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FDA approves Qsymia for treating teens with obesity
The indication is for use as additional therapy along with a reduced-calorie diet and increased physical activity in youth with obesity, defined as a body mass index of the 95th percentile or greater when standardized for age and sex.
Qsymia was first approved in July 2012 for chronic weight management in adults with an initial BMI of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) with one or more weight-related comorbidities, as an adjunct to lifestyle modification.
About 1 in 5 adolescents in the United States has obesity, according to the FDA.
The drug is the fourth to be approved for treating obesity in youth, along with liraglutide (Saxenda) and orlistat (Alli, Xenical), both approved down to age 12, and phentermine for those aged 16 and older.
The Qsymia approval was based on data from a phase 4 double-blind, placebo-controlled trial of 223 youth aged 12-16 with obesity who had not lost weight with lifestyle modifications. They were randomly assigned to Qsymia in doses of 7.5 mg phentermine/46 mg topiramate, 15 mg phentermine/92 mg topiramate, or placebo once daily, along with lifestyle counseling for all.
At 56 weeks, those taking the lower Qsymia dose lost an average of 4.8% of their BMI, and those on the higher dose lost 7.1%. In contrast, the placebo group gained about 3.3% of their BMI.
Because Qsymia increases the risk for oral clefts (lip and palate) in a fetus if taken during pregnancy, female patients should obtain negative pregnancy tests before starting the drug, take monthly pregnancy tests while on the drug, and use effective contraception throughout. Also because of the oral cleft risk, Qsymia is available only through an FDA program called a Risk Evaluation and Mitigation Strategy.
Additional potential adverse effects with Qsymia include increased heart rate and suicidal behavior/ideation. Patients should be advised to monitor for mood changes and discontinue the drug if depression or suicidal thoughts develop. The drug has also been linked to slowing of linear growth, so growth should be monitored in adolescents taking the drug, according to the FDA.
Qsymia is also associated with acute myopia, secondary angle closure glaucoma, visual problems, sleep disorders, cognitive impairment, metabolic acidosis, and decreased renal function.
The most common adverse reactions reported in the pediatric clinical trial included depression, dizziness, joint pain, fever, flu, and ankle sprain.
A version of this article first appeared on Medscape.com.
The indication is for use as additional therapy along with a reduced-calorie diet and increased physical activity in youth with obesity, defined as a body mass index of the 95th percentile or greater when standardized for age and sex.
Qsymia was first approved in July 2012 for chronic weight management in adults with an initial BMI of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) with one or more weight-related comorbidities, as an adjunct to lifestyle modification.
About 1 in 5 adolescents in the United States has obesity, according to the FDA.
The drug is the fourth to be approved for treating obesity in youth, along with liraglutide (Saxenda) and orlistat (Alli, Xenical), both approved down to age 12, and phentermine for those aged 16 and older.
The Qsymia approval was based on data from a phase 4 double-blind, placebo-controlled trial of 223 youth aged 12-16 with obesity who had not lost weight with lifestyle modifications. They were randomly assigned to Qsymia in doses of 7.5 mg phentermine/46 mg topiramate, 15 mg phentermine/92 mg topiramate, or placebo once daily, along with lifestyle counseling for all.
At 56 weeks, those taking the lower Qsymia dose lost an average of 4.8% of their BMI, and those on the higher dose lost 7.1%. In contrast, the placebo group gained about 3.3% of their BMI.
Because Qsymia increases the risk for oral clefts (lip and palate) in a fetus if taken during pregnancy, female patients should obtain negative pregnancy tests before starting the drug, take monthly pregnancy tests while on the drug, and use effective contraception throughout. Also because of the oral cleft risk, Qsymia is available only through an FDA program called a Risk Evaluation and Mitigation Strategy.
Additional potential adverse effects with Qsymia include increased heart rate and suicidal behavior/ideation. Patients should be advised to monitor for mood changes and discontinue the drug if depression or suicidal thoughts develop. The drug has also been linked to slowing of linear growth, so growth should be monitored in adolescents taking the drug, according to the FDA.
Qsymia is also associated with acute myopia, secondary angle closure glaucoma, visual problems, sleep disorders, cognitive impairment, metabolic acidosis, and decreased renal function.
The most common adverse reactions reported in the pediatric clinical trial included depression, dizziness, joint pain, fever, flu, and ankle sprain.
A version of this article first appeared on Medscape.com.
The indication is for use as additional therapy along with a reduced-calorie diet and increased physical activity in youth with obesity, defined as a body mass index of the 95th percentile or greater when standardized for age and sex.
Qsymia was first approved in July 2012 for chronic weight management in adults with an initial BMI of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) with one or more weight-related comorbidities, as an adjunct to lifestyle modification.
About 1 in 5 adolescents in the United States has obesity, according to the FDA.
The drug is the fourth to be approved for treating obesity in youth, along with liraglutide (Saxenda) and orlistat (Alli, Xenical), both approved down to age 12, and phentermine for those aged 16 and older.
The Qsymia approval was based on data from a phase 4 double-blind, placebo-controlled trial of 223 youth aged 12-16 with obesity who had not lost weight with lifestyle modifications. They were randomly assigned to Qsymia in doses of 7.5 mg phentermine/46 mg topiramate, 15 mg phentermine/92 mg topiramate, or placebo once daily, along with lifestyle counseling for all.
At 56 weeks, those taking the lower Qsymia dose lost an average of 4.8% of their BMI, and those on the higher dose lost 7.1%. In contrast, the placebo group gained about 3.3% of their BMI.
Because Qsymia increases the risk for oral clefts (lip and palate) in a fetus if taken during pregnancy, female patients should obtain negative pregnancy tests before starting the drug, take monthly pregnancy tests while on the drug, and use effective contraception throughout. Also because of the oral cleft risk, Qsymia is available only through an FDA program called a Risk Evaluation and Mitigation Strategy.
Additional potential adverse effects with Qsymia include increased heart rate and suicidal behavior/ideation. Patients should be advised to monitor for mood changes and discontinue the drug if depression or suicidal thoughts develop. The drug has also been linked to slowing of linear growth, so growth should be monitored in adolescents taking the drug, according to the FDA.
Qsymia is also associated with acute myopia, secondary angle closure glaucoma, visual problems, sleep disorders, cognitive impairment, metabolic acidosis, and decreased renal function.
The most common adverse reactions reported in the pediatric clinical trial included depression, dizziness, joint pain, fever, flu, and ankle sprain.
A version of this article first appeared on Medscape.com.
Obesity linked to smaller testes and possible infertility
new data suggest.
Testicular volume is a fertility marker directly related to sperm count that has halved in the past 40 years worldwide for unknown reasons. At the same time, childhood obesity has risen dramatically and infertility appears to have risen as well, Rossella Cannarella, MD, of the department of endocrinology and andrology, University of Catania (Italy), said at the annual meeting of the Endocrine Society.
According to recent Italian studies, between 14% and 23% of young men aged 18-19 had testicular hypotrophy. “Worryingly, we don’t know the reason for this hypotrophy. And therefore, they are at risk for future infertility,” Dr. Cannarella said during a press briefing.
Her study, which included a total of 264 male children and adolescents, also linked lower testicular volume to hyperinsulinemia and insulin resistance. “The testis is not quiescent in childhood and is sensitive to the hormone insulin. Obesity and metabolic impairment actually can have an effect and negative impact on Sertoli cell proliferation,” Dr. Cannarella said.
Screen testicular volume at all visits
If other studies confirm these results, she said that pediatricians should begin routinely assessing testicular volume at all visits as is now done with height and weight to identify early deflection of the testicular growth curve.
In addition, “include male infertility as a possible consequence of obesity in counseling of male obese children,” she advised.
Asked to comment, Amin Sedaghat Herati, MD, director of male infertility and men’s health at Johns Hopkins Hospital, and assistant professor of urology at Johns Hopkins Medicine, both in Baltimore, said in an interview: “I think what’s really interesting about this study is the association that they’ve made between testicular volume and obesity.”
But, he noted, “it does not implicate necessarily the development of infertility. It’s an extrapolation. So it’s a step towards the link between obesity and infertility, and it’s an important study to establish the association, but changes in testicular volume and even changes in semen panel don’t necessarily indicate fertility or infertility.”
The findings are “consistent with what we know as far as what obesity can potentially do to the activity of the cells in the testes. The authors are postulating that it’s more the support cells, called Sertoli cells, but I would say it’s probably all of the cells that are being affected by obesity and specifically elevated leptin levels,” Dr. Herati said.
He agrees with the recommendation that pediatricians screen all boys for testicular volume. “I agree it’s a good idea so they don’t miss any cases in which the testes don’t develop the way they should or any other conditions,” Dr. Herati said. “I think in general it’s a good practice, especially in the peripubertal stage, to make sure that kids are on the same growth curve and that they’re meeting their Tanner staging. [Pediatricians] should be looking at the size of the testes and tracking, maybe not at every visit, but at least on an annual basis.”
And, he noted, “I think any study that establishes a link that we can point to when we’re educating patients and parents is important.”
Links found between overweight/obesity, testicular hypotrophy
The study population included 61 male children and adolescents with normal weight, 53 with overweight, and 150 with obesity. Insulin resistance (Homeostatic Model Assessment for Insulin Resistance index ≥ 2.5) was present in 97 participants, 22 had prediabetes, and 3 had type 2 diabetes. Clinical data were collected retrospectively.
Among the boys aged 9-14 years, those with overweight and obesity had significantly lower testicular volume, compared with those of normal weight.
Those who were in Tanner Stage 1 were more likely to have overweight and obesity than those with normal weight, suggesting that “overweight and obese adolescents start puberty later than those of normal weight,” Dr. Cannarella said.
In the 14- to 16-year-old age group, those with insulin resistance had lower testicular volume, compared with those without insulin resistance (HOMA index < 2.5). The number of insulin-resistant adolescents was greater than that of controls in the Tanner stage 2 group.
In both the prepubertal (< 9 years) and pubertal (14-16 years) groups, hyperinsulinemia was associated with lower levels of testicular volume.
Hyperinsulinemia did not influence the timing of puberty onset.
No way to quantify the effect of obesity on fertility just yet
During a press briefing, Dr. Cannarella commented that obesity is likely just one of several factors influencing what appears to be an increase in male infertility over time. “It isn’t of course the only reason, but many factors in our environment have drastically changed, compared to 40 years ago, including the prevalence of heavy metals and endocrine disruptors, and of course, the change in habits and higher prevalence of metabolic disease. All of this has an impact on the proliferation of Sertoli cells in childhood and this may explain the trend toward the decline of sperm concentration and count.”
Longitudinal data are needed to establish cause and effect, she noted. “We need longitudinal studies that link the degrees of testicular volume with the degree of the sperm concentration and count starting from childhood and ending with the adult age. This is the missing link so far.”
Dr. Cannarella has reported no relevant financial relationships. Dr. Herati has reported being an advisor for Dadi, LiNA Medical, and Teleflex.
A version of this article first appeared on Medscape.com.
new data suggest.
Testicular volume is a fertility marker directly related to sperm count that has halved in the past 40 years worldwide for unknown reasons. At the same time, childhood obesity has risen dramatically and infertility appears to have risen as well, Rossella Cannarella, MD, of the department of endocrinology and andrology, University of Catania (Italy), said at the annual meeting of the Endocrine Society.
According to recent Italian studies, between 14% and 23% of young men aged 18-19 had testicular hypotrophy. “Worryingly, we don’t know the reason for this hypotrophy. And therefore, they are at risk for future infertility,” Dr. Cannarella said during a press briefing.
Her study, which included a total of 264 male children and adolescents, also linked lower testicular volume to hyperinsulinemia and insulin resistance. “The testis is not quiescent in childhood and is sensitive to the hormone insulin. Obesity and metabolic impairment actually can have an effect and negative impact on Sertoli cell proliferation,” Dr. Cannarella said.
Screen testicular volume at all visits
If other studies confirm these results, she said that pediatricians should begin routinely assessing testicular volume at all visits as is now done with height and weight to identify early deflection of the testicular growth curve.
In addition, “include male infertility as a possible consequence of obesity in counseling of male obese children,” she advised.
Asked to comment, Amin Sedaghat Herati, MD, director of male infertility and men’s health at Johns Hopkins Hospital, and assistant professor of urology at Johns Hopkins Medicine, both in Baltimore, said in an interview: “I think what’s really interesting about this study is the association that they’ve made between testicular volume and obesity.”
But, he noted, “it does not implicate necessarily the development of infertility. It’s an extrapolation. So it’s a step towards the link between obesity and infertility, and it’s an important study to establish the association, but changes in testicular volume and even changes in semen panel don’t necessarily indicate fertility or infertility.”
The findings are “consistent with what we know as far as what obesity can potentially do to the activity of the cells in the testes. The authors are postulating that it’s more the support cells, called Sertoli cells, but I would say it’s probably all of the cells that are being affected by obesity and specifically elevated leptin levels,” Dr. Herati said.
He agrees with the recommendation that pediatricians screen all boys for testicular volume. “I agree it’s a good idea so they don’t miss any cases in which the testes don’t develop the way they should or any other conditions,” Dr. Herati said. “I think in general it’s a good practice, especially in the peripubertal stage, to make sure that kids are on the same growth curve and that they’re meeting their Tanner staging. [Pediatricians] should be looking at the size of the testes and tracking, maybe not at every visit, but at least on an annual basis.”
And, he noted, “I think any study that establishes a link that we can point to when we’re educating patients and parents is important.”
Links found between overweight/obesity, testicular hypotrophy
The study population included 61 male children and adolescents with normal weight, 53 with overweight, and 150 with obesity. Insulin resistance (Homeostatic Model Assessment for Insulin Resistance index ≥ 2.5) was present in 97 participants, 22 had prediabetes, and 3 had type 2 diabetes. Clinical data were collected retrospectively.
Among the boys aged 9-14 years, those with overweight and obesity had significantly lower testicular volume, compared with those of normal weight.
Those who were in Tanner Stage 1 were more likely to have overweight and obesity than those with normal weight, suggesting that “overweight and obese adolescents start puberty later than those of normal weight,” Dr. Cannarella said.
In the 14- to 16-year-old age group, those with insulin resistance had lower testicular volume, compared with those without insulin resistance (HOMA index < 2.5). The number of insulin-resistant adolescents was greater than that of controls in the Tanner stage 2 group.
