Obesity

American children gained a lot of weight in the last year, setting a dangerous trajectory towards metabolic disease that requires urgent policy change, according to a new report from the Robert Wood Johnson Foundation.

“Our nation’s safety net is fragile, outdated, and out of reach for millions of eligible kids and caregivers,” said Jamie Bussel, senior program officer at the RWJF, and senior author of the report. She added that the pandemic further fractured an already broken system that disproportionately overlooks “children of color and those who live farthest from economic opportunity”.
 

It’s time to think ‘bigger and better’

Ms. Bussel said, during a press conference, that congress responded to the pandemic with “an array of policy solutions,” but it’s now time to think ‘bigger and better.’

“There have been huge flexibilities deployed across the safety net program and these have been really important reliefs, but the fact is many of them are temporary emergency relief measures,” she explained.

For the past 3 years, the RWJF’s annual State of Childhood Obesity report has drawn national and state obesity data from large surveys including the National Survey of Children’s Health, the Youth Risk Behavior Surveillance System, the WIC Participant and Program Characteristics Survey, and the National Health and Nutrition Examination Survey.

Similar to in past years, this year’s data show that rates of obesity and overweight have remained relatively steady and have been highest among minority and low-income populations. For example, data from the 2019-2020 National Survey of Children’s Health, along with an analysis conducted by the Health Resources and Services Administration’s Maternal and Child Health Bureau, show that one in six – or 16.2% – of youth aged 10-17 years have obesity.

While non-Hispanic Asian children had the lowest obesity rate (8.1%), followed by non-Hispanic White children (12.1%), rates were significantly higher for Hispanic (21.4%), non-Hispanic Black (23.8%), and non-Hispanic American Indian/Alaska Native (28.7%) children, according to the report.

“Additional years of data are needed to assess whether obesity rates changed after the onset of the pandemic,” explained Ms. Bussel.
 

Digging deeper

Other studies included in this year’s report were specifically designed to measure the impact of the pandemic, and show a distinct rise in overweight and obesity, especially in younger children. For example, a retrospective cohort study using data from Kaiser Permanente Southern California showed the rate of overweight and obesity in children aged 5-11 years rose to 45.7% between March 2020 and January 2021, up from 36.2% before the pandemic.

Another of these studies, which was based on national electronic health records of more than 430,000 children, showed the obesity rate crept from 19.3% to 22.4% between August 2019 and August 2020.

“The lid we had been trying desperately to put on the obesity epidemic has come off again,” said Sandra G Hassink, MD, MSc, who is medical director of the American Academy of Pediatrics Institute for Healthy Childhood Weight.

“In the absence of COVID we had been seeing slow upticks in the numbers – and in some groups we’d been thinking maybe we were headed toward stabilization – but these numbers blow that out of the water ... COVID has escalated the rates,” she said in an interview.

“Unfortunately, these two crises – the COVID pandemic, the childhood obesity epidemic – in so many ways have exacerbated one another,” said Ms. Bussel. “It’s not a huge surprise that we’re seeing an increase in childhood obesity rates given the complete and utter disruption of every single system that circumscribes our lives.”
 

The systems that feed obesity

Addressing childhood obesity requires targeting far beyond healthy eating and physical activity, Ms. Bussel said.

“As important is whether that child has a safe place to call home. Does mom or dad or their care provider have a stable income? Is there reliable transportation? Is their access to health insurance? Is there access to high-quality health care? ... All of those factors influence the child and the family’s opportunities to live well, be healthy, and be at a healthy weight,” she noted.

The report includes a list of five main policy recommendations.

• Making free, universal school meal programs permanent.
• Extending eligibility for WIC, the Special Supplemental Nutrition Program for Women, Infants, and Children, to postpartum mothers and to children through age 6.
• Extending and expanding other programs, such as the Child Tax Credit.
• Closing the Medicaid coverage gap.
• Developing a consistent approach to collecting obesity data organized by race, ethnicity, and income level.

“Collectively, over at least the course of the last generation or two, our policy approach to obesity prevention has not been sufficient. But that doesn’t mean all of our policy approaches have been failures,” Ms. Bussel said during an interview. “Policy change does not always need to be dramatic to have a real impact on families.”

Fighting complacency

For Dr. Hassink, one of the barriers to change is society’s level of acceptance. She said an identifiable explanation for pandemic weight gain doesn’t mean society should simply shrug it off.

“If we regarded childhood obesity as the population level catastrophe that it is for chronic disease maybe people would be activated around these policy changes,” she said.

“We’re accepting a disease process that wreaks havoc on people,” noted Dr. Hassink, who was not involved in the new report. “I think it’s hard for people to realize the magnitude of the disease burden that we’re seeing. If you’re in a weight management clinic or any pediatrician’s office you would see it – you would see kids coming in with liver disease, 9-year-olds on [continuous positive airway pressure] for sleep apnea, kids needing their hips pinned because they had a hip fracture because of obesity.

“So, those of us that see the disease burden see what’s behind those numbers. The sadness of what we’re talking about is we know a lot about what could push the dial and help reduce this epidemic and we’re not doing what we already know,” added Dr. Hassink.

Ms. Bussel and Dr. Hassink reported no conflicts.

American children gained a lot of weight in the last year, setting a dangerous trajectory towards metabolic disease that requires urgent policy change, according to a new report from the Robert Wood Johnson Foundation.

“Our nation’s safety net is fragile, outdated, and out of reach for millions of eligible kids and caregivers,” said Jamie Bussel, senior program officer at the RWJF, and senior author of the report. She added that the pandemic further fractured an already broken system that disproportionately overlooks “children of color and those who live farthest from economic opportunity”.
 

It’s time to think ‘bigger and better’

Ms. Bussel said, during a press conference, that congress responded to the pandemic with “an array of policy solutions,” but it’s now time to think ‘bigger and better.’

“There have been huge flexibilities deployed across the safety net program and these have been really important reliefs, but the fact is many of them are temporary emergency relief measures,” she explained.

For the past 3 years, the RWJF’s annual State of Childhood Obesity report has drawn national and state obesity data from large surveys including the National Survey of Children’s Health, the Youth Risk Behavior Surveillance System, the WIC Participant and Program Characteristics Survey, and the National Health and Nutrition Examination Survey.

Similar to in past years, this year’s data show that rates of obesity and overweight have remained relatively steady and have been highest among minority and low-income populations. For example, data from the 2019-2020 National Survey of Children’s Health, along with an analysis conducted by the Health Resources and Services Administration’s Maternal and Child Health Bureau, show that one in six – or 16.2% – of youth aged 10-17 years have obesity.

While non-Hispanic Asian children had the lowest obesity rate (8.1%), followed by non-Hispanic White children (12.1%), rates were significantly higher for Hispanic (21.4%), non-Hispanic Black (23.8%), and non-Hispanic American Indian/Alaska Native (28.7%) children, according to the report.

“Additional years of data are needed to assess whether obesity rates changed after the onset of the pandemic,” explained Ms. Bussel.
 

Digging deeper

Other studies included in this year’s report were specifically designed to measure the impact of the pandemic, and show a distinct rise in overweight and obesity, especially in younger children. For example, a retrospective cohort study using data from Kaiser Permanente Southern California showed the rate of overweight and obesity in children aged 5-11 years rose to 45.7% between March 2020 and January 2021, up from 36.2% before the pandemic.

Another of these studies, which was based on national electronic health records of more than 430,000 children, showed the obesity rate crept from 19.3% to 22.4% between August 2019 and August 2020.

“The lid we had been trying desperately to put on the obesity epidemic has come off again,” said Sandra G Hassink, MD, MSc, who is medical director of the American Academy of Pediatrics Institute for Healthy Childhood Weight.

“In the absence of COVID we had been seeing slow upticks in the numbers – and in some groups we’d been thinking maybe we were headed toward stabilization – but these numbers blow that out of the water ... COVID has escalated the rates,” she said in an interview.

“Unfortunately, these two crises – the COVID pandemic, the childhood obesity epidemic – in so many ways have exacerbated one another,” said Ms. Bussel. “It’s not a huge surprise that we’re seeing an increase in childhood obesity rates given the complete and utter disruption of every single system that circumscribes our lives.”
 

The systems that feed obesity

Addressing childhood obesity requires targeting far beyond healthy eating and physical activity, Ms. Bussel said.

“As important is whether that child has a safe place to call home. Does mom or dad or their care provider have a stable income? Is there reliable transportation? Is their access to health insurance? Is there access to high-quality health care? ... All of those factors influence the child and the family’s opportunities to live well, be healthy, and be at a healthy weight,” she noted.

The report includes a list of five main policy recommendations.

• Making free, universal school meal programs permanent.
• Extending eligibility for WIC, the Special Supplemental Nutrition Program for Women, Infants, and Children, to postpartum mothers and to children through age 6.
• Extending and expanding other programs, such as the Child Tax Credit.
• Closing the Medicaid coverage gap.
• Developing a consistent approach to collecting obesity data organized by race, ethnicity, and income level.

“Collectively, over at least the course of the last generation or two, our policy approach to obesity prevention has not been sufficient. But that doesn’t mean all of our policy approaches have been failures,” Ms. Bussel said during an interview. “Policy change does not always need to be dramatic to have a real impact on families.”

Fighting complacency

For Dr. Hassink, one of the barriers to change is society’s level of acceptance. She said an identifiable explanation for pandemic weight gain doesn’t mean society should simply shrug it off.

“If we regarded childhood obesity as the population level catastrophe that it is for chronic disease maybe people would be activated around these policy changes,” she said.

“We’re accepting a disease process that wreaks havoc on people,” noted Dr. Hassink, who was not involved in the new report. “I think it’s hard for people to realize the magnitude of the disease burden that we’re seeing. If you’re in a weight management clinic or any pediatrician’s office you would see it – you would see kids coming in with liver disease, 9-year-olds on [continuous positive airway pressure] for sleep apnea, kids needing their hips pinned because they had a hip fracture because of obesity.

“So, those of us that see the disease burden see what’s behind those numbers. The sadness of what we’re talking about is we know a lot about what could push the dial and help reduce this epidemic and we’re not doing what we already know,” added Dr. Hassink.

Ms. Bussel and Dr. Hassink reported no conflicts.

American children gained a lot of weight in the last year, setting a dangerous trajectory towards metabolic disease that requires urgent policy change, according to a new report from the Robert Wood Johnson Foundation.

“Our nation’s safety net is fragile, outdated, and out of reach for millions of eligible kids and caregivers,” said Jamie Bussel, senior program officer at the RWJF, and senior author of the report. She added that the pandemic further fractured an already broken system that disproportionately overlooks “children of color and those who live farthest from economic opportunity”.
 

It’s time to think ‘bigger and better’

Ms. Bussel said, during a press conference, that congress responded to the pandemic with “an array of policy solutions,” but it’s now time to think ‘bigger and better.’

“There have been huge flexibilities deployed across the safety net program and these have been really important reliefs, but the fact is many of them are temporary emergency relief measures,” she explained.

For the past 3 years, the RWJF’s annual State of Childhood Obesity report has drawn national and state obesity data from large surveys including the National Survey of Children’s Health, the Youth Risk Behavior Surveillance System, the WIC Participant and Program Characteristics Survey, and the National Health and Nutrition Examination Survey.

Similar to in past years, this year’s data show that rates of obesity and overweight have remained relatively steady and have been highest among minority and low-income populations. For example, data from the 2019-2020 National Survey of Children’s Health, along with an analysis conducted by the Health Resources and Services Administration’s Maternal and Child Health Bureau, show that one in six – or 16.2% – of youth aged 10-17 years have obesity.

While non-Hispanic Asian children had the lowest obesity rate (8.1%), followed by non-Hispanic White children (12.1%), rates were significantly higher for Hispanic (21.4%), non-Hispanic Black (23.8%), and non-Hispanic American Indian/Alaska Native (28.7%) children, according to the report.

“Additional years of data are needed to assess whether obesity rates changed after the onset of the pandemic,” explained Ms. Bussel.
 

