Clinical Endocrinology News

Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.

Fuse/Thinkstock

“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.

Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.

The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).

However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.

These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.

The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).

“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
 

Women especially benefit from red meat reduction

The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.

“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.

The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.

The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.

Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.

Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.

Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.

Fuse/Thinkstock

“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.

Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.

The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).

However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.

These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.

The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).

“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
 

Women especially benefit from red meat reduction

The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.

“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.

The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.

The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.

Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.

Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.

Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.

Fuse/Thinkstock

“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.

Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.

The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).

However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.

These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.

The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).

“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
 

Women especially benefit from red meat reduction

The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.

“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.

The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.

The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.

Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.

Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.

Being overweight or having obesity significantly increases the risk for liver disease and the likelihood of dying from it compared with being of normal weight, regardless of level of alcohol consumption, new research shows. 
"People in the overweight or obese range who drank were found to be at greater risk of liver diseases compared with participants within a healthy weight range who consumed alcohol at the same level," senior author Emmanuel Stamatakis, PhD, of the Charles Perkins Centre and the Faculty of Medicine and Health, Sydney, said in a press statement. 
"Even for people who drank within alcohol guidelines, participants classified as obese were at over 50% greater risk of liver disease," he said. 
"Obesity is an independent risk factor for steatosis, acute alcoholic hepatitis, and cirrhosis in alcoholic liver disease (ALD), which may increase the risk of mortality in ALD patients," the study's first author, Elif Inan-Eroglu, PhD, a postdoctoral research fellow at the Charles Perkins Centre, said in an interview. 
Further prospective studies are needed to better understand the underlying mechanisms behind the association between alcohol consumption and liver disease across different adiposity levels, the authors say. 
Meanwhile, the take-home message from the findings should be that "clinicians should consider the presence of overweight and obesity when they discuss defining safe alcohol levels for their patients, keeping in mind that there is no 'safe' level of alcohol," Dr. Inan-Eroglu said. 
"Alcohol drinking guidelines need to acknowledge that two-thirds of the adult population are overweight or obese and consider specific recommendations for this majority population group," he said.  

First and largest study of its kind 

Obesity, well-known to be an independent risk factor for nonalcoholic fatty liver disease (NAFLD), is also known to worsen outcomes in ALD. And likewise, alcohol consumption, the cause of ALD, can promote obesity and therefore increase the risk of NAFLD. 
Dr. Stamatakis and colleagues sought to evaluate the roles of the combined factors in terms of incidence and mortality in both ALD and NAFLD. 
For the study, published online May 31 in the European Journal of Clinical Nutrition, they evaluated data from 465,437 participants in the U.K. Biobank. The study is said to be the first and largest of its kind. 
In the cohort, a total of 1,090 liver disease deaths were recorded, including 230 deaths from ALD and 192 from NAFLD over an average follow-up of 10.5 years. 
After a multivariate adjustment, the overall risk of ALD, NAFLD, and liver disease incidence and mortality were significantly higher in participants who were overweight or had obesity, compared with those of normal weight, at all levels of alcohol consumption. 
For instance, among those with alcohol use exceeding guidelines, the risk of ALD was significantly increased in normal weight individuals versus never-drinkers (hazard ratio [HR], 5.38), and the risk was even higher among those who were also overweight or had obesity (HR, 8.58). 
In terms of the risk of death related to ALD, among those reporting alcohol consumption above guidelines, the risk was nearly double among those who were overweight or had obesity (HR, 10.29) versus those with normal weight (HR, 5.84), when each group was compared to those drinking within guidelines. 
Regarding NAFLD, consistent with evidence that low to moderate alcohol consumption is, in fact, linked to a reduced risk, those in the study who reported alcohol consumption within guidelines and normal weight did show a reduced risk of NAFLD compared with an index group of never-drinkers (HR, 0.85). 
However, being overweight or having obesity increased the risk of NAFLD in those participants (HR, 1.51). 
Furthermore, even those reporting alcohol consumption above guidelines who were of normal weight had a reduced risk of NAFLD compared with never drinkers of normal weight (HR, 0.89).   
Regarding the risk of liver disease among those reporting alcohol consumption above guidelines compared with never-drinkers, the risk was again lower among those of normal weight versus those who were overweight or had obesity (HR, 0.95 vs. 1.52), as were the risks of mortality (HR, 1.24 vs. 2.20). 
Overall, "we found evidence that being overweight/[having obesity] amplified the harmful effect of alcohol on the liver disease incidence and mortality," the authors conclude. 
The authors have reported no relevant financial relationships. 
A version of this article first appeared on Medscape.com