In both the prepubertal (< 9 years) and pubertal (14-16 years) groups, hyperinsulinemia was associated with lower levels of testicular volume.
Hyperinsulinemia did not influence the timing of puberty onset.
No way to quantify the effect of obesity on fertility just yet
During a press briefing, Dr. Cannarella commented that obesity is likely just one of several factors influencing what appears to be an increase in male infertility over time. “It isn’t of course the only reason, but many factors in our environment have drastically changed, compared to 40 years ago, including the prevalence of heavy metals and endocrine disruptors, and of course, the change in habits and higher prevalence of metabolic disease. All of this has an impact on the proliferation of Sertoli cells in childhood and this may explain the trend toward the decline of sperm concentration and count.”
Longitudinal data are needed to establish cause and effect, she noted. “We need longitudinal studies that link the degrees of testicular volume with the degree of the sperm concentration and count starting from childhood and ending with the adult age. This is the missing link so far.”
Dr. Cannarella has reported no relevant financial relationships. Dr. Herati has reported being an advisor for Dadi, LiNA Medical, and Teleflex.
A version of this article first appeared on Medscape.com.
new data suggest.
Testicular volume is a fertility marker directly related to sperm count that has halved in the past 40 years worldwide for unknown reasons. At the same time, childhood obesity has risen dramatically and infertility appears to have risen as well, Rossella Cannarella, MD, of the department of endocrinology and andrology, University of Catania (Italy), said at the annual meeting of the Endocrine Society.
According to recent Italian studies, between 14% and 23% of young men aged 18-19 had testicular hypotrophy. “Worryingly, we don’t know the reason for this hypotrophy. And therefore, they are at risk for future infertility,” Dr. Cannarella said during a press briefing.
Her study, which included a total of 264 male children and adolescents, also linked lower testicular volume to hyperinsulinemia and insulin resistance. “The testis is not quiescent in childhood and is sensitive to the hormone insulin. Obesity and metabolic impairment actually can have an effect and negative impact on Sertoli cell proliferation,” Dr. Cannarella said.
Screen testicular volume at all visits
If other studies confirm these results, she said that pediatricians should begin routinely assessing testicular volume at all visits as is now done with height and weight to identify early deflection of the testicular growth curve.
In addition, “include male infertility as a possible consequence of obesity in counseling of male obese children,” she advised.
Asked to comment, Amin Sedaghat Herati, MD, director of male infertility and men’s health at Johns Hopkins Hospital, and assistant professor of urology at Johns Hopkins Medicine, both in Baltimore, said in an interview: “I think what’s really interesting about this study is the association that they’ve made between testicular volume and obesity.”
But, he noted, “it does not implicate necessarily the development of infertility. It’s an extrapolation. So it’s a step towards the link between obesity and infertility, and it’s an important study to establish the association, but changes in testicular volume and even changes in semen panel don’t necessarily indicate fertility or infertility.”
The findings are “consistent with what we know as far as what obesity can potentially do to the activity of the cells in the testes. The authors are postulating that it’s more the support cells, called Sertoli cells, but I would say it’s probably all of the cells that are being affected by obesity and specifically elevated leptin levels,” Dr. Herati said.
He agrees with the recommendation that pediatricians screen all boys for testicular volume. “I agree it’s a good idea so they don’t miss any cases in which the testes don’t develop the way they should or any other conditions,” Dr. Herati said. “I think in general it’s a good practice, especially in the peripubertal stage, to make sure that kids are on the same growth curve and that they’re meeting their Tanner staging. [Pediatricians] should be looking at the size of the testes and tracking, maybe not at every visit, but at least on an annual basis.”
And, he noted, “I think any study that establishes a link that we can point to when we’re educating patients and parents is important.”
Links found between overweight/obesity, testicular hypotrophy
The study population included 61 male children and adolescents with normal weight, 53 with overweight, and 150 with obesity. Insulin resistance (Homeostatic Model Assessment for Insulin Resistance index ≥ 2.5) was present in 97 participants, 22 had prediabetes, and 3 had type 2 diabetes. Clinical data were collected retrospectively.
Among the boys aged 9-14 years, those with overweight and obesity had significantly lower testicular volume, compared with those of normal weight.
Those who were in Tanner Stage 1 were more likely to have overweight and obesity than those with normal weight, suggesting that “overweight and obese adolescents start puberty later than those of normal weight,” Dr. Cannarella said.
In the 14- to 16-year-old age group, those with insulin resistance had lower testicular volume, compared with those without insulin resistance (HOMA index < 2.5). The number of insulin-resistant adolescents was greater than that of controls in the Tanner stage 2 group.
In both the prepubertal (< 9 years) and pubertal (14-16 years) groups, hyperinsulinemia was associated with lower levels of testicular volume.
Hyperinsulinemia did not influence the timing of puberty onset.
No way to quantify the effect of obesity on fertility just yet
During a press briefing, Dr. Cannarella commented that obesity is likely just one of several factors influencing what appears to be an increase in male infertility over time. “It isn’t of course the only reason, but many factors in our environment have drastically changed, compared to 40 years ago, including the prevalence of heavy metals and endocrine disruptors, and of course, the change in habits and higher prevalence of metabolic disease. All of this has an impact on the proliferation of Sertoli cells in childhood and this may explain the trend toward the decline of sperm concentration and count.”
Longitudinal data are needed to establish cause and effect, she noted. “We need longitudinal studies that link the degrees of testicular volume with the degree of the sperm concentration and count starting from childhood and ending with the adult age. This is the missing link so far.”
Dr. Cannarella has reported no relevant financial relationships. Dr. Herati has reported being an advisor for Dadi, LiNA Medical, and Teleflex.
A version of this article first appeared on Medscape.com.
FROM ENDO 2022
Fatty liver disease drives rise in liver cancer deaths
LONDON – Around the world, nonalcoholic fatty liver disease (NAFLD) has driven an increase in deaths from liver cancer over the past decade, overtaking alcoholic liver disease, hepatitis B, and hepatitis C, according to an analysis of the Global Burden of Disease Study 2019.
A global rise in liver cancer deaths and chronic liver disease reflects changes in underlying health patterns, said Zobair Younossi, MD, MPH, professor and chair, department of medicine, Inova Fairfax Medical Campus, Falls Church, Va., who presented the analysis at the meeting sponsored by the European Association for the Study of the Liver.
Dr. Younossi told this news organization. “We have known about the increasing prevalence for some time, but now the outcomes in terms of mortality are catching up,” he said.
“The bottom line of this study is that the burden of this disease [NAFLD] is going up, and it will be the most important disease of the next decade or so,” he said, adding that “the largest annual percentage increase in rates of mortality from liver cancer or chronic liver disease cirrhosis is related to NAFLD.”
Specifically, during the decade of 2009–2019, the annual percent change of +1.33% in the global liver cancer death rate was driven by the fact that the APC for NAFLD was +2.47%. By comparison, the APC for alcoholic liver disease was +1.91%; for hepatitis B, the APC was +0.21%; and for hepatitis C, the APC was +1.12%.
Aleksander Krag, MD, PhD, professor and senior consultant of hepatology and director of Odense (Denmark) Liver Research Centre at SDU and Odense University Hospital, who chaired the session in which this presentation was a part, acknowledged the importance of recognizing the contribution of NAFLD to liver cancer mortality.
“Liver diseases are on the rise. They are the fastest rising cause of death in the United Kingdom, faster than heart disease and other cancers. NAFLD in particular is the fastest growing cause of liver cancer, and the leading cause in France and the United States,” he remarked.
Dr. Krag also highlighted the costs of disease management.
“Managing fatty liver disease in Europe is estimated at €35 billion in direct health care, so we need to do something now,” he stressed.
“The global burden of NAFLD is so high that we need both prevention and treatment tools,” Dr. Krag said. “Change to lifestyle is a ‘no-brainer’ and costs governments very little. For the sake of our young people, we need to take this very seriously. At a political level, we can easily implement this, for example, by banning junk food advertisements, but also educating young people and their families. Good drugs will also help.”
NAFLD: The liver manifestation of type 2 diabetes
About 25%-30% of the global population have NAFLD, and 3%-5% have NASH. Dr. Younossi highlighted that the U.S. transplant database shows that NAFLD was the second indication for all liver transplants in the country. NAFLD also was a leading cause of liver transplants for patients with hepatocellular carcinoma.
There are around 2 billion cases of chronic liver disease globally, he said. He noted that, over time, there has been an increase in all kinds of liver diseases, as reflected in the annual percent change.
“The global epidemic of obesity and type 2 diabetes is driving the rise in NAFLD, but even among lean people, the prevalence of NAFLD is around 9%,” Dr. Younossi said. “Alongside the eye and kidney complications of diabetes, this is the liver manifestation of type 2 diabetes.”
To assess global liver disease and death, Dr. Younossi and his colleagues turned to the Global Burden of Disease Study, which gathered data from around 7,000 investigators located across 22 different regions of the world, comprising 156 countries.
They calculated the incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) in relation to liver cancer and chronic liver disease, including the APC. They linked the data to changes in four liver diseases: NAFLD, alcoholic liver disease, hepatitis B infection, and hepatitis C infection.
The cases of NAFLD reported in the study had been diagnosed by ultrasound or other imaging. Importantly, the prevalence of NAFLD was adjusted for alcohol use in the various national populations, explained Dr. Younossi.
In 2019, they reported that the overall global prevalence of liver disease reached 1.69 billion (liver cancer, 0.04%; chronic liver disease, 99.96%), with an incidence of 2.59 million (liver cancer, 20.7%; chronic liver disease, 79.3%), mortality of 1.95 million (liver cancer, 24.8%; chronic liver disease, 75.3%), and DALYs of 58.7 million (liver cancer, 21.3%; chronic liver disease, 78.7%).
Between 2009 and 2019, deaths from liver cancer rose by 27.2%, and deaths from chronic liver disease rose by 10.6%. DALYs from liver cancer rose by 21.9%, and DALYs from chronic liver disease were up by 5.1%.
In contrast to the increase in liver cancer deaths, deaths from chronic liver disease decreased (APC, –0.18%). The decrease was driven by a decrease in hepatitis B (APC, –1.83%). APCs for hepatitis C (+0.37%), alcoholic liver disease (+0.45%), and NAFLD (+1.33%) increased.
“The burden of hepatitis B–related mortality has decreased because we have been so good at vaccinating people,” Dr. Younossi remarked.
NAFLD ‘exploding’ in Middle East, North Africa, and East Asia
The increase in NAFLD has been seen in all regions of the world, but a breakdown by region shows that NAFLD is primarily “exploding” with highest prevalence and mortality in the Middle East (mostly Egypt, Iran, and Turkey), North Africa, and East Asia, said Dr. Younossi. In addition, there are large increases in the West and South America.
“We knew that the prevalence was high in the Middle East, but we now know that mortality is also high, so we are connecting these data,” said Dr. Younossi.
Awareness lacking
Dr. Younossi pressed the fact that awareness among the general population, primary care providers, and policy makers is very low. “From my perspective, raising awareness of NAFLD is the No. 1 priority, and that is the value of this study.”
He added that more people will become aware as testing becomes more manageable.
“There are some noninvasive tests being developed, so in the future, we won’t have to do liver biopsies to diagnose these patients,” he said. “Currently, there are some excellent treatments being developed.”
“The [World Health Organization] does not mention NAFLD as an important noncommunicable disease, and this too has to change,” Dr. Younossi added.
Dr. Younossi has received research funds and/or has consulted for Abbott, Allergan, Bristol-Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk. Dr. Karg disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LONDON – Around the world, nonalcoholic fatty liver disease (NAFLD) has driven an increase in deaths from liver cancer over the past decade, overtaking alcoholic liver disease, hepatitis B, and hepatitis C, according to an analysis of the Global Burden of Disease Study 2019.
A global rise in liver cancer deaths and chronic liver disease reflects changes in underlying health patterns, said Zobair Younossi, MD, MPH, professor and chair, department of medicine, Inova Fairfax Medical Campus, Falls Church, Va., who presented the analysis at the meeting sponsored by the European Association for the Study of the Liver.
Dr. Younossi told this news organization. “We have known about the increasing prevalence for some time, but now the outcomes in terms of mortality are catching up,” he said.
“The bottom line of this study is that the burden of this disease [NAFLD] is going up, and it will be the most important disease of the next decade or so,” he said, adding that “the largest annual percentage increase in rates of mortality from liver cancer or chronic liver disease cirrhosis is related to NAFLD.”
Specifically, during the decade of 2009–2019, the annual percent change of +1.33% in the global liver cancer death rate was driven by the fact that the APC for NAFLD was +2.47%. By comparison, the APC for alcoholic liver disease was +1.91%; for hepatitis B, the APC was +0.21%; and for hepatitis C, the APC was +1.12%.
Aleksander Krag, MD, PhD, professor and senior consultant of hepatology and director of Odense (Denmark) Liver Research Centre at SDU and Odense University Hospital, who chaired the session in which this presentation was a part, acknowledged the importance of recognizing the contribution of NAFLD to liver cancer mortality.
“Liver diseases are on the rise. They are the fastest rising cause of death in the United Kingdom, faster than heart disease and other cancers. NAFLD in particular is the fastest growing cause of liver cancer, and the leading cause in France and the United States,” he remarked.
Dr. Krag also highlighted the costs of disease management.
“Managing fatty liver disease in Europe is estimated at €35 billion in direct health care, so we need to do something now,” he stressed.
“The global burden of NAFLD is so high that we need both prevention and treatment tools,” Dr. Krag said. “Change to lifestyle is a ‘no-brainer’ and costs governments very little. For the sake of our young people, we need to take this very seriously. At a political level, we can easily implement this, for example, by banning junk food advertisements, but also educating young people and their families. Good drugs will also help.”
NAFLD: The liver manifestation of type 2 diabetes
About 25%-30% of the global population have NAFLD, and 3%-5% have NASH. Dr. Younossi highlighted that the U.S. transplant database shows that NAFLD was the second indication for all liver transplants in the country. NAFLD also was a leading cause of liver transplants for patients with hepatocellular carcinoma.
There are around 2 billion cases of chronic liver disease globally, he said. He noted that, over time, there has been an increase in all kinds of liver diseases, as reflected in the annual percent change.
