skills are not sufficient for these individuals,” so they designed this new approach, Dr. Boutelle, of the University of California, San Diego, explained in a press release.

The regulation of cues (ROC) intervention trains individuals to respond to their hunger and to resist eating highly craved foods (internal management), in contrast to behavioral weight loss programs that focus on counting calories (external management), Dr. Boutelle explained in an email.

The results of the Providing Adult Collaborative Interventions for Ideal Changes (PACIFIC) clinical trial, including follow-up out to 2 years, were published  in JAMA Network Open.

Patients in the behavioral weight loss therapy group or the combined ROC and behavioral weight loss therapy group lost more weight at 6 months than patients in the ROC group – but then they slowly regained weight (whereas patients in the ROC group did not).

At 24 months, the three groups had a similar modest weight loss, compared with a control group that did not lose weight.

“We believe these internal management strategies are more durable over time,” said Dr. Boutelle.  

However, two obesity experts, who helped develop the Canadian Adult Obesity Clinical Practice Guidelines, cautioned in emails that the intervention is very labor-intensive with less than 5% weight loss.

Four interventions

The trial was conducted at the Center for Healthy Eating and Activity Research at the University of California, San Diego, from December 2015 to December 2019.

Researchers randomized 271 adults with a mean BMI of 35 kg/m² to one of four interventions:

• Regulation of cues: Patients were not given a prescribed diet but instead were given skills to tolerate cravings and respond better to hunger or satiety cues.
• Behavioral weight loss therapy: Patients were advised to follow a balanced, calorie-deficit diet based on their weight and given related skills.
• Combined regulation of cues plus behavioral weight loss therapy.
• Control: Patients received information about nutrition and stress management plus mindfulness training and were encouraged to find social support.

Therapy was given as 26 group sessions, 90 minutes each, over 12 months, with 16 weekly sessions, four biweekly sessions, and six monthly booster sessions.

Participants were asked to take part in 150 minutes of moderate to high intensity exercise each week and aim for 10,000 steps per day. All patients except those in the control group received a pedometer.

The patients were a mean age of 46 years, 82% were women and 62% were White.

At the end of the 12-month intervention, mean BMI had dropped by –1.18 kg/m² in the ROC group and by –1.58 kg/m² and –1.56 kg/m² in the other two groups, compared with the control group, where BMI was virtually unchanged.

At 24 months follow-up, mean BMI was similar (roughly 33.5 kg/m²) in the ROC, the behavioral weight loss therapy, and the ROC plus behavioral weight loss therapy groups.

There was weight regain from 12 months in the latter two groups but not in the ROC group.
 

‘Nice study, but not practical’

“This is a nice study, but in no way is it practical,” Sean Wharton, MD, summarized.

“I think it may have difficulty finding its way into everyday practice,” said Dr. Wharton, adjunct professor at McMaster University, Hamilton, Ontario.

Also, “it does not compare ROC to pharmacotherapy,” he added, which is “quickly becoming the gold standard for obesity management. We have learned that adding intensive behavioral therapy – more visits and possibly a liquid diet as part of the weight management and some light group counseling – to pharmacotherapy does not add much.”

However, Dr. Wharton conceded that if an individual did not want, or could not take, pharmacotherapy and had access to ROC sessions, this might be a good option.

“The challenge will be offering this labor-intensive tool to 40% of Americans living with obesity,” he said.

The ROC intervention “is very different than a GP’s office that may see a patient two to three times/year max, with limited supports,” Dr. Wharton pointed out.

“It is labor-intensive, not reproducible in most places, and cannot be sustained forever. There is no evidence that the learning remains past the treatment interval. For example, 2 to 3 years later, are patients still adhering to ROC? Is weight still decreased or do they need to come to classes every month forever?”  
 

‘Modest weight loss, doubtful long-term benefits’

Similarly, Arya M. Sharma, MD, said: “While this [ROC] approach may be helpful for some individuals, given the rather modest weight loss achieved (despite considerable efforts and a cash incentive), the long-term clinical benefits remain doubtful.”

The weight loss of less than 5% over 24 months is “in the ballpark of other behavioral weight-loss interventions,” said Dr. Sharma, of the University of Edmonton, Alberta, and past scientific director of Obesity Canada.  

“I’m not convinced” about less weight regain, he added. “The difference between the groups is minimal. While this approach may well help individuals better deal with food cues, it does not change the underlying biology of weight regain.”

“This approach at best may help prevent future weight gain in susceptible individuals,” he speculated. “I would consider this more as a weight-stabilization than a weight-loss strategy.”
 

Next steps

Insurance doesn’t always cover weight loss with a mental health professional, Dr. Boutelle agreed. “However, there are eating disorder categories that also apply to many of our food-cue-sensitive patients, including binge eating,” she noted.

“We believe that ROC is an alternative model for weight loss that could be offered to patients who are interested or for whom behavioral weight loss has not been successful ... who are highly food-cue-responsive.”

The group is writing a manual about the ROC program to disseminate to other behavior therapists. They are also studying ROC in another clinical trial, Solutions for Hunger and Regulating Eating (SHARE). The ROC program is being offered at the UC San Diego Center for Healthy Eating and Activity Research, of which Dr. Boutelle is director.

The study was supported by grants from the National Institutes of Health. The researchers have reported no relevant financial relationships. Dr. Wharton has reported receiving honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has reported receiving speakers bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.

A version of this article first appeared on Medscape.com.

A few years ago I tracked down my medical school interviewer to thank him for giving me the opportunity to do what I felt I was called to do. I was surprised that, after 15 years, he actually remembered me and remembered details like walking to the courtyard to meet my father who’d driven me to the interview.

Gratitude throughout my career has grounded me in moments of hardship and highlighted joyful times that give me peace. Sharing my gratitude and letting him know I was happy felt important to me.

Choosing to practice family medicine has a lot to do with why I am happy in my career today.

One of my frustrations with health care had been its emphasis on treatment of sickness, rather than a broader one that incorporated prevention of sickness. During my third year of medical school, I was following a family and sports medicine faculty member who was focusing on aspects of lifestyle medicine to help a patient remain active and age gracefully. Seeing opportunities to practice preventative medicine in family medicine made me realize the specialty was the perfect fit for me.
 

Food as medicine

While participating in rotations I also realized you can find a subspecialty within family medicine.

During my fourth year of medical school, I followed an attending who was seeing a patient for hypertension, prediabetes and hypercholesterolemia. The attending told the patient to eat “healthier,” gave her a handout, and scheduled a follow up appointment for 6 months later.

My thoughts were: “That’s it? That’s how we counsel patients to improve their dietary habits?”

As the patient was leaving the exam room, I asked her what type of oil she cooked with, and I proceeded to share culinary tips from my mother – who was a self-taught and early adopter of the food-as-medicine movement.

Once I started my residency, I knew I’d want to incorporate lifestyle and dietary approaches at many of my patient visits.

I scheduled patients every month to monitor their weight, follow up on chronic conditions, but more importantly, to engage them in their health and empower them to make small lifestyle changes each month and report their efforts. I felt like I was their health coach and cheerleader.
 

My career in family medicine

Entering the job market allowed me to form my philosophy of treating patients with a mind, body, and spirit approach. I chose to practice value-based care, which aligns with my lifestyle and preventative medicine approach .

I currently practice in a small family medicine–only clinic that is part of a larger multispecialty system. Primary care specialties in my organization are valued, respected and central to a patient’s well being and care. We are encouraged to spend time with patients, assess barriers to care and work collaboratively with our healthcare team, so that preventative medicine approaches take the lead in a patient’s health. This supportive culture and environment is one where my passion for food as medicine has thrived.

One day I forgot to pack a lunch and instead brought a grocery bag of items to make a salad. When I realized I made too much, I sent an email to my staff to get some “free salad in my office.” This serendipitous moment started an informal office “salad club” each week. Continued support from my staff and leadership, allowed me to consider further extending this teaching to my patients and my colleagues.

Three years ago, I helped adopt a sustainable plant-forward menu for our physician meetings, complete with a recipe from the menu for physicians to replicate at home or give to their patients.

I also pursued adoption of shared medical appointments for our medical group. These appointments apply the “see one, do one, teach one” model in medicine, but with culinary medicine as the focus.

Knowing that my patients are all connected to their families through food, I sought this as an opportunity to dive in further with wellness opportunities at their next meal. After almost 2 years of working on this project, I was able to host my first shared medical appointment with a group of patients on March 12, 2020. The next day schools closed, lockdowns occurred, and the world changed.
 

Opportunities highlighted by the pandemic

We always knew health care was broken but adding the increasingly longer hours and COVID vaccine–hesitant patients that the pandemic brought made everything look dark at times. What has helped me stay hopeful and energetic for system changes is feeling gratitude and seeking bright lights.

My experiences seeing patients in telehealth visits are examples of some of the bright lights I found in the pandemic. During these visits, patients showed me something from their pantry, and we’d go over nutritional labels together.

Additionally, my patients became engaged with their own conditions and wanted to improve them because of news articles highlighting risk factors for COVID-19, such as obesity. I had an active audience when it came to talking about food-as-medicine approaches to improving risk factors and immunity. And since everyone was listening, I didn’t stop at food. I also talked about physical health, stress resiliency, planetary diets, sleep, connections, and lastly vaccines!

Once the vaccines were distributed, I naturally gravitated to having those conversations with patients and colleagues and on social media. Plus, the pandemic gave us moments of simple times to slow down, take more rests, be less overscheduled, consider work-life priorities, and, lastly, to be okay with not being totally okay.

In practicing primary care, we have a unique role in seeing medicine from a whole body, whole person, whole family perspective. There is an opportunity to highlight what is broken in medicine and aim to make it whole.

I’m currently looking at shared medical appointments as a new standard way to provide care to all patients, because it improves access, provides better quality visits and aligns my values, mission, and purpose.

In the midst of the pandemic, I helped advocate for a sustainable plant-forward menu that was launched throughout four different hospitals in the Sharp HealthCare system, in California, in 2020. Knowing that patients were served a menu I played a role in, gave me solace.

As part of the hospital food and nutrition team, I am grateful for the opportunity I have to work on a broader mission to address social determinants of health and seek opportunities to help the system work for our patients.

Public health communication has been lacking in the pandemic, but another bright light is that we were still the trusted messengers to our patients and our communities. I’m continually honored and humbled to be trusted with a whole family’s health.

Dr. Neison practices family medicine and culinary medicine at Sharp Rees-Stealy Medical Group in San Diego, and is cochair of climate and planetary health for SRS Medical Group. You can follow her on Instagram, LinkedIn, and Facebook @Flavors4WellnessMD.

A few years ago I tracked down my medical school interviewer to thank him for giving me the opportunity to do what I felt I was called to do. I was surprised that, after 15 years, he actually remembered me and remembered details like walking to the courtyard to meet my father who’d driven me to the interview.

Gratitude throughout my career has grounded me in moments of hardship and highlighted joyful times that give me peace. Sharing my gratitude and letting him know I was happy felt important to me.

Choosing to practice family medicine has a lot to do with why I am happy in my career today.

One of my frustrations with health care had been its emphasis on treatment of sickness, rather than a broader one that incorporated prevention of sickness. During my third year of medical school, I was following a family and sports medicine faculty member who was focusing on aspects of lifestyle medicine to help a patient remain active and age gracefully. Seeing opportunities to practice preventative medicine in family medicine made me realize the specialty was the perfect fit for me.
 

Food as medicine

While participating in rotations I also realized you can find a subspecialty within family medicine.

During my fourth year of medical school, I followed an attending who was seeing a patient for hypertension, prediabetes and hypercholesterolemia. The attending told the patient to eat “healthier,” gave her a handout, and scheduled a follow up appointment for 6 months later.

My thoughts were: “That’s it? That’s how we counsel patients to improve their dietary habits?”

As the patient was leaving the exam room, I asked her what type of oil she cooked with, and I proceeded to share culinary tips from my mother – who was a self-taught and early adopter of the food-as-medicine movement.

Once I started my residency, I knew I’d want to incorporate lifestyle and dietary approaches at many of my patient visits.

I scheduled patients every month to monitor their weight, follow up on chronic conditions, but more importantly, to engage them in their health and empower them to make small lifestyle changes each month and report their efforts. I felt like I was their health coach and cheerleader.
 

My career in family medicine

Entering the job market allowed me to form my philosophy of treating patients with a mind, body, and spirit approach. I chose to practice value-based care, which aligns with my lifestyle and preventative medicine approach .

I currently practice in a small family medicine–only clinic that is part of a larger multispecialty system. Primary care specialties in my organization are valued, respected and central to a patient’s well being and care. We are encouraged to spend time with patients, assess barriers to care and work collaboratively with our healthcare team, so that preventative medicine approaches take the lead in a patient’s health. This supportive culture and environment is one where my passion for food as medicine has thrived.