Being overweight or having obesity significantly increases the risk for liver disease and the likelihood of dying from it compared with being of normal weight, regardless of level of alcohol consumption, new research shows. 
"People in the overweight or obese range who drank were found to be at greater risk of liver diseases compared with participants within a healthy weight range who consumed alcohol at the same level," senior author Emmanuel Stamatakis, PhD, of the Charles Perkins Centre and the Faculty of Medicine and Health, Sydney, said in a press statement. 
"Even for people who drank within alcohol guidelines, participants classified as obese were at over 50% greater risk of liver disease," he said. 
"Obesity is an independent risk factor for steatosis, acute alcoholic hepatitis, and cirrhosis in alcoholic liver disease (ALD), which may increase the risk of mortality in ALD patients," the study's first author, Elif Inan-Eroglu, PhD, a postdoctoral research fellow at the Charles Perkins Centre, said in an interview. 
Further prospective studies are needed to better understand the underlying mechanisms behind the association between alcohol consumption and liver disease across different adiposity levels, the authors say. 
Meanwhile, the take-home message from the findings should be that "clinicians should consider the presence of overweight and obesity when they discuss defining safe alcohol levels for their patients, keeping in mind that there is no 'safe' level of alcohol," Dr. Inan-Eroglu said. 
"Alcohol drinking guidelines need to acknowledge that two-thirds of the adult population are overweight or obese and consider specific recommendations for this majority population group," he said.  

First and largest study of its kind 

Obesity, well-known to be an independent risk factor for nonalcoholic fatty liver disease (NAFLD), is also known to worsen outcomes in ALD. And likewise, alcohol consumption, the cause of ALD, can promote obesity and therefore increase the risk of NAFLD. 
Dr. Stamatakis and colleagues sought to evaluate the roles of the combined factors in terms of incidence and mortality in both ALD and NAFLD. 
For the study, published online May 31 in the European Journal of Clinical Nutrition, they evaluated data from 465,437 participants in the U.K. Biobank. The study is said to be the first and largest of its kind. 
In the cohort, a total of 1,090 liver disease deaths were recorded, including 230 deaths from ALD and 192 from NAFLD over an average follow-up of 10.5 years. 
After a multivariate adjustment, the overall risk of ALD, NAFLD, and liver disease incidence and mortality were significantly higher in participants who were overweight or had obesity, compared with those of normal weight, at all levels of alcohol consumption. 
For instance, among those with alcohol use exceeding guidelines, the risk of ALD was significantly increased in normal weight individuals versus never-drinkers (hazard ratio [HR], 5.38), and the risk was even higher among those who were also overweight or had obesity (HR, 8.58). 
In terms of the risk of death related to ALD, among those reporting alcohol consumption above guidelines, the risk was nearly double among those who were overweight or had obesity (HR, 10.29) versus those with normal weight (HR, 5.84), when each group was compared to those drinking within guidelines. 
Regarding NAFLD, consistent with evidence that low to moderate alcohol consumption is, in fact, linked to a reduced risk, those in the study who reported alcohol consumption within guidelines and normal weight did show a reduced risk of NAFLD compared with an index group of never-drinkers (HR, 0.85). 
However, being overweight or having obesity increased the risk of NAFLD in those participants (HR, 1.51). 
Furthermore, even those reporting alcohol consumption above guidelines who were of normal weight had a reduced risk of NAFLD compared with never drinkers of normal weight (HR, 0.89).   
Regarding the risk of liver disease among those reporting alcohol consumption above guidelines compared with never-drinkers, the risk was again lower among those of normal weight versus those who were overweight or had obesity (HR, 0.95 vs. 1.52), as were the risks of mortality (HR, 1.24 vs. 2.20). 
Overall, "we found evidence that being overweight/[having obesity] amplified the harmful effect of alcohol on the liver disease incidence and mortality," the authors conclude. 
The authors have reported no relevant financial relationships. 
A version of this article first appeared on Medscape.com

Being overweight or having obesity significantly increases the risk for liver disease and the likelihood of dying from it compared with being of normal weight, regardless of level of alcohol consumption, new research shows. 
"People in the overweight or obese range who drank were found to be at greater risk of liver diseases compared with participants within a healthy weight range who consumed alcohol at the same level," senior author Emmanuel Stamatakis, PhD, of the Charles Perkins Centre and the Faculty of Medicine and Health, Sydney, said in a press statement. 
"Even for people who drank within alcohol guidelines, participants classified as obese were at over 50% greater risk of liver disease," he said. 
"Obesity is an independent risk factor for steatosis, acute alcoholic hepatitis, and cirrhosis in alcoholic liver disease (ALD), which may increase the risk of mortality in ALD patients," the study's first author, Elif Inan-Eroglu, PhD, a postdoctoral research fellow at the Charles Perkins Centre, said in an interview. 
Further prospective studies are needed to better understand the underlying mechanisms behind the association between alcohol consumption and liver disease across different adiposity levels, the authors say. 
Meanwhile, the take-home message from the findings should be that "clinicians should consider the presence of overweight and obesity when they discuss defining safe alcohol levels for their patients, keeping in mind that there is no 'safe' level of alcohol," Dr. Inan-Eroglu said. 
"Alcohol drinking guidelines need to acknowledge that two-thirds of the adult population are overweight or obese and consider specific recommendations for this majority population group," he said.  