“The global epidemic of obesity and type 2 diabetes is driving the rise in NAFLD, but even among lean people, the prevalence of NAFLD is around 9%,” Dr. Younossi said. “Alongside the eye and kidney complications of diabetes, this is the liver manifestation of type 2 diabetes.”
To assess global liver disease and death, Dr. Younossi and his colleagues turned to the Global Burden of Disease Study, which gathered data from around 7,000 investigators located across 22 different regions of the world, comprising 156 countries.
They calculated the incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) in relation to liver cancer and chronic liver disease, including the APC. They linked the data to changes in four liver diseases: NAFLD, alcoholic liver disease, hepatitis B infection, and hepatitis C infection.
The cases of NAFLD reported in the study had been diagnosed by ultrasound or other imaging. Importantly, the prevalence of NAFLD was adjusted for alcohol use in the various national populations, explained Dr. Younossi.
In 2019, they reported that the overall global prevalence of liver disease reached 1.69 billion (liver cancer, 0.04%; chronic liver disease, 99.96%), with an incidence of 2.59 million (liver cancer, 20.7%; chronic liver disease, 79.3%), mortality of 1.95 million (liver cancer, 24.8%; chronic liver disease, 75.3%), and DALYs of 58.7 million (liver cancer, 21.3%; chronic liver disease, 78.7%).
Between 2009 and 2019, deaths from liver cancer rose by 27.2%, and deaths from chronic liver disease rose by 10.6%. DALYs from liver cancer rose by 21.9%, and DALYs from chronic liver disease were up by 5.1%.
In contrast to the increase in liver cancer deaths, deaths from chronic liver disease decreased (APC, –0.18%). The decrease was driven by a decrease in hepatitis B (APC, –1.83%). APCs for hepatitis C (+0.37%), alcoholic liver disease (+0.45%), and NAFLD (+1.33%) increased.
“The burden of hepatitis B–related mortality has decreased because we have been so good at vaccinating people,” Dr. Younossi remarked.
NAFLD ‘exploding’ in Middle East, North Africa, and East Asia
The increase in NAFLD has been seen in all regions of the world, but a breakdown by region shows that NAFLD is primarily “exploding” with highest prevalence and mortality in the Middle East (mostly Egypt, Iran, and Turkey), North Africa, and East Asia, said Dr. Younossi. In addition, there are large increases in the West and South America.
“We knew that the prevalence was high in the Middle East, but we now know that mortality is also high, so we are connecting these data,” said Dr. Younossi.
Awareness lacking
Dr. Younossi pressed the fact that awareness among the general population, primary care providers, and policy makers is very low. “From my perspective, raising awareness of NAFLD is the No. 1 priority, and that is the value of this study.”
He added that more people will become aware as testing becomes more manageable.
“There are some noninvasive tests being developed, so in the future, we won’t have to do liver biopsies to diagnose these patients,” he said. “Currently, there are some excellent treatments being developed.”
“The [World Health Organization] does not mention NAFLD as an important noncommunicable disease, and this too has to change,” Dr. Younossi added.
Dr. Younossi has received research funds and/or has consulted for Abbott, Allergan, Bristol-Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk. Dr. Karg disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LONDON – Around the world, nonalcoholic fatty liver disease (NAFLD) has driven an increase in deaths from liver cancer over the past decade, overtaking alcoholic liver disease, hepatitis B, and hepatitis C, according to an analysis of the Global Burden of Disease Study 2019.
A global rise in liver cancer deaths and chronic liver disease reflects changes in underlying health patterns, said Zobair Younossi, MD, MPH, professor and chair, department of medicine, Inova Fairfax Medical Campus, Falls Church, Va., who presented the analysis at the meeting sponsored by the European Association for the Study of the Liver.
Dr. Younossi told this news organization. “We have known about the increasing prevalence for some time, but now the outcomes in terms of mortality are catching up,” he said.
“The bottom line of this study is that the burden of this disease [NAFLD] is going up, and it will be the most important disease of the next decade or so,” he said, adding that “the largest annual percentage increase in rates of mortality from liver cancer or chronic liver disease cirrhosis is related to NAFLD.”
Specifically, during the decade of 2009–2019, the annual percent change of +1.33% in the global liver cancer death rate was driven by the fact that the APC for NAFLD was +2.47%. By comparison, the APC for alcoholic liver disease was +1.91%; for hepatitis B, the APC was +0.21%; and for hepatitis C, the APC was +1.12%.
Aleksander Krag, MD, PhD, professor and senior consultant of hepatology and director of Odense (Denmark) Liver Research Centre at SDU and Odense University Hospital, who chaired the session in which this presentation was a part, acknowledged the importance of recognizing the contribution of NAFLD to liver cancer mortality.
“Liver diseases are on the rise. They are the fastest rising cause of death in the United Kingdom, faster than heart disease and other cancers. NAFLD in particular is the fastest growing cause of liver cancer, and the leading cause in France and the United States,” he remarked.
Dr. Krag also highlighted the costs of disease management.
“Managing fatty liver disease in Europe is estimated at €35 billion in direct health care, so we need to do something now,” he stressed.
“The global burden of NAFLD is so high that we need both prevention and treatment tools,” Dr. Krag said. “Change to lifestyle is a ‘no-brainer’ and costs governments very little. For the sake of our young people, we need to take this very seriously. At a political level, we can easily implement this, for example, by banning junk food advertisements, but also educating young people and their families. Good drugs will also help.”
NAFLD: The liver manifestation of type 2 diabetes
About 25%-30% of the global population have NAFLD, and 3%-5% have NASH. Dr. Younossi highlighted that the U.S. transplant database shows that NAFLD was the second indication for all liver transplants in the country. NAFLD also was a leading cause of liver transplants for patients with hepatocellular carcinoma.
There are around 2 billion cases of chronic liver disease globally, he said. He noted that, over time, there has been an increase in all kinds of liver diseases, as reflected in the annual percent change.
“The global epidemic of obesity and type 2 diabetes is driving the rise in NAFLD, but even among lean people, the prevalence of NAFLD is around 9%,” Dr. Younossi said. “Alongside the eye and kidney complications of diabetes, this is the liver manifestation of type 2 diabetes.”
To assess global liver disease and death, Dr. Younossi and his colleagues turned to the Global Burden of Disease Study, which gathered data from around 7,000 investigators located across 22 different regions of the world, comprising 156 countries.
They calculated the incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) in relation to liver cancer and chronic liver disease, including the APC. They linked the data to changes in four liver diseases: NAFLD, alcoholic liver disease, hepatitis B infection, and hepatitis C infection.
The cases of NAFLD reported in the study had been diagnosed by ultrasound or other imaging. Importantly, the prevalence of NAFLD was adjusted for alcohol use in the various national populations, explained Dr. Younossi.
In 2019, they reported that the overall global prevalence of liver disease reached 1.69 billion (liver cancer, 0.04%; chronic liver disease, 99.96%), with an incidence of 2.59 million (liver cancer, 20.7%; chronic liver disease, 79.3%), mortality of 1.95 million (liver cancer, 24.8%; chronic liver disease, 75.3%), and DALYs of 58.7 million (liver cancer, 21.3%; chronic liver disease, 78.7%).
Between 2009 and 2019, deaths from liver cancer rose by 27.2%, and deaths from chronic liver disease rose by 10.6%. DALYs from liver cancer rose by 21.9%, and DALYs from chronic liver disease were up by 5.1%.
In contrast to the increase in liver cancer deaths, deaths from chronic liver disease decreased (APC, –0.18%). The decrease was driven by a decrease in hepatitis B (APC, –1.83%). APCs for hepatitis C (+0.37%), alcoholic liver disease (+0.45%), and NAFLD (+1.33%) increased.
“The burden of hepatitis B–related mortality has decreased because we have been so good at vaccinating people,” Dr. Younossi remarked.
NAFLD ‘exploding’ in Middle East, North Africa, and East Asia
The increase in NAFLD has been seen in all regions of the world, but a breakdown by region shows that NAFLD is primarily “exploding” with highest prevalence and mortality in the Middle East (mostly Egypt, Iran, and Turkey), North Africa, and East Asia, said Dr. Younossi. In addition, there are large increases in the West and South America.
“We knew that the prevalence was high in the Middle East, but we now know that mortality is also high, so we are connecting these data,” said Dr. Younossi.
Awareness lacking
Dr. Younossi pressed the fact that awareness among the general population, primary care providers, and policy makers is very low. “From my perspective, raising awareness of NAFLD is the No. 1 priority, and that is the value of this study.”
He added that more people will become aware as testing becomes more manageable.
“There are some noninvasive tests being developed, so in the future, we won’t have to do liver biopsies to diagnose these patients,” he said. “Currently, there are some excellent treatments being developed.”
“The [World Health Organization] does not mention NAFLD as an important noncommunicable disease, and this too has to change,” Dr. Younossi added.
Dr. Younossi has received research funds and/or has consulted for Abbott, Allergan, Bristol-Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk. Dr. Karg disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ILC 2022
Low-protein Nordic diet promotes healthy eating in infants
The “Nordic diet” has shown health benefits in children and adults, but has not been studied in infants, said Ulrica Johansson, MD, of Umeå (Sweden) University, in a presentation on the study at the annual meeting of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.
A healthy and sustainable diet early in life could have a significant impact on future health, Dr. Johansson said in an interview.
Dr. Johansson and colleagues aimed to investigate the effect of a Nordic diet in infants aged 4-18 months in the OTIS trial. All infants were breastfed or formula-fed at baseline.
Study methods and results
A total of 250 infants aged 4-6 months were randomized to consuming a Nordic diet or a conventional diet. Those in the Nordic group received exposures to Nordic foods and flavors, including Nordic fruit, berries, vegetables, and roots. Those in the conventional group received baby food products that followed the current Swedish dietary recommendations for infants. The researchers collected data on dietary intake, biomarkers, and growth from baseline up to 18 months of age.
Notably, acceptance of all the flavors in the Nordic diet was high, including those with sour or bitter taste, such as cranberry and white radish, Dr. Johansson said in her presentation. Food refusals were few, and did not differ among the Nordic food offerings.
At both 12- and 18-month follow-ups, infants in the Nordic group consumed 42%-45% more fruits and vegetables compared with those in the conventional group (P < .001). Plasma folate levels also were significantly higher in the Nordic group compared with in the conventional group, at both 12 months and 18 months (P < .001 and P < .003, respectively).
The daily mean protein intake ranged from 17% to 29% lower in the Nordic group compared with in the conventional group, at both 12 months and 18 months. The intake of protein in terms of g/kg of body weight was significantly lower in the Nordic group, at both time points. Lower protein intake was confirmed by blood urea nitrogen measurements.
The protein intake in the Nordic group still fell within the safe level recommended for healthy growth in young children by the World Health Organization, noted Dr. Johansson, and no significant differences were observed in growth between the groups. Total energy intake, iron status, and duration of breastfeeding also remained similar between the groups throughout the study period.
Parents received support from research nurses via social media and monthly clinic visits, which she believes contributed to the success of the intervention, she said.
Nordic diet offers feasible encouragement of healthy eating
The key message for clinicians, and for parents of young children, is that “the protein-reduced, Nordic diet is both feasible and safe for infants’ growth, nutritional requirements, and development during the complementary feeding period,” Dr. Johansson said in an interview. “Thus, it may serve as a healthy and environmentally sustainable diet alternative for infants and their parents in the future.”
“Nordic foods are feasible to use when exposing infants to a variety of flavors so that healthy food preferences can be established early in life; Nordic berries and some root vegetables are preferable when introducing bitter and sour tastes during the sensitive period,” she added.
“Multicomponent interventions with long-term follow-up are required to advance the field of child nutrition research,” Dr. Johansson emphasized. Home-based interventions are lacking, and “more studies are needed to bridge the gap in research between the transfer period from baby food to family food at 1-2 years of age.”
Large, randomized controlled studies of Nordic diet during infancy and later childhood are needed as well, said Dr. Johansson. “The long-term effects of the Nordic diet during this highly dynamic period of childhood need continued follow-up to school age to give indications of any lasting health effects,” and the researchers plan to follow the current study population at 7 years of age.
Findings reinforce need for better nutrition
Previous research documents concern for childhood obesity associated with higher intake of protein, fats and overall calories in infancy, said Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview. “The inclusion of high-calorie, high-fat foods contributes to obesity in all children, so focusing on intake of fruits and vegetables is extremely important early in life,” she said.
A key barrier to the widespread use of a Nordic-type diet is that and vegetables tend to be more expensive than other foods and may not be readily available to all families, especially lower income families, Dr. Haut added.
However, for primary care clinicians, the current study reinforces the need to encourage the intake of fruits and vegetables at all ages, beginning in infancy, she said.
Looking ahead, “there is still limited information in the literature about the ideal recommended daily protein, except for increased amounts needed for preterm infants, early infancy, and during periods of healing,” Dr. Haut emphasized. “Some controls for this study were not included in the abstract, such as monitoring what foods were given to the infants in the conventional group. Parent and caregiver interpretation of recommendations can be highly variable,” she noted. Also, “The activity levels of late infancy and toddlers can vary in terms of energy usage, especially when crawling, walking, running and other exercise-related activities begin. These factors were not readily available in the abstract/study,” she said.
The OTIS trial was sponsored by Semper. Dr. Johansson had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News.
The “Nordic diet” has shown health benefits in children and adults, but has not been studied in infants, said Ulrica Johansson, MD, of Umeå (Sweden) University, in a presentation on the study at the annual meeting of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.
A healthy and sustainable diet early in life could have a significant impact on future health, Dr. Johansson said in an interview.
Dr. Johansson and colleagues aimed to investigate the effect of a Nordic diet in infants aged 4-18 months in the OTIS trial. All infants were breastfed or formula-fed at baseline.
Study methods and results
A total of 250 infants aged 4-6 months were randomized to consuming a Nordic diet or a conventional diet. Those in the Nordic group received exposures to Nordic foods and flavors, including Nordic fruit, berries, vegetables, and roots. Those in the conventional group received baby food products that followed the current Swedish dietary recommendations for infants. The researchers collected data on dietary intake, biomarkers, and growth from baseline up to 18 months of age.
Notably, acceptance of all the flavors in the Nordic diet was high, including those with sour or bitter taste, such as cranberry and white radish, Dr. Johansson said in her presentation. Food refusals were few, and did not differ among the Nordic food offerings.