One day I forgot to pack a lunch and instead brought a grocery bag of items to make a salad. When I realized I made too much, I sent an email to my staff to get some “free salad in my office.” This serendipitous moment started an informal office “salad club” each week. Continued support from my staff and leadership, allowed me to consider further extending this teaching to my patients and my colleagues.

Three years ago, I helped adopt a sustainable plant-forward menu for our physician meetings, complete with a recipe from the menu for physicians to replicate at home or give to their patients.

I also pursued adoption of shared medical appointments for our medical group. These appointments apply the “see one, do one, teach one” model in medicine, but with culinary medicine as the focus.

Knowing that my patients are all connected to their families through food, I sought this as an opportunity to dive in further with wellness opportunities at their next meal. After almost 2 years of working on this project, I was able to host my first shared medical appointment with a group of patients on March 12, 2020. The next day schools closed, lockdowns occurred, and the world changed.
 

Opportunities highlighted by the pandemic

We always knew health care was broken but adding the increasingly longer hours and COVID vaccine–hesitant patients that the pandemic brought made everything look dark at times. What has helped me stay hopeful and energetic for system changes is feeling gratitude and seeking bright lights.

My experiences seeing patients in telehealth visits are examples of some of the bright lights I found in the pandemic. During these visits, patients showed me something from their pantry, and we’d go over nutritional labels together.

Additionally, my patients became engaged with their own conditions and wanted to improve them because of news articles highlighting risk factors for COVID-19, such as obesity. I had an active audience when it came to talking about food-as-medicine approaches to improving risk factors and immunity. And since everyone was listening, I didn’t stop at food. I also talked about physical health, stress resiliency, planetary diets, sleep, connections, and lastly vaccines!

Once the vaccines were distributed, I naturally gravitated to having those conversations with patients and colleagues and on social media. Plus, the pandemic gave us moments of simple times to slow down, take more rests, be less overscheduled, consider work-life priorities, and, lastly, to be okay with not being totally okay.

In practicing primary care, we have a unique role in seeing medicine from a whole body, whole person, whole family perspective. There is an opportunity to highlight what is broken in medicine and aim to make it whole.

I’m currently looking at shared medical appointments as a new standard way to provide care to all patients, because it improves access, provides better quality visits and aligns my values, mission, and purpose.

In the midst of the pandemic, I helped advocate for a sustainable plant-forward menu that was launched throughout four different hospitals in the Sharp HealthCare system, in California, in 2020. Knowing that patients were served a menu I played a role in, gave me solace.

As part of the hospital food and nutrition team, I am grateful for the opportunity I have to work on a broader mission to address social determinants of health and seek opportunities to help the system work for our patients.

Public health communication has been lacking in the pandemic, but another bright light is that we were still the trusted messengers to our patients and our communities. I’m continually honored and humbled to be trusted with a whole family’s health.

Dr. Neison practices family medicine and culinary medicine at Sharp Rees-Stealy Medical Group in San Diego, and is cochair of climate and planetary health for SRS Medical Group. You can follow her on Instagram, LinkedIn, and Facebook @Flavors4WellnessMD.

A few years ago I tracked down my medical school interviewer to thank him for giving me the opportunity to do what I felt I was called to do. I was surprised that, after 15 years, he actually remembered me and remembered details like walking to the courtyard to meet my father who’d driven me to the interview.

Gratitude throughout my career has grounded me in moments of hardship and highlighted joyful times that give me peace. Sharing my gratitude and letting him know I was happy felt important to me.

Choosing to practice family medicine has a lot to do with why I am happy in my career today.

One of my frustrations with health care had been its emphasis on treatment of sickness, rather than a broader one that incorporated prevention of sickness. During my third year of medical school, I was following a family and sports medicine faculty member who was focusing on aspects of lifestyle medicine to help a patient remain active and age gracefully. Seeing opportunities to practice preventative medicine in family medicine made me realize the specialty was the perfect fit for me.
 

Food as medicine

While participating in rotations I also realized you can find a subspecialty within family medicine.

During my fourth year of medical school, I followed an attending who was seeing a patient for hypertension, prediabetes and hypercholesterolemia. The attending told the patient to eat “healthier,” gave her a handout, and scheduled a follow up appointment for 6 months later.

My thoughts were: “That’s it? That’s how we counsel patients to improve their dietary habits?”

As the patient was leaving the exam room, I asked her what type of oil she cooked with, and I proceeded to share culinary tips from my mother – who was a self-taught and early adopter of the food-as-medicine movement.

Once I started my residency, I knew I’d want to incorporate lifestyle and dietary approaches at many of my patient visits.

I scheduled patients every month to monitor their weight, follow up on chronic conditions, but more importantly, to engage them in their health and empower them to make small lifestyle changes each month and report their efforts. I felt like I was their health coach and cheerleader.
 

My career in family medicine

Entering the job market allowed me to form my philosophy of treating patients with a mind, body, and spirit approach. I chose to practice value-based care, which aligns with my lifestyle and preventative medicine approach .

I currently practice in a small family medicine–only clinic that is part of a larger multispecialty system. Primary care specialties in my organization are valued, respected and central to a patient’s well being and care. We are encouraged to spend time with patients, assess barriers to care and work collaboratively with our healthcare team, so that preventative medicine approaches take the lead in a patient’s health. This supportive culture and environment is one where my passion for food as medicine has thrived.

One day I forgot to pack a lunch and instead brought a grocery bag of items to make a salad. When I realized I made too much, I sent an email to my staff to get some “free salad in my office.” This serendipitous moment started an informal office “salad club” each week. Continued support from my staff and leadership, allowed me to consider further extending this teaching to my patients and my colleagues.

Three years ago, I helped adopt a sustainable plant-forward menu for our physician meetings, complete with a recipe from the menu for physicians to replicate at home or give to their patients.

I also pursued adoption of shared medical appointments for our medical group. These appointments apply the “see one, do one, teach one” model in medicine, but with culinary medicine as the focus.

Knowing that my patients are all connected to their families through food, I sought this as an opportunity to dive in further with wellness opportunities at their next meal. After almost 2 years of working on this project, I was able to host my first shared medical appointment with a group of patients on March 12, 2020. The next day schools closed, lockdowns occurred, and the world changed.
 

Opportunities highlighted by the pandemic

We always knew health care was broken but adding the increasingly longer hours and COVID vaccine–hesitant patients that the pandemic brought made everything look dark at times. What has helped me stay hopeful and energetic for system changes is feeling gratitude and seeking bright lights.

My experiences seeing patients in telehealth visits are examples of some of the bright lights I found in the pandemic. During these visits, patients showed me something from their pantry, and we’d go over nutritional labels together.

Additionally, my patients became engaged with their own conditions and wanted to improve them because of news articles highlighting risk factors for COVID-19, such as obesity. I had an active audience when it came to talking about food-as-medicine approaches to improving risk factors and immunity. And since everyone was listening, I didn’t stop at food. I also talked about physical health, stress resiliency, planetary diets, sleep, connections, and lastly vaccines!

Once the vaccines were distributed, I naturally gravitated to having those conversations with patients and colleagues and on social media. Plus, the pandemic gave us moments of simple times to slow down, take more rests, be less overscheduled, consider work-life priorities, and, lastly, to be okay with not being totally okay.

In practicing primary care, we have a unique role in seeing medicine from a whole body, whole person, whole family perspective. There is an opportunity to highlight what is broken in medicine and aim to make it whole.

I’m currently looking at shared medical appointments as a new standard way to provide care to all patients, because it improves access, provides better quality visits and aligns my values, mission, and purpose.

In the midst of the pandemic, I helped advocate for a sustainable plant-forward menu that was launched throughout four different hospitals in the Sharp HealthCare system, in California, in 2020. Knowing that patients were served a menu I played a role in, gave me solace.

As part of the hospital food and nutrition team, I am grateful for the opportunity I have to work on a broader mission to address social determinants of health and seek opportunities to help the system work for our patients.

Public health communication has been lacking in the pandemic, but another bright light is that we were still the trusted messengers to our patients and our communities. I’m continually honored and humbled to be trusted with a whole family’s health.

Dr. Neison practices family medicine and culinary medicine at Sharp Rees-Stealy Medical Group in San Diego, and is cochair of climate and planetary health for SRS Medical Group. You can follow her on Instagram, LinkedIn, and Facebook @Flavors4WellnessMD.

Doctors are advising women who have had bariatric surgery to wait at least 2 years before trying to conceive to reduce the risk of a small-for-gestational-age baby.

In fact, babies conceived less than 2 years post bariatric surgery are 15 times more likely to be small for gestational age as those conceived after this cut-off point, new study findings indicate.

Ana Carreira, MD, Coimbra Hospital and University Centre, Portugal, presented the findings as a poster at the European Congress on Obesity (ECO) 2022.

“The prevalence of small-for-gestational-age babies was similar across the different types of bariatric surgery, and we calculated that the cut-off for the bariatric-surgery-to-conception interval for a lower risk of small for gestational age babies was 24.5 months,” Dr. Carreira reported.

The study also found that for each additional month after the 2-year time point from bariatric surgery to conception, there was a 4.2-g (0.15-oz) increase in birth weight, and there was a 5% lower risk for a small-for-gestational-age neonate. 

“Clinically, this is very significant,” she told this news organization.

“While it may be possible to slightly adjust this on an individual basis, it is important that women who are undergoing bariatric surgery are aware of the risk of early conception and of the benefits of delaying pregnancy,” she added.

Asked to comment, Kari Johansson, PhD, of the Karolinska Institute, Stockholm, who has worked in the field, said: “These increased risks have been hypothesized to potentially be attributed to the inadequate in utero availability of nutrients to the fetus, especially during the first year post bariatric surgery when the rapid and largest weight loss occurs. This is why many clinical guidelines recommend women wait 12-24 months until getting pregnant.”

Indeed, the American College of Obstetricians and Gynecologists recommends women wait 12-24 months post bariatric surgery before trying to conceive.

Dr. Johansson also noted, however, that there were no significant increased risks of adverse outcomes between pregnancies with a surgery-to-conception interval of 12 months or less versus over 12 months in a recent meta-analysis. But those authors also concluded that large cohorts with sufficient power are needed “before any definite conclusions can be made on the optimal surgery-to-conception interval,” she cautioned.
 

All types of bariatric surgery investigated

Bariatric surgery, which is increasingly popular in women of reproductive age, involves rapid weight loss, which can trigger improved fertility, Dr. Carreira explained. Currently, clinics generally advise women to wait at least 1 year before trying for a baby post-surgery.

Dr. Carreira and colleagues conducted the study because “the optimal bariatric-surgery-to-conception interval has yet to be determined,” and they wanted to examine the issue of small-for-gestational-age babies in particular, she noted. They also examined outcomes after a number of different bariatric procedures.

They retrospectively reviewed a cohort of 48 post surgery pregnancies (in 2008-2020) with a minimum follow-up of 30 weeks and determined the proportion of small-for-gestational-age neonates, defined as having a birth weight less than the 10th percentile according to National Center for Health Statistics growth charts.

Mean maternal age was 34.3 years, mean body mass index at conception was 30.9 kg/m², and 70.8% had a bariatric-surgery-to-conception interval of over 24 months, 14.6% of 12-24 months, and 14.6% of less than 12 months.

Bariatric surgeries included adjustable gastric banding (22.9%), sleeve gastrectomy (35.4%), Roux-en-Y gastric bypass (37.5%), and biliopancreatic diversion (4.2%).

Overall, mean birth weight was 2.98 kg (6.6 lb) and the prevalence of small-for-gestational-age babies was 26.3%.

“For an interval of less than 24 months, around 60% of babies were small for gestational age,” Dr. Carreira noted. 

Most babies who were small for gestational age were conceived at 18 months (median), and those who were not were conceived at 59 months (median).

And, after adjustment for maternal comorbidities, the odds ratio for a small-for-gestational-age neonate was 15.1 (95% confidence interval, 2.4-93.1) for a baby conceived less than 24 months after surgery.  

“Some people think the interval can change according to the type of bariatric surgery, but we found no difference in findings according to [surgery] type,” added Dr. Carreira.

She pointed out that after discharge from their endocrinology clinic (after bariatric surgery), the women are cared for by their family doctor, “and we find that when they return to us in pregnancy their nutrient deficiencies have not been properly addressed. They need to be addressed at least 6 months prior to conception.”

“We recommend that women wait at least 2 years after bariatric surgery before trying to conceive, irrespective of the type of surgery,” she reiterated.

Dr. Carreira and Dr. Johansson have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Doctors are advising women who have had bariatric surgery to wait at least 2 years before trying to conceive to reduce the risk of a small-for-gestational-age baby.