First and largest study of its kind 

Obesity, well-known to be an independent risk factor for nonalcoholic fatty liver disease (NAFLD), is also known to worsen outcomes in ALD. And likewise, alcohol consumption, the cause of ALD, can promote obesity and therefore increase the risk of NAFLD. 
Dr. Stamatakis and colleagues sought to evaluate the roles of the combined factors in terms of incidence and mortality in both ALD and NAFLD. 
For the study, published online May 31 in the European Journal of Clinical Nutrition, they evaluated data from 465,437 participants in the U.K. Biobank. The study is said to be the first and largest of its kind. 
In the cohort, a total of 1,090 liver disease deaths were recorded, including 230 deaths from ALD and 192 from NAFLD over an average follow-up of 10.5 years. 
After a multivariate adjustment, the overall risk of ALD, NAFLD, and liver disease incidence and mortality were significantly higher in participants who were overweight or had obesity, compared with those of normal weight, at all levels of alcohol consumption. 
For instance, among those with alcohol use exceeding guidelines, the risk of ALD was significantly increased in normal weight individuals versus never-drinkers (hazard ratio [HR], 5.38), and the risk was even higher among those who were also overweight or had obesity (HR, 8.58). 
In terms of the risk of death related to ALD, among those reporting alcohol consumption above guidelines, the risk was nearly double among those who were overweight or had obesity (HR, 10.29) versus those with normal weight (HR, 5.84), when each group was compared to those drinking within guidelines. 
Regarding NAFLD, consistent with evidence that low to moderate alcohol consumption is, in fact, linked to a reduced risk, those in the study who reported alcohol consumption within guidelines and normal weight did show a reduced risk of NAFLD compared with an index group of never-drinkers (HR, 0.85). 
However, being overweight or having obesity increased the risk of NAFLD in those participants (HR, 1.51). 
Furthermore, even those reporting alcohol consumption above guidelines who were of normal weight had a reduced risk of NAFLD compared with never drinkers of normal weight (HR, 0.89).   
Regarding the risk of liver disease among those reporting alcohol consumption above guidelines compared with never-drinkers, the risk was again lower among those of normal weight versus those who were overweight or had obesity (HR, 0.95 vs. 1.52), as were the risks of mortality (HR, 1.24 vs. 2.20). 
Overall, "we found evidence that being overweight/[having obesity] amplified the harmful effect of alcohol on the liver disease incidence and mortality," the authors conclude. 
The authors have reported no relevant financial relationships. 
A version of this article first appeared on Medscape.com

It follows that, as the prevalence of obesity among people with type 1 diabetes mellitus (T1DM) increases, so would the incidence of nonalcoholic fatty liver (NAFL), as it does in type 2 diabetes.

However, researchers in Finland report that the incidence of NAFL in T1DM is much lower, and that the use of the waist-to-height ratio to calculate midsection girth could be a low-cost alternative to MRI and computed tomography to more precisely diagnose NAFL in T1DM.

In a cross-sectional analysis of 121 adults with T1DM in the Finnish Diabetic Nephropathy study, known as FinnDiane, researchers from the University of Helsinki report in Diabetes Care that a waist-to-height ratio of 0.5 showed a relatively high rate of accuracy for identifying NAFL that was statistically significant (P = .04).

Lead author Erika B. Parente, MD, PhD, a researcher at the Folkhälsän Research Center in Helsinki, noted that the findings do not identify any causality between what the researchers called visceral adiposity and NAFL. “As long as they have accumulation of fat in the center of body and they can develop this low-grade inflammation that also goes to insulin-load sensitivity, people with T1DM can accumulate fat in the liver as do people with T2DM and the general population,” she said in an interview.

These findings build on her group’s previous work published in Scientific Reports showing a strong relationship between waist-to-height ratio and visceral fat percentage in adults with T1DM. The most recent FinnDiane analysis found no similar relationship between NAFL and fat tissue in the hips, arms and legs, and total adipose tissue.
 

Better than BMI as a measure

“We also found that waist-to-height ratio is better than body mass index to identify those individuals at higher risk of having NAFL,” Dr. Parente said. However, it’s not possible to predict which patients referred to imaging evaluation after being screened by waist-to-height ratio of 0.5 will surely have NAFL, she added.

That answer, she said, would require a longitudinal and cost-effectiveness study with larger population.

The waist-to-height ratio cutoff of 0.5 showed an 86% sensitivity and 55% specificity for NAFL, whereas BMI of 26.6 kg/m² showed an 79% sensitivity and 57% specificity.

“The most important message from our research is that health care professionals should be aware that individuals with T1DM can have NAFL, and waist-to-height ratio may help to identify those at higher risk,” she said.

The prevalence of NAFL among the adults with T1DM in the study was 11.6%, which is lower than the prevalence other studies reported in T2DM – 76% in a U.S. study – and in the general population – ranging from 19% to 46%. This underscores, Dr. Parente noted, the importance of using waist-to-height ratio in T1DM patients to determine the status of NAFL.

She said that few studies have investigated the consequences of NAFL in T1DM, pointing to two that linked NAFL with chronic kidney disease and cardiovascular disease in T1DM (Diabetes Care. 2014;37:1729-36; J Hepatol. 2010;53:713-8). “Most of the studies about the consequences of NAFL included people with T2DM,” she said. “From our research, we cannot conclude about the impact of NAFL in cardiovascular or kidney complications in our population because this is a cross-sectional study.”

That question may be answered by a future follow-up study of the ongoing FinnDiane study, she said.