Digging deeper

Other studies included in this year’s report were specifically designed to measure the impact of the pandemic, and show a distinct rise in overweight and obesity, especially in younger children. For example, a retrospective cohort study using data from Kaiser Permanente Southern California showed the rate of overweight and obesity in children aged 5-11 years rose to 45.7% between March 2020 and January 2021, up from 36.2% before the pandemic.

Another of these studies, which was based on national electronic health records of more than 430,000 children, showed the obesity rate crept from 19.3% to 22.4% between August 2019 and August 2020.

“The lid we had been trying desperately to put on the obesity epidemic has come off again,” said Sandra G Hassink, MD, MSc, who is medical director of the American Academy of Pediatrics Institute for Healthy Childhood Weight.

“In the absence of COVID we had been seeing slow upticks in the numbers – and in some groups we’d been thinking maybe we were headed toward stabilization – but these numbers blow that out of the water ... COVID has escalated the rates,” she said in an interview.

“Unfortunately, these two crises – the COVID pandemic, the childhood obesity epidemic – in so many ways have exacerbated one another,” said Ms. Bussel. “It’s not a huge surprise that we’re seeing an increase in childhood obesity rates given the complete and utter disruption of every single system that circumscribes our lives.”
 

The systems that feed obesity

Addressing childhood obesity requires targeting far beyond healthy eating and physical activity, Ms. Bussel said.

“As important is whether that child has a safe place to call home. Does mom or dad or their care provider have a stable income? Is there reliable transportation? Is their access to health insurance? Is there access to high-quality health care? ... All of those factors influence the child and the family’s opportunities to live well, be healthy, and be at a healthy weight,” she noted.

The report includes a list of five main policy recommendations.

• Making free, universal school meal programs permanent.
• Extending eligibility for WIC, the Special Supplemental Nutrition Program for Women, Infants, and Children, to postpartum mothers and to children through age 6.
• Extending and expanding other programs, such as the Child Tax Credit.
• Closing the Medicaid coverage gap.
• Developing a consistent approach to collecting obesity data organized by race, ethnicity, and income level.

“Collectively, over at least the course of the last generation or two, our policy approach to obesity prevention has not been sufficient. But that doesn’t mean all of our policy approaches have been failures,” Ms. Bussel said during an interview. “Policy change does not always need to be dramatic to have a real impact on families.”

Fighting complacency

For Dr. Hassink, one of the barriers to change is society’s level of acceptance. She said an identifiable explanation for pandemic weight gain doesn’t mean society should simply shrug it off.

“If we regarded childhood obesity as the population level catastrophe that it is for chronic disease maybe people would be activated around these policy changes,” she said.

“We’re accepting a disease process that wreaks havoc on people,” noted Dr. Hassink, who was not involved in the new report. “I think it’s hard for people to realize the magnitude of the disease burden that we’re seeing. If you’re in a weight management clinic or any pediatrician’s office you would see it – you would see kids coming in with liver disease, 9-year-olds on [continuous positive airway pressure] for sleep apnea, kids needing their hips pinned because they had a hip fracture because of obesity.

“So, those of us that see the disease burden see what’s behind those numbers. The sadness of what we’re talking about is we know a lot about what could push the dial and help reduce this epidemic and we’re not doing what we already know,” added Dr. Hassink.

Ms. Bussel and Dr. Hassink reported no conflicts.

For the past 18 months, we’ve all been focused on defeating the COVID-19 pandemic and preparing for the effects of cancer screenings that were delayed or put off entirely. But COVID isn’t the only epidemic we’re facing in the United States. Obesity is the second leading cause of preventable death in the United States. and its related diseases account for $480.7 billion in direct health care costs, with an additional $1.24 trillion in indirect costs from lost economic productivity.

More than two in five Americans are obese and that number is predicted to grow to more than half of the U.S. population by 2030. Obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD), a buildup of fat in the liver with little or no inflammation or cell damage that affects one in three (30%-37%) of adults in the U.S.

NAFLD can progress to nonalcoholic steatohepatitis (NASH), which affects about 1 in 10 (8%-12%) of adults in the U.S. NASH is fat in the liver with inflammation and cell damage, and it can lead to fibrosis and liver failure. The number of patients we see with NALFD and NASH continues to rise and it’s taking its toll. One in five people who have NASH will have the disease progress to liver cirrhosis. NASH is expected to be the leading cause of liver transplant in the U.S. for the next 5 years.
 

Stemming the tide of NAFLD and NASH

The best way to fight NAFLD and NASH is to prevent it in the first place by maintaining a healthy weight and exercising most days of the week. In terms of diet, limiting sugar and eating a diet rich in vegetables, whole grains, and healthy fats can prevent the factors that lead to liver disease.

If this were easy, we wouldn’t be facing the obesity epidemic that is plaguing the United States. One of the issues is that medicine has only recognized obesity as a disease for less than 10 years. We aren’t trained in medical school, residencies, or fellowships in managing obesity, beyond advising people to exercise and eat right. We know this doesn’t work.

That’s why many independent GI groups are exploring comprehensive weight management programs that take a holistic approach to weight management involving a team of health care providers and educators helping patients gradually exercise more and eat healthy while providing a social support system to lose weight and keep it off.
 

The best way to educate is to listen first

As gastroenterologists, we see many obesity-related issues and have an opportunity to intervene before other more serious issues show up – like cancer, hypertension, and stroke. And educating the public and primary care physicians is key to ensuring that patients who are high risk are screened for liver disease.

Some GI practices leverage awareness events such as International NASH Day in June, or National Liver Cancer Awareness Month in October, to provide primary care physicians and patients with educational materials about making healthier choices and what options are available to screen for NAFLD and NASH.

While the awareness events offer a ready-made context for outreach, the physicians in my practice work year-round to provide information on liver disease. When patients are brought in for issues that may indicate future problems, we look for signs of chronic liver disease and educate them and their family members about liver disease and cirrhosis.

Discussions of weight are very personal, and it’s important to approach the conversation with sensitivity. It’s also good to understand as best as possible any cultural implications of discussing a person’s weight to ensure that the patient or their family members are not embarrassed by the discussion. I find that oftentimes the best approach is to listen to the patient and hear what factors are influencing their ability to exercise and eat healthy foods so that you can work together to find the best solution.

It’s also important to recognize that racial disparities exist in many aspects of NAFLD, including prevalence, severity, genetic predisposition, and overall chance of recovery. For instance, Hispanics and Asian Americans have a higher prevalence of NAFLD, compared with other ethnic and racial groups.
 

Early detection is key

Screenings have become a lot simpler and more convenient. There are alternatives to the painful, expensive liver biopsy. There are blood biomarker tests designed to assess liver fibrosis in patients. Specialized vibration-controlled transient elastography, such as Fibroscan, can measure scarring and fat buildup in the liver. And because it’s noninvasive, it doesn’t come with the same risks as a traditional liver biopsy. It also costs about four or five times less, which is important in this era of value-based care.

These simple tests can be reassuring, or they can lead down another path of treating the disease, but not being screened at all can come at a steep price. Severe fibrosis can lead to cirrhosis, a dangerous condition where the liver can no longer function correctly. NAFLD and NASH can also lead to liver cancer.

There are some medications that are in phase 2 and some in phase 3 clinical trials that aim to reduce fatty liver by cutting down fibrosis and steatosis, and there are other medications that can be used to help with weight loss. But the reality is that lifestyle changes are currently the best way to reverse NAFLD or stop it from progressing to NASH or cirrhosis.
 

Join an innovative practice

For the next 20 years, the obesity epidemic will be the biggest issue facing our society and a major focus of our cancer prevention efforts. Early-career physicians who are looking to join an independent GI practice should ask questions to determine whether the partners in the practice are taking a comprehensive approach to treating issues of obesity, NAFLD, NASH, and liver disease. Discuss what steps the practice takes to educate primary care physicians and their patients about the dangers of NAFLD and NASH.

We’re looking for early-career physicians who are entrepreneurial, not just for the sake of the practice, but because the future is in digital technologies and chronic care management, such as Chronwell, that help people maintain health through remote care and coaching. We want people who are thinking about fixing the problems of today and tomorrow with new technologies and scalable solutions. Through education and new screening and treatment options, we can ensure that fewer people develop serious liver disease or cancer.
 

Dr. Sanjay Sandhir is a practicing gastroenterologist at Dayton Gastroenterology, One GI in Ohio and is an executive committee member of the Digestive Health Physicians Association. He has no conflicts to declare.

For the past 18 months, we’ve all been focused on defeating the COVID-19 pandemic and preparing for the effects of cancer screenings that were delayed or put off entirely. But COVID isn’t the only epidemic we’re facing in the United States. Obesity is the second leading cause of preventable death in the United States. and its related diseases account for $480.7 billion in direct health care costs, with an additional $1.24 trillion in indirect costs from lost economic productivity.

More than two in five Americans are obese and that number is predicted to grow to more than half of the U.S. population by 2030. Obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD), a buildup of fat in the liver with little or no inflammation or cell damage that affects one in three (30%-37%) of adults in the U.S.

NAFLD can progress to nonalcoholic steatohepatitis (NASH), which affects about 1 in 10 (8%-12%) of adults in the U.S. NASH is fat in the liver with inflammation and cell damage, and it can lead to fibrosis and liver failure. The number of patients we see with NALFD and NASH continues to rise and it’s taking its toll. One in five people who have NASH will have the disease progress to liver cirrhosis. NASH is expected to be the leading cause of liver transplant in the U.S. for the next 5 years.
 

Stemming the tide of NAFLD and NASH

The best way to fight NAFLD and NASH is to prevent it in the first place by maintaining a healthy weight and exercising most days of the week. In terms of diet, limiting sugar and eating a diet rich in vegetables, whole grains, and healthy fats can prevent the factors that lead to liver disease.

If this were easy, we wouldn’t be facing the obesity epidemic that is plaguing the United States. One of the issues is that medicine has only recognized obesity as a disease for less than 10 years. We aren’t trained in medical school, residencies, or fellowships in managing obesity, beyond advising people to exercise and eat right. We know this doesn’t work.

That’s why many independent GI groups are exploring comprehensive weight management programs that take a holistic approach to weight management involving a team of health care providers and educators helping patients gradually exercise more and eat healthy while providing a social support system to lose weight and keep it off.
 

The best way to educate is to listen first

As gastroenterologists, we see many obesity-related issues and have an opportunity to intervene before other more serious issues show up – like cancer, hypertension, and stroke. And educating the public and primary care physicians is key to ensuring that patients who are high risk are screened for liver disease.

Some GI practices leverage awareness events such as International NASH Day in June, or National Liver Cancer Awareness Month in October, to provide primary care physicians and patients with educational materials about making healthier choices and what options are available to screen for NAFLD and NASH.

While the awareness events offer a ready-made context for outreach, the physicians in my practice work year-round to provide information on liver disease. When patients are brought in for issues that may indicate future problems, we look for signs of chronic liver disease and educate them and their family members about liver disease and cirrhosis.

Discussions of weight are very personal, and it’s important to approach the conversation with sensitivity. It’s also good to understand as best as possible any cultural implications of discussing a person’s weight to ensure that the patient or their family members are not embarrassed by the discussion. I find that oftentimes the best approach is to listen to the patient and hear what factors are influencing their ability to exercise and eat healthy foods so that you can work together to find the best solution.

It’s also important to recognize that racial disparities exist in many aspects of NAFLD, including prevalence, severity, genetic predisposition, and overall chance of recovery. For instance, Hispanics and Asian Americans have a higher prevalence of NAFLD, compared with other ethnic and racial groups.
 

Early detection is key

Screenings have become a lot simpler and more convenient. There are alternatives to the painful, expensive liver biopsy. There are blood biomarker tests designed to assess liver fibrosis in patients. Specialized vibration-controlled transient elastography, such as Fibroscan, can measure scarring and fat buildup in the liver. And because it’s noninvasive, it doesn’t come with the same risks as a traditional liver biopsy. It also costs about four or five times less, which is important in this era of value-based care.