In fact, babies conceived less than 2 years post bariatric surgery are 15 times more likely to be small for gestational age as those conceived after this cut-off point, new study findings indicate.

Ana Carreira, MD, Coimbra Hospital and University Centre, Portugal, presented the findings as a poster at the European Congress on Obesity (ECO) 2022.

“The prevalence of small-for-gestational-age babies was similar across the different types of bariatric surgery, and we calculated that the cut-off for the bariatric-surgery-to-conception interval for a lower risk of small for gestational age babies was 24.5 months,” Dr. Carreira reported.

The study also found that for each additional month after the 2-year time point from bariatric surgery to conception, there was a 4.2-g (0.15-oz) increase in birth weight, and there was a 5% lower risk for a small-for-gestational-age neonate. 

“Clinically, this is very significant,” she told this news organization.

“While it may be possible to slightly adjust this on an individual basis, it is important that women who are undergoing bariatric surgery are aware of the risk of early conception and of the benefits of delaying pregnancy,” she added.

Asked to comment, Kari Johansson, PhD, of the Karolinska Institute, Stockholm, who has worked in the field, said: “These increased risks have been hypothesized to potentially be attributed to the inadequate in utero availability of nutrients to the fetus, especially during the first year post bariatric surgery when the rapid and largest weight loss occurs. This is why many clinical guidelines recommend women wait 12-24 months until getting pregnant.”

Indeed, the American College of Obstetricians and Gynecologists recommends women wait 12-24 months post bariatric surgery before trying to conceive.

Dr. Johansson also noted, however, that there were no significant increased risks of adverse outcomes between pregnancies with a surgery-to-conception interval of 12 months or less versus over 12 months in a recent meta-analysis. But those authors also concluded that large cohorts with sufficient power are needed “before any definite conclusions can be made on the optimal surgery-to-conception interval,” she cautioned.
 

All types of bariatric surgery investigated

Bariatric surgery, which is increasingly popular in women of reproductive age, involves rapid weight loss, which can trigger improved fertility, Dr. Carreira explained. Currently, clinics generally advise women to wait at least 1 year before trying for a baby post-surgery.

Dr. Carreira and colleagues conducted the study because “the optimal bariatric-surgery-to-conception interval has yet to be determined,” and they wanted to examine the issue of small-for-gestational-age babies in particular, she noted. They also examined outcomes after a number of different bariatric procedures.

They retrospectively reviewed a cohort of 48 post surgery pregnancies (in 2008-2020) with a minimum follow-up of 30 weeks and determined the proportion of small-for-gestational-age neonates, defined as having a birth weight less than the 10th percentile according to National Center for Health Statistics growth charts.

Mean maternal age was 34.3 years, mean body mass index at conception was 30.9 kg/m², and 70.8% had a bariatric-surgery-to-conception interval of over 24 months, 14.6% of 12-24 months, and 14.6% of less than 12 months.

Bariatric surgeries included adjustable gastric banding (22.9%), sleeve gastrectomy (35.4%), Roux-en-Y gastric bypass (37.5%), and biliopancreatic diversion (4.2%).

Overall, mean birth weight was 2.98 kg (6.6 lb) and the prevalence of small-for-gestational-age babies was 26.3%.

“For an interval of less than 24 months, around 60% of babies were small for gestational age,” Dr. Carreira noted. 

Most babies who were small for gestational age were conceived at 18 months (median), and those who were not were conceived at 59 months (median).

And, after adjustment for maternal comorbidities, the odds ratio for a small-for-gestational-age neonate was 15.1 (95% confidence interval, 2.4-93.1) for a baby conceived less than 24 months after surgery.  

“Some people think the interval can change according to the type of bariatric surgery, but we found no difference in findings according to [surgery] type,” added Dr. Carreira.

She pointed out that after discharge from their endocrinology clinic (after bariatric surgery), the women are cared for by their family doctor, “and we find that when they return to us in pregnancy their nutrient deficiencies have not been properly addressed. They need to be addressed at least 6 months prior to conception.”

“We recommend that women wait at least 2 years after bariatric surgery before trying to conceive, irrespective of the type of surgery,” she reiterated.

Dr. Carreira and Dr. Johansson have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Doctors are advising women who have had bariatric surgery to wait at least 2 years before trying to conceive to reduce the risk of a small-for-gestational-age baby.

In fact, babies conceived less than 2 years post bariatric surgery are 15 times more likely to be small for gestational age as those conceived after this cut-off point, new study findings indicate.

Ana Carreira, MD, Coimbra Hospital and University Centre, Portugal, presented the findings as a poster at the European Congress on Obesity (ECO) 2022.

“The prevalence of small-for-gestational-age babies was similar across the different types of bariatric surgery, and we calculated that the cut-off for the bariatric-surgery-to-conception interval for a lower risk of small for gestational age babies was 24.5 months,” Dr. Carreira reported.

The study also found that for each additional month after the 2-year time point from bariatric surgery to conception, there was a 4.2-g (0.15-oz) increase in birth weight, and there was a 5% lower risk for a small-for-gestational-age neonate. 

“Clinically, this is very significant,” she told this news organization.

“While it may be possible to slightly adjust this on an individual basis, it is important that women who are undergoing bariatric surgery are aware of the risk of early conception and of the benefits of delaying pregnancy,” she added.

Asked to comment, Kari Johansson, PhD, of the Karolinska Institute, Stockholm, who has worked in the field, said: “These increased risks have been hypothesized to potentially be attributed to the inadequate in utero availability of nutrients to the fetus, especially during the first year post bariatric surgery when the rapid and largest weight loss occurs. This is why many clinical guidelines recommend women wait 12-24 months until getting pregnant.”

Indeed, the American College of Obstetricians and Gynecologists recommends women wait 12-24 months post bariatric surgery before trying to conceive.

Dr. Johansson also noted, however, that there were no significant increased risks of adverse outcomes between pregnancies with a surgery-to-conception interval of 12 months or less versus over 12 months in a recent meta-analysis. But those authors also concluded that large cohorts with sufficient power are needed “before any definite conclusions can be made on the optimal surgery-to-conception interval,” she cautioned.
 

All types of bariatric surgery investigated

Bariatric surgery, which is increasingly popular in women of reproductive age, involves rapid weight loss, which can trigger improved fertility, Dr. Carreira explained. Currently, clinics generally advise women to wait at least 1 year before trying for a baby post-surgery.

Dr. Carreira and colleagues conducted the study because “the optimal bariatric-surgery-to-conception interval has yet to be determined,” and they wanted to examine the issue of small-for-gestational-age babies in particular, she noted. They also examined outcomes after a number of different bariatric procedures.

They retrospectively reviewed a cohort of 48 post surgery pregnancies (in 2008-2020) with a minimum follow-up of 30 weeks and determined the proportion of small-for-gestational-age neonates, defined as having a birth weight less than the 10th percentile according to National Center for Health Statistics growth charts.

Mean maternal age was 34.3 years, mean body mass index at conception was 30.9 kg/m², and 70.8% had a bariatric-surgery-to-conception interval of over 24 months, 14.6% of 12-24 months, and 14.6% of less than 12 months.

Bariatric surgeries included adjustable gastric banding (22.9%), sleeve gastrectomy (35.4%), Roux-en-Y gastric bypass (37.5%), and biliopancreatic diversion (4.2%).

Overall, mean birth weight was 2.98 kg (6.6 lb) and the prevalence of small-for-gestational-age babies was 26.3%.

“For an interval of less than 24 months, around 60% of babies were small for gestational age,” Dr. Carreira noted. 

Most babies who were small for gestational age were conceived at 18 months (median), and those who were not were conceived at 59 months (median).

And, after adjustment for maternal comorbidities, the odds ratio for a small-for-gestational-age neonate was 15.1 (95% confidence interval, 2.4-93.1) for a baby conceived less than 24 months after surgery.  

“Some people think the interval can change according to the type of bariatric surgery, but we found no difference in findings according to [surgery] type,” added Dr. Carreira.

She pointed out that after discharge from their endocrinology clinic (after bariatric surgery), the women are cared for by their family doctor, “and we find that when they return to us in pregnancy their nutrient deficiencies have not been properly addressed. They need to be addressed at least 6 months prior to conception.”

“We recommend that women wait at least 2 years after bariatric surgery before trying to conceive, irrespective of the type of surgery,” she reiterated.

Dr. Carreira and Dr. Johansson have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Only 43% of early child care programs in the United States met guidelines for both sufficient opportunities outdoors and 60-90 minutes of physical activity daily, according to researchers.

To date, no national study has examined these factors, according to Maria H. Boyle, MS, RD, with Abt Associates in Cambridge, Mass., and colleagues. They conducted the study published online in Pediatrics.

The results came “even employing a relatively lenient interpretation of the guidance,” the authors noted, and have particular significance because about 60% of preschool children in the United States are enrolled in center-based care.

Nearly three-fourths of the programs (74%) met the outdoor-opportunities guideline, but only 50% met the physical activity guideline.

Caring for Our Children (CFOC) guidance from the American Academy of Pediatrics recommends at least two outdoor physical activity opportunities (weather permitting) and at least 60-90 minutes allotted for moderate and vigorous physical activities each day during care for children aged 1-6 years.

Still, “children are frequently observed to be sedentary or inactive when in child care settings,” the authors wrote.

They found that some of the main barriers included weather and staff not joining outdoor play.

The researchers used the Study of Nutrition and Activity in Child Care Settings (SNACS), which assesses opportunities for physical activity opportunities and sedentary occasions for children aged 1-5 years at programs participating in the U.S. Department of Agriculture Child and Adult Care Food Program.

Their sample included 227 classrooms: 96 in child care centers and 131 in Head Start programs.

On 1 day (from February to July 2017) an observer in each sampled classroom recorded whether there were designated outdoor and indoor spaces for physical activity, whether that was a playground or other outdoor play space, such as a field, grassy area, or other open area, or parking lot used for play.

They looked for a separate indoor room or gym for active play and how many minutes the class spent in these spaces, and whether there were physical activity facilitators. They made note of barriers, including weather that was too hot or too cold or involved precipitation.

The data show that while almost all programs observed (97%) had dedicated outdoor play space, only 34% had a separate dedicated indoor play space – a gym, for example, or another room separate from main classrooms.

“Of those without a separate indoor play space, virtually all (99.8%) indicated a classroom was available for indoor play.”


 

Weather and staff not participating in play are barriers

After adjustment for program characteristics, weather barriers resulted in an average 74 fewer minutes daily allotted to physical activity (P < .001).

Another large barrier was staff not participating in play. That was associated with 31 fewer minutes per day allotted for physical activity (P < .001).

“Given the critical role of child care staff as gatekeepers in allowing and encouraging physical activity, it is as important to measure sedentary time when children are not permitted to be active as to measure time when they have opportunity to be active,” the authors wrote. “Best practice guidelines emphasize limiting time children are expected to stay seated during care.”

William Roberts, MD, professor in the department of family medicine and community health at the University of Minnesota in Minneapolis, said in an interview that the findings in this paper help quantify a public health concern as inactivity early sets a harmful precedent.

“Inactive kids too often become inactive adults subject to the long list of noncommunicable chronic diseases associated with lack of regular exercise,” he said.

Lack of movement in childhood, in a program setting or at home, contributes to the obesity epidemic, he pointed out.

“They also do not develop the motor and social skills associated with free play and physical activity,” he said.

He said the findings in this study can guide questions when choosing a child care program. He noted that parents should ask: “What are the opportunities for free play and physical activity?”

The authors and Dr. Roberts declared no relevant financial relationships.

Only 43% of early child care programs in the United States met guidelines for both sufficient opportunities outdoors and 60-90 minutes of physical activity daily, according to researchers.

To date, no national study has examined these factors, according to Maria H. Boyle, MS, RD, with Abt Associates in Cambridge, Mass., and colleagues. They conducted the study published online in Pediatrics.

The results came “even employing a relatively lenient interpretation of the guidance,” the authors noted, and have particular significance because about 60% of preschool children in the United States are enrolled in center-based care.

Nearly three-fourths of the programs (74%) met the outdoor-opportunities guideline, but only 50% met the physical activity guideline.

Caring for Our Children (CFOC) guidance from the American Academy of Pediatrics recommends at least two outdoor physical activity opportunities (weather permitting) and at least 60-90 minutes allotted for moderate and vigorous physical activities each day during care for children aged 1-6 years.

Still, “children are frequently observed to be sedentary or inactive when in child care settings,” the authors wrote.

They found that some of the main barriers included weather and staff not joining outdoor play.

The researchers used the Study of Nutrition and Activity in Child Care Settings (SNACS), which assesses opportunities for physical activity opportunities and sedentary occasions for children aged 1-5 years at programs participating in the U.S. Department of Agriculture Child and Adult Care Food Program.