The study is a “good reminder” that people with central adiposity and metabolic syndrome can develop NAFL disease, said Jeanne Marie Clark, MD, MPH, of Johns Hopkins University, Baltimore. “Even patients we may not think of having insulin resistance, such as those with T1DM.”

However, Dr. Clark added, “I do not think we can really determine which measure of central adiposity is best.” She noted that the study was “pretty small” with only 14 patients who had NAFL disease. “Waist-to-height ratio is certainly a reasonable option,” she added. “Waist circumference alone is known to be a strong predictor. I would say some measure is better than none, and it should be more routine in clinical practice.”

Dr. Parente disclosed financial relationships with Eli Lilly, Abbott, AstraZeneca, Sanofi, and Boehringer Ingelheim. Two of eight coauthors disclosed financial relationships with AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Fresenius, GE Healthcare, Medscape, Merck Sharpe and Dohme, Mundipharma, Novo Nordisk, Peer-Voice, Sanofi, and Sciarc. The remaining coauthors had no disclosures.

Dr. Clark had no disclosures.

It follows that, as the prevalence of obesity among people with type 1 diabetes mellitus (T1DM) increases, so would the incidence of nonalcoholic fatty liver (NAFL), as it does in type 2 diabetes.

However, researchers in Finland report that the incidence of NAFL in T1DM is much lower, and that the use of the waist-to-height ratio to calculate midsection girth could be a low-cost alternative to MRI and computed tomography to more precisely diagnose NAFL in T1DM.

In a cross-sectional analysis of 121 adults with T1DM in the Finnish Diabetic Nephropathy study, known as FinnDiane, researchers from the University of Helsinki report in Diabetes Care that a waist-to-height ratio of 0.5 showed a relatively high rate of accuracy for identifying NAFL that was statistically significant (P = .04).

Lead author Erika B. Parente, MD, PhD, a researcher at the Folkhälsän Research Center in Helsinki, noted that the findings do not identify any causality between what the researchers called visceral adiposity and NAFL. “As long as they have accumulation of fat in the center of body and they can develop this low-grade inflammation that also goes to insulin-load sensitivity, people with T1DM can accumulate fat in the liver as do people with T2DM and the general population,” she said in an interview.

These findings build on her group’s previous work published in Scientific Reports showing a strong relationship between waist-to-height ratio and visceral fat percentage in adults with T1DM. The most recent FinnDiane analysis found no similar relationship between NAFL and fat tissue in the hips, arms and legs, and total adipose tissue.
 

Better than BMI as a measure

“We also found that waist-to-height ratio is better than body mass index to identify those individuals at higher risk of having NAFL,” Dr. Parente said. However, it’s not possible to predict which patients referred to imaging evaluation after being screened by waist-to-height ratio of 0.5 will surely have NAFL, she added.

That answer, she said, would require a longitudinal and cost-effectiveness study with larger population.

The waist-to-height ratio cutoff of 0.5 showed an 86% sensitivity and 55% specificity for NAFL, whereas BMI of 26.6 kg/m² showed an 79% sensitivity and 57% specificity.

“The most important message from our research is that health care professionals should be aware that individuals with T1DM can have NAFL, and waist-to-height ratio may help to identify those at higher risk,” she said.

The prevalence of NAFL among the adults with T1DM in the study was 11.6%, which is lower than the prevalence other studies reported in T2DM – 76% in a U.S. study – and in the general population – ranging from 19% to 46%. This underscores, Dr. Parente noted, the importance of using waist-to-height ratio in T1DM patients to determine the status of NAFL.

She said that few studies have investigated the consequences of NAFL in T1DM, pointing to two that linked NAFL with chronic kidney disease and cardiovascular disease in T1DM (Diabetes Care. 2014;37:1729-36; J Hepatol. 2010;53:713-8). “Most of the studies about the consequences of NAFL included people with T2DM,” she said. “From our research, we cannot conclude about the impact of NAFL in cardiovascular or kidney complications in our population because this is a cross-sectional study.”

That question may be answered by a future follow-up study of the ongoing FinnDiane study, she said.

The study is a “good reminder” that people with central adiposity and metabolic syndrome can develop NAFL disease, said Jeanne Marie Clark, MD, MPH, of Johns Hopkins University, Baltimore. “Even patients we may not think of having insulin resistance, such as those with T1DM.”

However, Dr. Clark added, “I do not think we can really determine which measure of central adiposity is best.” She noted that the study was “pretty small” with only 14 patients who had NAFL disease. “Waist-to-height ratio is certainly a reasonable option,” she added. “Waist circumference alone is known to be a strong predictor. I would say some measure is better than none, and it should be more routine in clinical practice.”

Dr. Parente disclosed financial relationships with Eli Lilly, Abbott, AstraZeneca, Sanofi, and Boehringer Ingelheim. Two of eight coauthors disclosed financial relationships with AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Fresenius, GE Healthcare, Medscape, Merck Sharpe and Dohme, Mundipharma, Novo Nordisk, Peer-Voice, Sanofi, and Sciarc. The remaining coauthors had no disclosures.

Dr. Clark had no disclosures.