At both 12- and 18-month follow-ups, infants in the Nordic group consumed 42%-45% more fruits and vegetables compared with those in the conventional group (P < .001). Plasma folate levels also were significantly higher in the Nordic group compared with in the conventional group, at both 12 months and 18 months (P < .001 and P < .003, respectively).
The daily mean protein intake ranged from 17% to 29% lower in the Nordic group compared with in the conventional group, at both 12 months and 18 months. The intake of protein in terms of g/kg of body weight was significantly lower in the Nordic group, at both time points. Lower protein intake was confirmed by blood urea nitrogen measurements.
The protein intake in the Nordic group still fell within the safe level recommended for healthy growth in young children by the World Health Organization, noted Dr. Johansson, and no significant differences were observed in growth between the groups. Total energy intake, iron status, and duration of breastfeeding also remained similar between the groups throughout the study period.
Parents received support from research nurses via social media and monthly clinic visits, which she believes contributed to the success of the intervention, she said.
Nordic diet offers feasible encouragement of healthy eating
The key message for clinicians, and for parents of young children, is that “the protein-reduced, Nordic diet is both feasible and safe for infants’ growth, nutritional requirements, and development during the complementary feeding period,” Dr. Johansson said in an interview. “Thus, it may serve as a healthy and environmentally sustainable diet alternative for infants and their parents in the future.”
“Nordic foods are feasible to use when exposing infants to a variety of flavors so that healthy food preferences can be established early in life; Nordic berries and some root vegetables are preferable when introducing bitter and sour tastes during the sensitive period,” she added.
“Multicomponent interventions with long-term follow-up are required to advance the field of child nutrition research,” Dr. Johansson emphasized. Home-based interventions are lacking, and “more studies are needed to bridge the gap in research between the transfer period from baby food to family food at 1-2 years of age.”
Large, randomized controlled studies of Nordic diet during infancy and later childhood are needed as well, said Dr. Johansson. “The long-term effects of the Nordic diet during this highly dynamic period of childhood need continued follow-up to school age to give indications of any lasting health effects,” and the researchers plan to follow the current study population at 7 years of age.
Findings reinforce need for better nutrition
Previous research documents concern for childhood obesity associated with higher intake of protein, fats and overall calories in infancy, said Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview. “The inclusion of high-calorie, high-fat foods contributes to obesity in all children, so focusing on intake of fruits and vegetables is extremely important early in life,” she said.
A key barrier to the widespread use of a Nordic-type diet is that and vegetables tend to be more expensive than other foods and may not be readily available to all families, especially lower income families, Dr. Haut added.
However, for primary care clinicians, the current study reinforces the need to encourage the intake of fruits and vegetables at all ages, beginning in infancy, she said.
Looking ahead, “there is still limited information in the literature about the ideal recommended daily protein, except for increased amounts needed for preterm infants, early infancy, and during periods of healing,” Dr. Haut emphasized. “Some controls for this study were not included in the abstract, such as monitoring what foods were given to the infants in the conventional group. Parent and caregiver interpretation of recommendations can be highly variable,” she noted. Also, “The activity levels of late infancy and toddlers can vary in terms of energy usage, especially when crawling, walking, running and other exercise-related activities begin. These factors were not readily available in the abstract/study,” she said.
The OTIS trial was sponsored by Semper. Dr. Johansson had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News.
The “Nordic diet” has shown health benefits in children and adults, but has not been studied in infants, said Ulrica Johansson, MD, of Umeå (Sweden) University, in a presentation on the study at the annual meeting of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.
A healthy and sustainable diet early in life could have a significant impact on future health, Dr. Johansson said in an interview.
Dr. Johansson and colleagues aimed to investigate the effect of a Nordic diet in infants aged 4-18 months in the OTIS trial. All infants were breastfed or formula-fed at baseline.
Study methods and results
A total of 250 infants aged 4-6 months were randomized to consuming a Nordic diet or a conventional diet. Those in the Nordic group received exposures to Nordic foods and flavors, including Nordic fruit, berries, vegetables, and roots. Those in the conventional group received baby food products that followed the current Swedish dietary recommendations for infants. The researchers collected data on dietary intake, biomarkers, and growth from baseline up to 18 months of age.
Notably, acceptance of all the flavors in the Nordic diet was high, including those with sour or bitter taste, such as cranberry and white radish, Dr. Johansson said in her presentation. Food refusals were few, and did not differ among the Nordic food offerings.
At both 12- and 18-month follow-ups, infants in the Nordic group consumed 42%-45% more fruits and vegetables compared with those in the conventional group (P < .001). Plasma folate levels also were significantly higher in the Nordic group compared with in the conventional group, at both 12 months and 18 months (P < .001 and P < .003, respectively).
The daily mean protein intake ranged from 17% to 29% lower in the Nordic group compared with in the conventional group, at both 12 months and 18 months. The intake of protein in terms of g/kg of body weight was significantly lower in the Nordic group, at both time points. Lower protein intake was confirmed by blood urea nitrogen measurements.
The protein intake in the Nordic group still fell within the safe level recommended for healthy growth in young children by the World Health Organization, noted Dr. Johansson, and no significant differences were observed in growth between the groups. Total energy intake, iron status, and duration of breastfeeding also remained similar between the groups throughout the study period.
Parents received support from research nurses via social media and monthly clinic visits, which she believes contributed to the success of the intervention, she said.
Nordic diet offers feasible encouragement of healthy eating
The key message for clinicians, and for parents of young children, is that “the protein-reduced, Nordic diet is both feasible and safe for infants’ growth, nutritional requirements, and development during the complementary feeding period,” Dr. Johansson said in an interview. “Thus, it may serve as a healthy and environmentally sustainable diet alternative for infants and their parents in the future.”
“Nordic foods are feasible to use when exposing infants to a variety of flavors so that healthy food preferences can be established early in life; Nordic berries and some root vegetables are preferable when introducing bitter and sour tastes during the sensitive period,” she added.
“Multicomponent interventions with long-term follow-up are required to advance the field of child nutrition research,” Dr. Johansson emphasized. Home-based interventions are lacking, and “more studies are needed to bridge the gap in research between the transfer period from baby food to family food at 1-2 years of age.”
Large, randomized controlled studies of Nordic diet during infancy and later childhood are needed as well, said Dr. Johansson. “The long-term effects of the Nordic diet during this highly dynamic period of childhood need continued follow-up to school age to give indications of any lasting health effects,” and the researchers plan to follow the current study population at 7 years of age.
Findings reinforce need for better nutrition
Previous research documents concern for childhood obesity associated with higher intake of protein, fats and overall calories in infancy, said Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview. “The inclusion of high-calorie, high-fat foods contributes to obesity in all children, so focusing on intake of fruits and vegetables is extremely important early in life,” she said.
A key barrier to the widespread use of a Nordic-type diet is that and vegetables tend to be more expensive than other foods and may not be readily available to all families, especially lower income families, Dr. Haut added.
However, for primary care clinicians, the current study reinforces the need to encourage the intake of fruits and vegetables at all ages, beginning in infancy, she said.
Looking ahead, “there is still limited information in the literature about the ideal recommended daily protein, except for increased amounts needed for preterm infants, early infancy, and during periods of healing,” Dr. Haut emphasized. “Some controls for this study were not included in the abstract, such as monitoring what foods were given to the infants in the conventional group. Parent and caregiver interpretation of recommendations can be highly variable,” she noted. Also, “The activity levels of late infancy and toddlers can vary in terms of energy usage, especially when crawling, walking, running and other exercise-related activities begin. These factors were not readily available in the abstract/study,” she said.
The OTIS trial was sponsored by Semper. Dr. Johansson had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News.
FROM ESPGHAN 2022
Pediatric obesity disparities widen
Lower levels of household income and education in the United States are associated with higher rates of adolescent obesity. These socioeconomic disparities “have widened during the last two decades,” new research shows.
Because obesity in adolescence has immediate and long-term health consequences, this phenomenon “may exacerbate socioeconomic disparities in chronic diseases into adulthood,” study author Ryunosuke Goto, MD, of University of Tokyo Hospital, and colleagues reported in JAMA Pediatrics.
Groups with higher rates of obesity may also be less likely to access treatment, said Kyung E. Rhee, MD, professor of pediatrics at University of California, San Diego School of Medicine, who was not involved in the new analysis.
“These are the families who have a harder time getting to the doctor’s office or getting to programs because they are working multiple jobs, or they don’t have as much flexibility,” Dr. Rhee told this news organization.
20 years of data
A recent study showed a relationship between socioeconomic status (SES) and weight in adults. Research examining current trends in adolescents has been limited, however, according to the authors of the new study.
To address this gap, Dr. Goto and colleagues looked at obesity trends among approximately 20,000 U.S. children aged 10-19 years using cross-sectional data from the 1999-2018 National Health and Nutrition Examination Surveys.
They compared the prevalence of obesity among participants whose household income was 138% of the federal poverty level or less versus those with higher levels of household income. They also examined obesity prevalence according to whether the head of household had graduated college.
Relative to higher-income households, adolescents from lower-income households were more likely to be non-Hispanic Black (21.7% vs. 10.4%) or Hispanic (30.6% vs. 13.4%) and to have an unmarried parent (54.5% vs. 23%). They were also more likely to have obesity (22.8% vs. 17.3%).
The prevalence of obesity likewise was higher among adolescents whose head of household did not have a college degree (21.8% vs. 11.6%).
In an analysis that adjusted for race, ethnicity, height, and marital status of the head of household, the prevalence of obesity increased over 20 years, particularly among adolescents from lower-income homes, the researchers reported.
Lower income was associated with an increase in obesity prevalence of 4.2 percentage points, and less education was associated with an increase in obesity prevalence of 9 percentage points.
By 2015-2018, the gap in obesity prevalence between low-income households and higher-income households was 6.4 percentage points more than it had been during 1999-2002 (95% confidence interval, 1.5-11.4). “When we assessed linear trends, the gap in obesity prevalence by income and education increased by an average of 1.5 (95% CI, 0.4-2.6) and 1.1 (95% CI, 0.0-2.3) percentage points every 4 years, respectively,” according to the researchers.
How to treat
Separately, researchers are studying ways to help treat patients with obesity and increase access to treatment. To that end, Dr. Rhee and colleagues developed a new program called Guided Self-Help Obesity Treatment in the Doctor’s Office (GOT Doc).
The guided self-help program was designed to provide similar resources as a leading treatment approach – family-based treatment – but in a less intensive, more accessible way.
Results from a randomized trial comparing this guided self-help approach with family-based treatment were published in Pediatrics.
The trial included 159 children and their parents. The children had an average age of 9.6 years and body mass index z-score of 2.1. Participants were primarily Latinx and from lower income neighborhoods.
Whereas family-based treatment included hour-long sessions at an academic center, the guided self-help program featured a 20-minute session in the office where patients typically see their primary care physician.
Both programs covered how to self-monitor food intake, set healthy goals, and modify the home environment to promote behavioral change. They also discussed body image, bullying, and emotional health. The program is framed around developing a healthy lifestyle rather than weight loss itself, Dr. Rhee said.
Children in both groups had significant reductions in their body mass index percentiles after the 6-month treatment programs. The reductions were largely maintained at 6-month follow-up.
Families in the guided self-help program, however, had a 67% lower risk of dropping out of the study and reported greater satisfaction and convenience. They attended more than half of the treatment sessions, whereas participants assigned to family-based treatment attended 1 in 5 sessions, on average.
The trial was conducted before the COVID-19 pandemic. Next, the researchers plan to test delivery of a guided self-help program via video calls, Dr. Rhee said.
Having options readily available for families who are interested in treatment for obesity proved valuable to clinicians, Dr. Rhee said. “They could then just refer them down the hall to the interventionist who was there, who was going to then work with the family to make these changes,” she said.
The study by Dr. Goto and colleagues was supported by grants from the Japan Society for the Promotion of Science. The trial by Dr. Rhee et al. was supported by a grant from the Health Resources and Services Administration. Neither research team had conflict of interest disclosures.
A version of this article first appeared on Medscape.com.
Lower levels of household income and education in the United States are associated with higher rates of adolescent obesity. These socioeconomic disparities “have widened during the last two decades,” new research shows.
Because obesity in adolescence has immediate and long-term health consequences, this phenomenon “may exacerbate socioeconomic disparities in chronic diseases into adulthood,” study author Ryunosuke Goto, MD, of University of Tokyo Hospital, and colleagues reported in JAMA Pediatrics.
Groups with higher rates of obesity may also be less likely to access treatment, said Kyung E. Rhee, MD, professor of pediatrics at University of California, San Diego School of Medicine, who was not involved in the new analysis.
“These are the families who have a harder time getting to the doctor’s office or getting to programs because they are working multiple jobs, or they don’t have as much flexibility,” Dr. Rhee told this news organization.
20 years of data
A recent study showed a relationship between socioeconomic status (SES) and weight in adults. Research examining current trends in adolescents has been limited, however, according to the authors of the new study.
To address this gap, Dr. Goto and colleagues looked at obesity trends among approximately 20,000 U.S. children aged 10-19 years using cross-sectional data from the 1999-2018 National Health and Nutrition Examination Surveys.
They compared the prevalence of obesity among participants whose household income was 138% of the federal poverty level or less versus those with higher levels of household income. They also examined obesity prevalence according to whether the head of household had graduated college.
Relative to higher-income households, adolescents from lower-income households were more likely to be non-Hispanic Black (21.7% vs. 10.4%) or Hispanic (30.6% vs. 13.4%) and to have an unmarried parent (54.5% vs. 23%). They were also more likely to have obesity (22.8% vs. 17.3%).
The prevalence of obesity likewise was higher among adolescents whose head of household did not have a college degree (21.8% vs. 11.6%).
In an analysis that adjusted for race, ethnicity, height, and marital status of the head of household, the prevalence of obesity increased over 20 years, particularly among adolescents from lower-income homes, the researchers reported.
Lower income was associated with an increase in obesity prevalence of 4.2 percentage points, and less education was associated with an increase in obesity prevalence of 9 percentage points.