These simple tests can be reassuring, or they can lead down another path of treating the disease, but not being screened at all can come at a steep price. Severe fibrosis can lead to cirrhosis, a dangerous condition where the liver can no longer function correctly. NAFLD and NASH can also lead to liver cancer.

There are some medications that are in phase 2 and some in phase 3 clinical trials that aim to reduce fatty liver by cutting down fibrosis and steatosis, and there are other medications that can be used to help with weight loss. But the reality is that lifestyle changes are currently the best way to reverse NAFLD or stop it from progressing to NASH or cirrhosis.
 

Join an innovative practice

For the next 20 years, the obesity epidemic will be the biggest issue facing our society and a major focus of our cancer prevention efforts. Early-career physicians who are looking to join an independent GI practice should ask questions to determine whether the partners in the practice are taking a comprehensive approach to treating issues of obesity, NAFLD, NASH, and liver disease. Discuss what steps the practice takes to educate primary care physicians and their patients about the dangers of NAFLD and NASH.

We’re looking for early-career physicians who are entrepreneurial, not just for the sake of the practice, but because the future is in digital technologies and chronic care management, such as Chronwell, that help people maintain health through remote care and coaching. We want people who are thinking about fixing the problems of today and tomorrow with new technologies and scalable solutions. Through education and new screening and treatment options, we can ensure that fewer people develop serious liver disease or cancer.
 

Dr. Sanjay Sandhir is a practicing gastroenterologist at Dayton Gastroenterology, One GI in Ohio and is an executive committee member of the Digestive Health Physicians Association. He has no conflicts to declare.

For the past 18 months, we’ve all been focused on defeating the COVID-19 pandemic and preparing for the effects of cancer screenings that were delayed or put off entirely. But COVID isn’t the only epidemic we’re facing in the United States. Obesity is the second leading cause of preventable death in the United States. and its related diseases account for $480.7 billion in direct health care costs, with an additional $1.24 trillion in indirect costs from lost economic productivity.

More than two in five Americans are obese and that number is predicted to grow to more than half of the U.S. population by 2030. Obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD), a buildup of fat in the liver with little or no inflammation or cell damage that affects one in three (30%-37%) of adults in the U.S.

NAFLD can progress to nonalcoholic steatohepatitis (NASH), which affects about 1 in 10 (8%-12%) of adults in the U.S. NASH is fat in the liver with inflammation and cell damage, and it can lead to fibrosis and liver failure. The number of patients we see with NALFD and NASH continues to rise and it’s taking its toll. One in five people who have NASH will have the disease progress to liver cirrhosis. NASH is expected to be the leading cause of liver transplant in the U.S. for the next 5 years.
 

Stemming the tide of NAFLD and NASH

The best way to fight NAFLD and NASH is to prevent it in the first place by maintaining a healthy weight and exercising most days of the week. In terms of diet, limiting sugar and eating a diet rich in vegetables, whole grains, and healthy fats can prevent the factors that lead to liver disease.

If this were easy, we wouldn’t be facing the obesity epidemic that is plaguing the United States. One of the issues is that medicine has only recognized obesity as a disease for less than 10 years. We aren’t trained in medical school, residencies, or fellowships in managing obesity, beyond advising people to exercise and eat right. We know this doesn’t work.

That’s why many independent GI groups are exploring comprehensive weight management programs that take a holistic approach to weight management involving a team of health care providers and educators helping patients gradually exercise more and eat healthy while providing a social support system to lose weight and keep it off.
 

The best way to educate is to listen first

As gastroenterologists, we see many obesity-related issues and have an opportunity to intervene before other more serious issues show up – like cancer, hypertension, and stroke. And educating the public and primary care physicians is key to ensuring that patients who are high risk are screened for liver disease.

Some GI practices leverage awareness events such as International NASH Day in June, or National Liver Cancer Awareness Month in October, to provide primary care physicians and patients with educational materials about making healthier choices and what options are available to screen for NAFLD and NASH.

While the awareness events offer a ready-made context for outreach, the physicians in my practice work year-round to provide information on liver disease. When patients are brought in for issues that may indicate future problems, we look for signs of chronic liver disease and educate them and their family members about liver disease and cirrhosis.

Discussions of weight are very personal, and it’s important to approach the conversation with sensitivity. It’s also good to understand as best as possible any cultural implications of discussing a person’s weight to ensure that the patient or their family members are not embarrassed by the discussion. I find that oftentimes the best approach is to listen to the patient and hear what factors are influencing their ability to exercise and eat healthy foods so that you can work together to find the best solution.

It’s also important to recognize that racial disparities exist in many aspects of NAFLD, including prevalence, severity, genetic predisposition, and overall chance of recovery. For instance, Hispanics and Asian Americans have a higher prevalence of NAFLD, compared with other ethnic and racial groups.
 

Early detection is key

Screenings have become a lot simpler and more convenient. There are alternatives to the painful, expensive liver biopsy. There are blood biomarker tests designed to assess liver fibrosis in patients. Specialized vibration-controlled transient elastography, such as Fibroscan, can measure scarring and fat buildup in the liver. And because it’s noninvasive, it doesn’t come with the same risks as a traditional liver biopsy. It also costs about four or five times less, which is important in this era of value-based care.

These simple tests can be reassuring, or they can lead down another path of treating the disease, but not being screened at all can come at a steep price. Severe fibrosis can lead to cirrhosis, a dangerous condition where the liver can no longer function correctly. NAFLD and NASH can also lead to liver cancer.

There are some medications that are in phase 2 and some in phase 3 clinical trials that aim to reduce fatty liver by cutting down fibrosis and steatosis, and there are other medications that can be used to help with weight loss. But the reality is that lifestyle changes are currently the best way to reverse NAFLD or stop it from progressing to NASH or cirrhosis.
 

Join an innovative practice

For the next 20 years, the obesity epidemic will be the biggest issue facing our society and a major focus of our cancer prevention efforts. Early-career physicians who are looking to join an independent GI practice should ask questions to determine whether the partners in the practice are taking a comprehensive approach to treating issues of obesity, NAFLD, NASH, and liver disease. Discuss what steps the practice takes to educate primary care physicians and their patients about the dangers of NAFLD and NASH.

We’re looking for early-career physicians who are entrepreneurial, not just for the sake of the practice, but because the future is in digital technologies and chronic care management, such as Chronwell, that help people maintain health through remote care and coaching. We want people who are thinking about fixing the problems of today and tomorrow with new technologies and scalable solutions. Through education and new screening and treatment options, we can ensure that fewer people develop serious liver disease or cancer.
 

Dr. Sanjay Sandhir is a practicing gastroenterologist at Dayton Gastroenterology, One GI in Ohio and is an executive committee member of the Digestive Health Physicians Association. He has no conflicts to declare.

Men had a much higher rate of death following bariatric surgery performed in Austria during 2010-2018, compared with women in a retrospective analysis of nearly 20,000 patients based on health insurance records.

The reason may be that men undergoing bariatric surgery have “worse overall health at the time of surgery” than women, Hannes Beiglböck, MD, suggested at the annual meeting of the European Association for the Study of Diabetes.

The results also showed that “men tend to be older [at time of surgery] and that might have the biggest impact on outcomes after bariatric surgery,” said Dr. Beiglböck, a researcher in the division of endocrinology and metabolism at the Medical University of Vienna.

The findings confirm those of prior studies in various worldwide locations, he noted; that is, men undergoing bariatric surgery tend to be older than women and have more comorbidities and perioperative mortality. 

Dr. Beiglböck also highlighted earlier reports that indicate “profound” sex-specific differences in why patients undergo bariatric surgery, with men often driven by a medical condition and women motivated by appearance.

Hence, for men, it may be important to focus on preoperative counseling to try to get them to think about bariatric surgery earlier, “which may improve their postsurgical mortality rate,” he observed.
 

Nearly threefold higher mortality among men

Dr. Beiglböck and associates used medical claims data filed with the Austrian health system, which includes nearly all residents. In 2010-2018, 19,901 Austrian patients underwent bariatric surgery, and researchers tracked their outcomes for a median of 5.4 years, through April 2020.

During the 9-year period, 74% of patients who underwent bariatric surgery were women, again, a finding consistent with prior reports from other countries.

The 5,220 men were an average of 41.8 years old, with 65% undergoing gastric bypass and 30% gastric banding. The 14,681 women were an average of 40.1 years old, with 70% undergoing gastric bypass and 22% gastric banding.

During follow-up, 367 patients (1.8%) died. Among men, the overall mortality rate was 2.6-fold higher, compared with women (1.3% vs. 3.4%) and average mortality per year was 2.8-fold higher (0.64% vs. 0.24%).

The rate of death on the day of surgery among men also substantially exceeded that of women (0.29% vs. 0.05%), as did death within 30 days of surgery (0.48% vs. 0.08%). All of these between-sex differences were significant.

Baseline prevalence of four categories of comorbidities and how these differed by sex among patients who died during follow-up was also examined. Underlying cardiovascular disease was prevalent in 299 patients (81% of the deceased group), 200 (54%) had a psychiatric disorder, 138 (38%) had diabetes, and 132 (36%) had a malignancy.

The prevalence of cardiovascular disease and psychiatric disorders was roughly the same in men and women. Men had a significantly higher prevalence of diabetes, and a higher proportion of women had a malignancy.
 

Consistent with U.S. studies

A U.S. report in 2015 documented a higher prevalence of comorbidities and more severe illness among men undergoing bariatric surgery, compared with women, noted session chair Zhila Semnani-Azad, PhD, a researcher in the department of nutrition at Harvard School of Public Health in Boston.

“I think the [Austrian] data presented have relevance to the U.S. population,” Dr. Semnani-Azad said in an interview.

“The main limitation of these univariate analyses is they don’t account for potential confounding variables that could affect the association, such as lifestyle variables, age, and family history. There is always potential for other variables” to influence apparent sex-specific associations, she commented. Another limitation is the small total number of deaths analyzed, at 367.

“These results are a good starting point for future studies. More work is needed to better understand the impact of comorbidities and sex on postsurgical mortality,” Dr. Semnani-Azad concluded.

Dr. Beiglböck and Dr. Semnani-Azad have reported no relevant financial relationships.

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

Men had a much higher rate of death following bariatric surgery performed in Austria during 2010-2018, compared with women in a retrospective analysis of nearly 20,000 patients based on health insurance records.

The reason may be that men undergoing bariatric surgery have “worse overall health at the time of surgery” than women, Hannes Beiglböck, MD, suggested at the annual meeting of the European Association for the Study of Diabetes.

The results also showed that “men tend to be older [at time of surgery] and that might have the biggest impact on outcomes after bariatric surgery,” said Dr. Beiglböck, a researcher in the division of endocrinology and metabolism at the Medical University of Vienna.

The findings confirm those of prior studies in various worldwide locations, he noted; that is, men undergoing bariatric surgery tend to be older than women and have more comorbidities and perioperative mortality. 

Dr. Beiglböck also highlighted earlier reports that indicate “profound” sex-specific differences in why patients undergo bariatric surgery, with men often driven by a medical condition and women motivated by appearance.

Hence, for men, it may be important to focus on preoperative counseling to try to get them to think about bariatric surgery earlier, “which may improve their postsurgical mortality rate,” he observed.
 

Nearly threefold higher mortality among men

Dr. Beiglböck and associates used medical claims data filed with the Austrian health system, which includes nearly all residents. In 2010-2018, 19,901 Austrian patients underwent bariatric surgery, and researchers tracked their outcomes for a median of 5.4 years, through April 2020.

During the 9-year period, 74% of patients who underwent bariatric surgery were women, again, a finding consistent with prior reports from other countries.

The 5,220 men were an average of 41.8 years old, with 65% undergoing gastric bypass and 30% gastric banding. The 14,681 women were an average of 40.1 years old, with 70% undergoing gastric bypass and 22% gastric banding.