It follows that, as the prevalence of obesity among people with type 1 diabetes mellitus (T1DM) increases, so would the incidence of nonalcoholic fatty liver (NAFL), as it does in type 2 diabetes.

However, researchers in Finland report that the incidence of NAFL in T1DM is much lower, and that the use of the waist-to-height ratio to calculate midsection girth could be a low-cost alternative to MRI and computed tomography to more precisely diagnose NAFL in T1DM.

In a cross-sectional analysis of 121 adults with T1DM in the Finnish Diabetic Nephropathy study, known as FinnDiane, researchers from the University of Helsinki report in Diabetes Care that a waist-to-height ratio of 0.5 showed a relatively high rate of accuracy for identifying NAFL that was statistically significant (P = .04).

Lead author Erika B. Parente, MD, PhD, a researcher at the Folkhälsän Research Center in Helsinki, noted that the findings do not identify any causality between what the researchers called visceral adiposity and NAFL. “As long as they have accumulation of fat in the center of body and they can develop this low-grade inflammation that also goes to insulin-load sensitivity, people with T1DM can accumulate fat in the liver as do people with T2DM and the general population,” she said in an interview.

These findings build on her group’s previous work published in Scientific Reports showing a strong relationship between waist-to-height ratio and visceral fat percentage in adults with T1DM. The most recent FinnDiane analysis found no similar relationship between NAFL and fat tissue in the hips, arms and legs, and total adipose tissue.
 

Better than BMI as a measure

“We also found that waist-to-height ratio is better than body mass index to identify those individuals at higher risk of having NAFL,” Dr. Parente said. However, it’s not possible to predict which patients referred to imaging evaluation after being screened by waist-to-height ratio of 0.5 will surely have NAFL, she added.

That answer, she said, would require a longitudinal and cost-effectiveness study with larger population.

The waist-to-height ratio cutoff of 0.5 showed an 86% sensitivity and 55% specificity for NAFL, whereas BMI of 26.6 kg/m² showed an 79% sensitivity and 57% specificity.

“The most important message from our research is that health care professionals should be aware that individuals with T1DM can have NAFL, and waist-to-height ratio may help to identify those at higher risk,” she said.

The prevalence of NAFL among the adults with T1DM in the study was 11.6%, which is lower than the prevalence other studies reported in T2DM – 76% in a U.S. study – and in the general population – ranging from 19% to 46%. This underscores, Dr. Parente noted, the importance of using waist-to-height ratio in T1DM patients to determine the status of NAFL.

She said that few studies have investigated the consequences of NAFL in T1DM, pointing to two that linked NAFL with chronic kidney disease and cardiovascular disease in T1DM (Diabetes Care. 2014;37:1729-36; J Hepatol. 2010;53:713-8). “Most of the studies about the consequences of NAFL included people with T2DM,” she said. “From our research, we cannot conclude about the impact of NAFL in cardiovascular or kidney complications in our population because this is a cross-sectional study.”

That question may be answered by a future follow-up study of the ongoing FinnDiane study, she said.

The study is a “good reminder” that people with central adiposity and metabolic syndrome can develop NAFL disease, said Jeanne Marie Clark, MD, MPH, of Johns Hopkins University, Baltimore. “Even patients we may not think of having insulin resistance, such as those with T1DM.”

However, Dr. Clark added, “I do not think we can really determine which measure of central adiposity is best.” She noted that the study was “pretty small” with only 14 patients who had NAFL disease. “Waist-to-height ratio is certainly a reasonable option,” she added. “Waist circumference alone is known to be a strong predictor. I would say some measure is better than none, and it should be more routine in clinical practice.”

Dr. Parente disclosed financial relationships with Eli Lilly, Abbott, AstraZeneca, Sanofi, and Boehringer Ingelheim. Two of eight coauthors disclosed financial relationships with AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Fresenius, GE Healthcare, Medscape, Merck Sharpe and Dohme, Mundipharma, Novo Nordisk, Peer-Voice, Sanofi, and Sciarc. The remaining coauthors had no disclosures.

Dr. Clark had no disclosures.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

Women with osteoporosis, low bone density, or a previous vertebral fracture show significant increases in the risk of hearing loss compared to those without osteoporosis, according to a new study with more than 3 decades of follow-up.

The use of bisphosphonate therapy did not alter the risk, the researchers found.

“To the best of our knowledge, this is the first large longitudinal study to evaluate the relations of bone density, bisphosphonate use, fractures, and risk of hearing loss,” reported Sharon Curhan, MD, and colleagues in research published online in the Journal of the American Geriatric Society.

“In this large nationwide longitudinal study of nearly 144,000 women with up to 34 years of follow-up, we found that osteoporosis or low bone density was independently associated with higher risk of incident moderate or worse hearing loss,” the authors wrote.

“The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates,” they added.
 

Participants were from the nurses’ health study and NHS II

With recent research suggesting a potential link between bisphosphonate use and prevention of noise-induced hearing loss in mice, Dr. Curhan, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston, and colleagues turned to the large longitudinal cohorts of the Nurses’ Health Study (NHS), conducted from 1982 to 2016, and the Nurses’ Health Study II (NHS II), from 1995 to 2017.