Their sample included 227 classrooms: 96 in child care centers and 131 in Head Start programs.

On 1 day (from February to July 2017) an observer in each sampled classroom recorded whether there were designated outdoor and indoor spaces for physical activity, whether that was a playground or other outdoor play space, such as a field, grassy area, or other open area, or parking lot used for play.

They looked for a separate indoor room or gym for active play and how many minutes the class spent in these spaces, and whether there were physical activity facilitators. They made note of barriers, including weather that was too hot or too cold or involved precipitation.

The data show that while almost all programs observed (97%) had dedicated outdoor play space, only 34% had a separate dedicated indoor play space – a gym, for example, or another room separate from main classrooms.

“Of those without a separate indoor play space, virtually all (99.8%) indicated a classroom was available for indoor play.”


 

Weather and staff not participating in play are barriers

After adjustment for program characteristics, weather barriers resulted in an average 74 fewer minutes daily allotted to physical activity (P < .001).

Another large barrier was staff not participating in play. That was associated with 31 fewer minutes per day allotted for physical activity (P < .001).

“Given the critical role of child care staff as gatekeepers in allowing and encouraging physical activity, it is as important to measure sedentary time when children are not permitted to be active as to measure time when they have opportunity to be active,” the authors wrote. “Best practice guidelines emphasize limiting time children are expected to stay seated during care.”

William Roberts, MD, professor in the department of family medicine and community health at the University of Minnesota in Minneapolis, said in an interview that the findings in this paper help quantify a public health concern as inactivity early sets a harmful precedent.

“Inactive kids too often become inactive adults subject to the long list of noncommunicable chronic diseases associated with lack of regular exercise,” he said.

Lack of movement in childhood, in a program setting or at home, contributes to the obesity epidemic, he pointed out.

“They also do not develop the motor and social skills associated with free play and physical activity,” he said.

He said the findings in this study can guide questions when choosing a child care program. He noted that parents should ask: “What are the opportunities for free play and physical activity?”

The authors and Dr. Roberts declared no relevant financial relationships.

Only 43% of early child care programs in the United States met guidelines for both sufficient opportunities outdoors and 60-90 minutes of physical activity daily, according to researchers.

To date, no national study has examined these factors, according to Maria H. Boyle, MS, RD, with Abt Associates in Cambridge, Mass., and colleagues. They conducted the study published online in Pediatrics.

The results came “even employing a relatively lenient interpretation of the guidance,” the authors noted, and have particular significance because about 60% of preschool children in the United States are enrolled in center-based care.

Nearly three-fourths of the programs (74%) met the outdoor-opportunities guideline, but only 50% met the physical activity guideline.

Caring for Our Children (CFOC) guidance from the American Academy of Pediatrics recommends at least two outdoor physical activity opportunities (weather permitting) and at least 60-90 minutes allotted for moderate and vigorous physical activities each day during care for children aged 1-6 years.

Still, “children are frequently observed to be sedentary or inactive when in child care settings,” the authors wrote.

They found that some of the main barriers included weather and staff not joining outdoor play.

The researchers used the Study of Nutrition and Activity in Child Care Settings (SNACS), which assesses opportunities for physical activity opportunities and sedentary occasions for children aged 1-5 years at programs participating in the U.S. Department of Agriculture Child and Adult Care Food Program.

Their sample included 227 classrooms: 96 in child care centers and 131 in Head Start programs.

On 1 day (from February to July 2017) an observer in each sampled classroom recorded whether there were designated outdoor and indoor spaces for physical activity, whether that was a playground or other outdoor play space, such as a field, grassy area, or other open area, or parking lot used for play.

They looked for a separate indoor room or gym for active play and how many minutes the class spent in these spaces, and whether there were physical activity facilitators. They made note of barriers, including weather that was too hot or too cold or involved precipitation.

The data show that while almost all programs observed (97%) had dedicated outdoor play space, only 34% had a separate dedicated indoor play space – a gym, for example, or another room separate from main classrooms.

“Of those without a separate indoor play space, virtually all (99.8%) indicated a classroom was available for indoor play.”


 

Weather and staff not participating in play are barriers

After adjustment for program characteristics, weather barriers resulted in an average 74 fewer minutes daily allotted to physical activity (P < .001).

Another large barrier was staff not participating in play. That was associated with 31 fewer minutes per day allotted for physical activity (P < .001).

“Given the critical role of child care staff as gatekeepers in allowing and encouraging physical activity, it is as important to measure sedentary time when children are not permitted to be active as to measure time when they have opportunity to be active,” the authors wrote. “Best practice guidelines emphasize limiting time children are expected to stay seated during care.”

William Roberts, MD, professor in the department of family medicine and community health at the University of Minnesota in Minneapolis, said in an interview that the findings in this paper help quantify a public health concern as inactivity early sets a harmful precedent.

“Inactive kids too often become inactive adults subject to the long list of noncommunicable chronic diseases associated with lack of regular exercise,” he said.

Lack of movement in childhood, in a program setting or at home, contributes to the obesity epidemic, he pointed out.

“They also do not develop the motor and social skills associated with free play and physical activity,” he said.

He said the findings in this study can guide questions when choosing a child care program. He noted that parents should ask: “What are the opportunities for free play and physical activity?”

The authors and Dr. Roberts declared no relevant financial relationships.

According to the latest evidence, the ketogenic diet is emerging as an effective strategy not only to promote weight loss, but also to manage many comorbidities associated with obesity, including COVID-19. This development was revealed during the 8th International Scientific Symposium New Frontiers in Scientific Research, organized by PronoKal Group and held in Barcelona. During this conference, international multidisciplinary experts in the study and management of obesity presented the latest data on the benefits of treatment based on a very-low-calorie ketogenic diet.

“Nutritional ketosis has gained great interest in recent years because it is shown to have beneficial properties for health and promotes healthy aging, increasing longevity,” said Ana Belén Crujeiras, BSc, PhD, principal investigator of the Health Research Institute of Santiago de Compostela-Galician Health Service (IDIS-SERGAS) Group of Epigenomics in Endocrinology and Nutrition and the Biomedical Research Networking Center for Obesity and Nutrition Physiopathology (CIBEROBN). “Furthermore, in the case of obesity, we have more and more evidence that it is an effective treatment, mainly because to achieve this metabolic state (ketosis), routes that require the combustion of fats are activated, and this induces body weight loss.”

The specialist stressed that several strategies are used to induce nutritional ketosis. They are characterized by low carbohydrate consumption (low-carbohydrate and high-fat diet; low-carbohydrate, low-fat diet; and intermittent fasting). But Dr. Crujeiras warned that to use it as a treatment for a disease such as obesity, it must be backed by strong and solid scientific evidence, moving away from the concept of fad diets.

In this sense, since 2010, Dr. Crujeiras’ team has developed several studies focused on analyzing the efficacy and safety of treatment with a very-low-calorie ketogenic diet, the results of which have been published in high-impact journals.

Dr. Crujeiras commented on the main conclusions drawn from these investigations. “Our work has shown that the very-low-calorie ketogenic diet is effective for rapid weight loss and maintenance of lost weight, as well as reducing fat mass, primarily visceral fat mass.

“In this sense, a very interesting result is that despite the strong weight loss it induces, it preserves muscle mass and function and improves resting metabolic rate. These two variables are important, because all therapeutic strategies that exist to lose weight lead to a significant reduction in fat-free mass and also a reduction in energy expenditure at rest. This factor is associated with the risk of regaining lost weight, which is currently the great challenge in the treatment of obesity,” she added.
 

Specific methylation pattern

Dr. Crujeiras indicated that other notable evidence is the favorable impact on an emotional and psychological level. “To determine whether the caloric restriction of this diet and the strong weight loss that it involves were associated with an increased desire to eat, we also carried out an analysis with psychobiological tests. These results led us to conclude that this guideline is accompanied by a reduction of anxiety about food and an improvement in psychobiological parameters, thus increasing the quality of life of these patients.”

The specialist also mentioned that studies currently in progress show that the beneficial effect of this diet could be mediated by epigenetic mechanisms. “In our group, we have identified a specific DNA methylation pattern in people with obesity and we wondered if the very-low-calorie ketogenic diet would be able to reverse that methylome.

“We conducted a study in which we collected blood samples from patients on the very-low-calorie ketogenic diet (600 to 800 kcal/day) drawn before treatment, at peak ketosis, and at the end of treatment. After determining the global pattern of DNA in all patients with obesity targeted with this strategy and through bioinformatic analysis, we were able to obtain a methylation pattern. The results showed that after weight loss on the very-low-calorie ketogenic diet, the methylome that obese people initially had [was] reversed and matched that of normal-weight people.

“Continuing with this bioinformatic analysis more comprehensively, we wanted to see what kind of genes were differentially methylated, especially by the action of the ketosis itself. We found that most of the genes that exhibited differential methylation (in total, 292 identified) belonged to pathways that were involved in the regulation of metabolism, adipose tissue function, CNS function, and also carcinogenesis,” she continued.
 

Immunomodulatory effect

Dr. Crujeiras said that her research group also observed the modulatory role of the very-low-calorie ketogenic diet in the functioning of the immune system, “something that was not seen after similar weight loss induced by bariatric surgery. We analyzed this data in the context of the situation created by COVID-19, taking into account the evidence that people with obesity, compared to those with normal weight, have a higher risk of becoming infected and of having a poor evolution of the infection.”

In this regard, Dr. Crujeiras’ team launched an investigation to study the ACE2 gene methylation pattern, comparing obesity with normal weight and the situation after following a very-low-calorie ketogenic diet or undergoing bariatric surgery. “We observed that the methylation pattern of this gene in obese people was increased, compared to normal-weight people,” she explained, “and this increase was observed mainly in visceral adipose tissue. However, we did not see this in subcutaneous adipose tissue, which is in agreement with the hypothesis that visceral adipose tissue is that mostly associated with obesity-related comorbidities.

“Likewise, the very-low-calorie ketogenic diet was associated with decreased ACE2 methylation, along with increased exposure of this gene. However, after bariatric surgery, no significant changes were observed, so we deduce that we are protecting the patient in some way from inflammation and, therefore, from the potential of serious illness if they become infected.

“In light of these results, we wanted to dig deeper into what was happening with the immune system of obese patients and that inflammation after a very-low-calorie ketogenic diet. We conducted a new study, currently under review in the journal Clinical Nutrition, with the same approach, comparing this diet with a standard hypocaloric balanced diet and bariatric surgery, in which we analyzed a wide battery of cytokines (32). We have observed a differential pattern between the very-low-calorie ketogenic diet and bariatric surgery.

“The results confirm our hypothesis that the very-low-calorie ketogenic diet remodels the inflammatory status of obese patients, and we were also able to verify that the increase in ketone bodies has immunomodulatory properties that were previously demonstrated in preclinical and animal models, which is associated with increased immune function in these patients,” added Dr. Crujeiras.
 

Personalization and weight regain

In regard to the next steps to take in the knowledge and clinical application of the benefits of this dietary strategy, Dr. Crujeiras said that despite the fact that this diet is known to be effective, it is currently prescribed in a standard manner to all patients, “but there is some variability in the response and also a high risk of regaining weight, as is the case with any nutritional intervention strategy, with that ‘regain’ of lost weight being the main challenge in the treatment of obesity. In this sense, the epigenomic and epigenetic markers that we have identified could help us optimize treatment.”

She added that the future lies in establishing an algorithm that encompasses the patient’s exposome data, along with their genetic and epigenetic profile, to properly classify patients and prescribe a personalized precision therapeutic strategy.

Luca Busetto, MD, cochair of the Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO), also insisted on the challenge posed by the individualized application of the very-low-calorie ketogenic diet, emphasizing that this diet should always be prescribed by a doctor after an appropriate assessment of the patient. “Obesity is not a matter of willpower or motivation, and most people with obesity have struggled their entire lives and failed because their biology tends to cause weight regain. Therefore, we should try to offer them the options that we currently have, including the very-low-calorie ketogenic diet, adapting them as much as possible to the profile of each patient.”

During his speech, Dr. Busetto presented the recent European guidelines for the management of obesity in adults with a very-low-calorie ketogenic diet, endorsed by EASO, and analyzed the main strengths of these recommendations.

Dr. Busetto remarked that three important points clearly justify the use of the very-low-calorie ketogenic diet. The first is the speed with which the initial weight loss occurs. Recent studies have looked at the benefits of a significant loss of excess weight early in a weight-loss diet, and although this is an association rather than a cause, the results strongly suggest that rapid initial weight loss increases the chance of the result being maintained in the long term. This clashes with the traditional recommendation of losing weight little by little as a strategy to achieve long-term results, but it must be taken into account that there are many myths in the treatment of obesity that current evidence is dismantling with new data – and this is one of them.