By 2015-2018, the gap in obesity prevalence between low-income households and higher-income households was 6.4 percentage points more than it had been during 1999-2002 (95% confidence interval, 1.5-11.4). “When we assessed linear trends, the gap in obesity prevalence by income and education increased by an average of 1.5 (95% CI, 0.4-2.6) and 1.1 (95% CI, 0.0-2.3) percentage points every 4 years, respectively,” according to the researchers.
How to treat
Separately, researchers are studying ways to help treat patients with obesity and increase access to treatment. To that end, Dr. Rhee and colleagues developed a new program called Guided Self-Help Obesity Treatment in the Doctor’s Office (GOT Doc).
The guided self-help program was designed to provide similar resources as a leading treatment approach – family-based treatment – but in a less intensive, more accessible way.
Results from a randomized trial comparing this guided self-help approach with family-based treatment were published in Pediatrics.
The trial included 159 children and their parents. The children had an average age of 9.6 years and body mass index z-score of 2.1. Participants were primarily Latinx and from lower income neighborhoods.
Whereas family-based treatment included hour-long sessions at an academic center, the guided self-help program featured a 20-minute session in the office where patients typically see their primary care physician.
Both programs covered how to self-monitor food intake, set healthy goals, and modify the home environment to promote behavioral change. They also discussed body image, bullying, and emotional health. The program is framed around developing a healthy lifestyle rather than weight loss itself, Dr. Rhee said.
Children in both groups had significant reductions in their body mass index percentiles after the 6-month treatment programs. The reductions were largely maintained at 6-month follow-up.
Families in the guided self-help program, however, had a 67% lower risk of dropping out of the study and reported greater satisfaction and convenience. They attended more than half of the treatment sessions, whereas participants assigned to family-based treatment attended 1 in 5 sessions, on average.
The trial was conducted before the COVID-19 pandemic. Next, the researchers plan to test delivery of a guided self-help program via video calls, Dr. Rhee said.
Having options readily available for families who are interested in treatment for obesity proved valuable to clinicians, Dr. Rhee said. “They could then just refer them down the hall to the interventionist who was there, who was going to then work with the family to make these changes,” she said.
The study by Dr. Goto and colleagues was supported by grants from the Japan Society for the Promotion of Science. The trial by Dr. Rhee et al. was supported by a grant from the Health Resources and Services Administration. Neither research team had conflict of interest disclosures.
A version of this article first appeared on Medscape.com.
Lower levels of household income and education in the United States are associated with higher rates of adolescent obesity. These socioeconomic disparities “have widened during the last two decades,” new research shows.
Because obesity in adolescence has immediate and long-term health consequences, this phenomenon “may exacerbate socioeconomic disparities in chronic diseases into adulthood,” study author Ryunosuke Goto, MD, of University of Tokyo Hospital, and colleagues reported in JAMA Pediatrics.
Groups with higher rates of obesity may also be less likely to access treatment, said Kyung E. Rhee, MD, professor of pediatrics at University of California, San Diego School of Medicine, who was not involved in the new analysis.
“These are the families who have a harder time getting to the doctor’s office or getting to programs because they are working multiple jobs, or they don’t have as much flexibility,” Dr. Rhee told this news organization.
20 years of data
A recent study showed a relationship between socioeconomic status (SES) and weight in adults. Research examining current trends in adolescents has been limited, however, according to the authors of the new study.
To address this gap, Dr. Goto and colleagues looked at obesity trends among approximately 20,000 U.S. children aged 10-19 years using cross-sectional data from the 1999-2018 National Health and Nutrition Examination Surveys.
They compared the prevalence of obesity among participants whose household income was 138% of the federal poverty level or less versus those with higher levels of household income. They also examined obesity prevalence according to whether the head of household had graduated college.
Relative to higher-income households, adolescents from lower-income households were more likely to be non-Hispanic Black (21.7% vs. 10.4%) or Hispanic (30.6% vs. 13.4%) and to have an unmarried parent (54.5% vs. 23%). They were also more likely to have obesity (22.8% vs. 17.3%).
The prevalence of obesity likewise was higher among adolescents whose head of household did not have a college degree (21.8% vs. 11.6%).
In an analysis that adjusted for race, ethnicity, height, and marital status of the head of household, the prevalence of obesity increased over 20 years, particularly among adolescents from lower-income homes, the researchers reported.
Lower income was associated with an increase in obesity prevalence of 4.2 percentage points, and less education was associated with an increase in obesity prevalence of 9 percentage points.
By 2015-2018, the gap in obesity prevalence between low-income households and higher-income households was 6.4 percentage points more than it had been during 1999-2002 (95% confidence interval, 1.5-11.4). “When we assessed linear trends, the gap in obesity prevalence by income and education increased by an average of 1.5 (95% CI, 0.4-2.6) and 1.1 (95% CI, 0.0-2.3) percentage points every 4 years, respectively,” according to the researchers.
How to treat
Separately, researchers are studying ways to help treat patients with obesity and increase access to treatment. To that end, Dr. Rhee and colleagues developed a new program called Guided Self-Help Obesity Treatment in the Doctor’s Office (GOT Doc).
The guided self-help program was designed to provide similar resources as a leading treatment approach – family-based treatment – but in a less intensive, more accessible way.
Results from a randomized trial comparing this guided self-help approach with family-based treatment were published in Pediatrics.
The trial included 159 children and their parents. The children had an average age of 9.6 years and body mass index z-score of 2.1. Participants were primarily Latinx and from lower income neighborhoods.
Whereas family-based treatment included hour-long sessions at an academic center, the guided self-help program featured a 20-minute session in the office where patients typically see their primary care physician.
Both programs covered how to self-monitor food intake, set healthy goals, and modify the home environment to promote behavioral change. They also discussed body image, bullying, and emotional health. The program is framed around developing a healthy lifestyle rather than weight loss itself, Dr. Rhee said.
Children in both groups had significant reductions in their body mass index percentiles after the 6-month treatment programs. The reductions were largely maintained at 6-month follow-up.
Families in the guided self-help program, however, had a 67% lower risk of dropping out of the study and reported greater satisfaction and convenience. They attended more than half of the treatment sessions, whereas participants assigned to family-based treatment attended 1 in 5 sessions, on average.
The trial was conducted before the COVID-19 pandemic. Next, the researchers plan to test delivery of a guided self-help program via video calls, Dr. Rhee said.
Having options readily available for families who are interested in treatment for obesity proved valuable to clinicians, Dr. Rhee said. “They could then just refer them down the hall to the interventionist who was there, who was going to then work with the family to make these changes,” she said.
The study by Dr. Goto and colleagues was supported by grants from the Japan Society for the Promotion of Science. The trial by Dr. Rhee et al. was supported by a grant from the Health Resources and Services Administration. Neither research team had conflict of interest disclosures.
A version of this article first appeared on Medscape.com.
FDA approves setmelanotide for obesity in Bardet-Biedl syndrome
The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.
BBS affects an estimated 1,500-2,500 people in the United States.
Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.
Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.
Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.
As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.
These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.
The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
Safety, effectiveness in 66-week trial in 44 patients
The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.
After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.
The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.
- After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
- 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
- In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
- At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.
Setmelanotide is associated with the following warnings and precautions:
- Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
- Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
- Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
- Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.
The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.
BBS affects an estimated 1,500-2,500 people in the United States.
Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.
Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.
Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.
As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.
These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.
The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
Safety, effectiveness in 66-week trial in 44 patients
The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.
After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.
The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.
- After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
- 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
- In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
- At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.
Setmelanotide is associated with the following warnings and precautions:
- Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
- Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
- Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
- Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.
The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.
BBS affects an estimated 1,500-2,500 people in the United States.
Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.
Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.
Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.
As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.
These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.
The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
Safety, effectiveness in 66-week trial in 44 patients
The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.
After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.
The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.
- After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
- 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
- In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
- At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.
Setmelanotide is associated with the following warnings and precautions:
- Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
- Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
- Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
- Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.
The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.
A version of this article first appeared on Medscape.com.
Can the ketogenic diet treat polycystic ovary syndrome?
MADRID – During the International Scientific Symposium “New Frontiers in Scientific Research” that recently took place in Barcelona, specialists analyzed the role of the very-low-calorie ketogenic diet. This analysis was in relation to three comorbidities that have a higher incidence among overweight and obese patients: polycystic ovary syndrome, nonalcoholic fatty liver disease, and type 2 diabetes. The experts’ aim? To analyze and update the latest evidence on the benefits of this dietary choice.
Polycystic ovary syndrome
Alessandra Gambineri, MD, PhD, associate professor at the department of medicine and surgery (DIMEC) at the University of Bologna, Italy, addressed the link between obesity and polycystic ovary syndrome, which she described as a chronic disease that affects about 10% of women of childbearing age and that presents diverse phenotypes with different characteristics.
“The pathophysiology of this syndrome is characterized by the interaction of three factors: androgen excess, adipose tissue dysfunction, and insulin resistance. These factors interact with each other and are expressed differently in each phenotype,” said Dr. Gambineri.
She indicated that adipose tissue dysfunction is central to this pathology. This centrality results from its association with secretions, such as free fatty acids, proinflammatory cytokines, certain adipokines that promote insulin resistance, glucocorticosteroids, androgens, and oxidative stress.
“Similarly, the oxidative stress that characterizes this syndrome is increasingly present in obese individuals,” said Dr. Gambineri. “This oxidative stress also produces ovary hypotoxicity that aggravates ovulatory function. In this context, the very-low-calorie ketogenic diet can be useful in several ways: weight reduction; promoting the loss of mainly visceral/abdominal fat; decreasing lipotoxicity; and improving inflammation, hyperinsulinemia, and insulin resistance.”
This was the path followed to carry out a study that aimed to analyze the effects of the very-low-calorie ketogenic diet on manifestations of polycystic ovary syndrome in the obesity phenotype. Dr. Gambineri presented its results.
“The objective was to compare the effects of a very-low-calorie ketogenic diet and the standard low-calorie (hypocaloric) diet as a control group,” she said. “The effects studied include body weight, insulin resistance, menstrual cycle, ovulation, ovarian morphology, and hyperandrogenism in a population of 30 obese women with polycystic ovary syndrome and insulin resistance.”
Study participants had a diagnosis of polycystic ovary syndrome as defined by the National Institutes of Health criteria and were aged 18-45 years. These women were randomly assigned to two groups of equal size: experimental (very-low-calorie ketogenic diet) and control (hypocaloric diet). “The women assigned to the experimental group followed the ketogenic stage for eight weeks and then moved to the second, low-calorie diet phase for an additional eight weeks, while those in the control group (hypocaloric diet) followed the low-calorie diet for all 16 weeks.”
The primary outcomes were changes in weight and body composition, specifically fat mass and lean mass, measured by bioimpedance. “The changes observed in the following aspects were considered secondary outcomes: abdominal fat distribution, metabolic parameters, ovulation, ovarian morphology, hirsutism, hyperandrogenism, psychological well-being, and psychological distress,” said Dr. Gambineri. “Any reduction in the ovarian stroma, the area where androgens are synthesized, was also analyzed.”
The study authors found that although BMI decreased in both groups, this reduction was greater in the group that followed the very-low-calorie ketogenic diet. Significant weight loss was observed in both groups, 12.4 kg versus 4.7 kg. Significant differences were also observed in waist circumference (−8.1% in the experimental group vs. −2.2% in the control group), fat mass (−15.1% vs. −8.5%), and free testosterone (−30.3% vs. +10.6%). Only the experimental group saw a reduction in insulin.
“A key point regarding hyperandrogenism, especially regarding what’s referred to as free testosterone, there was only a significant reduction in the very-low-calorie ketogenic diet group,” said Dr. Gambineri. “This reduction was especially evident in the first part of the study, coinciding with the ketogenic period. The reason for this effect lies in the significant increase in the concentration of sex hormone-binding globulins, SHB6. Said globulins bind to the testosterone present in female blood, producing a reduction in free testosterone, a very important effect considering that this syndrome is an androgenic disorder. Furthermore, current treatments for polycystic ovary syndrome do not reduce free testosterone as much as this dietary approach does.”
For the specialist, among all these positive effects in these patients, perhaps most important is the notable improvement that occurs in ovulation. “At the beginning of the study, only 38.5% of the participants in the experimental group and 14.3% of those in the control group had ovulatory cycles. After the intervention, 84.6% managed to ovulate, compared to 35.7% who achieved this goal in the other group.”
Dr. Gambineri suggested that this method is “valid for reducing fat mass and rapidly improving hyperandrogenism and ovulatory dysfunction in women with obesity and polycystic ovary syndrome.”
Reversing type 2 diabetes?
Daniela Sofrà, MD, an endocrinologist specializing in diabetology at La Source Clinic, Lausanne, Switzerland, reviewed the current evidence on the role of the very-low-calorie ketogenic diet in the management of type 2 diabetes.
“It’s time to rethink diabetes treatment and focus efforts on managing obesity as an associated factor,” she said. “One of the hypotheses being examined in this regard is the twin cycle, which postulates that type 2 diabetes is the result of excess fat in the liver. This in turn is associated with insulin resistance with pancreas dysfunction.”
Dr. Sofrà added that there is a study documenting for the first time the reversibility of the morphology of the diabetic pancreas after caloric restriction with the very-low-calorie ketogenic diet. “The reason for this effect is the use of visceral and intrahepatic fat, which can lead to the remission of the clinical manifestation of type 2 diabetes, understanding as such the definition made by the American Diabetes Association: glycosylated hemoglobin < 6.5% without pharmacological therapy.”
Specifically, the results of this research showed that after following the very-low-calorie ketogenic diet and achieving a 15% weight loss (mean weight loss of the participants), liver glucose levels returned to normal levels within 7 days. Beta cell function returned to near normal within 8 weeks.
“Subsequent studies have shown the durability of remission of type 2 diabetes, thanks to the reactivation of the insulin-secreting function of beta cells that had become dedifferentiated in the face of chronic nutrient excess. Specifically, 6 out of 10 patients maintained glycosylated hemoglobin < 6% after 6 months without the need for pharmacological therapy,” Dr. Sofrà added.
Likewise, she highlighted that the probability of achieving remission is mainly determined by the duration of the disease. “The years with diabetes are one of the main predictors of the response that the patient will have with this dietary intervention. Studies have shown that remission is possible in patients with diabetes for less than 6 years, although there are other projects that indicate that it can be achieved with up to 10 years’ duration.”