In total, the primary analysis included 60,821 women in the NHS and 83,078 in the NHS II.

Women in the NHS were aged 36-61 years at baseline and 70-95 years at the end of follow-up, while in the NHS II, women were aged 31-48 years at baseline and 53-70 years at the end of follow-up.

After multivariate adjustment for key factors including age, race/ethnicity, oral hormone use, and a variety of other factors, women in the NHS with osteoporosis had an increased risk of moderate or worse hearing loss, as self-reported every 2 years, compared to those without osteoporosis (relative risk, 1.14; 95% confidence interval, 1.09-1.19).

And in the NHS II, which also included data on low bone density, the risk of self-reported hearing loss was higher among those with osteoporosis or low bone density (RR, 1.30; 95% CI, 1.21-1.40).

No significant differences were observed in hearing loss risk based on whether women were treated with bisphosphonates, with the mean duration of use of the medication being 5.8 years in the NHS and 3.4 years in the NHS II.

Those who sustained a vertebral fracture also had a higher risk of hearing loss in both studies (NHS: RR, 1.31; NHS II: RR, 1.39).

However, the increased risk of hearing loss was not observed with hip fracture.

“Our findings of up to a 40% higher risk among women with vertebral fracture, but not hip fracture, were intriguing and merit further study,” the authors noted.

“The discordant findings between these skeletal sites may reflect differences in composition and metabolism of bones in the spine and hip and could provide insight into the pathophysiological changes in the ear that may lead to hearing loss,” they added.
 

Audiometric subanalysis

In an analysis of a subcohort of 3,749 women looking at audiometric thresholds for a more precise measure of hearing loss, women with osteoporosis or low bone density continued to show significantly worse hearing loss when treated with bisphosphonates compared to those without osteoporosis or low bone density.

However, there were no significant hearing loss differences among those with osteoporosis who did not take bisphosphonates versus those without osteoporosis.

The authors speculate that the use of bisphosphonates could have been indicative of more severe osteoporosis, hence the poorer audiometric thresholds.

In an interview, Dr. Curhan said the details of bisphosphonate use, such as type and duration, and their role in hearing loss should be further evaluated.

“Possibly, a potential influence of bisphosphonates on the relation of osteoporosis and hearing loss in humans may depend on the type, dose, and timing of bisphosphonate administration,” she observed. “This is an important question for further study.”
 

Mechanisms: Bone loss may extend to ear structures

In terms of the mechanisms linking osteoporosis itself to hearing loss, the authors noted that bone loss, in addition to compromising more prominent skeletal sites, could logically extend to bone-related structures in the ear.

“Bone mass at peripheral sites is correlated with bone mass at central sites, such as hip and spine, with correlation coefficients between 0.6 and 0.7,” they explained. “Plausibly, systemic bone demineralization could involve the temporal bone, the otic capsule, and the middle ear ossicles.”

They noted that hearing loss has been linked to other pathologic bone disorders, including otosclerosis and Paget disease.

Furthermore, imbalances in bone formation and resorption in osteoporosis may lead to alterations in ionic metabolism, which can lead to hearing loss.

Looking ahead, Dr. Curhan and colleagues plan to further examine whether calcium and vitamin D, which are associated with the prevention of osteoporosis, have a role in preventing hearing loss.

In the meantime, the findings underscore that clinicians treating patients with osteoporosis should routinely check patients’ hearing, Dr. Curhan said.

“Undetected and untreated hearing loss can adversely impact social interactions, physical and mental well-being, and daily life,” she said.

“Early detection of hearing loss offers greater opportunity for successful management and to learn strategies for rehabilitation and prevention of further progression.”

The study received support from the National Institutes of Health.
 

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

Women with osteoporosis, low bone density, or a previous vertebral fracture show significant increases in the risk of hearing loss compared to those without osteoporosis, according to a new study with more than 3 decades of follow-up.

The use of bisphosphonate therapy did not alter the risk, the researchers found.

“To the best of our knowledge, this is the first large longitudinal study to evaluate the relations of bone density, bisphosphonate use, fractures, and risk of hearing loss,” reported Sharon Curhan, MD, and colleagues in research published online in the Journal of the American Geriatric Society.

“In this large nationwide longitudinal study of nearly 144,000 women with up to 34 years of follow-up, we found that osteoporosis or low bone density was independently associated with higher risk of incident moderate or worse hearing loss,” the authors wrote.

“The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates,” they added.
 

Participants were from the nurses’ health study and NHS II

With recent research suggesting a potential link between bisphosphonate use and prevention of noise-induced hearing loss in mice, Dr. Curhan, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston, and colleagues turned to the large longitudinal cohorts of the Nurses’ Health Study (NHS), conducted from 1982 to 2016, and the Nurses’ Health Study II (NHS II), from 1995 to 2017.

In total, the primary analysis included 60,821 women in the NHS and 83,078 in the NHS II.

Women in the NHS were aged 36-61 years at baseline and 70-95 years at the end of follow-up, while in the NHS II, women were aged 31-48 years at baseline and 53-70 years at the end of follow-up.