Secondly, the effect of the very-low-calorie ketogenic diet can be added to other treatments. This has been demonstrated by studies carried out with liraglutide that showed that this dietary strategy optimizes results, compared with patients who had been treated only with this drug. The third point that justifies the use of the very-low-calorie ketogenic diet is the management of obesity comorbidities. Several investigations demonstrate the effectiveness of this diet in this regard, especially in the case of type 2 diabetes. Data suggest that the substantial weight reductions achieved with it also favor the remission of these comorbidities in many patients.
 

EASO ‘approval’

Dr. Busetto pointed out that, based on this evidence, the OMTF proposed the development of standards to be included in the EASO guidelines, since there had been no specific recommendation on the very-low-calorie ketogenic diet.

“The main objective of these European guidelines was to provide data referenced by scientific evidence and to suggest a common protocol for the use of this dietary strategy,” he added.

For this, a very exhaustive meta-analysis was carried out, researching all the publications that compared the very-low-calorie ketogenic diet with other diets. The results showed the superiority of the former method for the reduction of body mass index and weight and fat mass, with no difference in lean (muscle) mass, despite significant weight loss in these patients.

This evidence also demonstrates a reduction and an improvement in metabolic markers, specifically glucose metabolism and lipid metabolism.

“The final conclusions of the study corroborate that the very-low-calorie ketogenic diet can be recommended as an effective and safe tool for people with obesity, especially those with severe obesity or comorbidities (joint disease, preoperative period to bariatric surgery, metabolic and cardiovascular diseases) who need immediate, substantial weight loss. In addition, it can be prescribed to specific groups of patients with obesity after considering potential contraindications and under medical follow-up,” said Dr. Busetto.

In Dr. Busetto’s opinion, it would be convenient to refer to this approach as a method, instead of as a diet, “because, in reality, the state of ketosis is limited in time, and if the ketogenic phase is stopped without a continuity plan, obviously weight is regained. In addition, the method approach may increase adherence by patients.”

Finally, Dr. Busetto emphasized the importance of integrating this type of treatment into a long-term lifestyle strategy (including habits, exercise, and nutritional advice). “We must start from the basis that obesity is a chronic and relapsing disease, whose management should also be chronic and probably maintained throughout life.”

Dr. Crujeiras and Dr. Busetto have disclosed no relevant financial relationships. PronoKal Group has recently become part of Nestlé Health Science.

A version of this article appeared on Medscape.com. It was translated from Medscape Spanish Edition.

According to the latest evidence, the ketogenic diet is emerging as an effective strategy not only to promote weight loss, but also to manage many comorbidities associated with obesity, including COVID-19. This development was revealed during the 8th International Scientific Symposium New Frontiers in Scientific Research, organized by PronoKal Group and held in Barcelona. During this conference, international multidisciplinary experts in the study and management of obesity presented the latest data on the benefits of treatment based on a very-low-calorie ketogenic diet.

“Nutritional ketosis has gained great interest in recent years because it is shown to have beneficial properties for health and promotes healthy aging, increasing longevity,” said Ana Belén Crujeiras, BSc, PhD, principal investigator of the Health Research Institute of Santiago de Compostela-Galician Health Service (IDIS-SERGAS) Group of Epigenomics in Endocrinology and Nutrition and the Biomedical Research Networking Center for Obesity and Nutrition Physiopathology (CIBEROBN). “Furthermore, in the case of obesity, we have more and more evidence that it is an effective treatment, mainly because to achieve this metabolic state (ketosis), routes that require the combustion of fats are activated, and this induces body weight loss.”

The specialist stressed that several strategies are used to induce nutritional ketosis. They are characterized by low carbohydrate consumption (low-carbohydrate and high-fat diet; low-carbohydrate, low-fat diet; and intermittent fasting). But Dr. Crujeiras warned that to use it as a treatment for a disease such as obesity, it must be backed by strong and solid scientific evidence, moving away from the concept of fad diets.

In this sense, since 2010, Dr. Crujeiras’ team has developed several studies focused on analyzing the efficacy and safety of treatment with a very-low-calorie ketogenic diet, the results of which have been published in high-impact journals.

Dr. Crujeiras commented on the main conclusions drawn from these investigations. “Our work has shown that the very-low-calorie ketogenic diet is effective for rapid weight loss and maintenance of lost weight, as well as reducing fat mass, primarily visceral fat mass.

“In this sense, a very interesting result is that despite the strong weight loss it induces, it preserves muscle mass and function and improves resting metabolic rate. These two variables are important, because all therapeutic strategies that exist to lose weight lead to a significant reduction in fat-free mass and also a reduction in energy expenditure at rest. This factor is associated with the risk of regaining lost weight, which is currently the great challenge in the treatment of obesity,” she added.
 

Specific methylation pattern

Dr. Crujeiras indicated that other notable evidence is the favorable impact on an emotional and psychological level. “To determine whether the caloric restriction of this diet and the strong weight loss that it involves were associated with an increased desire to eat, we also carried out an analysis with psychobiological tests. These results led us to conclude that this guideline is accompanied by a reduction of anxiety about food and an improvement in psychobiological parameters, thus increasing the quality of life of these patients.”

The specialist also mentioned that studies currently in progress show that the beneficial effect of this diet could be mediated by epigenetic mechanisms. “In our group, we have identified a specific DNA methylation pattern in people with obesity and we wondered if the very-low-calorie ketogenic diet would be able to reverse that methylome.

“We conducted a study in which we collected blood samples from patients on the very-low-calorie ketogenic diet (600 to 800 kcal/day) drawn before treatment, at peak ketosis, and at the end of treatment. After determining the global pattern of DNA in all patients with obesity targeted with this strategy and through bioinformatic analysis, we were able to obtain a methylation pattern. The results showed that after weight loss on the very-low-calorie ketogenic diet, the methylome that obese people initially had [was] reversed and matched that of normal-weight people.

“Continuing with this bioinformatic analysis more comprehensively, we wanted to see what kind of genes were differentially methylated, especially by the action of the ketosis itself. We found that most of the genes that exhibited differential methylation (in total, 292 identified) belonged to pathways that were involved in the regulation of metabolism, adipose tissue function, CNS function, and also carcinogenesis,” she continued.
 

Immunomodulatory effect

Dr. Crujeiras said that her research group also observed the modulatory role of the very-low-calorie ketogenic diet in the functioning of the immune system, “something that was not seen after similar weight loss induced by bariatric surgery. We analyzed this data in the context of the situation created by COVID-19, taking into account the evidence that people with obesity, compared to those with normal weight, have a higher risk of becoming infected and of having a poor evolution of the infection.”

In this regard, Dr. Crujeiras’ team launched an investigation to study the ACE2 gene methylation pattern, comparing obesity with normal weight and the situation after following a very-low-calorie ketogenic diet or undergoing bariatric surgery. “We observed that the methylation pattern of this gene in obese people was increased, compared to normal-weight people,” she explained, “and this increase was observed mainly in visceral adipose tissue. However, we did not see this in subcutaneous adipose tissue, which is in agreement with the hypothesis that visceral adipose tissue is that mostly associated with obesity-related comorbidities.

“Likewise, the very-low-calorie ketogenic diet was associated with decreased ACE2 methylation, along with increased exposure of this gene. However, after bariatric surgery, no significant changes were observed, so we deduce that we are protecting the patient in some way from inflammation and, therefore, from the potential of serious illness if they become infected.

“In light of these results, we wanted to dig deeper into what was happening with the immune system of obese patients and that inflammation after a very-low-calorie ketogenic diet. We conducted a new study, currently under review in the journal Clinical Nutrition, with the same approach, comparing this diet with a standard hypocaloric balanced diet and bariatric surgery, in which we analyzed a wide battery of cytokines (32). We have observed a differential pattern between the very-low-calorie ketogenic diet and bariatric surgery.

“The results confirm our hypothesis that the very-low-calorie ketogenic diet remodels the inflammatory status of obese patients, and we were also able to verify that the increase in ketone bodies has immunomodulatory properties that were previously demonstrated in preclinical and animal models, which is associated with increased immune function in these patients,” added Dr. Crujeiras.
 

Personalization and weight regain

In regard to the next steps to take in the knowledge and clinical application of the benefits of this dietary strategy, Dr. Crujeiras said that despite the fact that this diet is known to be effective, it is currently prescribed in a standard manner to all patients, “but there is some variability in the response and also a high risk of regaining weight, as is the case with any nutritional intervention strategy, with that ‘regain’ of lost weight being the main challenge in the treatment of obesity. In this sense, the epigenomic and epigenetic markers that we have identified could help us optimize treatment.”

She added that the future lies in establishing an algorithm that encompasses the patient’s exposome data, along with their genetic and epigenetic profile, to properly classify patients and prescribe a personalized precision therapeutic strategy.

Luca Busetto, MD, cochair of the Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO), also insisted on the challenge posed by the individualized application of the very-low-calorie ketogenic diet, emphasizing that this diet should always be prescribed by a doctor after an appropriate assessment of the patient. “Obesity is not a matter of willpower or motivation, and most people with obesity have struggled their entire lives and failed because their biology tends to cause weight regain. Therefore, we should try to offer them the options that we currently have, including the very-low-calorie ketogenic diet, adapting them as much as possible to the profile of each patient.”

During his speech, Dr. Busetto presented the recent European guidelines for the management of obesity in adults with a very-low-calorie ketogenic diet, endorsed by EASO, and analyzed the main strengths of these recommendations.

Dr. Busetto remarked that three important points clearly justify the use of the very-low-calorie ketogenic diet. The first is the speed with which the initial weight loss occurs. Recent studies have looked at the benefits of a significant loss of excess weight early in a weight-loss diet, and although this is an association rather than a cause, the results strongly suggest that rapid initial weight loss increases the chance of the result being maintained in the long term. This clashes with the traditional recommendation of losing weight little by little as a strategy to achieve long-term results, but it must be taken into account that there are many myths in the treatment of obesity that current evidence is dismantling with new data – and this is one of them.

Secondly, the effect of the very-low-calorie ketogenic diet can be added to other treatments. This has been demonstrated by studies carried out with liraglutide that showed that this dietary strategy optimizes results, compared with patients who had been treated only with this drug. The third point that justifies the use of the very-low-calorie ketogenic diet is the management of obesity comorbidities. Several investigations demonstrate the effectiveness of this diet in this regard, especially in the case of type 2 diabetes. Data suggest that the substantial weight reductions achieved with it also favor the remission of these comorbidities in many patients.
 

EASO ‘approval’

Dr. Busetto pointed out that, based on this evidence, the OMTF proposed the development of standards to be included in the EASO guidelines, since there had been no specific recommendation on the very-low-calorie ketogenic diet.

“The main objective of these European guidelines was to provide data referenced by scientific evidence and to suggest a common protocol for the use of this dietary strategy,” he added.

For this, a very exhaustive meta-analysis was carried out, researching all the publications that compared the very-low-calorie ketogenic diet with other diets. The results showed the superiority of the former method for the reduction of body mass index and weight and fat mass, with no difference in lean (muscle) mass, despite significant weight loss in these patients.

This evidence also demonstrates a reduction and an improvement in metabolic markers, specifically glucose metabolism and lipid metabolism.

“The final conclusions of the study corroborate that the very-low-calorie ketogenic diet can be recommended as an effective and safe tool for people with obesity, especially those with severe obesity or comorbidities (joint disease, preoperative period to bariatric surgery, metabolic and cardiovascular diseases) who need immediate, substantial weight loss. In addition, it can be prescribed to specific groups of patients with obesity after considering potential contraindications and under medical follow-up,” said Dr. Busetto.

In Dr. Busetto’s opinion, it would be convenient to refer to this approach as a method, instead of as a diet, “because, in reality, the state of ketosis is limited in time, and if the ketogenic phase is stopped without a continuity plan, obviously weight is regained. In addition, the method approach may increase adherence by patients.”

Finally, Dr. Busetto emphasized the importance of integrating this type of treatment into a long-term lifestyle strategy (including habits, exercise, and nutritional advice). “We must start from the basis that obesity is a chronic and relapsing disease, whose management should also be chronic and probably maintained throughout life.”

Dr. Crujeiras and Dr. Busetto have disclosed no relevant financial relationships. PronoKal Group has recently become part of Nestlé Health Science.

A version of this article appeared on Medscape.com. It was translated from Medscape Spanish Edition.

According to the latest evidence, the ketogenic diet is emerging as an effective strategy not only to promote weight loss, but also to manage many comorbidities associated with obesity, including COVID-19. This development was revealed during the 8th International Scientific Symposium New Frontiers in Scientific Research, organized by PronoKal Group and held in Barcelona. During this conference, international multidisciplinary experts in the study and management of obesity presented the latest data on the benefits of treatment based on a very-low-calorie ketogenic diet.