Based on these data, Dr. Sofrà emphasized the pleiotropic effects of the very-low-calorie ketogenic diet on glycemic control, favoring the possible remission of diabetes or the reduction of drugs, as well as the reduction of the HOMA-IR index (insulin resistance) and waist circumference in people with type 2 diabetes.
Nonalcoholic fatty liver disease
The third comorbidity of obesity that may benefit from the very-low-calorie ketogenic diet is hepatic steatosis, or nonalcoholic fatty liver disease, said Hardy Walle, MD, an internal medicine specialist and director/founder of the Bodymed center, Kirkel, Germany, and one of the authors of this research.
“Recent research shows that ectopic fat and nonalcoholic fatty liver disease could be considered a cause, or at least one of the causes, of most of the diseases that affect the population as a consequence of overweight and obesity,” said Dr. Walle. “Some authors have stated that without fatty liver, there is no type 2 diabetes.”
Dr. Walle pointed out that between 30% and 40% of the adult population has nonalcoholic fatty liver disease, a percentage that increases considerably in people with obesity, reaching 70% prevalence and increasing, in the case of type 2 diabetes, to almost 90%. “Even normal weight does not rule out fatty liver; in fact, about 15% of people with nonalcoholic fatty liver disease are not overweight.”
In a setting where there are no approved drugs for the treatment of fatty liver (the current standard approach focuses on lifestyle interventions), a short-term hypocaloric diet (or liver fasting) is considered an effective method for management of this pathology. This principle was demonstrated by a study by the Saarland University, Saarbrücken, Germany, that Dr. Walle used to illustrate this statement.
“The participants (60 patients with hepatic steatosis) followed a hypocaloric diet (less than 1,000 kcal/day) for 14 days with a formula rich in protein and fiber specially developed for the treatment of nonalcoholic fatty liver disease. A fibroscan was then performed with controlled attenuation parameter measurement to quantify fatty liver disease. The results showed not only a significant improvement in nonalcoholic fatty liver disease parameters but also a marked improvement in all relevant metabolic parameters (serum lipids, liver enzymes),” explained Dr. Walle.
“This evidence leads us to affirm that the concept of hepatic fasting (by means of a hypocaloric diet) marks a point of reference for a future treatment approach for nonalcoholic fatty liver disease,” he concluded.
The study that Dr. Gambineri presented was carried out with the collaboration of the Pronokal Group (Nestlé Health Science). Dr. Gambineri, Dr. Sofrà, and Dr. Walle disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MADRID – During the International Scientific Symposium “New Frontiers in Scientific Research” that recently took place in Barcelona, specialists analyzed the role of the very-low-calorie ketogenic diet. This analysis was in relation to three comorbidities that have a higher incidence among overweight and obese patients: polycystic ovary syndrome, nonalcoholic fatty liver disease, and type 2 diabetes. The experts’ aim? To analyze and update the latest evidence on the benefits of this dietary choice.
Polycystic ovary syndrome
Alessandra Gambineri, MD, PhD, associate professor at the department of medicine and surgery (DIMEC) at the University of Bologna, Italy, addressed the link between obesity and polycystic ovary syndrome, which she described as a chronic disease that affects about 10% of women of childbearing age and that presents diverse phenotypes with different characteristics.
“The pathophysiology of this syndrome is characterized by the interaction of three factors: androgen excess, adipose tissue dysfunction, and insulin resistance. These factors interact with each other and are expressed differently in each phenotype,” said Dr. Gambineri.
She indicated that adipose tissue dysfunction is central to this pathology. This centrality results from its association with secretions, such as free fatty acids, proinflammatory cytokines, certain adipokines that promote insulin resistance, glucocorticosteroids, androgens, and oxidative stress.
“Similarly, the oxidative stress that characterizes this syndrome is increasingly present in obese individuals,” said Dr. Gambineri. “This oxidative stress also produces ovary hypotoxicity that aggravates ovulatory function. In this context, the very-low-calorie ketogenic diet can be useful in several ways: weight reduction; promoting the loss of mainly visceral/abdominal fat; decreasing lipotoxicity; and improving inflammation, hyperinsulinemia, and insulin resistance.”
This was the path followed to carry out a study that aimed to analyze the effects of the very-low-calorie ketogenic diet on manifestations of polycystic ovary syndrome in the obesity phenotype. Dr. Gambineri presented its results.
“The objective was to compare the effects of a very-low-calorie ketogenic diet and the standard low-calorie (hypocaloric) diet as a control group,” she said. “The effects studied include body weight, insulin resistance, menstrual cycle, ovulation, ovarian morphology, and hyperandrogenism in a population of 30 obese women with polycystic ovary syndrome and insulin resistance.”
Study participants had a diagnosis of polycystic ovary syndrome as defined by the National Institutes of Health criteria and were aged 18-45 years. These women were randomly assigned to two groups of equal size: experimental (very-low-calorie ketogenic diet) and control (hypocaloric diet). “The women assigned to the experimental group followed the ketogenic stage for eight weeks and then moved to the second, low-calorie diet phase for an additional eight weeks, while those in the control group (hypocaloric diet) followed the low-calorie diet for all 16 weeks.”
The primary outcomes were changes in weight and body composition, specifically fat mass and lean mass, measured by bioimpedance. “The changes observed in the following aspects were considered secondary outcomes: abdominal fat distribution, metabolic parameters, ovulation, ovarian morphology, hirsutism, hyperandrogenism, psychological well-being, and psychological distress,” said Dr. Gambineri. “Any reduction in the ovarian stroma, the area where androgens are synthesized, was also analyzed.”
The study authors found that although BMI decreased in both groups, this reduction was greater in the group that followed the very-low-calorie ketogenic diet. Significant weight loss was observed in both groups, 12.4 kg versus 4.7 kg. Significant differences were also observed in waist circumference (−8.1% in the experimental group vs. −2.2% in the control group), fat mass (−15.1% vs. −8.5%), and free testosterone (−30.3% vs. +10.6%). Only the experimental group saw a reduction in insulin.
“A key point regarding hyperandrogenism, especially regarding what’s referred to as free testosterone, there was only a significant reduction in the very-low-calorie ketogenic diet group,” said Dr. Gambineri. “This reduction was especially evident in the first part of the study, coinciding with the ketogenic period. The reason for this effect lies in the significant increase in the concentration of sex hormone-binding globulins, SHB6. Said globulins bind to the testosterone present in female blood, producing a reduction in free testosterone, a very important effect considering that this syndrome is an androgenic disorder. Furthermore, current treatments for polycystic ovary syndrome do not reduce free testosterone as much as this dietary approach does.”
For the specialist, among all these positive effects in these patients, perhaps most important is the notable improvement that occurs in ovulation. “At the beginning of the study, only 38.5% of the participants in the experimental group and 14.3% of those in the control group had ovulatory cycles. After the intervention, 84.6% managed to ovulate, compared to 35.7% who achieved this goal in the other group.”
Dr. Gambineri suggested that this method is “valid for reducing fat mass and rapidly improving hyperandrogenism and ovulatory dysfunction in women with obesity and polycystic ovary syndrome.”
Reversing type 2 diabetes?
Daniela Sofrà, MD, an endocrinologist specializing in diabetology at La Source Clinic, Lausanne, Switzerland, reviewed the current evidence on the role of the very-low-calorie ketogenic diet in the management of type 2 diabetes.
“It’s time to rethink diabetes treatment and focus efforts on managing obesity as an associated factor,” she said. “One of the hypotheses being examined in this regard is the twin cycle, which postulates that type 2 diabetes is the result of excess fat in the liver. This in turn is associated with insulin resistance with pancreas dysfunction.”
Dr. Sofrà added that there is a study documenting for the first time the reversibility of the morphology of the diabetic pancreas after caloric restriction with the very-low-calorie ketogenic diet. “The reason for this effect is the use of visceral and intrahepatic fat, which can lead to the remission of the clinical manifestation of type 2 diabetes, understanding as such the definition made by the American Diabetes Association: glycosylated hemoglobin < 6.5% without pharmacological therapy.”
Specifically, the results of this research showed that after following the very-low-calorie ketogenic diet and achieving a 15% weight loss (mean weight loss of the participants), liver glucose levels returned to normal levels within 7 days. Beta cell function returned to near normal within 8 weeks.
“Subsequent studies have shown the durability of remission of type 2 diabetes, thanks to the reactivation of the insulin-secreting function of beta cells that had become dedifferentiated in the face of chronic nutrient excess. Specifically, 6 out of 10 patients maintained glycosylated hemoglobin < 6% after 6 months without the need for pharmacological therapy,” Dr. Sofrà added.
Likewise, she highlighted that the probability of achieving remission is mainly determined by the duration of the disease. “The years with diabetes are one of the main predictors of the response that the patient will have with this dietary intervention. Studies have shown that remission is possible in patients with diabetes for less than 6 years, although there are other projects that indicate that it can be achieved with up to 10 years’ duration.”
Based on these data, Dr. Sofrà emphasized the pleiotropic effects of the very-low-calorie ketogenic diet on glycemic control, favoring the possible remission of diabetes or the reduction of drugs, as well as the reduction of the HOMA-IR index (insulin resistance) and waist circumference in people with type 2 diabetes.
Nonalcoholic fatty liver disease
The third comorbidity of obesity that may benefit from the very-low-calorie ketogenic diet is hepatic steatosis, or nonalcoholic fatty liver disease, said Hardy Walle, MD, an internal medicine specialist and director/founder of the Bodymed center, Kirkel, Germany, and one of the authors of this research.
“Recent research shows that ectopic fat and nonalcoholic fatty liver disease could be considered a cause, or at least one of the causes, of most of the diseases that affect the population as a consequence of overweight and obesity,” said Dr. Walle. “Some authors have stated that without fatty liver, there is no type 2 diabetes.”
Dr. Walle pointed out that between 30% and 40% of the adult population has nonalcoholic fatty liver disease, a percentage that increases considerably in people with obesity, reaching 70% prevalence and increasing, in the case of type 2 diabetes, to almost 90%. “Even normal weight does not rule out fatty liver; in fact, about 15% of people with nonalcoholic fatty liver disease are not overweight.”
In a setting where there are no approved drugs for the treatment of fatty liver (the current standard approach focuses on lifestyle interventions), a short-term hypocaloric diet (or liver fasting) is considered an effective method for management of this pathology. This principle was demonstrated by a study by the Saarland University, Saarbrücken, Germany, that Dr. Walle used to illustrate this statement.
“The participants (60 patients with hepatic steatosis) followed a hypocaloric diet (less than 1,000 kcal/day) for 14 days with a formula rich in protein and fiber specially developed for the treatment of nonalcoholic fatty liver disease. A fibroscan was then performed with controlled attenuation parameter measurement to quantify fatty liver disease. The results showed not only a significant improvement in nonalcoholic fatty liver disease parameters but also a marked improvement in all relevant metabolic parameters (serum lipids, liver enzymes),” explained Dr. Walle.
“This evidence leads us to affirm that the concept of hepatic fasting (by means of a hypocaloric diet) marks a point of reference for a future treatment approach for nonalcoholic fatty liver disease,” he concluded.
The study that Dr. Gambineri presented was carried out with the collaboration of the Pronokal Group (Nestlé Health Science). Dr. Gambineri, Dr. Sofrà, and Dr. Walle disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MADRID – During the International Scientific Symposium “New Frontiers in Scientific Research” that recently took place in Barcelona, specialists analyzed the role of the very-low-calorie ketogenic diet. This analysis was in relation to three comorbidities that have a higher incidence among overweight and obese patients: polycystic ovary syndrome, nonalcoholic fatty liver disease, and type 2 diabetes. The experts’ aim? To analyze and update the latest evidence on the benefits of this dietary choice.
Polycystic ovary syndrome
Alessandra Gambineri, MD, PhD, associate professor at the department of medicine and surgery (DIMEC) at the University of Bologna, Italy, addressed the link between obesity and polycystic ovary syndrome, which she described as a chronic disease that affects about 10% of women of childbearing age and that presents diverse phenotypes with different characteristics.
“The pathophysiology of this syndrome is characterized by the interaction of three factors: androgen excess, adipose tissue dysfunction, and insulin resistance. These factors interact with each other and are expressed differently in each phenotype,” said Dr. Gambineri.
She indicated that adipose tissue dysfunction is central to this pathology. This centrality results from its association with secretions, such as free fatty acids, proinflammatory cytokines, certain adipokines that promote insulin resistance, glucocorticosteroids, androgens, and oxidative stress.
“Similarly, the oxidative stress that characterizes this syndrome is increasingly present in obese individuals,” said Dr. Gambineri. “This oxidative stress also produces ovary hypotoxicity that aggravates ovulatory function. In this context, the very-low-calorie ketogenic diet can be useful in several ways: weight reduction; promoting the loss of mainly visceral/abdominal fat; decreasing lipotoxicity; and improving inflammation, hyperinsulinemia, and insulin resistance.”
This was the path followed to carry out a study that aimed to analyze the effects of the very-low-calorie ketogenic diet on manifestations of polycystic ovary syndrome in the obesity phenotype. Dr. Gambineri presented its results.
“The objective was to compare the effects of a very-low-calorie ketogenic diet and the standard low-calorie (hypocaloric) diet as a control group,” she said. “The effects studied include body weight, insulin resistance, menstrual cycle, ovulation, ovarian morphology, and hyperandrogenism in a population of 30 obese women with polycystic ovary syndrome and insulin resistance.”
Study participants had a diagnosis of polycystic ovary syndrome as defined by the National Institutes of Health criteria and were aged 18-45 years. These women were randomly assigned to two groups of equal size: experimental (very-low-calorie ketogenic diet) and control (hypocaloric diet). “The women assigned to the experimental group followed the ketogenic stage for eight weeks and then moved to the second, low-calorie diet phase for an additional eight weeks, while those in the control group (hypocaloric diet) followed the low-calorie diet for all 16 weeks.”
The primary outcomes were changes in weight and body composition, specifically fat mass and lean mass, measured by bioimpedance. “The changes observed in the following aspects were considered secondary outcomes: abdominal fat distribution, metabolic parameters, ovulation, ovarian morphology, hirsutism, hyperandrogenism, psychological well-being, and psychological distress,” said Dr. Gambineri. “Any reduction in the ovarian stroma, the area where androgens are synthesized, was also analyzed.”