After multivariate adjustment for key factors including age, race/ethnicity, oral hormone use, and a variety of other factors, women in the NHS with osteoporosis had an increased risk of moderate or worse hearing loss, as self-reported every 2 years, compared to those without osteoporosis (relative risk, 1.14; 95% confidence interval, 1.09-1.19).

And in the NHS II, which also included data on low bone density, the risk of self-reported hearing loss was higher among those with osteoporosis or low bone density (RR, 1.30; 95% CI, 1.21-1.40).

No significant differences were observed in hearing loss risk based on whether women were treated with bisphosphonates, with the mean duration of use of the medication being 5.8 years in the NHS and 3.4 years in the NHS II.

Those who sustained a vertebral fracture also had a higher risk of hearing loss in both studies (NHS: RR, 1.31; NHS II: RR, 1.39).

However, the increased risk of hearing loss was not observed with hip fracture.

“Our findings of up to a 40% higher risk among women with vertebral fracture, but not hip fracture, were intriguing and merit further study,” the authors noted.

“The discordant findings between these skeletal sites may reflect differences in composition and metabolism of bones in the spine and hip and could provide insight into the pathophysiological changes in the ear that may lead to hearing loss,” they added.
 

Audiometric subanalysis

In an analysis of a subcohort of 3,749 women looking at audiometric thresholds for a more precise measure of hearing loss, women with osteoporosis or low bone density continued to show significantly worse hearing loss when treated with bisphosphonates compared to those without osteoporosis or low bone density.

However, there were no significant hearing loss differences among those with osteoporosis who did not take bisphosphonates versus those without osteoporosis.

The authors speculate that the use of bisphosphonates could have been indicative of more severe osteoporosis, hence the poorer audiometric thresholds.

In an interview, Dr. Curhan said the details of bisphosphonate use, such as type and duration, and their role in hearing loss should be further evaluated.

“Possibly, a potential influence of bisphosphonates on the relation of osteoporosis and hearing loss in humans may depend on the type, dose, and timing of bisphosphonate administration,” she observed. “This is an important question for further study.”
 

Mechanisms: Bone loss may extend to ear structures

In terms of the mechanisms linking osteoporosis itself to hearing loss, the authors noted that bone loss, in addition to compromising more prominent skeletal sites, could logically extend to bone-related structures in the ear.

“Bone mass at peripheral sites is correlated with bone mass at central sites, such as hip and spine, with correlation coefficients between 0.6 and 0.7,” they explained. “Plausibly, systemic bone demineralization could involve the temporal bone, the otic capsule, and the middle ear ossicles.”

They noted that hearing loss has been linked to other pathologic bone disorders, including otosclerosis and Paget disease.

Furthermore, imbalances in bone formation and resorption in osteoporosis may lead to alterations in ionic metabolism, which can lead to hearing loss.

Looking ahead, Dr. Curhan and colleagues plan to further examine whether calcium and vitamin D, which are associated with the prevention of osteoporosis, have a role in preventing hearing loss.

In the meantime, the findings underscore that clinicians treating patients with osteoporosis should routinely check patients’ hearing, Dr. Curhan said.

“Undetected and untreated hearing loss can adversely impact social interactions, physical and mental well-being, and daily life,” she said.

“Early detection of hearing loss offers greater opportunity for successful management and to learn strategies for rehabilitation and prevention of further progression.”

The study received support from the National Institutes of Health.
 

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

Women with osteoporosis, low bone density, or a previous vertebral fracture show significant increases in the risk of hearing loss compared to those without osteoporosis, according to a new study with more than 3 decades of follow-up.

The use of bisphosphonate therapy did not alter the risk, the researchers found.

“To the best of our knowledge, this is the first large longitudinal study to evaluate the relations of bone density, bisphosphonate use, fractures, and risk of hearing loss,” reported Sharon Curhan, MD, and colleagues in research published online in the Journal of the American Geriatric Society.

“In this large nationwide longitudinal study of nearly 144,000 women with up to 34 years of follow-up, we found that osteoporosis or low bone density was independently associated with higher risk of incident moderate or worse hearing loss,” the authors wrote.

“The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates,” they added.
 

Participants were from the nurses’ health study and NHS II

With recent research suggesting a potential link between bisphosphonate use and prevention of noise-induced hearing loss in mice, Dr. Curhan, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston, and colleagues turned to the large longitudinal cohorts of the Nurses’ Health Study (NHS), conducted from 1982 to 2016, and the Nurses’ Health Study II (NHS II), from 1995 to 2017.

In total, the primary analysis included 60,821 women in the NHS and 83,078 in the NHS II.

Women in the NHS were aged 36-61 years at baseline and 70-95 years at the end of follow-up, while in the NHS II, women were aged 31-48 years at baseline and 53-70 years at the end of follow-up.

After multivariate adjustment for key factors including age, race/ethnicity, oral hormone use, and a variety of other factors, women in the NHS with osteoporosis had an increased risk of moderate or worse hearing loss, as self-reported every 2 years, compared to those without osteoporosis (relative risk, 1.14; 95% confidence interval, 1.09-1.19).

And in the NHS II, which also included data on low bone density, the risk of self-reported hearing loss was higher among those with osteoporosis or low bone density (RR, 1.30; 95% CI, 1.21-1.40).