“Nutritional ketosis has gained great interest in recent years because it is shown to have beneficial properties for health and promotes healthy aging, increasing longevity,” said Ana Belén Crujeiras, BSc, PhD, principal investigator of the Health Research Institute of Santiago de Compostela-Galician Health Service (IDIS-SERGAS) Group of Epigenomics in Endocrinology and Nutrition and the Biomedical Research Networking Center for Obesity and Nutrition Physiopathology (CIBEROBN). “Furthermore, in the case of obesity, we have more and more evidence that it is an effective treatment, mainly because to achieve this metabolic state (ketosis), routes that require the combustion of fats are activated, and this induces body weight loss.”

The specialist stressed that several strategies are used to induce nutritional ketosis. They are characterized by low carbohydrate consumption (low-carbohydrate and high-fat diet; low-carbohydrate, low-fat diet; and intermittent fasting). But Dr. Crujeiras warned that to use it as a treatment for a disease such as obesity, it must be backed by strong and solid scientific evidence, moving away from the concept of fad diets.

In this sense, since 2010, Dr. Crujeiras’ team has developed several studies focused on analyzing the efficacy and safety of treatment with a very-low-calorie ketogenic diet, the results of which have been published in high-impact journals.

Dr. Crujeiras commented on the main conclusions drawn from these investigations. “Our work has shown that the very-low-calorie ketogenic diet is effective for rapid weight loss and maintenance of lost weight, as well as reducing fat mass, primarily visceral fat mass.

“In this sense, a very interesting result is that despite the strong weight loss it induces, it preserves muscle mass and function and improves resting metabolic rate. These two variables are important, because all therapeutic strategies that exist to lose weight lead to a significant reduction in fat-free mass and also a reduction in energy expenditure at rest. This factor is associated with the risk of regaining lost weight, which is currently the great challenge in the treatment of obesity,” she added.
 

Specific methylation pattern

Dr. Crujeiras indicated that other notable evidence is the favorable impact on an emotional and psychological level. “To determine whether the caloric restriction of this diet and the strong weight loss that it involves were associated with an increased desire to eat, we also carried out an analysis with psychobiological tests. These results led us to conclude that this guideline is accompanied by a reduction of anxiety about food and an improvement in psychobiological parameters, thus increasing the quality of life of these patients.”

The specialist also mentioned that studies currently in progress show that the beneficial effect of this diet could be mediated by epigenetic mechanisms. “In our group, we have identified a specific DNA methylation pattern in people with obesity and we wondered if the very-low-calorie ketogenic diet would be able to reverse that methylome.

“We conducted a study in which we collected blood samples from patients on the very-low-calorie ketogenic diet (600 to 800 kcal/day) drawn before treatment, at peak ketosis, and at the end of treatment. After determining the global pattern of DNA in all patients with obesity targeted with this strategy and through bioinformatic analysis, we were able to obtain a methylation pattern. The results showed that after weight loss on the very-low-calorie ketogenic diet, the methylome that obese people initially had [was] reversed and matched that of normal-weight people.

“Continuing with this bioinformatic analysis more comprehensively, we wanted to see what kind of genes were differentially methylated, especially by the action of the ketosis itself. We found that most of the genes that exhibited differential methylation (in total, 292 identified) belonged to pathways that were involved in the regulation of metabolism, adipose tissue function, CNS function, and also carcinogenesis,” she continued.
 

Immunomodulatory effect

Dr. Crujeiras said that her research group also observed the modulatory role of the very-low-calorie ketogenic diet in the functioning of the immune system, “something that was not seen after similar weight loss induced by bariatric surgery. We analyzed this data in the context of the situation created by COVID-19, taking into account the evidence that people with obesity, compared to those with normal weight, have a higher risk of becoming infected and of having a poor evolution of the infection.”

In this regard, Dr. Crujeiras’ team launched an investigation to study the ACE2 gene methylation pattern, comparing obesity with normal weight and the situation after following a very-low-calorie ketogenic diet or undergoing bariatric surgery. “We observed that the methylation pattern of this gene in obese people was increased, compared to normal-weight people,” she explained, “and this increase was observed mainly in visceral adipose tissue. However, we did not see this in subcutaneous adipose tissue, which is in agreement with the hypothesis that visceral adipose tissue is that mostly associated with obesity-related comorbidities.

“Likewise, the very-low-calorie ketogenic diet was associated with decreased ACE2 methylation, along with increased exposure of this gene. However, after bariatric surgery, no significant changes were observed, so we deduce that we are protecting the patient in some way from inflammation and, therefore, from the potential of serious illness if they become infected.

“In light of these results, we wanted to dig deeper into what was happening with the immune system of obese patients and that inflammation after a very-low-calorie ketogenic diet. We conducted a new study, currently under review in the journal Clinical Nutrition, with the same approach, comparing this diet with a standard hypocaloric balanced diet and bariatric surgery, in which we analyzed a wide battery of cytokines (32). We have observed a differential pattern between the very-low-calorie ketogenic diet and bariatric surgery.

“The results confirm our hypothesis that the very-low-calorie ketogenic diet remodels the inflammatory status of obese patients, and we were also able to verify that the increase in ketone bodies has immunomodulatory properties that were previously demonstrated in preclinical and animal models, which is associated with increased immune function in these patients,” added Dr. Crujeiras.
 

Personalization and weight regain

In regard to the next steps to take in the knowledge and clinical application of the benefits of this dietary strategy, Dr. Crujeiras said that despite the fact that this diet is known to be effective, it is currently prescribed in a standard manner to all patients, “but there is some variability in the response and also a high risk of regaining weight, as is the case with any nutritional intervention strategy, with that ‘regain’ of lost weight being the main challenge in the treatment of obesity. In this sense, the epigenomic and epigenetic markers that we have identified could help us optimize treatment.”

She added that the future lies in establishing an algorithm that encompasses the patient’s exposome data, along with their genetic and epigenetic profile, to properly classify patients and prescribe a personalized precision therapeutic strategy.

Luca Busetto, MD, cochair of the Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO), also insisted on the challenge posed by the individualized application of the very-low-calorie ketogenic diet, emphasizing that this diet should always be prescribed by a doctor after an appropriate assessment of the patient. “Obesity is not a matter of willpower or motivation, and most people with obesity have struggled their entire lives and failed because their biology tends to cause weight regain. Therefore, we should try to offer them the options that we currently have, including the very-low-calorie ketogenic diet, adapting them as much as possible to the profile of each patient.”

During his speech, Dr. Busetto presented the recent European guidelines for the management of obesity in adults with a very-low-calorie ketogenic diet, endorsed by EASO, and analyzed the main strengths of these recommendations.

Dr. Busetto remarked that three important points clearly justify the use of the very-low-calorie ketogenic diet. The first is the speed with which the initial weight loss occurs. Recent studies have looked at the benefits of a significant loss of excess weight early in a weight-loss diet, and although this is an association rather than a cause, the results strongly suggest that rapid initial weight loss increases the chance of the result being maintained in the long term. This clashes with the traditional recommendation of losing weight little by little as a strategy to achieve long-term results, but it must be taken into account that there are many myths in the treatment of obesity that current evidence is dismantling with new data – and this is one of them.

Secondly, the effect of the very-low-calorie ketogenic diet can be added to other treatments. This has been demonstrated by studies carried out with liraglutide that showed that this dietary strategy optimizes results, compared with patients who had been treated only with this drug. The third point that justifies the use of the very-low-calorie ketogenic diet is the management of obesity comorbidities. Several investigations demonstrate the effectiveness of this diet in this regard, especially in the case of type 2 diabetes. Data suggest that the substantial weight reductions achieved with it also favor the remission of these comorbidities in many patients.
 

EASO ‘approval’

Dr. Busetto pointed out that, based on this evidence, the OMTF proposed the development of standards to be included in the EASO guidelines, since there had been no specific recommendation on the very-low-calorie ketogenic diet.

“The main objective of these European guidelines was to provide data referenced by scientific evidence and to suggest a common protocol for the use of this dietary strategy,” he added.

For this, a very exhaustive meta-analysis was carried out, researching all the publications that compared the very-low-calorie ketogenic diet with other diets. The results showed the superiority of the former method for the reduction of body mass index and weight and fat mass, with no difference in lean (muscle) mass, despite significant weight loss in these patients.

This evidence also demonstrates a reduction and an improvement in metabolic markers, specifically glucose metabolism and lipid metabolism.

“The final conclusions of the study corroborate that the very-low-calorie ketogenic diet can be recommended as an effective and safe tool for people with obesity, especially those with severe obesity or comorbidities (joint disease, preoperative period to bariatric surgery, metabolic and cardiovascular diseases) who need immediate, substantial weight loss. In addition, it can be prescribed to specific groups of patients with obesity after considering potential contraindications and under medical follow-up,” said Dr. Busetto.

In Dr. Busetto’s opinion, it would be convenient to refer to this approach as a method, instead of as a diet, “because, in reality, the state of ketosis is limited in time, and if the ketogenic phase is stopped without a continuity plan, obviously weight is regained. In addition, the method approach may increase adherence by patients.”

Finally, Dr. Busetto emphasized the importance of integrating this type of treatment into a long-term lifestyle strategy (including habits, exercise, and nutritional advice). “We must start from the basis that obesity is a chronic and relapsing disease, whose management should also be chronic and probably maintained throughout life.”

Dr. Crujeiras and Dr. Busetto have disclosed no relevant financial relationships. PronoKal Group has recently become part of Nestlé Health Science.

A version of this article appeared on Medscape.com. It was translated from Medscape Spanish Edition.

The “twincretin” era for treating patients with type 2 diabetes has begun, with the Food and Drug Administration’s approval of tirzepatide for this indication on May 13, making it the first approved agent that works as a dual agonist for the two principal human incretins.

Tirzepatide represents “an important advance in the treatment of type 2 diabetes,” the FDA’s Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders, and obesity, said in a statement released by the agency.

That advance is based on tirzepatide’s engineering, which gives it agonist properties for both the glucagonlike peptide–1 (GLP-1) receptor, as well as the glucose-dependent insulinotropic polypeptide (GIP). Several agents are already approved for U.S. use from the class with single-agonist activity on the GLP-1 receptor, including semaglutide (Ozempic for treating patients with type 2 diabetes; Wegovy for weight loss).

The FDA’s approved label includes all three dosages of tirzepatide that underwent testing in the pivotal trials: 5 mg, 10 mg, and 15 mg, each delivered by subcutaneous injection once a week. Also approved was the 2.5-mg/week dose used when starting a patient on the agent. Gradual up-titration appears to minimize possible gastrointestinal adverse effects during initial tirzepatide use.

Tirzepatide, which will be marketed by Lilly as Mounjaro, will hit the U.S. market with much anticipation, based on results from five pivotal trials, all reported during the past year or so, that established the drug’s unprecedented efficacy for reducing hemoglobin A1c levels as well as triggering significant weight loss in most patients with a generally benign safety profile.
 

‘Impressive’ effects

The effects from tirzepatide on A1c and weight seen in these studies was “impressive, and will likely drive use of this agent,” commented Carol H. Wysham, MD, an endocrinologist at the MultiCare Rockwood Clinic in Spokane, Wash.

Tirzepatide received good notices in several editorials that accompanied the published reports of the pivotal trials. The first of these, a commentary from two U.K.-based endocrinologists, said that “tirzepatide appears to represent an advancement over current GLP-1 analogues, providing enhanced glycemic and weight benefits without an added penalty in terms of gastrointestinal adverse effects.”

The pivotal trials included head-to-head comparisons between tirzepatide and a 1.0-mg/week dose of semaglutide, as well as comparisons with each of two long-acting insulin analogs, insulin glargine (Lantus) and insulin degludec (Tresiba).

“These are the most important comparators,” Dr. Wysham said.

“Tirzepatide was appropriately compared with the best-in-class and most effective glucose-lowering agents currently available,” said Ildiko Lingvay, MD, an endocrinologist and professor at the University of Texas Southwestern Medical Center in Dallas.

“Given its outstanding efficacy at both lowering glucose and weight, I expect tirzepatide to have quick uptake among patients with diabetes,” Dr. Lingvay said. “The only limiting factor will be cost,” she added in an interview, highlighting the major stumbling block that could limit tirzepatide’s uptake.

“As with any new medication, access will be the biggest barrier to uptake,” agreed Alice Y.Y. Cheng, MD, an endocrinologist at the University of Toronto.
 