The study authors found that although BMI decreased in both groups, this reduction was greater in the group that followed the very-low-calorie ketogenic diet. Significant weight loss was observed in both groups, 12.4 kg versus 4.7 kg. Significant differences were also observed in waist circumference (−8.1% in the experimental group vs. −2.2% in the control group), fat mass (−15.1% vs. −8.5%), and free testosterone (−30.3% vs. +10.6%). Only the experimental group saw a reduction in insulin.
“A key point regarding hyperandrogenism, especially regarding what’s referred to as free testosterone, there was only a significant reduction in the very-low-calorie ketogenic diet group,” said Dr. Gambineri. “This reduction was especially evident in the first part of the study, coinciding with the ketogenic period. The reason for this effect lies in the significant increase in the concentration of sex hormone-binding globulins, SHB6. Said globulins bind to the testosterone present in female blood, producing a reduction in free testosterone, a very important effect considering that this syndrome is an androgenic disorder. Furthermore, current treatments for polycystic ovary syndrome do not reduce free testosterone as much as this dietary approach does.”
For the specialist, among all these positive effects in these patients, perhaps most important is the notable improvement that occurs in ovulation. “At the beginning of the study, only 38.5% of the participants in the experimental group and 14.3% of those in the control group had ovulatory cycles. After the intervention, 84.6% managed to ovulate, compared to 35.7% who achieved this goal in the other group.”
Dr. Gambineri suggested that this method is “valid for reducing fat mass and rapidly improving hyperandrogenism and ovulatory dysfunction in women with obesity and polycystic ovary syndrome.”
Reversing type 2 diabetes?
Daniela Sofrà, MD, an endocrinologist specializing in diabetology at La Source Clinic, Lausanne, Switzerland, reviewed the current evidence on the role of the very-low-calorie ketogenic diet in the management of type 2 diabetes.
“It’s time to rethink diabetes treatment and focus efforts on managing obesity as an associated factor,” she said. “One of the hypotheses being examined in this regard is the twin cycle, which postulates that type 2 diabetes is the result of excess fat in the liver. This in turn is associated with insulin resistance with pancreas dysfunction.”
Dr. Sofrà added that there is a study documenting for the first time the reversibility of the morphology of the diabetic pancreas after caloric restriction with the very-low-calorie ketogenic diet. “The reason for this effect is the use of visceral and intrahepatic fat, which can lead to the remission of the clinical manifestation of type 2 diabetes, understanding as such the definition made by the American Diabetes Association: glycosylated hemoglobin < 6.5% without pharmacological therapy.”
Specifically, the results of this research showed that after following the very-low-calorie ketogenic diet and achieving a 15% weight loss (mean weight loss of the participants), liver glucose levels returned to normal levels within 7 days. Beta cell function returned to near normal within 8 weeks.
“Subsequent studies have shown the durability of remission of type 2 diabetes, thanks to the reactivation of the insulin-secreting function of beta cells that had become dedifferentiated in the face of chronic nutrient excess. Specifically, 6 out of 10 patients maintained glycosylated hemoglobin < 6% after 6 months without the need for pharmacological therapy,” Dr. Sofrà added.
Likewise, she highlighted that the probability of achieving remission is mainly determined by the duration of the disease. “The years with diabetes are one of the main predictors of the response that the patient will have with this dietary intervention. Studies have shown that remission is possible in patients with diabetes for less than 6 years, although there are other projects that indicate that it can be achieved with up to 10 years’ duration.”
Based on these data, Dr. Sofrà emphasized the pleiotropic effects of the very-low-calorie ketogenic diet on glycemic control, favoring the possible remission of diabetes or the reduction of drugs, as well as the reduction of the HOMA-IR index (insulin resistance) and waist circumference in people with type 2 diabetes.
Nonalcoholic fatty liver disease
The third comorbidity of obesity that may benefit from the very-low-calorie ketogenic diet is hepatic steatosis, or nonalcoholic fatty liver disease, said Hardy Walle, MD, an internal medicine specialist and director/founder of the Bodymed center, Kirkel, Germany, and one of the authors of this research.
“Recent research shows that ectopic fat and nonalcoholic fatty liver disease could be considered a cause, or at least one of the causes, of most of the diseases that affect the population as a consequence of overweight and obesity,” said Dr. Walle. “Some authors have stated that without fatty liver, there is no type 2 diabetes.”
Dr. Walle pointed out that between 30% and 40% of the adult population has nonalcoholic fatty liver disease, a percentage that increases considerably in people with obesity, reaching 70% prevalence and increasing, in the case of type 2 diabetes, to almost 90%. “Even normal weight does not rule out fatty liver; in fact, about 15% of people with nonalcoholic fatty liver disease are not overweight.”
In a setting where there are no approved drugs for the treatment of fatty liver (the current standard approach focuses on lifestyle interventions), a short-term hypocaloric diet (or liver fasting) is considered an effective method for management of this pathology. This principle was demonstrated by a study by the Saarland University, Saarbrücken, Germany, that Dr. Walle used to illustrate this statement.
“The participants (60 patients with hepatic steatosis) followed a hypocaloric diet (less than 1,000 kcal/day) for 14 days with a formula rich in protein and fiber specially developed for the treatment of nonalcoholic fatty liver disease. A fibroscan was then performed with controlled attenuation parameter measurement to quantify fatty liver disease. The results showed not only a significant improvement in nonalcoholic fatty liver disease parameters but also a marked improvement in all relevant metabolic parameters (serum lipids, liver enzymes),” explained Dr. Walle.
“This evidence leads us to affirm that the concept of hepatic fasting (by means of a hypocaloric diet) marks a point of reference for a future treatment approach for nonalcoholic fatty liver disease,” he concluded.
The study that Dr. Gambineri presented was carried out with the collaboration of the Pronokal Group (Nestlé Health Science). Dr. Gambineri, Dr. Sofrà, and Dr. Walle disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Ultra-processed: Doctors debate whether putting this label on foods is useful
The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”
According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.
During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.
Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.
Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.
Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.
To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.
“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”
A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.
Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.
“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.
In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.
He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.
Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.
Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.
Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.
If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
UPF definition doesn’t flag some unhealthy foods
Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.
The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.
“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.
The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”
She added that the UPF concept deserves a more formalized and rigorous evaluation.
“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
Doctor’s take on usefulness of discussing UPF concept with patients
Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.
“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”
The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.
“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”
He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”
Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.
“Guilt as a motivator isn’t really highly successful,” he said, in an interview.
Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.
The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”
According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.
During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.
Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.
Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.
Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.
To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.
“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”
A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.
Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.
“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.
In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.
He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.
Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.
Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.
Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.
If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
UPF definition doesn’t flag some unhealthy foods
Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.
The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.
“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.
The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”
She added that the UPF concept deserves a more formalized and rigorous evaluation.
“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
Doctor’s take on usefulness of discussing UPF concept with patients
Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.
“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”
The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.
“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”
He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”
Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.
“Guilt as a motivator isn’t really highly successful,” he said, in an interview.
Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.
The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”
According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.
During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.
Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.
Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.
Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.
To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.
“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”
A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.
Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.
“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.
In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.
He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.
Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.
Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.
Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.
If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
UPF definition doesn’t flag some unhealthy foods
Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.
The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.
“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.
The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”
She added that the UPF concept deserves a more formalized and rigorous evaluation.
“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
Doctor’s take on usefulness of discussing UPF concept with patients
Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.
“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”
The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.
“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”
He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”
Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.
“Guilt as a motivator isn’t really highly successful,” he said, in an interview.
Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.
FROM NUTRITION 2022
Center-based childcare associated with healthier body weight
The findings of the prospective Canadian study suggest that professional childcare centers that engage in standard practices are having a positive and lasting impact on children’s health, reported lead author Michaela Kucab, RD, MHSc, of the University of Toronto and colleagues.
“Attending center-based childcare in early childhood may influence important health behaviors including nutrition, physical activity, and routines related to child growth and weight status,” the investigators wrote in their abstract, which Ms. Kucab presented at the virtual conference sponsored by the American Society for Nutrition.
Their study involved 3,503 children who attended childcare in Canada during early childhood (mean age at baseline was 2.7 years) with follow-up from ages 4-10.
Overweight/obesity risk reduced
Children who received full-time, center-based care had a 22% lower risk of overweight/obesity and a mean body mass index z score (zBMI) that was 0.11 points lower at age 4 and 7 years than those who received non–center-based care. The benefits of center-based care were even more pronounced among children from lower-income families, who, at age 10, had a 48% lower risk of overweight/obesity and a mean zBMI that was 0.32 points lower with center-based versus non–center-based care.
In a written comment, Ms. Kucab and principal author Jonathon Maguire, MD, MSc, of the University of Toronto, explained that the former difference in zBMI translates to approximately half a pound of bodyweight in an average child, whereas the larger difference in zBMI among children from lower-income families would amount to approximately three pounds. They emphasized that these are rough estimations.
Ms. Kucab and Dr. Maguire noted that body weight differences correlated with the amount of time spent in center-based care.
“There was an observed trend, whereby the estimated mean difference [in zBMI] became slightly larger (or stronger) with a higher intensity of center-based childcare compared to non–center-based childcare,” they said.
To learn more about the earliest impacts of center-based care, the investigators are conducting a clinical trial, The Nutrition Recommendation Intervention Trials in Children’s Health Care (NuRISH), which will involve 600 children aged younger than 2 years.
Center-based childcare may reduce disadvantages of low-income children
“Although more research is needed, our findings suggest that center-based childcare may help” reduce disadvantages children from low-income families experience related to their heath,” Ms. Kucab said in a press release.
Laurent Legault, MD, an associate professor specializing in endocrinology in the department of pediatrics at McGill University, Montreal, highlighted the “quite significant” sample size of more than 3,000 participants, noting that “it’s quite tough to have numerous children” involved in a study, especially with several years of follow-up.
Dr. Legault also praised the investigators for considering socioeconomic status, “which is absolutely paramount, because, unfortunately, it’s not necessarily an even playing field for these families.”
He said the findings deserve to be promoted, as they highlight the benefits of center-based care, including ones with room for physical activity, opportunities for social interaction with other children, and a structured routine.
Still, Dr. Legault said it’s “very difficult to pinpoint specifically” what led to healthier body weights. “The problem, of course, is that obesity is very multifactorial in nature,” although “early intervention is more likely to be efficient.”
Center-based care appears to be one such intervention, he said, which should “push people to make centered care more affordable and easy to access for everyone.”The investigators and Dr. Legault reported no conflicts of interest.
The findings of the prospective Canadian study suggest that professional childcare centers that engage in standard practices are having a positive and lasting impact on children’s health, reported lead author Michaela Kucab, RD, MHSc, of the University of Toronto and colleagues.
“Attending center-based childcare in early childhood may influence important health behaviors including nutrition, physical activity, and routines related to child growth and weight status,” the investigators wrote in their abstract, which Ms. Kucab presented at the virtual conference sponsored by the American Society for Nutrition.
Their study involved 3,503 children who attended childcare in Canada during early childhood (mean age at baseline was 2.7 years) with follow-up from ages 4-10.
Overweight/obesity risk reduced
Children who received full-time, center-based care had a 22% lower risk of overweight/obesity and a mean body mass index z score (zBMI) that was 0.11 points lower at age 4 and 7 years than those who received non–center-based care. The benefits of center-based care were even more pronounced among children from lower-income families, who, at age 10, had a 48% lower risk of overweight/obesity and a mean zBMI that was 0.32 points lower with center-based versus non–center-based care.
In a written comment, Ms. Kucab and principal author Jonathon Maguire, MD, MSc, of the University of Toronto, explained that the former difference in zBMI translates to approximately half a pound of bodyweight in an average child, whereas the larger difference in zBMI among children from lower-income families would amount to approximately three pounds. They emphasized that these are rough estimations.
Ms. Kucab and Dr. Maguire noted that body weight differences correlated with the amount of time spent in center-based care.
“There was an observed trend, whereby the estimated mean difference [in zBMI] became slightly larger (or stronger) with a higher intensity of center-based childcare compared to non–center-based childcare,” they said.
To learn more about the earliest impacts of center-based care, the investigators are conducting a clinical trial, The Nutrition Recommendation Intervention Trials in Children’s Health Care (NuRISH), which will involve 600 children aged younger than 2 years.
Center-based childcare may reduce disadvantages of low-income children
“Although more research is needed, our findings suggest that center-based childcare may help” reduce disadvantages children from low-income families experience related to their heath,” Ms. Kucab said in a press release.
Laurent Legault, MD, an associate professor specializing in endocrinology in the department of pediatrics at McGill University, Montreal, highlighted the “quite significant” sample size of more than 3,000 participants, noting that “it’s quite tough to have numerous children” involved in a study, especially with several years of follow-up.
Dr. Legault also praised the investigators for considering socioeconomic status, “which is absolutely paramount, because, unfortunately, it’s not necessarily an even playing field for these families.”
He said the findings deserve to be promoted, as they highlight the benefits of center-based care, including ones with room for physical activity, opportunities for social interaction with other children, and a structured routine.
Still, Dr. Legault said it’s “very difficult to pinpoint specifically” what led to healthier body weights. “The problem, of course, is that obesity is very multifactorial in nature,” although “early intervention is more likely to be efficient.”
Center-based care appears to be one such intervention, he said, which should “push people to make centered care more affordable and easy to access for everyone.”The investigators and Dr. Legault reported no conflicts of interest.
The findings of the prospective Canadian study suggest that professional childcare centers that engage in standard practices are having a positive and lasting impact on children’s health, reported lead author Michaela Kucab, RD, MHSc, of the University of Toronto and colleagues.
“Attending center-based childcare in early childhood may influence important health behaviors including nutrition, physical activity, and routines related to child growth and weight status,” the investigators wrote in their abstract, which Ms. Kucab presented at the virtual conference sponsored by the American Society for Nutrition.
Their study involved 3,503 children who attended childcare in Canada during early childhood (mean age at baseline was 2.7 years) with follow-up from ages 4-10.
Overweight/obesity risk reduced
Children who received full-time, center-based care had a 22% lower risk of overweight/obesity and a mean body mass index z score (zBMI) that was 0.11 points lower at age 4 and 7 years than those who received non–center-based care. The benefits of center-based care were even more pronounced among children from lower-income families, who, at age 10, had a 48% lower risk of overweight/obesity and a mean zBMI that was 0.32 points lower with center-based versus non–center-based care.