During follow-up, 367 patients (1.8%) died. Among men, the overall mortality rate was 2.6-fold higher, compared with women (1.3% vs. 3.4%) and average mortality per year was 2.8-fold higher (0.64% vs. 0.24%).

The rate of death on the day of surgery among men also substantially exceeded that of women (0.29% vs. 0.05%), as did death within 30 days of surgery (0.48% vs. 0.08%). All of these between-sex differences were significant.

Baseline prevalence of four categories of comorbidities and how these differed by sex among patients who died during follow-up was also examined. Underlying cardiovascular disease was prevalent in 299 patients (81% of the deceased group), 200 (54%) had a psychiatric disorder, 138 (38%) had diabetes, and 132 (36%) had a malignancy.

The prevalence of cardiovascular disease and psychiatric disorders was roughly the same in men and women. Men had a significantly higher prevalence of diabetes, and a higher proportion of women had a malignancy.
 

Consistent with U.S. studies

A U.S. report in 2015 documented a higher prevalence of comorbidities and more severe illness among men undergoing bariatric surgery, compared with women, noted session chair Zhila Semnani-Azad, PhD, a researcher in the department of nutrition at Harvard School of Public Health in Boston.

“I think the [Austrian] data presented have relevance to the U.S. population,” Dr. Semnani-Azad said in an interview.

“The main limitation of these univariate analyses is they don’t account for potential confounding variables that could affect the association, such as lifestyle variables, age, and family history. There is always potential for other variables” to influence apparent sex-specific associations, she commented. Another limitation is the small total number of deaths analyzed, at 367.

“These results are a good starting point for future studies. More work is needed to better understand the impact of comorbidities and sex on postsurgical mortality,” Dr. Semnani-Azad concluded.

Dr. Beiglböck and Dr. Semnani-Azad have reported no relevant financial relationships.

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

Men had a much higher rate of death following bariatric surgery performed in Austria during 2010-2018, compared with women in a retrospective analysis of nearly 20,000 patients based on health insurance records.

The reason may be that men undergoing bariatric surgery have “worse overall health at the time of surgery” than women, Hannes Beiglböck, MD, suggested at the annual meeting of the European Association for the Study of Diabetes.

The results also showed that “men tend to be older [at time of surgery] and that might have the biggest impact on outcomes after bariatric surgery,” said Dr. Beiglböck, a researcher in the division of endocrinology and metabolism at the Medical University of Vienna.

The findings confirm those of prior studies in various worldwide locations, he noted; that is, men undergoing bariatric surgery tend to be older than women and have more comorbidities and perioperative mortality. 

Dr. Beiglböck also highlighted earlier reports that indicate “profound” sex-specific differences in why patients undergo bariatric surgery, with men often driven by a medical condition and women motivated by appearance.

Hence, for men, it may be important to focus on preoperative counseling to try to get them to think about bariatric surgery earlier, “which may improve their postsurgical mortality rate,” he observed.
 

Nearly threefold higher mortality among men

Dr. Beiglböck and associates used medical claims data filed with the Austrian health system, which includes nearly all residents. In 2010-2018, 19,901 Austrian patients underwent bariatric surgery, and researchers tracked their outcomes for a median of 5.4 years, through April 2020.

During the 9-year period, 74% of patients who underwent bariatric surgery were women, again, a finding consistent with prior reports from other countries.

The 5,220 men were an average of 41.8 years old, with 65% undergoing gastric bypass and 30% gastric banding. The 14,681 women were an average of 40.1 years old, with 70% undergoing gastric bypass and 22% gastric banding.

During follow-up, 367 patients (1.8%) died. Among men, the overall mortality rate was 2.6-fold higher, compared with women (1.3% vs. 3.4%) and average mortality per year was 2.8-fold higher (0.64% vs. 0.24%).

The rate of death on the day of surgery among men also substantially exceeded that of women (0.29% vs. 0.05%), as did death within 30 days of surgery (0.48% vs. 0.08%). All of these between-sex differences were significant.

Baseline prevalence of four categories of comorbidities and how these differed by sex among patients who died during follow-up was also examined. Underlying cardiovascular disease was prevalent in 299 patients (81% of the deceased group), 200 (54%) had a psychiatric disorder, 138 (38%) had diabetes, and 132 (36%) had a malignancy.

The prevalence of cardiovascular disease and psychiatric disorders was roughly the same in men and women. Men had a significantly higher prevalence of diabetes, and a higher proportion of women had a malignancy.
 

Consistent with U.S. studies

A U.S. report in 2015 documented a higher prevalence of comorbidities and more severe illness among men undergoing bariatric surgery, compared with women, noted session chair Zhila Semnani-Azad, PhD, a researcher in the department of nutrition at Harvard School of Public Health in Boston.

“I think the [Austrian] data presented have relevance to the U.S. population,” Dr. Semnani-Azad said in an interview.

“The main limitation of these univariate analyses is they don’t account for potential confounding variables that could affect the association, such as lifestyle variables, age, and family history. There is always potential for other variables” to influence apparent sex-specific associations, she commented. Another limitation is the small total number of deaths analyzed, at 367.

“These results are a good starting point for future studies. More work is needed to better understand the impact of comorbidities and sex on postsurgical mortality,” Dr. Semnani-Azad concluded.

Dr. Beiglböck and Dr. Semnani-Azad have reported no relevant financial relationships.

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

Weight loss of at least 15% of body weight should become the “initial principal treatment goal” for many patients with type 2 diabetes, according to a new review and proposal published by an international quartet of diabetologists.

Although this proposition currently has formal backing from just the four authors of the article published in the Lancet, their recommendation to elevate substantial weight loss to the front line of management for many patients with type 2 diabetes drew quick support from leaders of several diabetes organizations, albeit with some caveats.

“Our main message is that treatment of obesity should be the future of diabetes treatment,” summed up Ildiko Lingvay, MD, lead author of the new review and proposal, at the annual meeting of the European Association for the Study of Diabetes.

“Right now, a relatively small percentage of clinicians [who treat patients with type 2 diabetes] address obesity and know how to treat it. That has to change. Every clinician who treats diabetes needs to know how to treat obesity,” said Dr. Lingvay, a professor in the division of endocrinology at the University of Texas Southwestern Medical Center, Dallas.

This requires a sea change in the way clinicians approach treating patients with type 2 diabetes, which until now has generally involved “exclusive focus on glycemic control,” the authors wrote. “Practice management should refocus to effectively incorporate weight management to treat patients with type 2 diabetes.”

Successfully implementing their new, proposed change in focus “will take fundamental change,” noted Dr. Lingvay, who expressed hope that international guidelines will soon endorse this approach, an action that would be “a huge step in the right direction.”
 

Target weight-loss drugs to the right patients.

Initial reactions from representatives of several diabetes and obesity groups suggested that official endorsements of this management strategy for at least a subset of patients with type 2 diabetes may be forthcoming.

“The American Diabetes Association’s standards of care is aligned with this approach in focusing on obesity as a target of management in people with type 2 diabetes,” commented Nuha A. El Sayed, MD, vice president for health care improvement for the ADA. An “area of discussion” is the specific weight-loss target of at least 15%, because patients benefit from more modest weight losses of 5%-7%, and a target loss of 15% may not be achievable for some patients, she noted in a statement.

The ADA’s leadership and its professional practice committee will “carefully consider” the new, published proposal, added Dr. El Sayed, a diabetologist at the Joslin Diabetes Center in Boston.

Similar caution over generalizability of the 15% loss target came from Stefano Del Prato, MD, president of the European Society for the Study of Diabetes.

“Not everyone responds to the same extent” to the newest pharmaceuticals for facilitating weight loss, such as the glucagonlike peptide-1 receptor agonists, so the ideal would be to try to “identify patients who respond better to weight loss and can lose at least 15% of their weight. We need to improve our ability to identify patients who respond better,” said Dr. Del Prato, a professor of endocrinology and metabolism at the University of Pisa (Italy).

Despite this, he agreed in an interview that “a significant reduction in body weight should be seen as a target for treatment of type 2 diabetes,”

“Appropriate training for obesity management is essential for those working on type 2 diabetes prevention or management,” commented Jason C.G. Halford, PhD, a professor of biological psychology at the University Of Leeds (England), and president of the European Association for the Study of Obesity.

For some patients with type 2 diabetes “losing 10%-15% of body weight can mean their diabetes goes into remission,” and “losing even a small amount of weight can be life changing, it can help people better manage their blood sugars and blood pressure, and reduce their risk for developing diabetes complications like heart disease and sight loss,” commented Lucy Chambers, PhD, head of research communications for Diabetes UK.

15% loss is a ‘reachable’ goal

Dr. Lingvay and coauthors acknowledged that weight loss of less than 15% can benefit many patients with type 2 diabetes, but they felt that a loss of at least 15% gives patients a realistic and potentially potent goal to strive for.

At least 15% loss “is a goal that is beneficial and reachable for many patients. Not everyone will get there, but the closer that patients get to this, or beyond, the bigger their benefit,” she explained. “There is no magic number” for exactly how much weight a patient needs to lose to improve their health. Dr. Lingvay also highlighted that weight loss is a better target for patients than remission of their diabetes because remission may no longer be possible in patients with longstanding type 2 diabetes.

The review divides patients with type 2 diabetes into three subgroups: those with adiposity-related disease, which includes about 40%-70% of patients with type 2 diabetes; patients with cardiovascular disease as their most prominent comorbidity, a subgroup that includes about a third of patients with type 2 diabetes; and the remaining patients with primarily beta-cell dysfunction with a principle morbidity of hyperglycemia, comprising about 10%-20% of patients with type 2 diabetes. Patients in the adiposity-related diabetes subgroup form the primary target group for interventions focused on weight loss.

Incretin-based weight-loss agents propel change.

The review also links the timing of the new recommendations to recent evidence that treatment with relatively new medications from classes such as the GLP-1 receptor agonists can produce weight loss of at least 15% in most patients with type 2 diabetes, especially those with the adiposity-related form of the disease.

“The number of patients who can achieve and maintain weight loss with lifestyle alone is limited, and while bariatric surgery is very effective [for producing substantial weight loss], only a minority of patients have access to it,” and the necessary scalability of surgery is doubtful, said Priya Sumithran, MBBS, PhD, an endocrinologist and leader of the obesity research group at the University of Melbourne, and a coauthor on the new review. Compelling evidence now exists that the gap between lifestyle interventions and bariatric surgery can now be filled by a new generation of incretin-based agents that can safely produce substantial weight loss.

New agents that work as GLP-1 receptor agonists and on related incretin pathways “have changed how we think about treating type 2 diabetes,” Dr. Lingvay declared.

Dr. Lingvay and Dr. Del Prato have each been consultants to numerous drug companies. Dr. Sumithran has been an adviser to and speaker on behalf of Novo Nordisk. Dr. El Sayed, Dr. Halford, and Dr. Chambers had no relevant disclosures.

mzoler@mdedge.com

Weight loss of at least 15% of body weight should become the “initial principal treatment goal” for many patients with type 2 diabetes, according to a new review and proposal published by an international quartet of diabetologists.

Although this proposition currently has formal backing from just the four authors of the article published in the Lancet, their recommendation to elevate substantial weight loss to the front line of management for many patients with type 2 diabetes drew quick support from leaders of several diabetes organizations, albeit with some caveats.

“Our main message is that treatment of obesity should be the future of diabetes treatment,” summed up Ildiko Lingvay, MD, lead author of the new review and proposal, at the annual meeting of the European Association for the Study of Diabetes.

“Right now, a relatively small percentage of clinicians [who treat patients with type 2 diabetes] address obesity and know how to treat it. That has to change. Every clinician who treats diabetes needs to know how to treat obesity,” said Dr. Lingvay, a professor in the division of endocrinology at the University of Texas Southwestern Medical Center, Dallas.