No significant differences were observed in hearing loss risk based on whether women were treated with bisphosphonates, with the mean duration of use of the medication being 5.8 years in the NHS and 3.4 years in the NHS II.

Those who sustained a vertebral fracture also had a higher risk of hearing loss in both studies (NHS: RR, 1.31; NHS II: RR, 1.39).

However, the increased risk of hearing loss was not observed with hip fracture.

“Our findings of up to a 40% higher risk among women with vertebral fracture, but not hip fracture, were intriguing and merit further study,” the authors noted.

“The discordant findings between these skeletal sites may reflect differences in composition and metabolism of bones in the spine and hip and could provide insight into the pathophysiological changes in the ear that may lead to hearing loss,” they added.
 

Audiometric subanalysis

In an analysis of a subcohort of 3,749 women looking at audiometric thresholds for a more precise measure of hearing loss, women with osteoporosis or low bone density continued to show significantly worse hearing loss when treated with bisphosphonates compared to those without osteoporosis or low bone density.

However, there were no significant hearing loss differences among those with osteoporosis who did not take bisphosphonates versus those without osteoporosis.

The authors speculate that the use of bisphosphonates could have been indicative of more severe osteoporosis, hence the poorer audiometric thresholds.

In an interview, Dr. Curhan said the details of bisphosphonate use, such as type and duration, and their role in hearing loss should be further evaluated.

“Possibly, a potential influence of bisphosphonates on the relation of osteoporosis and hearing loss in humans may depend on the type, dose, and timing of bisphosphonate administration,” she observed. “This is an important question for further study.”
 

Mechanisms: Bone loss may extend to ear structures

In terms of the mechanisms linking osteoporosis itself to hearing loss, the authors noted that bone loss, in addition to compromising more prominent skeletal sites, could logically extend to bone-related structures in the ear.

“Bone mass at peripheral sites is correlated with bone mass at central sites, such as hip and spine, with correlation coefficients between 0.6 and 0.7,” they explained. “Plausibly, systemic bone demineralization could involve the temporal bone, the otic capsule, and the middle ear ossicles.”

They noted that hearing loss has been linked to other pathologic bone disorders, including otosclerosis and Paget disease.

Furthermore, imbalances in bone formation and resorption in osteoporosis may lead to alterations in ionic metabolism, which can lead to hearing loss.

Looking ahead, Dr. Curhan and colleagues plan to further examine whether calcium and vitamin D, which are associated with the prevention of osteoporosis, have a role in preventing hearing loss.

In the meantime, the findings underscore that clinicians treating patients with osteoporosis should routinely check patients’ hearing, Dr. Curhan said.

“Undetected and untreated hearing loss can adversely impact social interactions, physical and mental well-being, and daily life,” she said.

“Early detection of hearing loss offers greater opportunity for successful management and to learn strategies for rehabilitation and prevention of further progression.”

The study received support from the National Institutes of Health.
 

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

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

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

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

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

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

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

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

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

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

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

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.

Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m²) or are overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.

Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.

This weight-loss drug is currently under review by the European Medicines Agency.

Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.


 

‘Game changer’ drug tested in STEP clinical trial program

The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.

The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.

As previously reported by this news organization, all trials were in adults with overweight or obesity:

•  was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
•  was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
•  was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
•  was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).

In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.

The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.

The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.

A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”

“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
 

Welcome Addition, But Will Insurance Coverage, Price Thwart Access?

Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”

The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.

And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.

Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.

However, insurance coverage and price could block uptake.

“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”

“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.

“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”

However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”

“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.

Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.

The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.

And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
 

CVOT and oral format trials for obesity on the horizon

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.

And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.

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

This article was updated 6/7/21.

The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.

Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m²) or are overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.

Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.

This weight-loss drug is currently under review by the European Medicines Agency.

Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.


 

‘Game changer’ drug tested in STEP clinical trial program

The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.

The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.

As previously reported by this news organization, all trials were in adults with overweight or obesity:

•  was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
•  was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
•  was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
•  was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).

In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.

The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.

The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.

A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”

“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
 

Welcome Addition, But Will Insurance Coverage, Price Thwart Access?

Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”

The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.

And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.

Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.

However, insurance coverage and price could block uptake.

“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”

“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.

“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”

However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”

“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.

Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.

The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.

And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
 

CVOT and oral format trials for obesity on the horizon

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.

And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.

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

This article was updated 6/7/21.

The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.

Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m²) or are overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.

Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.

This weight-loss drug is currently under review by the European Medicines Agency.

Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.


 

‘Game changer’ drug tested in STEP clinical trial program

The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.

The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.

As previously reported by this news organization, all trials were in adults with overweight or obesity:

•  was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
•  was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
•  was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
•  was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).

In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.

The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.

The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.

A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”

“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
 

Welcome Addition, But Will Insurance Coverage, Price Thwart Access?

Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”

The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.

And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.

Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.

However, insurance coverage and price could block uptake.

“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”

“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.

“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”

However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”

“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.

Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.

The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.

And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
 

CVOT and oral format trials for obesity on the horizon

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.

And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.

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

This article was updated 6/7/21.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.