In a written comment, Ms. Kucab and principal author Jonathon Maguire, MD, MSc, of the University of Toronto, explained that the former difference in zBMI translates to approximately half a pound of bodyweight in an average child, whereas the larger difference in zBMI among children from lower-income families would amount to approximately three pounds. They emphasized that these are rough estimations.
Ms. Kucab and Dr. Maguire noted that body weight differences correlated with the amount of time spent in center-based care.
“There was an observed trend, whereby the estimated mean difference [in zBMI] became slightly larger (or stronger) with a higher intensity of center-based childcare compared to non–center-based childcare,” they said.
To learn more about the earliest impacts of center-based care, the investigators are conducting a clinical trial, The Nutrition Recommendation Intervention Trials in Children’s Health Care (NuRISH), which will involve 600 children aged younger than 2 years.
Center-based childcare may reduce disadvantages of low-income children
“Although more research is needed, our findings suggest that center-based childcare may help” reduce disadvantages children from low-income families experience related to their heath,” Ms. Kucab said in a press release.
Laurent Legault, MD, an associate professor specializing in endocrinology in the department of pediatrics at McGill University, Montreal, highlighted the “quite significant” sample size of more than 3,000 participants, noting that “it’s quite tough to have numerous children” involved in a study, especially with several years of follow-up.
Dr. Legault also praised the investigators for considering socioeconomic status, “which is absolutely paramount, because, unfortunately, it’s not necessarily an even playing field for these families.”
He said the findings deserve to be promoted, as they highlight the benefits of center-based care, including ones with room for physical activity, opportunities for social interaction with other children, and a structured routine.
Still, Dr. Legault said it’s “very difficult to pinpoint specifically” what led to healthier body weights. “The problem, of course, is that obesity is very multifactorial in nature,” although “early intervention is more likely to be efficient.”
Center-based care appears to be one such intervention, he said, which should “push people to make centered care more affordable and easy to access for everyone.”The investigators and Dr. Legault reported no conflicts of interest.
FROM NUTRITION 2022
Avexitide promising for hypoglycemia after weight-loss surgery
Avexitide (Eiger Biopharmaceuticals), a first-in-class glucagonlike peptide (GLP)–1 receptor blocker, significantly reduced hypoglycemia in patients with refractory postbariatric hypoglycemia, new research finds.
Postbariatric hypoglycemia is a complication of bariatric surgery that is estimated to occur in about 29%-34% of people who undergo Roux-en-Y gastric bypass and in 11%-23% of those who undergo vertical sleeve gastrectomy. It typically manifests about 1-3 hours after meals and can lead to severe neuroglycopenic symptoms including blurred vision, confusion, drowsiness, and incoordination.
In addition, more than one-third (37%) with the condition have hypoglycemic unawareness. This can lead to seizures in about 59%, loss of consciousness and hospitalization in 50%, motor vehicle accidents, and even death. More than 90% with the condition consider themselves disabled, and 41% report being unable to work.
There are no currently approved medical treatments for postbariatric hypoglycemia. The standard of care is medical nutrition therapy involving a low-carbohydrate diet with carb restriction and small, frequent mixed meals. If this doesn’t work, off-label stepped pharmacotherapy has been tried, including acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).
But “these are limited by efficacy and tolerability,” said Marilyn Tan, MD, who presented the findings from the phase 2 trial of avexitide at the annual meeting of the Endocrine Society.
In very severe cases, gastrostomy tubes or bypass reversal are options but those lead to weight regain and incomplete efficacy. “Safe, effective, and targeted therapies are needed urgently for postbariatric hypoglycemia,” said Dr. Tan, of the department of endocrinology at Stanford (Calif.) University.
The pathophysiology isn’t fully understood, but there appears to be an exaggerated GLP-1 response that leads to abnormal insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (formerly exendin 9-39), blocks the GLP-1 receptor and mitigates the excessive GLP-1 response, she explained.
Asked to comment, session moderator Michelle Van Name, MD, told this news organization, “This is a problem and it’s important for us to understand more about it and to identify different treatment options so these patients can continue to live their full, healthy lives post bariatric surgery.”
And, avexitide also holds potential for treating congenital hyperinsulinism, “which is a very challenging disease to treat in babies,” noted Dr. Van Name, a pediatric endocrinologist at Yale University, New Haven, Conn.
Drug reduced all levels of hypoglycemia, across surgery types
The study enrolled 14 women and 2 men with severe refractory postbariatric surgery hypoglycemia despite medical nutrition therapy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven patients (43.7%) had experienced loss of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.
They were randomly assigned to either subcutaneous 45 mg of avexitide twice daily or 90 mg once daily for 14 days each, with a 2-day washout period followed by a switch to the other dose.
Both doses resulted in significant reductions in hypoglycemia as measured by self–blood glucose monitoring. The once-daily dose reduced level 1 hypoglycemia (glucose < 70 mg/dL) by 67.5% and it reduced level 2 (< 54 mg/dL) by 53.3% (P = .0043).
Even greater reductions were seen in severe hypoglycemia (that is, altered mental status/requiring assistance) – by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003).
“This is consistent with what we’ve seen in prior avexitide trials,” Dr. Tan noted.
More hypoglycemic events were captured using blinded continuous glucose monitoring (CGM), since it picked up episodes of which the patient was unaware. There were significant reductions in percentage time spent in level 1 and level 2 hypoglycemia, as well as in absolute number of hypoglycemic events over 14 days.
Here, the effect was greater with the once-daily 90 mg dose, with reductions of up to 65% in time spent and number of events, but results for the twice-daily dose were also significant, Dr. Tan said.
The drug was effective across all surgical subtypes. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and “robust responses to avexitide subcutaneous injections. This supports the critical role of GLP-1,” Dr. Tan said.
There were no severe adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection-site reaction/bruising. All were mild and self-limited and resolved without treatment. No participants withdrew from the study.
Eiger Biopharmaceuticals is currently working with the U.S. Food and Drug Administration and the European Medicines Agency to design a phase 3 trial.
The study is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Dr. Tan receives research support from Eiger Biopharmaceuticals as a site investigator. Dr. Van Name is an investigator for a trial sponsored by Provention Bio.
A version of this article first appeared on Medscape.com.
Avexitide (Eiger Biopharmaceuticals), a first-in-class glucagonlike peptide (GLP)–1 receptor blocker, significantly reduced hypoglycemia in patients with refractory postbariatric hypoglycemia, new research finds.
Postbariatric hypoglycemia is a complication of bariatric surgery that is estimated to occur in about 29%-34% of people who undergo Roux-en-Y gastric bypass and in 11%-23% of those who undergo vertical sleeve gastrectomy. It typically manifests about 1-3 hours after meals and can lead to severe neuroglycopenic symptoms including blurred vision, confusion, drowsiness, and incoordination.
In addition, more than one-third (37%) with the condition have hypoglycemic unawareness. This can lead to seizures in about 59%, loss of consciousness and hospitalization in 50%, motor vehicle accidents, and even death. More than 90% with the condition consider themselves disabled, and 41% report being unable to work.
There are no currently approved medical treatments for postbariatric hypoglycemia. The standard of care is medical nutrition therapy involving a low-carbohydrate diet with carb restriction and small, frequent mixed meals. If this doesn’t work, off-label stepped pharmacotherapy has been tried, including acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).
But “these are limited by efficacy and tolerability,” said Marilyn Tan, MD, who presented the findings from the phase 2 trial of avexitide at the annual meeting of the Endocrine Society.
In very severe cases, gastrostomy tubes or bypass reversal are options but those lead to weight regain and incomplete efficacy. “Safe, effective, and targeted therapies are needed urgently for postbariatric hypoglycemia,” said Dr. Tan, of the department of endocrinology at Stanford (Calif.) University.
The pathophysiology isn’t fully understood, but there appears to be an exaggerated GLP-1 response that leads to abnormal insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (formerly exendin 9-39), blocks the GLP-1 receptor and mitigates the excessive GLP-1 response, she explained.
Asked to comment, session moderator Michelle Van Name, MD, told this news organization, “This is a problem and it’s important for us to understand more about it and to identify different treatment options so these patients can continue to live their full, healthy lives post bariatric surgery.”
And, avexitide also holds potential for treating congenital hyperinsulinism, “which is a very challenging disease to treat in babies,” noted Dr. Van Name, a pediatric endocrinologist at Yale University, New Haven, Conn.
Drug reduced all levels of hypoglycemia, across surgery types
The study enrolled 14 women and 2 men with severe refractory postbariatric surgery hypoglycemia despite medical nutrition therapy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven patients (43.7%) had experienced loss of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.
They were randomly assigned to either subcutaneous 45 mg of avexitide twice daily or 90 mg once daily for 14 days each, with a 2-day washout period followed by a switch to the other dose.
Both doses resulted in significant reductions in hypoglycemia as measured by self–blood glucose monitoring. The once-daily dose reduced level 1 hypoglycemia (glucose < 70 mg/dL) by 67.5% and it reduced level 2 (< 54 mg/dL) by 53.3% (P = .0043).
Even greater reductions were seen in severe hypoglycemia (that is, altered mental status/requiring assistance) – by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003).
“This is consistent with what we’ve seen in prior avexitide trials,” Dr. Tan noted.
More hypoglycemic events were captured using blinded continuous glucose monitoring (CGM), since it picked up episodes of which the patient was unaware. There were significant reductions in percentage time spent in level 1 and level 2 hypoglycemia, as well as in absolute number of hypoglycemic events over 14 days.
Here, the effect was greater with the once-daily 90 mg dose, with reductions of up to 65% in time spent and number of events, but results for the twice-daily dose were also significant, Dr. Tan said.
The drug was effective across all surgical subtypes. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and “robust responses to avexitide subcutaneous injections. This supports the critical role of GLP-1,” Dr. Tan said.
There were no severe adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection-site reaction/bruising. All were mild and self-limited and resolved without treatment. No participants withdrew from the study.
Eiger Biopharmaceuticals is currently working with the U.S. Food and Drug Administration and the European Medicines Agency to design a phase 3 trial.
The study is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Dr. Tan receives research support from Eiger Biopharmaceuticals as a site investigator. Dr. Van Name is an investigator for a trial sponsored by Provention Bio.
A version of this article first appeared on Medscape.com.
Avexitide (Eiger Biopharmaceuticals), a first-in-class glucagonlike peptide (GLP)–1 receptor blocker, significantly reduced hypoglycemia in patients with refractory postbariatric hypoglycemia, new research finds.
Postbariatric hypoglycemia is a complication of bariatric surgery that is estimated to occur in about 29%-34% of people who undergo Roux-en-Y gastric bypass and in 11%-23% of those who undergo vertical sleeve gastrectomy. It typically manifests about 1-3 hours after meals and can lead to severe neuroglycopenic symptoms including blurred vision, confusion, drowsiness, and incoordination.
In addition, more than one-third (37%) with the condition have hypoglycemic unawareness. This can lead to seizures in about 59%, loss of consciousness and hospitalization in 50%, motor vehicle accidents, and even death. More than 90% with the condition consider themselves disabled, and 41% report being unable to work.
There are no currently approved medical treatments for postbariatric hypoglycemia. The standard of care is medical nutrition therapy involving a low-carbohydrate diet with carb restriction and small, frequent mixed meals. If this doesn’t work, off-label stepped pharmacotherapy has been tried, including acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).
But “these are limited by efficacy and tolerability,” said Marilyn Tan, MD, who presented the findings from the phase 2 trial of avexitide at the annual meeting of the Endocrine Society.
In very severe cases, gastrostomy tubes or bypass reversal are options but those lead to weight regain and incomplete efficacy. “Safe, effective, and targeted therapies are needed urgently for postbariatric hypoglycemia,” said Dr. Tan, of the department of endocrinology at Stanford (Calif.) University.
The pathophysiology isn’t fully understood, but there appears to be an exaggerated GLP-1 response that leads to abnormal insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (formerly exendin 9-39), blocks the GLP-1 receptor and mitigates the excessive GLP-1 response, she explained.
Asked to comment, session moderator Michelle Van Name, MD, told this news organization, “This is a problem and it’s important for us to understand more about it and to identify different treatment options so these patients can continue to live their full, healthy lives post bariatric surgery.”
And, avexitide also holds potential for treating congenital hyperinsulinism, “which is a very challenging disease to treat in babies,” noted Dr. Van Name, a pediatric endocrinologist at Yale University, New Haven, Conn.
Drug reduced all levels of hypoglycemia, across surgery types
The study enrolled 14 women and 2 men with severe refractory postbariatric surgery hypoglycemia despite medical nutrition therapy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven patients (43.7%) had experienced loss of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.
They were randomly assigned to either subcutaneous 45 mg of avexitide twice daily or 90 mg once daily for 14 days each, with a 2-day washout period followed by a switch to the other dose.
Both doses resulted in significant reductions in hypoglycemia as measured by self–blood glucose monitoring. The once-daily dose reduced level 1 hypoglycemia (glucose < 70 mg/dL) by 67.5% and it reduced level 2 (< 54 mg/dL) by 53.3% (P = .0043).
Even greater reductions were seen in severe hypoglycemia (that is, altered mental status/requiring assistance) – by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003).
“This is consistent with what we’ve seen in prior avexitide trials,” Dr. Tan noted.
More hypoglycemic events were captured using blinded continuous glucose monitoring (CGM), since it picked up episodes of which the patient was unaware. There were significant reductions in percentage time spent in level 1 and level 2 hypoglycemia, as well as in absolute number of hypoglycemic events over 14 days.
Here, the effect was greater with the once-daily 90 mg dose, with reductions of up to 65% in time spent and number of events, but results for the twice-daily dose were also significant, Dr. Tan said.
The drug was effective across all surgical subtypes. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and “robust responses to avexitide subcutaneous injections. This supports the critical role of GLP-1,” Dr. Tan said.
There were no severe adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection-site reaction/bruising. All were mild and self-limited and resolved without treatment. No participants withdrew from the study.
Eiger Biopharmaceuticals is currently working with the U.S. Food and Drug Administration and the European Medicines Agency to design a phase 3 trial.
The study is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Dr. Tan receives research support from Eiger Biopharmaceuticals as a site investigator. Dr. Van Name is an investigator for a trial sponsored by Provention Bio.
A version of this article first appeared on Medscape.com.
FROM ENDO 2022