This requires a sea change in the way clinicians approach treating patients with type 2 diabetes, which until now has generally involved “exclusive focus on glycemic control,” the authors wrote. “Practice management should refocus to effectively incorporate weight management to treat patients with type 2 diabetes.”

Successfully implementing their new, proposed change in focus “will take fundamental change,” noted Dr. Lingvay, who expressed hope that international guidelines will soon endorse this approach, an action that would be “a huge step in the right direction.”
 

Target weight-loss drugs to the right patients.

Initial reactions from representatives of several diabetes and obesity groups suggested that official endorsements of this management strategy for at least a subset of patients with type 2 diabetes may be forthcoming.

“The American Diabetes Association’s standards of care is aligned with this approach in focusing on obesity as a target of management in people with type 2 diabetes,” commented Nuha A. El Sayed, MD, vice president for health care improvement for the ADA. An “area of discussion” is the specific weight-loss target of at least 15%, because patients benefit from more modest weight losses of 5%-7%, and a target loss of 15% may not be achievable for some patients, she noted in a statement.

The ADA’s leadership and its professional practice committee will “carefully consider” the new, published proposal, added Dr. El Sayed, a diabetologist at the Joslin Diabetes Center in Boston.

Similar caution over generalizability of the 15% loss target came from Stefano Del Prato, MD, president of the European Society for the Study of Diabetes.

“Not everyone responds to the same extent” to the newest pharmaceuticals for facilitating weight loss, such as the glucagonlike peptide-1 receptor agonists, so the ideal would be to try to “identify patients who respond better to weight loss and can lose at least 15% of their weight. We need to improve our ability to identify patients who respond better,” said Dr. Del Prato, a professor of endocrinology and metabolism at the University of Pisa (Italy).

Despite this, he agreed in an interview that “a significant reduction in body weight should be seen as a target for treatment of type 2 diabetes,”

“Appropriate training for obesity management is essential for those working on type 2 diabetes prevention or management,” commented Jason C.G. Halford, PhD, a professor of biological psychology at the University Of Leeds (England), and president of the European Association for the Study of Obesity.

For some patients with type 2 diabetes “losing 10%-15% of body weight can mean their diabetes goes into remission,” and “losing even a small amount of weight can be life changing, it can help people better manage their blood sugars and blood pressure, and reduce their risk for developing diabetes complications like heart disease and sight loss,” commented Lucy Chambers, PhD, head of research communications for Diabetes UK.

15% loss is a ‘reachable’ goal

Dr. Lingvay and coauthors acknowledged that weight loss of less than 15% can benefit many patients with type 2 diabetes, but they felt that a loss of at least 15% gives patients a realistic and potentially potent goal to strive for.

At least 15% loss “is a goal that is beneficial and reachable for many patients. Not everyone will get there, but the closer that patients get to this, or beyond, the bigger their benefit,” she explained. “There is no magic number” for exactly how much weight a patient needs to lose to improve their health. Dr. Lingvay also highlighted that weight loss is a better target for patients than remission of their diabetes because remission may no longer be possible in patients with longstanding type 2 diabetes.

The review divides patients with type 2 diabetes into three subgroups: those with adiposity-related disease, which includes about 40%-70% of patients with type 2 diabetes; patients with cardiovascular disease as their most prominent comorbidity, a subgroup that includes about a third of patients with type 2 diabetes; and the remaining patients with primarily beta-cell dysfunction with a principle morbidity of hyperglycemia, comprising about 10%-20% of patients with type 2 diabetes. Patients in the adiposity-related diabetes subgroup form the primary target group for interventions focused on weight loss.

Incretin-based weight-loss agents propel change.

The review also links the timing of the new recommendations to recent evidence that treatment with relatively new medications from classes such as the GLP-1 receptor agonists can produce weight loss of at least 15% in most patients with type 2 diabetes, especially those with the adiposity-related form of the disease.

“The number of patients who can achieve and maintain weight loss with lifestyle alone is limited, and while bariatric surgery is very effective [for producing substantial weight loss], only a minority of patients have access to it,” and the necessary scalability of surgery is doubtful, said Priya Sumithran, MBBS, PhD, an endocrinologist and leader of the obesity research group at the University of Melbourne, and a coauthor on the new review. Compelling evidence now exists that the gap between lifestyle interventions and bariatric surgery can now be filled by a new generation of incretin-based agents that can safely produce substantial weight loss.

New agents that work as GLP-1 receptor agonists and on related incretin pathways “have changed how we think about treating type 2 diabetes,” Dr. Lingvay declared.

Dr. Lingvay and Dr. Del Prato have each been consultants to numerous drug companies. Dr. Sumithran has been an adviser to and speaker on behalf of Novo Nordisk. Dr. El Sayed, Dr. Halford, and Dr. Chambers had no relevant disclosures.

mzoler@mdedge.com

Weight loss of at least 15% of body weight should become the “initial principal treatment goal” for many patients with type 2 diabetes, according to a new review and proposal published by an international quartet of diabetologists.

Although this proposition currently has formal backing from just the four authors of the article published in the Lancet, their recommendation to elevate substantial weight loss to the front line of management for many patients with type 2 diabetes drew quick support from leaders of several diabetes organizations, albeit with some caveats.

“Our main message is that treatment of obesity should be the future of diabetes treatment,” summed up Ildiko Lingvay, MD, lead author of the new review and proposal, at the annual meeting of the European Association for the Study of Diabetes.

“Right now, a relatively small percentage of clinicians [who treat patients with type 2 diabetes] address obesity and know how to treat it. That has to change. Every clinician who treats diabetes needs to know how to treat obesity,” said Dr. Lingvay, a professor in the division of endocrinology at the University of Texas Southwestern Medical Center, Dallas.

This requires a sea change in the way clinicians approach treating patients with type 2 diabetes, which until now has generally involved “exclusive focus on glycemic control,” the authors wrote. “Practice management should refocus to effectively incorporate weight management to treat patients with type 2 diabetes.”

Successfully implementing their new, proposed change in focus “will take fundamental change,” noted Dr. Lingvay, who expressed hope that international guidelines will soon endorse this approach, an action that would be “a huge step in the right direction.”
 

Target weight-loss drugs to the right patients.

Initial reactions from representatives of several diabetes and obesity groups suggested that official endorsements of this management strategy for at least a subset of patients with type 2 diabetes may be forthcoming.

“The American Diabetes Association’s standards of care is aligned with this approach in focusing on obesity as a target of management in people with type 2 diabetes,” commented Nuha A. El Sayed, MD, vice president for health care improvement for the ADA. An “area of discussion” is the specific weight-loss target of at least 15%, because patients benefit from more modest weight losses of 5%-7%, and a target loss of 15% may not be achievable for some patients, she noted in a statement.

The ADA’s leadership and its professional practice committee will “carefully consider” the new, published proposal, added Dr. El Sayed, a diabetologist at the Joslin Diabetes Center in Boston.

Similar caution over generalizability of the 15% loss target came from Stefano Del Prato, MD, president of the European Society for the Study of Diabetes.

“Not everyone responds to the same extent” to the newest pharmaceuticals for facilitating weight loss, such as the glucagonlike peptide-1 receptor agonists, so the ideal would be to try to “identify patients who respond better to weight loss and can lose at least 15% of their weight. We need to improve our ability to identify patients who respond better,” said Dr. Del Prato, a professor of endocrinology and metabolism at the University of Pisa (Italy).

Despite this, he agreed in an interview that “a significant reduction in body weight should be seen as a target for treatment of type 2 diabetes,”

“Appropriate training for obesity management is essential for those working on type 2 diabetes prevention or management,” commented Jason C.G. Halford, PhD, a professor of biological psychology at the University Of Leeds (England), and president of the European Association for the Study of Obesity.

For some patients with type 2 diabetes “losing 10%-15% of body weight can mean their diabetes goes into remission,” and “losing even a small amount of weight can be life changing, it can help people better manage their blood sugars and blood pressure, and reduce their risk for developing diabetes complications like heart disease and sight loss,” commented Lucy Chambers, PhD, head of research communications for Diabetes UK.

15% loss is a ‘reachable’ goal

Dr. Lingvay and coauthors acknowledged that weight loss of less than 15% can benefit many patients with type 2 diabetes, but they felt that a loss of at least 15% gives patients a realistic and potentially potent goal to strive for.

At least 15% loss “is a goal that is beneficial and reachable for many patients. Not everyone will get there, but the closer that patients get to this, or beyond, the bigger their benefit,” she explained. “There is no magic number” for exactly how much weight a patient needs to lose to improve their health. Dr. Lingvay also highlighted that weight loss is a better target for patients than remission of their diabetes because remission may no longer be possible in patients with longstanding type 2 diabetes.

The review divides patients with type 2 diabetes into three subgroups: those with adiposity-related disease, which includes about 40%-70% of patients with type 2 diabetes; patients with cardiovascular disease as their most prominent comorbidity, a subgroup that includes about a third of patients with type 2 diabetes; and the remaining patients with primarily beta-cell dysfunction with a principle morbidity of hyperglycemia, comprising about 10%-20% of patients with type 2 diabetes. Patients in the adiposity-related diabetes subgroup form the primary target group for interventions focused on weight loss.

Incretin-based weight-loss agents propel change.

The review also links the timing of the new recommendations to recent evidence that treatment with relatively new medications from classes such as the GLP-1 receptor agonists can produce weight loss of at least 15% in most patients with type 2 diabetes, especially those with the adiposity-related form of the disease.

“The number of patients who can achieve and maintain weight loss with lifestyle alone is limited, and while bariatric surgery is very effective [for producing substantial weight loss], only a minority of patients have access to it,” and the necessary scalability of surgery is doubtful, said Priya Sumithran, MBBS, PhD, an endocrinologist and leader of the obesity research group at the University of Melbourne, and a coauthor on the new review. Compelling evidence now exists that the gap between lifestyle interventions and bariatric surgery can now be filled by a new generation of incretin-based agents that can safely produce substantial weight loss.

New agents that work as GLP-1 receptor agonists and on related incretin pathways “have changed how we think about treating type 2 diabetes,” Dr. Lingvay declared.

Dr. Lingvay and Dr. Del Prato have each been consultants to numerous drug companies. Dr. Sumithran has been an adviser to and speaker on behalf of Novo Nordisk. Dr. El Sayed, Dr. Halford, and Dr. Chambers had no relevant disclosures.

mzoler@mdedge.com

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

Prurigo pigmentosa, an uncommon inflammatory skin condition also known as Nagashima disease, is growing in frequency, possibly as a result of increased interest in the ketogenic diet, according to a dermatologist, who reviewed skin conditions common to patients of Asian descent at the Skin of Color Update 2021.

“Ketogenic diets are gaining popularity globally for weight loss. After 2-4 weeks [on a strict ketogenic diet], some patients start to notice very pruritic papules on their trunk, the so-called keto rash,” reported Hye Jin Chung, MD, director of the Asian Skin Clinic, Beth Israel Deaconess Medical Center, Boston. “Keto rash is actually prurigo pigmentosa.”

The exact pathogenesis of prurigo pigmentosa, a highly pruritic macular and papular rash with gross reticular pigmentation, is unclear, but Dr. Chung reported that the strong link with ketosis might explain why more cases are now being encountered outside of east Asia. Ketosis or conditions associated with a high risk for ketosis, such as anorexia nervosa, diabetes mellitus, or recent bariatric surgery, have been linked to prurigo pigmentosa in all skin types and ethnicities.

“I tell my residents that this is a disease you will never forget after your first case,” she said.

The differential diagnosis includes contact dermatitis and other inflammatory disorders, but Dr. Chung said that the reticular pattern of the lesions is a relatively unique feature. Confluent and reticulated papillomatosis (CARP) shares a pattern of reticulated lesions, but Dr. Chung said it lacks the inflammatory erythematous papules and the severe pruritus common to prurigo pigmentosa.

Histologically, the pattern evolves. It begins as a perivascular infiltration dominated by neutrophils and eosinophils with hyperkeratosis, acanthosis, and spongiosis. Over time, Dr. Chung said that the histologic picture shows an increasing degree of dyskeratosis as keratinocytes die.