Lingering uncertainties

The timing of the comparison with semaglutide leaves some unanswered questions. The SURPASS-2 trial compared the three primary tirzepatide regimens (5 mg, 10 mg, and 15 mg/week) with a 1.0-mg/week dose of semaglutide, which was at the time the only approved dosage of semaglutide for patients with type 2 diabetes. Since then, a 2.0-mg/week dosage of semaglutide (Ozempic) received U.S. approval for treating patients with type 2 diabetes, and a 2.4-mg/week dosage (Wegovy) received an FDA nod for treating people with obesity.

The lack of head-to-head data for tirzepatide against the 2.0-mg/week dose of semaglutide “leaves a clinical gap,” said Dr. Cheng. Tirzepatide “represents an advance over semaglutide at the 1-mg/week dose, but we do not know for sure compared to the higher dose.”

Another important limitation for tirzepatide right now is that the agent’s obligatory cardiovascular outcome trial, SURPASS CVOT, with about 12,500 enrolled patients, will not have findings out until about 2025, leaving uncertainty until then about tirzepatide’s cardiovascular effects.

“We are missing the cardiovascular outcome data – very important data will come” from that trial, noted Dr. Wysham. “There will be some reluctance to use the agent in high-risk patients until we see the results.”

Given tirzepatide’s proven efficacy so far, the missing cardiovascular results “are not a limitation for most patients, but for patients with preexisting cardiovascular disease I will continue to use agents with proven benefits until the SURPASS CVOT results come out,” Dr. Lingvay said.

And then there is the cost issue, something that Lilly had not yet publicly addressed at the time that the FDA announced its decision.

An analysis of cost effectiveness published by the U.S. Institute for Clinical and Economic Review in February 2022 concluded that tirzepatide had a better impact on patient quality of life, compared with 1.0 mg/week semaglutide for treating patients with type 2 diabetes, which gave it a modest pricing cushion, compared with semaglutide of about $5,500 per quality-adjusted life-year gained. But the researchers who prepared the report admitted that tirzepatide’s cost-effectiveness was hard to estimate without knowing the drug’s actual price.  

Dr. Wysham has financial ties to AstraZeneca, Abbott, Boehringer Ingelheim, Intercept, Janssen, Mylan, Novo Nordisk, and Sanofi. Dr. Lingvay has dies to Lilly, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Pfizer, and Mylan, Intarcia, MannKind, Valeritas, and several other drug and device makers.

A version of this article first appeared on Medscape.com.

The “twincretin” era for treating patients with type 2 diabetes has begun, with the Food and Drug Administration’s approval of tirzepatide for this indication on May 13, making it the first approved agent that works as a dual agonist for the two principal human incretins.

Tirzepatide represents “an important advance in the treatment of type 2 diabetes,” the FDA’s Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders, and obesity, said in a statement released by the agency.

That advance is based on tirzepatide’s engineering, which gives it agonist properties for both the glucagonlike peptide–1 (GLP-1) receptor, as well as the glucose-dependent insulinotropic polypeptide (GIP). Several agents are already approved for U.S. use from the class with single-agonist activity on the GLP-1 receptor, including semaglutide (Ozempic for treating patients with type 2 diabetes; Wegovy for weight loss).

The FDA’s approved label includes all three dosages of tirzepatide that underwent testing in the pivotal trials: 5 mg, 10 mg, and 15 mg, each delivered by subcutaneous injection once a week. Also approved was the 2.5-mg/week dose used when starting a patient on the agent. Gradual up-titration appears to minimize possible gastrointestinal adverse effects during initial tirzepatide use.

Tirzepatide, which will be marketed by Lilly as Mounjaro, will hit the U.S. market with much anticipation, based on results from five pivotal trials, all reported during the past year or so, that established the drug’s unprecedented efficacy for reducing hemoglobin A1c levels as well as triggering significant weight loss in most patients with a generally benign safety profile.
 

‘Impressive’ effects

The effects from tirzepatide on A1c and weight seen in these studies was “impressive, and will likely drive use of this agent,” commented Carol H. Wysham, MD, an endocrinologist at the MultiCare Rockwood Clinic in Spokane, Wash.

Tirzepatide received good notices in several editorials that accompanied the published reports of the pivotal trials. The first of these, a commentary from two U.K.-based endocrinologists, said that “tirzepatide appears to represent an advancement over current GLP-1 analogues, providing enhanced glycemic and weight benefits without an added penalty in terms of gastrointestinal adverse effects.”

The pivotal trials included head-to-head comparisons between tirzepatide and a 1.0-mg/week dose of semaglutide, as well as comparisons with each of two long-acting insulin analogs, insulin glargine (Lantus) and insulin degludec (Tresiba).

“These are the most important comparators,” Dr. Wysham said.

“Tirzepatide was appropriately compared with the best-in-class and most effective glucose-lowering agents currently available,” said Ildiko Lingvay, MD, an endocrinologist and professor at the University of Texas Southwestern Medical Center in Dallas.

“Given its outstanding efficacy at both lowering glucose and weight, I expect tirzepatide to have quick uptake among patients with diabetes,” Dr. Lingvay said. “The only limiting factor will be cost,” she added in an interview, highlighting the major stumbling block that could limit tirzepatide’s uptake.

“As with any new medication, access will be the biggest barrier to uptake,” agreed Alice Y.Y. Cheng, MD, an endocrinologist at the University of Toronto.
 

Lingering uncertainties

The timing of the comparison with semaglutide leaves some unanswered questions. The SURPASS-2 trial compared the three primary tirzepatide regimens (5 mg, 10 mg, and 15 mg/week) with a 1.0-mg/week dose of semaglutide, which was at the time the only approved dosage of semaglutide for patients with type 2 diabetes. Since then, a 2.0-mg/week dosage of semaglutide (Ozempic) received U.S. approval for treating patients with type 2 diabetes, and a 2.4-mg/week dosage (Wegovy) received an FDA nod for treating people with obesity.

The lack of head-to-head data for tirzepatide against the 2.0-mg/week dose of semaglutide “leaves a clinical gap,” said Dr. Cheng. Tirzepatide “represents an advance over semaglutide at the 1-mg/week dose, but we do not know for sure compared to the higher dose.”

Another important limitation for tirzepatide right now is that the agent’s obligatory cardiovascular outcome trial, SURPASS CVOT, with about 12,500 enrolled patients, will not have findings out until about 2025, leaving uncertainty until then about tirzepatide’s cardiovascular effects.

“We are missing the cardiovascular outcome data – very important data will come” from that trial, noted Dr. Wysham. “There will be some reluctance to use the agent in high-risk patients until we see the results.”

Given tirzepatide’s proven efficacy so far, the missing cardiovascular results “are not a limitation for most patients, but for patients with preexisting cardiovascular disease I will continue to use agents with proven benefits until the SURPASS CVOT results come out,” Dr. Lingvay said.

And then there is the cost issue, something that Lilly had not yet publicly addressed at the time that the FDA announced its decision.

An analysis of cost effectiveness published by the U.S. Institute for Clinical and Economic Review in February 2022 concluded that tirzepatide had a better impact on patient quality of life, compared with 1.0 mg/week semaglutide for treating patients with type 2 diabetes, which gave it a modest pricing cushion, compared with semaglutide of about $5,500 per quality-adjusted life-year gained. But the researchers who prepared the report admitted that tirzepatide’s cost-effectiveness was hard to estimate without knowing the drug’s actual price.  

Dr. Wysham has financial ties to AstraZeneca, Abbott, Boehringer Ingelheim, Intercept, Janssen, Mylan, Novo Nordisk, and Sanofi. Dr. Lingvay has dies to Lilly, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Pfizer, and Mylan, Intarcia, MannKind, Valeritas, and several other drug and device makers.

A version of this article first appeared on Medscape.com.

The “twincretin” era for treating patients with type 2 diabetes has begun, with the Food and Drug Administration’s approval of tirzepatide for this indication on May 13, making it the first approved agent that works as a dual agonist for the two principal human incretins.

Tirzepatide represents “an important advance in the treatment of type 2 diabetes,” the FDA’s Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders, and obesity, said in a statement released by the agency.

That advance is based on tirzepatide’s engineering, which gives it agonist properties for both the glucagonlike peptide–1 (GLP-1) receptor, as well as the glucose-dependent insulinotropic polypeptide (GIP). Several agents are already approved for U.S. use from the class with single-agonist activity on the GLP-1 receptor, including semaglutide (Ozempic for treating patients with type 2 diabetes; Wegovy for weight loss).

The FDA’s approved label includes all three dosages of tirzepatide that underwent testing in the pivotal trials: 5 mg, 10 mg, and 15 mg, each delivered by subcutaneous injection once a week. Also approved was the 2.5-mg/week dose used when starting a patient on the agent. Gradual up-titration appears to minimize possible gastrointestinal adverse effects during initial tirzepatide use.

Tirzepatide, which will be marketed by Lilly as Mounjaro, will hit the U.S. market with much anticipation, based on results from five pivotal trials, all reported during the past year or so, that established the drug’s unprecedented efficacy for reducing hemoglobin A1c levels as well as triggering significant weight loss in most patients with a generally benign safety profile.
 

‘Impressive’ effects

The effects from tirzepatide on A1c and weight seen in these studies was “impressive, and will likely drive use of this agent,” commented Carol H. Wysham, MD, an endocrinologist at the MultiCare Rockwood Clinic in Spokane, Wash.

Tirzepatide received good notices in several editorials that accompanied the published reports of the pivotal trials. The first of these, a commentary from two U.K.-based endocrinologists, said that “tirzepatide appears to represent an advancement over current GLP-1 analogues, providing enhanced glycemic and weight benefits without an added penalty in terms of gastrointestinal adverse effects.”

The pivotal trials included head-to-head comparisons between tirzepatide and a 1.0-mg/week dose of semaglutide, as well as comparisons with each of two long-acting insulin analogs, insulin glargine (Lantus) and insulin degludec (Tresiba).

“These are the most important comparators,” Dr. Wysham said.

“Tirzepatide was appropriately compared with the best-in-class and most effective glucose-lowering agents currently available,” said Ildiko Lingvay, MD, an endocrinologist and professor at the University of Texas Southwestern Medical Center in Dallas.

“Given its outstanding efficacy at both lowering glucose and weight, I expect tirzepatide to have quick uptake among patients with diabetes,” Dr. Lingvay said. “The only limiting factor will be cost,” she added in an interview, highlighting the major stumbling block that could limit tirzepatide’s uptake.

“As with any new medication, access will be the biggest barrier to uptake,” agreed Alice Y.Y. Cheng, MD, an endocrinologist at the University of Toronto.
 

Lingering uncertainties

The timing of the comparison with semaglutide leaves some unanswered questions. The SURPASS-2 trial compared the three primary tirzepatide regimens (5 mg, 10 mg, and 15 mg/week) with a 1.0-mg/week dose of semaglutide, which was at the time the only approved dosage of semaglutide for patients with type 2 diabetes. Since then, a 2.0-mg/week dosage of semaglutide (Ozempic) received U.S. approval for treating patients with type 2 diabetes, and a 2.4-mg/week dosage (Wegovy) received an FDA nod for treating people with obesity.

The lack of head-to-head data for tirzepatide against the 2.0-mg/week dose of semaglutide “leaves a clinical gap,” said Dr. Cheng. Tirzepatide “represents an advance over semaglutide at the 1-mg/week dose, but we do not know for sure compared to the higher dose.”

Another important limitation for tirzepatide right now is that the agent’s obligatory cardiovascular outcome trial, SURPASS CVOT, with about 12,500 enrolled patients, will not have findings out until about 2025, leaving uncertainty until then about tirzepatide’s cardiovascular effects.

“We are missing the cardiovascular outcome data – very important data will come” from that trial, noted Dr. Wysham. “There will be some reluctance to use the agent in high-risk patients until we see the results.”

Given tirzepatide’s proven efficacy so far, the missing cardiovascular results “are not a limitation for most patients, but for patients with preexisting cardiovascular disease I will continue to use agents with proven benefits until the SURPASS CVOT results come out,” Dr. Lingvay said.

And then there is the cost issue, something that Lilly had not yet publicly addressed at the time that the FDA announced its decision.

An analysis of cost effectiveness published by the U.S. Institute for Clinical and Economic Review in February 2022 concluded that tirzepatide had a better impact on patient quality of life, compared with 1.0 mg/week semaglutide for treating patients with type 2 diabetes, which gave it a modest pricing cushion, compared with semaglutide of about $5,500 per quality-adjusted life-year gained. But the researchers who prepared the report admitted that tirzepatide’s cost-effectiveness was hard to estimate without knowing the drug’s actual price.  

Dr. Wysham has financial ties to AstraZeneca, Abbott, Boehringer Ingelheim, Intercept, Janssen, Mylan, Novo Nordisk, and Sanofi. Dr. Lingvay has dies to Lilly, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Pfizer, and Mylan, Intarcia, MannKind, Valeritas, and several other drug and device makers.