Prurigo pigmentosa was first described 50 years ago by Masaji Nagashima, MD, who published a report on eight patients in Japan with a pruriginous truncal dermatosis featuring symmetrical pigmentation. Most subsequent reports were also from Japan or other east Asian countries, but it has since spread.

This global spread was captured in a recently published review of 115 published studies and case reports from 24 countries. In this review, the proportion of studies from Europe (36.5%) approached that of those from east Asia (38.2%), even if 76% of the patients for whom race was reported were of Asian ethnicity.

Of the 369 patients evaluated in these studies and case reports, 72.1% were female. The mean age was 25.6 years. In the studies originating outside of Asia, prurigo pigmentosa was reported in a spectrum of skin types and ethnicities, including Whites, Blacks, and Hispanics. The lowest reported incidence has been in the latter two groups, but the authors of the review speculated that this condition is likely being underdiagnosed in non-Asian individuals.

Dr. Chung agreed, and she cautioned that the consequences typically result in a significant delay for achieving disease control. In recounting a recent case of prurigo pigmentosa at her center, she said that the 59-year-old Asian patient had been initiated on topical steroids and oral antihistamines by her primary care physician before she was referred. This is a common and reasonable strategy for a highly pruritic rash potentially caused by contact dermatitis, but it is ineffective for this disorder.

“Prurigo pigmentosa requires anti-inflammatory agents,” she explained. She said that doxycycline and minocycline are the treatments of choice, but noted that there are also reports of efficacy with dapsone, macrolide antibiotics, and isotretinoin.

In her most recent case, she initiated the patient on 100 mg of doxycycline twice daily. There was significant improvement within 2 weeks, and the rash resolved within a month with no relapse in follow-up that now exceeds 12 months, Dr. Chung said.

According to Dr. Chung, Asian-Americans are the most rapidly growing ethnic group in the United States, making it increasingly important to be familiar with conditions common or unique to Asian skin, but prurigo pigmentosa is no longer confined to those of Asian descent. She encouraged clinicians to recognize this disorder to reduce the common delays to effective treatment.

The senior author of the recently published review of studies, Jensen Yeung, MD, of the department of dermatology, University of Toronto, agreed. He, too, believes that dermatologists need to increase their awareness of the signs and symptoms of prurigo pigmentosa – and not just in Asian patients or patients of Asian descent.

“This diagnosis is often missed,” he contended in an interview. “This condition has become more common in the past 5 years in my clinical experience.” He added that the increasing incidence might not just be related to better diagnostic accuracy, although the most significant of other possible explanations “is not yet well understood.”

Dr. Chung reports that she has no relevant financial relationships to disclose. Dr. Yeung reports financial relationships with more than 25 pharmaceutical companies, some of which produce treatments employed in the control of prurigo pigmentosa.

Prurigo pigmentosa, an uncommon inflammatory skin condition also known as Nagashima disease, is growing in frequency, possibly as a result of increased interest in the ketogenic diet, according to a dermatologist, who reviewed skin conditions common to patients of Asian descent at the Skin of Color Update 2021.

“Ketogenic diets are gaining popularity globally for weight loss. After 2-4 weeks [on a strict ketogenic diet], some patients start to notice very pruritic papules on their trunk, the so-called keto rash,” reported Hye Jin Chung, MD, director of the Asian Skin Clinic, Beth Israel Deaconess Medical Center, Boston. “Keto rash is actually prurigo pigmentosa.”

The exact pathogenesis of prurigo pigmentosa, a highly pruritic macular and papular rash with gross reticular pigmentation, is unclear, but Dr. Chung reported that the strong link with ketosis might explain why more cases are now being encountered outside of east Asia. Ketosis or conditions associated with a high risk for ketosis, such as anorexia nervosa, diabetes mellitus, or recent bariatric surgery, have been linked to prurigo pigmentosa in all skin types and ethnicities.

“I tell my residents that this is a disease you will never forget after your first case,” she said.

The differential diagnosis includes contact dermatitis and other inflammatory disorders, but Dr. Chung said that the reticular pattern of the lesions is a relatively unique feature. Confluent and reticulated papillomatosis (CARP) shares a pattern of reticulated lesions, but Dr. Chung said it lacks the inflammatory erythematous papules and the severe pruritus common to prurigo pigmentosa.

Histologically, the pattern evolves. It begins as a perivascular infiltration dominated by neutrophils and eosinophils with hyperkeratosis, acanthosis, and spongiosis. Over time, Dr. Chung said that the histologic picture shows an increasing degree of dyskeratosis as keratinocytes die.

Prurigo pigmentosa was first described 50 years ago by Masaji Nagashima, MD, who published a report on eight patients in Japan with a pruriginous truncal dermatosis featuring symmetrical pigmentation. Most subsequent reports were also from Japan or other east Asian countries, but it has since spread.

This global spread was captured in a recently published review of 115 published studies and case reports from 24 countries. In this review, the proportion of studies from Europe (36.5%) approached that of those from east Asia (38.2%), even if 76% of the patients for whom race was reported were of Asian ethnicity.

Of the 369 patients evaluated in these studies and case reports, 72.1% were female. The mean age was 25.6 years. In the studies originating outside of Asia, prurigo pigmentosa was reported in a spectrum of skin types and ethnicities, including Whites, Blacks, and Hispanics. The lowest reported incidence has been in the latter two groups, but the authors of the review speculated that this condition is likely being underdiagnosed in non-Asian individuals.

Dr. Chung agreed, and she cautioned that the consequences typically result in a significant delay for achieving disease control. In recounting a recent case of prurigo pigmentosa at her center, she said that the 59-year-old Asian patient had been initiated on topical steroids and oral antihistamines by her primary care physician before she was referred. This is a common and reasonable strategy for a highly pruritic rash potentially caused by contact dermatitis, but it is ineffective for this disorder.

“Prurigo pigmentosa requires anti-inflammatory agents,” she explained. She said that doxycycline and minocycline are the treatments of choice, but noted that there are also reports of efficacy with dapsone, macrolide antibiotics, and isotretinoin.

In her most recent case, she initiated the patient on 100 mg of doxycycline twice daily. There was significant improvement within 2 weeks, and the rash resolved within a month with no relapse in follow-up that now exceeds 12 months, Dr. Chung said.

According to Dr. Chung, Asian-Americans are the most rapidly growing ethnic group in the United States, making it increasingly important to be familiar with conditions common or unique to Asian skin, but prurigo pigmentosa is no longer confined to those of Asian descent. She encouraged clinicians to recognize this disorder to reduce the common delays to effective treatment.

The senior author of the recently published review of studies, Jensen Yeung, MD, of the department of dermatology, University of Toronto, agreed. He, too, believes that dermatologists need to increase their awareness of the signs and symptoms of prurigo pigmentosa – and not just in Asian patients or patients of Asian descent.

“This diagnosis is often missed,” he contended in an interview. “This condition has become more common in the past 5 years in my clinical experience.” He added that the increasing incidence might not just be related to better diagnostic accuracy, although the most significant of other possible explanations “is not yet well understood.”

Dr. Chung reports that she has no relevant financial relationships to disclose. Dr. Yeung reports financial relationships with more than 25 pharmaceutical companies, some of which produce treatments employed in the control of prurigo pigmentosa.

Prurigo pigmentosa, an uncommon inflammatory skin condition also known as Nagashima disease, is growing in frequency, possibly as a result of increased interest in the ketogenic diet, according to a dermatologist, who reviewed skin conditions common to patients of Asian descent at the Skin of Color Update 2021.

“Ketogenic diets are gaining popularity globally for weight loss. After 2-4 weeks [on a strict ketogenic diet], some patients start to notice very pruritic papules on their trunk, the so-called keto rash,” reported Hye Jin Chung, MD, director of the Asian Skin Clinic, Beth Israel Deaconess Medical Center, Boston. “Keto rash is actually prurigo pigmentosa.”

The exact pathogenesis of prurigo pigmentosa, a highly pruritic macular and papular rash with gross reticular pigmentation, is unclear, but Dr. Chung reported that the strong link with ketosis might explain why more cases are now being encountered outside of east Asia. Ketosis or conditions associated with a high risk for ketosis, such as anorexia nervosa, diabetes mellitus, or recent bariatric surgery, have been linked to prurigo pigmentosa in all skin types and ethnicities.

“I tell my residents that this is a disease you will never forget after your first case,” she said.

The differential diagnosis includes contact dermatitis and other inflammatory disorders, but Dr. Chung said that the reticular pattern of the lesions is a relatively unique feature. Confluent and reticulated papillomatosis (CARP) shares a pattern of reticulated lesions, but Dr. Chung said it lacks the inflammatory erythematous papules and the severe pruritus common to prurigo pigmentosa.

Histologically, the pattern evolves. It begins as a perivascular infiltration dominated by neutrophils and eosinophils with hyperkeratosis, acanthosis, and spongiosis. Over time, Dr. Chung said that the histologic picture shows an increasing degree of dyskeratosis as keratinocytes die.

Prurigo pigmentosa was first described 50 years ago by Masaji Nagashima, MD, who published a report on eight patients in Japan with a pruriginous truncal dermatosis featuring symmetrical pigmentation. Most subsequent reports were also from Japan or other east Asian countries, but it has since spread.

This global spread was captured in a recently published review of 115 published studies and case reports from 24 countries. In this review, the proportion of studies from Europe (36.5%) approached that of those from east Asia (38.2%), even if 76% of the patients for whom race was reported were of Asian ethnicity.

Of the 369 patients evaluated in these studies and case reports, 72.1% were female. The mean age was 25.6 years. In the studies originating outside of Asia, prurigo pigmentosa was reported in a spectrum of skin types and ethnicities, including Whites, Blacks, and Hispanics. The lowest reported incidence has been in the latter two groups, but the authors of the review speculated that this condition is likely being underdiagnosed in non-Asian individuals.

Dr. Chung agreed, and she cautioned that the consequences typically result in a significant delay for achieving disease control. In recounting a recent case of prurigo pigmentosa at her center, she said that the 59-year-old Asian patient had been initiated on topical steroids and oral antihistamines by her primary care physician before she was referred. This is a common and reasonable strategy for a highly pruritic rash potentially caused by contact dermatitis, but it is ineffective for this disorder.

“Prurigo pigmentosa requires anti-inflammatory agents,” she explained. She said that doxycycline and minocycline are the treatments of choice, but noted that there are also reports of efficacy with dapsone, macrolide antibiotics, and isotretinoin.

In her most recent case, she initiated the patient on 100 mg of doxycycline twice daily. There was significant improvement within 2 weeks, and the rash resolved within a month with no relapse in follow-up that now exceeds 12 months, Dr. Chung said.

According to Dr. Chung, Asian-Americans are the most rapidly growing ethnic group in the United States, making it increasingly important to be familiar with conditions common or unique to Asian skin, but prurigo pigmentosa is no longer confined to those of Asian descent. She encouraged clinicians to recognize this disorder to reduce the common delays to effective treatment.

The senior author of the recently published review of studies, Jensen Yeung, MD, of the department of dermatology, University of Toronto, agreed. He, too, believes that dermatologists need to increase their awareness of the signs and symptoms of prurigo pigmentosa – and not just in Asian patients or patients of Asian descent.

“This diagnosis is often missed,” he contended in an interview. “This condition has become more common in the past 5 years in my clinical experience.” He added that the increasing incidence might not just be related to better diagnostic accuracy, although the most significant of other possible explanations “is not yet well understood.”

Dr. Chung reports that she has no relevant financial relationships to disclose. Dr. Yeung reports financial relationships with more than 25 pharmaceutical companies, some of which produce treatments employed in the control of prurigo pigmentosa.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

Time-restricted eating – where caloric intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories – has “generated impressive [animal] data in preventing or reversing metabolic diseases associated with obesity,” and “more rigorous human studies are needed,” conclude the authors of a new review.

“Time-restricted eating is an easy-to-follow and effective dietary strategy that requires less mental math than counting calories,” said senior author Satchidananda Panda, PhD, of the Panda Lab at the Salk Institute for Biological Studies, La Jolla, Calif.

It “can improve sleep and a person’s quality of life as well as reduce the risk of obesity, diabetes, and heart disease,” he noted in a press release from the Endocrine Society.

“People who are trying to lose weight and live a healthier lifestyle should pay more attention to when they eat as well as what they eat,” Dr. Panda advised.

Moreover, “eating at random times breaks the synchrony of our internal program [circadian clock] and make us prone to diseases,” so it is important to eat at consistent times.

Furthermore, time-restricted eating, a type of intermittent fasting, “is a lifestyle that anyone can adopt,” he noted, which “can help eliminate health disparities and lets everyone live a healthy and fulfilling life.”

The article, by Emily N. Manoogian, PhD, a postdoctoral fellow in the same lab, and colleagues was published online Sept. 22 in Endocrine Reviews.

The authors suggest that health care providers should encourage high-risk patients (such as those with obesity) to monitor their eating and sleeping times and make easy-to-implement behavior changes, such as decreasing after-dinner snacking and going to bed at the same time each day.
 

Animal experiments, early studies in humans

In animal experiments, time-restricted feeding without reducing caloric intake prevented or attenuated the severity of metabolic diseases including obesity, glucose intolerance, hepatic steatosis, dyslipidemia, and age-related decline in cardiac function, Dr. Manoogian and colleagues report.

In pilot human studies, time-restricted eating with or without explicit calorie reduction was associated with reductions in body weight, glucose intolerance, hypertension, and dyslipidemia.

Most studies did not restrict calories or provide dietary recommendations, yet participants commonly reduced their caloric intake by 7%-22%.
 

39 published clinical trials, many upcoming ones

The authors identified 39 clinical trials of time-restricted eating, which were mostly published in the past 2 years, with the earliest one published in 2013.

Most studies were short and small (4-12 weeks, 10-20 participants) and were of people with obesity, healthy adults, and athletes. Most of the trials had an 8- to 10-hour daily “eating window.”

Body weight decreased in 24 of 39 studies, and “importantly,” time-restricted eating was feasible and safe in all studies, the authors note.

“Larger randomized controlled trials are needed as many of the studies to date are smaller pre-post or crossover trials,” Dr. Manoogian and colleagues summarize. “Yet, the replication of findings, even in diverse patient populations, speaks to the potential impact of [time-restricted eating] as a health intervention.”

The many ongoing international clinical trials of time-restricted eating that are listed on clinicaltrials.gov should improve our understanding of time-restricted eating, they add.

Some of the larger trials are in participants with prediabetes (344 participants, NCT03504683), diabetes (144 participants, NCT04155619), metabolic syndrome (118 participants, NCT04057339), and firefighters on 24-hour shifts (150 participants, NCT03533023). There are also smaller pilot studies in participants with cancer (NCT04243512) and polycystic ovary syndrome (NCT03792282).
 

Be consistent; do not eat within 3 hours of bedtime

In the meantime, the review authors offer several tips:

• Because high melatonin levels (late at night or early morning) can inhibit proper response to food, choose a time to eat that starts at least an hour after waking and stops at least 3 hours before bedtime. If you sleep 8 hours, that leaves 12 hours for the time-restricted eating window.
• Try to eat within the same time window each day.
• Some research suggests eating earlier in the eating phase is better than eating later.

The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, the National Cancer Institute, the Larry l. Hillblom Foundation, the Wu Tsai Human Performance Alliance, the U.S. Department of Defense, and the Federal Emergency Management Agency. Dr. Panda has reported receiving royalties from his book, The Circadian Code. The other authors have reported no relevant financial disclosures.

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

Time-restricted eating – where caloric intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories – has “generated impressive [animal] data in preventing or reversing metabolic diseases associated with obesity,” and “more rigorous human studies are needed,” conclude the authors of a new review.

“Time-restricted eating is an easy-to-follow and effective dietary strategy that requires less mental math than counting calories,” said senior author Satchidananda Panda, PhD, of the Panda Lab at the Salk Institute for Biological Studies, La Jolla, Calif.

It “can improve sleep and a person’s quality of life as well as reduce the risk of obesity, diabetes, and heart disease,” he noted in a press release from the Endocrine Society.

“People who are trying to lose weight and live a healthier lifestyle should pay more attention to when they eat as well as what they eat,” Dr. Panda advised.

Moreover, “eating at random times breaks the synchrony of our internal program [circadian clock] and make us prone to diseases,” so it is important to eat at consistent times.

Furthermore, time-restricted eating, a type of intermittent fasting, “is a lifestyle that anyone can adopt,” he noted, which “can help eliminate health disparities and lets everyone live a healthy and fulfilling life.”

The article, by Emily N. Manoogian, PhD, a postdoctoral fellow in the same lab, and colleagues was published online Sept. 22 in Endocrine Reviews.

The authors suggest that health care providers should encourage high-risk patients (such as those with obesity) to monitor their eating and sleeping times and make easy-to-implement behavior changes, such as decreasing after-dinner snacking and going to bed at the same time each day.
 

Animal experiments, early studies in humans

In animal experiments, time-restricted feeding without reducing caloric intake prevented or attenuated the severity of metabolic diseases including obesity, glucose intolerance, hepatic steatosis, dyslipidemia, and age-related decline in cardiac function, Dr. Manoogian and colleagues report.

In pilot human studies, time-restricted eating with or without explicit calorie reduction was associated with reductions in body weight, glucose intolerance, hypertension, and dyslipidemia.

Most studies did not restrict calories or provide dietary recommendations, yet participants commonly reduced their caloric intake by 7%-22%.
 

39 published clinical trials, many upcoming ones

The authors identified 39 clinical trials of time-restricted eating, which were mostly published in the past 2 years, with the earliest one published in 2013.

Most studies were short and small (4-12 weeks, 10-20 participants) and were of people with obesity, healthy adults, and athletes. Most of the trials had an 8- to 10-hour daily “eating window.”

Body weight decreased in 24 of 39 studies, and “importantly,” time-restricted eating was feasible and safe in all studies, the authors note.

“Larger randomized controlled trials are needed as many of the studies to date are smaller pre-post or crossover trials,” Dr. Manoogian and colleagues summarize. “Yet, the replication of findings, even in diverse patient populations, speaks to the potential impact of [time-restricted eating] as a health intervention.”

The many ongoing international clinical trials of time-restricted eating that are listed on clinicaltrials.gov should improve our understanding of time-restricted eating, they add.

Some of the larger trials are in participants with prediabetes (344 participants, NCT03504683), diabetes (144 participants, NCT04155619), metabolic syndrome (118 participants, NCT04057339), and firefighters on 24-hour shifts (150 participants, NCT03533023). There are also smaller pilot studies in participants with cancer (NCT04243512) and polycystic ovary syndrome (NCT03792282).
 

Be consistent; do not eat within 3 hours of bedtime

In the meantime, the review authors offer several tips:

• Because high melatonin levels (late at night or early morning) can inhibit proper response to food, choose a time to eat that starts at least an hour after waking and stops at least 3 hours before bedtime. If you sleep 8 hours, that leaves 12 hours for the time-restricted eating window.
• Try to eat within the same time window each day.
• Some research suggests eating earlier in the eating phase is better than eating later.

The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, the National Cancer Institute, the Larry l. Hillblom Foundation, the Wu Tsai Human Performance Alliance, the U.S. Department of Defense, and the Federal Emergency Management Agency. Dr. Panda has reported receiving royalties from his book, The Circadian Code. The other authors have reported no relevant financial disclosures.

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

Time-restricted eating – where caloric intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories – has “generated impressive [animal] data in preventing or reversing metabolic diseases associated with obesity,” and “more rigorous human studies are needed,” conclude the authors of a new review.

“Time-restricted eating is an easy-to-follow and effective dietary strategy that requires less mental math than counting calories,” said senior author Satchidananda Panda, PhD, of the Panda Lab at the Salk Institute for Biological Studies, La Jolla, Calif.

It “can improve sleep and a person’s quality of life as well as reduce the risk of obesity, diabetes, and heart disease,” he noted in a press release from the Endocrine Society.

“People who are trying to lose weight and live a healthier lifestyle should pay more attention to when they eat as well as what they eat,” Dr. Panda advised.

Moreover, “eating at random times breaks the synchrony of our internal program [circadian clock] and make us prone to diseases,” so it is important to eat at consistent times.

Furthermore, time-restricted eating, a type of intermittent fasting, “is a lifestyle that anyone can adopt,” he noted, which “can help eliminate health disparities and lets everyone live a healthy and fulfilling life.”

The article, by Emily N. Manoogian, PhD, a postdoctoral fellow in the same lab, and colleagues was published online Sept. 22 in Endocrine Reviews.

The authors suggest that health care providers should encourage high-risk patients (such as those with obesity) to monitor their eating and sleeping times and make easy-to-implement behavior changes, such as decreasing after-dinner snacking and going to bed at the same time each day.
 

Animal experiments, early studies in humans

In animal experiments, time-restricted feeding without reducing caloric intake prevented or attenuated the severity of metabolic diseases including obesity, glucose intolerance, hepatic steatosis, dyslipidemia, and age-related decline in cardiac function, Dr. Manoogian and colleagues report.

In pilot human studies, time-restricted eating with or without explicit calorie reduction was associated with reductions in body weight, glucose intolerance, hypertension, and dyslipidemia.

Most studies did not restrict calories or provide dietary recommendations, yet participants commonly reduced their caloric intake by 7%-22%.
 

39 published clinical trials, many upcoming ones

The authors identified 39 clinical trials of time-restricted eating, which were mostly published in the past 2 years, with the earliest one published in 2013.

Most studies were short and small (4-12 weeks, 10-20 participants) and were of people with obesity, healthy adults, and athletes. Most of the trials had an 8- to 10-hour daily “eating window.”

Body weight decreased in 24 of 39 studies, and “importantly,” time-restricted eating was feasible and safe in all studies, the authors note.

“Larger randomized controlled trials are needed as many of the studies to date are smaller pre-post or crossover trials,” Dr. Manoogian and colleagues summarize. “Yet, the replication of findings, even in diverse patient populations, speaks to the potential impact of [time-restricted eating] as a health intervention.”

The many ongoing international clinical trials of time-restricted eating that are listed on clinicaltrials.gov should improve our understanding of time-restricted eating, they add.

Some of the larger trials are in participants with prediabetes (344 participants, NCT03504683), diabetes (144 participants, NCT04155619), metabolic syndrome (118 participants, NCT04057339), and firefighters on 24-hour shifts (150 participants, NCT03533023). There are also smaller pilot studies in participants with cancer (NCT04243512) and polycystic ovary syndrome (NCT03792282).
 

Be consistent; do not eat within 3 hours of bedtime

In the meantime, the review authors offer several tips:

• Because high melatonin levels (late at night or early morning) can inhibit proper response to food, choose a time to eat that starts at least an hour after waking and stops at least 3 hours before bedtime. If you sleep 8 hours, that leaves 12 hours for the time-restricted eating window.
• Try to eat within the same time window each day.
• Some research suggests eating earlier in the eating phase is better than eating later.

The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, the National Cancer Institute, the Larry l. Hillblom Foundation, the Wu Tsai Human Performance Alliance, the U.S. Department of Defense, and the Federal Emergency Management Agency. Dr. Panda has reported receiving royalties from his book, The Circadian Code. The other authors have reported no relevant financial disclosures.

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

Women with a history of polycystic ovary syndrome (PCOS) are more likely to experience somatic and urogenital symptoms post menopause, but they were no more likely to experience severe hot flashes than were other women with similar characteristics, according to research presented Sept. 24 at the hybrid annual meeting of the North American Menopause Society.