A version of this article first appeared on Medscape.com.

People with nonalcoholic fatty liver disease (NAFLD) and a lean or healthy body mass index are at increased risk for peripheral vascular disease, stroke, and cardiovascular disease, a surprise finding from a new study reveals.

“Our team had expected to see that those with a normal BMI would have a lower prevalence of any metabolic or cardiovascular conditions,” lead researcher Karn Wijarnpreecha, MD, MPH, said during a media briefing that previewed select research for Digestive Disease Week^® (DDW) 2022. “So, we were very surprised to find this link to cardiovascular disease.”

The investigators saw this increased risk of cardiovascular disease despite this group having a lower prevalence of atherosclerotic risk factors and metabolic disease.

This first study of its kind suggests physicians should consider the risk of cardiovascular disease in all patients with NAFLD, not just in those who are overweight or living with obesity – groups traditionally thought to carry more risk.

NAFLD in lean individuals is not a benign disease.

“NAFLD patients with a normal BMI are often overlooked because we assume that the risk for more serious conditions is lower than for those who are overweight or obese. But this way of thinking may be putting these patients at risk,” added Dr. Wijarnpreecha, who is a transplant hepatology fellow at the University of Michigan, Ann Arbor.

Key findings

Approximately 25% of U.S. adults live with NAFLD, an umbrella term for liver conditions in people who drink little to no alcohol. It is characterized by too much fat stored in the liver. Although most people have no symptoms, the condition can lead to other dangerous conditions, such as diabetes, cardiovascular disease, and cirrhosis of the liver, Dr. Wijarnpreecha said.

The investigators retrospectively studied a cohort of 18,793 adults diagnosed with NAFLD at the University of Michigan Hospital from 2012-2021. One aim was to compare the prevalence of cirrhosis, cardiovascular disease, metabolic diseases, and chronic kidney disease in relation to BMI.

They also classified people into four BMI categories: lean, overweight, obesity class 1, and obesity class 2-3.

Compared with non-lean patients, lean patients had a higher prevalence of peripheral arterial disease and stroke and a similar rate of cardiovascular disease based on identification of ICD codes.

Almost 6% of lean patients had peripheral arterial disease, compared with rates of approximately 4%-5% in overweight people and people with obesity. Similarly, more than 6% of the lean group experienced a stroke compared with 5% or less of the other BMI groups.

“We found that lean patients with NAFLD also had a significant higher prevalence of cardiovascular disease, independent of age, sex, race, smoking status, diabetes, hypertension, and dyslipidemia,” Dr. Wijarnpreecha said.

At the same time, compared with non-lean patients, lean patients had a lower prevalence of cirrhosis, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease in an analysis that adjusted for confounders.
 

Exploring the unknown

Researchers now have a mystery on their hands: What is causing this unexpected higher risk of cardiovascular disease in lean people with NAFLD?

Loren Laine, MD, chief of the section of digestive diseases at Yale University School of Medicine, New Haven, Conn., and moderator of the media briefing, asked Wijarnpreecha for his leading theory behind this connection.

“We think that could be from a difference in lifestyle, diet, exercise, genetics, or even gut microbiota,” Dr. Wijarnpreecha replied. “But these are factors that we did not capture from this current study.”

“We are preparing to conduct additional research with longitudinal data to better understand NAFLD in lean patients,” Dr. Wijarnpreecha added.

“It’s an interesting finding, but there are some questions from this retrospective study,” said Arun J. Sanyal, MD, when asked to comment on the study.

Identifying and quantifying any alcohol use, smoking, or hypertension that could also have contributed to increased cardiovascular risk would be useful. Another question relates to how the population with NAFLD was identified. Was NAFLD an incidental finding in their diagnosis, asked Dr. Sanyal, director of the Stravitz-Sanyal Institute for Liver Disease & Metabolic Health at Virginia Commonwealth University, Richmond.

“I’m not dissing the study,” he said, “But like all the observations like this, I think we have to kick the tires.”

It’s an “important new observation” that requires further study to fully understand what it means and what the therapeutic implications might be. It is also important to assess any possible confounders and any causal relationship among these factors, Dr. Sanyal added.

“There’s no question it is important to continue to do these types of studies,” he added. “Through this kind of research we find new things that lead to the science that can then significantly change how we approach these issues.”

A version of this article first appeared on Medscape.com. This article was updated on May 18, 2022.

People with nonalcoholic fatty liver disease (NAFLD) and a lean or healthy body mass index are at increased risk for peripheral vascular disease, stroke, and cardiovascular disease, a surprise finding from a new study reveals.

“Our team had expected to see that those with a normal BMI would have a lower prevalence of any metabolic or cardiovascular conditions,” lead researcher Karn Wijarnpreecha, MD, MPH, said during a media briefing that previewed select research for Digestive Disease Week^® (DDW) 2022. “So, we were very surprised to find this link to cardiovascular disease.”

The investigators saw this increased risk of cardiovascular disease despite this group having a lower prevalence of atherosclerotic risk factors and metabolic disease.

This first study of its kind suggests physicians should consider the risk of cardiovascular disease in all patients with NAFLD, not just in those who are overweight or living with obesity – groups traditionally thought to carry more risk.

NAFLD in lean individuals is not a benign disease.

“NAFLD patients with a normal BMI are often overlooked because we assume that the risk for more serious conditions is lower than for those who are overweight or obese. But this way of thinking may be putting these patients at risk,” added Dr. Wijarnpreecha, who is a transplant hepatology fellow at the University of Michigan, Ann Arbor.

Key findings

Approximately 25% of U.S. adults live with NAFLD, an umbrella term for liver conditions in people who drink little to no alcohol. It is characterized by too much fat stored in the liver. Although most people have no symptoms, the condition can lead to other dangerous conditions, such as diabetes, cardiovascular disease, and cirrhosis of the liver, Dr. Wijarnpreecha said.

The investigators retrospectively studied a cohort of 18,793 adults diagnosed with NAFLD at the University of Michigan Hospital from 2012-2021. One aim was to compare the prevalence of cirrhosis, cardiovascular disease, metabolic diseases, and chronic kidney disease in relation to BMI.

They also classified people into four BMI categories: lean, overweight, obesity class 1, and obesity class 2-3.

Compared with non-lean patients, lean patients had a higher prevalence of peripheral arterial disease and stroke and a similar rate of cardiovascular disease based on identification of ICD codes.

Almost 6% of lean patients had peripheral arterial disease, compared with rates of approximately 4%-5% in overweight people and people with obesity. Similarly, more than 6% of the lean group experienced a stroke compared with 5% or less of the other BMI groups.

“We found that lean patients with NAFLD also had a significant higher prevalence of cardiovascular disease, independent of age, sex, race, smoking status, diabetes, hypertension, and dyslipidemia,” Dr. Wijarnpreecha said.

At the same time, compared with non-lean patients, lean patients had a lower prevalence of cirrhosis, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease in an analysis that adjusted for confounders.
 

Exploring the unknown

Researchers now have a mystery on their hands: What is causing this unexpected higher risk of cardiovascular disease in lean people with NAFLD?

Loren Laine, MD, chief of the section of digestive diseases at Yale University School of Medicine, New Haven, Conn., and moderator of the media briefing, asked Wijarnpreecha for his leading theory behind this connection.

“We think that could be from a difference in lifestyle, diet, exercise, genetics, or even gut microbiota,” Dr. Wijarnpreecha replied. “But these are factors that we did not capture from this current study.”

“We are preparing to conduct additional research with longitudinal data to better understand NAFLD in lean patients,” Dr. Wijarnpreecha added.

“It’s an interesting finding, but there are some questions from this retrospective study,” said Arun J. Sanyal, MD, when asked to comment on the study.

Identifying and quantifying any alcohol use, smoking, or hypertension that could also have contributed to increased cardiovascular risk would be useful. Another question relates to how the population with NAFLD was identified. Was NAFLD an incidental finding in their diagnosis, asked Dr. Sanyal, director of the Stravitz-Sanyal Institute for Liver Disease & Metabolic Health at Virginia Commonwealth University, Richmond.

“I’m not dissing the study,” he said, “But like all the observations like this, I think we have to kick the tires.”

It’s an “important new observation” that requires further study to fully understand what it means and what the therapeutic implications might be. It is also important to assess any possible confounders and any causal relationship among these factors, Dr. Sanyal added.

“There’s no question it is important to continue to do these types of studies,” he added. “Through this kind of research we find new things that lead to the science that can then significantly change how we approach these issues.”

A version of this article first appeared on Medscape.com. This article was updated on May 18, 2022.

People with nonalcoholic fatty liver disease (NAFLD) and a lean or healthy body mass index are at increased risk for peripheral vascular disease, stroke, and cardiovascular disease, a surprise finding from a new study reveals.

“Our team had expected to see that those with a normal BMI would have a lower prevalence of any metabolic or cardiovascular conditions,” lead researcher Karn Wijarnpreecha, MD, MPH, said during a media briefing that previewed select research for Digestive Disease Week^® (DDW) 2022. “So, we were very surprised to find this link to cardiovascular disease.”

The investigators saw this increased risk of cardiovascular disease despite this group having a lower prevalence of atherosclerotic risk factors and metabolic disease.

This first study of its kind suggests physicians should consider the risk of cardiovascular disease in all patients with NAFLD, not just in those who are overweight or living with obesity – groups traditionally thought to carry more risk.

NAFLD in lean individuals is not a benign disease.

“NAFLD patients with a normal BMI are often overlooked because we assume that the risk for more serious conditions is lower than for those who are overweight or obese. But this way of thinking may be putting these patients at risk,” added Dr. Wijarnpreecha, who is a transplant hepatology fellow at the University of Michigan, Ann Arbor.

Key findings

Approximately 25% of U.S. adults live with NAFLD, an umbrella term for liver conditions in people who drink little to no alcohol. It is characterized by too much fat stored in the liver. Although most people have no symptoms, the condition can lead to other dangerous conditions, such as diabetes, cardiovascular disease, and cirrhosis of the liver, Dr. Wijarnpreecha said.

The investigators retrospectively studied a cohort of 18,793 adults diagnosed with NAFLD at the University of Michigan Hospital from 2012-2021. One aim was to compare the prevalence of cirrhosis, cardiovascular disease, metabolic diseases, and chronic kidney disease in relation to BMI.

They also classified people into four BMI categories: lean, overweight, obesity class 1, and obesity class 2-3.

Compared with non-lean patients, lean patients had a higher prevalence of peripheral arterial disease and stroke and a similar rate of cardiovascular disease based on identification of ICD codes.

Almost 6% of lean patients had peripheral arterial disease, compared with rates of approximately 4%-5% in overweight people and people with obesity. Similarly, more than 6% of the lean group experienced a stroke compared with 5% or less of the other BMI groups.

“We found that lean patients with NAFLD also had a significant higher prevalence of cardiovascular disease, independent of age, sex, race, smoking status, diabetes, hypertension, and dyslipidemia,” Dr. Wijarnpreecha said.

At the same time, compared with non-lean patients, lean patients had a lower prevalence of cirrhosis, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease in an analysis that adjusted for confounders.
 

Exploring the unknown

Researchers now have a mystery on their hands: What is causing this unexpected higher risk of cardiovascular disease in lean people with NAFLD?

Loren Laine, MD, chief of the section of digestive diseases at Yale University School of Medicine, New Haven, Conn., and moderator of the media briefing, asked Wijarnpreecha for his leading theory behind this connection.

“We think that could be from a difference in lifestyle, diet, exercise, genetics, or even gut microbiota,” Dr. Wijarnpreecha replied. “But these are factors that we did not capture from this current study.”

“We are preparing to conduct additional research with longitudinal data to better understand NAFLD in lean patients,” Dr. Wijarnpreecha added.

“It’s an interesting finding, but there are some questions from this retrospective study,” said Arun J. Sanyal, MD, when asked to comment on the study.

Identifying and quantifying any alcohol use, smoking, or hypertension that could also have contributed to increased cardiovascular risk would be useful. Another question relates to how the population with NAFLD was identified. Was NAFLD an incidental finding in their diagnosis, asked Dr. Sanyal, director of the Stravitz-Sanyal Institute for Liver Disease & Metabolic Health at Virginia Commonwealth University, Richmond.

“I’m not dissing the study,” he said, “But like all the observations like this, I think we have to kick the tires.”

It’s an “important new observation” that requires further study to fully understand what it means and what the therapeutic implications might be. It is also important to assess any possible confounders and any causal relationship among these factors, Dr. Sanyal added.

“There’s no question it is important to continue to do these types of studies,” he added. “Through this kind of research we find new things that lead to the science that can then significantly change how we approach these issues.”

A version of this article first appeared on Medscape.com. This article was updated on May 18, 2022.