PCOS and vasomotor symptoms are each risk factors for cardiovascular disease, so researchers wanted to find out whether they were linked to one another, which might indicate that they are markers for the same underlying mechanisms that increase heart disease risk. The lack of an association, however, raises questions about how much each of these conditions might independently increase cardiovascular risk.

“Should we take a little more time to truly risk-assess these patients not just with their ASCVD risk score, but take into account that they have PCOS and they’re going through menopause, and how severe their hot flashes are?” asked Angie S. Lobo, MD, an internal medicine specialist at Mayo Clinic in Rochester, Minn., when she discussed her findings in an interview.

The association between PCOS and urogenital symptoms was surprising, Dr. Lobo said, but she said she suspects the reason for the finding may be the self-reported nature of the study.

“If you ask the question, you get the answer,” Dr. Lobo said. ”Are we just not asking the right questions to our patients? And should we be doing this more often? This is an exciting finding because there’s so much room to improve the clinical care of our patients.”

The researchers analyzed data from 3,308 women, ages 45-60, in a cross-sectional study from the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The study occurred at Mayo Clinic locations between May 2015 and December 2019 in Rochester, Minn., in Scottsdale, Ariz., and in Jacksonville, Fla.

The women were an average 53 years old and were primarily White, educated, and postmenopausal. Among the 4.6% of women with a self-reported history of PCOS, 56% of them reported depression symptoms, compared to 42% of women without PCOS. Those with PCOS also had nearly twice the prevalence of obesity – 42% versus 22.5% among women without PCOS – and had a higher average overall score on the Menopause Rating Scale (17.7 vs. 14.7; P < .001).

Although women with PCOS initially had a greater burden of psychological symptoms on the same scale, that association disappeared after adjustment for menopause status, body mass index, depression, anxiety, and current use of hormone therapy. Even after adjustment, however, women with PCOS had higher average scores for somatic symptoms (6.7 vs. 5.6) and urogenital symptoms (5.2 vs. 4.3) than those of women without PCOS (P < .001).

Severe or very severe hot flashes were no more likely in women with a history of PCOS than in the other women in the study.

”The mechanisms underlying the correlation between PCOS and menopause symptoms in the psychological and urogenital symptom domains requires further study, although the well-known association between PCOS and mood disorders may explain the high psychological symptom burden in these women during the menopause transition,” the authors concluded.

Rachael B. Smith, DO, clinical assistant professor of ob.gyn. at the University of Arizona in Phoenix, said she was not surprised to see an association between PCOS and menopause symptoms overall, but she was surprised that PCOS did not correlate with severity of vasomotor symptoms. But Dr. Smith pointed out that the sample size of women with PCOS is fairly small (n = 151).

“Given that PCOS prevalence is about 6%-10%, I feel this association should be further studied to improve our counseling and treatment for this PCOS population,” Dr. Smith, who was not involved in the research, said in an interview. “The take-home message for physicians is improved patient-tailored counseling that takes into account patients’ prior medical history of PCOS.”

Although it will require more research to find out, Dr. Smith said she suspects that PCOS and vasomotor symptoms are additive risk factors for cardiovascular disease. She also noted that the study is limited by the homogeneity of the study population.

The research was funded by the National Institutes of Health. Dr. Lobo and Dr. Smith had no disclosures.

Women with a history of polycystic ovary syndrome (PCOS) are more likely to experience somatic and urogenital symptoms post menopause, but they were no more likely to experience severe hot flashes than were other women with similar characteristics, according to research presented Sept. 24 at the hybrid annual meeting of the North American Menopause Society.

PCOS and vasomotor symptoms are each risk factors for cardiovascular disease, so researchers wanted to find out whether they were linked to one another, which might indicate that they are markers for the same underlying mechanisms that increase heart disease risk. The lack of an association, however, raises questions about how much each of these conditions might independently increase cardiovascular risk.

“Should we take a little more time to truly risk-assess these patients not just with their ASCVD risk score, but take into account that they have PCOS and they’re going through menopause, and how severe their hot flashes are?” asked Angie S. Lobo, MD, an internal medicine specialist at Mayo Clinic in Rochester, Minn., when she discussed her findings in an interview.

The association between PCOS and urogenital symptoms was surprising, Dr. Lobo said, but she said she suspects the reason for the finding may be the self-reported nature of the study.

“If you ask the question, you get the answer,” Dr. Lobo said. ”Are we just not asking the right questions to our patients? And should we be doing this more often? This is an exciting finding because there’s so much room to improve the clinical care of our patients.”

The researchers analyzed data from 3,308 women, ages 45-60, in a cross-sectional study from the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The study occurred at Mayo Clinic locations between May 2015 and December 2019 in Rochester, Minn., in Scottsdale, Ariz., and in Jacksonville, Fla.

The women were an average 53 years old and were primarily White, educated, and postmenopausal. Among the 4.6% of women with a self-reported history of PCOS, 56% of them reported depression symptoms, compared to 42% of women without PCOS. Those with PCOS also had nearly twice the prevalence of obesity – 42% versus 22.5% among women without PCOS – and had a higher average overall score on the Menopause Rating Scale (17.7 vs. 14.7; P < .001).

Although women with PCOS initially had a greater burden of psychological symptoms on the same scale, that association disappeared after adjustment for menopause status, body mass index, depression, anxiety, and current use of hormone therapy. Even after adjustment, however, women with PCOS had higher average scores for somatic symptoms (6.7 vs. 5.6) and urogenital symptoms (5.2 vs. 4.3) than those of women without PCOS (P < .001).

Severe or very severe hot flashes were no more likely in women with a history of PCOS than in the other women in the study.

”The mechanisms underlying the correlation between PCOS and menopause symptoms in the psychological and urogenital symptom domains requires further study, although the well-known association between PCOS and mood disorders may explain the high psychological symptom burden in these women during the menopause transition,” the authors concluded.

Rachael B. Smith, DO, clinical assistant professor of ob.gyn. at the University of Arizona in Phoenix, said she was not surprised to see an association between PCOS and menopause symptoms overall, but she was surprised that PCOS did not correlate with severity of vasomotor symptoms. But Dr. Smith pointed out that the sample size of women with PCOS is fairly small (n = 151).

“Given that PCOS prevalence is about 6%-10%, I feel this association should be further studied to improve our counseling and treatment for this PCOS population,” Dr. Smith, who was not involved in the research, said in an interview. “The take-home message for physicians is improved patient-tailored counseling that takes into account patients’ prior medical history of PCOS.”

Although it will require more research to find out, Dr. Smith said she suspects that PCOS and vasomotor symptoms are additive risk factors for cardiovascular disease. She also noted that the study is limited by the homogeneity of the study population.

The research was funded by the National Institutes of Health. Dr. Lobo and Dr. Smith had no disclosures.

Women with a history of polycystic ovary syndrome (PCOS) are more likely to experience somatic and urogenital symptoms post menopause, but they were no more likely to experience severe hot flashes than were other women with similar characteristics, according to research presented Sept. 24 at the hybrid annual meeting of the North American Menopause Society.

PCOS and vasomotor symptoms are each risk factors for cardiovascular disease, so researchers wanted to find out whether they were linked to one another, which might indicate that they are markers for the same underlying mechanisms that increase heart disease risk. The lack of an association, however, raises questions about how much each of these conditions might independently increase cardiovascular risk.

“Should we take a little more time to truly risk-assess these patients not just with their ASCVD risk score, but take into account that they have PCOS and they’re going through menopause, and how severe their hot flashes are?” asked Angie S. Lobo, MD, an internal medicine specialist at Mayo Clinic in Rochester, Minn., when she discussed her findings in an interview.

The association between PCOS and urogenital symptoms was surprising, Dr. Lobo said, but she said she suspects the reason for the finding may be the self-reported nature of the study.

“If you ask the question, you get the answer,” Dr. Lobo said. ”Are we just not asking the right questions to our patients? And should we be doing this more often? This is an exciting finding because there’s so much room to improve the clinical care of our patients.”

The researchers analyzed data from 3,308 women, ages 45-60, in a cross-sectional study from the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The study occurred at Mayo Clinic locations between May 2015 and December 2019 in Rochester, Minn., in Scottsdale, Ariz., and in Jacksonville, Fla.

The women were an average 53 years old and were primarily White, educated, and postmenopausal. Among the 4.6% of women with a self-reported history of PCOS, 56% of them reported depression symptoms, compared to 42% of women without PCOS. Those with PCOS also had nearly twice the prevalence of obesity – 42% versus 22.5% among women without PCOS – and had a higher average overall score on the Menopause Rating Scale (17.7 vs. 14.7; P < .001).

Although women with PCOS initially had a greater burden of psychological symptoms on the same scale, that association disappeared after adjustment for menopause status, body mass index, depression, anxiety, and current use of hormone therapy. Even after adjustment, however, women with PCOS had higher average scores for somatic symptoms (6.7 vs. 5.6) and urogenital symptoms (5.2 vs. 4.3) than those of women without PCOS (P < .001).

Severe or very severe hot flashes were no more likely in women with a history of PCOS than in the other women in the study.

”The mechanisms underlying the correlation between PCOS and menopause symptoms in the psychological and urogenital symptom domains requires further study, although the well-known association between PCOS and mood disorders may explain the high psychological symptom burden in these women during the menopause transition,” the authors concluded.

Rachael B. Smith, DO, clinical assistant professor of ob.gyn. at the University of Arizona in Phoenix, said she was not surprised to see an association between PCOS and menopause symptoms overall, but she was surprised that PCOS did not correlate with severity of vasomotor symptoms. But Dr. Smith pointed out that the sample size of women with PCOS is fairly small (n = 151).

“Given that PCOS prevalence is about 6%-10%, I feel this association should be further studied to improve our counseling and treatment for this PCOS population,” Dr. Smith, who was not involved in the research, said in an interview. “The take-home message for physicians is improved patient-tailored counseling that takes into account patients’ prior medical history of PCOS.”

Although it will require more research to find out, Dr. Smith said she suspects that PCOS and vasomotor symptoms are additive risk factors for cardiovascular disease. She also noted that the study is limited by the homogeneity of the study population.

The research was funded by the National Institutes of Health. Dr. Lobo and Dr. Smith had no disclosures.

Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension. 

verbaska_studio/thinkstockphotos

The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.

“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization. 

“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”

However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.

“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”

According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”

“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.

He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.

The statement is aimed at both primary care providers and specialists.
 

Diet, physical activity help, but weight regain common

Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.

To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.  

The effect of intermittent fasting on blood pressure control is not clear, the statement noted.

It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.

“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
 

Other options to address obesity, hypertension

Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.

The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).

The long-term effects of antiobesity medications on blood pressure are mixed.

However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.

Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.

In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.

Unanswered questions, future research directions

In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.

Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”

They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:

• What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
• Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
• What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?

“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.

Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

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

Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension. 

verbaska_studio/thinkstockphotos

The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.

“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization. 

“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”

However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.

“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”

According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”

“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.

He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.

The statement is aimed at both primary care providers and specialists.
 

Diet, physical activity help, but weight regain common

Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.

To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.  

The effect of intermittent fasting on blood pressure control is not clear, the statement noted.

It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.

“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
 

Other options to address obesity, hypertension

Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.

The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).

The long-term effects of antiobesity medications on blood pressure are mixed.

However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.

Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.

In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.

Unanswered questions, future research directions

In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.

Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”

They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:

• What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
• Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
• What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?

“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.

Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

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

Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension. 

verbaska_studio/thinkstockphotos

The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.

“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization. 

“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”

However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.

“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”

According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”

“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.

He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.

The statement is aimed at both primary care providers and specialists.
 

Diet, physical activity help, but weight regain common

Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.

To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.  

The effect of intermittent fasting on blood pressure control is not clear, the statement noted.

It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.

“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
 

Other options to address obesity, hypertension

Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.

The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).

The long-term effects of antiobesity medications on blood pressure are mixed.

However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.

Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.

In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.

Unanswered questions, future research directions

In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.

Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”

They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:

• What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
• Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
• What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?

“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.

Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

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