Diabetes

Lots of things can disrupt your gut health over the years. A high-sugar diet, stress, antibiotics – all are linked to bad changes in the gut microbiome, the microbes that live in your intestinal tract. And this can raise the risk of diseases.

But what if you could erase all that damage, restoring your gut to a time when you were younger and healthier?

It could be possible, scientists say, by having people take a sample of their own stool when they are young to be put back into their colons when they are older.

While the science to back this up isn’t quite there yet, some researchers are saying we shouldn’t wait. They are calling on existing stool banks to let people start banking their stool now, so it’s there for them to use if the science becomes available.

But how would that work?

First, you’d go to a stool bank and provide a fresh sample of your poop, which would be screened for diseases, washed, processed, and deposited into a long-term storage facility.

Then, down the road, if you get a condition such as inflammatory bowel disease, heart disease, or type 2 diabetes – or if you have a procedure that wipes out your microbiome, like a course of antibiotics or chemotherapy – doctors could use your preserved stool to “re-colonize” your gut, restoring it to its earlier, healthier state, said Scott Weiss, MD, professor of medicine at Harvard Medical School, Boston, and a coauthor of a recent paper on the topic. They would do that using fecal microbiota transplantation, or FMT.

Timing is everything. You’d want a sample from when you’re healthy – say, between the ages of 18 and 35, or before a chronic condition is likely, said Dr. Weiss. But if you’re still healthy into your late 30s, 40s, or even 50s, providing a sample then could still benefit you later in life.

If we could pull off a banking system like this, it could have the potential to treat autoimmune disease, inflammatory bowel disease, diabetes, obesity, and heart disease – or even reverse the effects of aging. How can we make this happen?
 

Stool banks of today

While stool banks do exist today, the samples inside are destined not for the original donors but rather for sick patients hoping to treat an illness. Using FMT, doctors transfer the fecal material to the patient’s colon, restoring helpful gut microbiota.

Some research shows FMT may help treat inflammatory bowel diseases, such as Crohn’s or ulcerative colitis. Animal studies suggest it could help treat obesity, lengthen lifespan, and reverse some effects of aging, such as age-related decline in brain function. Other clinical trials are looking into its potential as a cancer treatment, said Dr. Weiss.

But outside the lab, FMT is mainly used for one purpose: to treat Clostridioides difficile infection. It works even better than antibiotics, research shows.

But first you need to find a healthy donor, and that’s harder than you might think.
 

Finding healthy stool samples

Banking our bodily substances is nothing new. Blood banks, for example, are common throughout the United States, and cord blood banking – preserving blood from a baby’s umbilical cord to aid possible future medical needs of the child – is becoming more popular. Sperm donors are highly sought after, and doctors regularly transplant kidneys and bone marrow to patients in need.

So why are we so particular about poop?

Part of the reason may be because feces (like blood, for that matter) can harbor disease – which is why it’s so important to find healthy stool donors. Problem is, this can be surprisingly hard to do.

To donate fecal matter, people must go through a rigorous screening process, said Majdi Osman, MD, chief medical officer for OpenBiome, a nonprofit microbiome research organization.

Until recently, OpenBiome operated a stool donation program, though it has since shifted its focus to research. Potential donors were screened for diseases and mental health conditions, pathogens, and antibiotic resistance. The pass rate was less than 3%.

“We take a very cautious approach because the association between diseases and the microbiome is still being understood,” Dr. Osman said.

FMT also carries risks – though so far, they seem mild. Side effects include mild diarrhea, nausea, belly pain, and fatigue. (The reason? Even the healthiest donor stool may not mix perfectly with your own.)

That’s where the idea of using your own stool comes in, said Yang-Yu Liu, PhD, a Harvard researcher who studies the microbiome and the lead author of the paper mentioned above. It’s not just more appealing but may also be a better “match” for your body.
 

Should you bank your stool?

While the researchers say we have reason to be optimistic about the future, it’s important to remember that many challenges remain. FMT is early in development, and there’s a lot about the microbiome we still don’t know.

There’s no guarantee, for example, that restoring a person’s microbiome to its formerly disease-free state will keep diseases at bay forever, said Dr. Weiss. If your genes raise your odds of having Crohn’s, for instance, it’s possible the disease could come back.

We also don’t know how long stool samples can be preserved, said Dr. Liu. Stool banks currently store fecal matter for 1 or 2 years, not decades. To protect the proteins and DNA structures for that long, samples would likely need to be stashed at the liquid nitrogen storage temperature of –196° C. (Currently, samples are stored at about –80° C.) Even then, testing would be needed to confirm if the fragile microorganisms in the stool can survive.

This raises another question: Who’s going to regulate all this?

The FDA regulates the use of FMT as a drug for the treatment of C. diff, but as Dr. Liu pointed out, many gastroenterologists consider the gut microbiota an organ. In that case, human fecal matter could be regulated the same way blood, bone, or even egg cells are.

Cord blood banking may be a helpful model, Dr. Liu said.

“We don’t have to start from scratch.”

Then there’s the question of cost. Cord blood banks could be a point of reference for that too, the researchers say. They charge about $1,500 to $2,820 for the first collection and processing, plus a yearly storage fee of $185 to $370.

Despite the unknowns, one thing is for sure: The interest in fecal banking is real – and growing. At least one microbiome firm, Cordlife Group Limited, based in Singapore, announced that it has started to allow people to bank their stool for future use.

“More people should talk about it and think about it,” said Dr. Liu.

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

Lots of things can disrupt your gut health over the years. A high-sugar diet, stress, antibiotics – all are linked to bad changes in the gut microbiome, the microbes that live in your intestinal tract. And this can raise the risk of diseases.

But what if you could erase all that damage, restoring your gut to a time when you were younger and healthier?

It could be possible, scientists say, by having people take a sample of their own stool when they are young to be put back into their colons when they are older.

While the science to back this up isn’t quite there yet, some researchers are saying we shouldn’t wait. They are calling on existing stool banks to let people start banking their stool now, so it’s there for them to use if the science becomes available.

But how would that work?

First, you’d go to a stool bank and provide a fresh sample of your poop, which would be screened for diseases, washed, processed, and deposited into a long-term storage facility.

Then, down the road, if you get a condition such as inflammatory bowel disease, heart disease, or type 2 diabetes – or if you have a procedure that wipes out your microbiome, like a course of antibiotics or chemotherapy – doctors could use your preserved stool to “re-colonize” your gut, restoring it to its earlier, healthier state, said Scott Weiss, MD, professor of medicine at Harvard Medical School, Boston, and a coauthor of a recent paper on the topic. They would do that using fecal microbiota transplantation, or FMT.

Timing is everything. You’d want a sample from when you’re healthy – say, between the ages of 18 and 35, or before a chronic condition is likely, said Dr. Weiss. But if you’re still healthy into your late 30s, 40s, or even 50s, providing a sample then could still benefit you later in life.

If we could pull off a banking system like this, it could have the potential to treat autoimmune disease, inflammatory bowel disease, diabetes, obesity, and heart disease – or even reverse the effects of aging. How can we make this happen?
 

Stool banks of today

While stool banks do exist today, the samples inside are destined not for the original donors but rather for sick patients hoping to treat an illness. Using FMT, doctors transfer the fecal material to the patient’s colon, restoring helpful gut microbiota.

Some research shows FMT may help treat inflammatory bowel diseases, such as Crohn’s or ulcerative colitis. Animal studies suggest it could help treat obesity, lengthen lifespan, and reverse some effects of aging, such as age-related decline in brain function. Other clinical trials are looking into its potential as a cancer treatment, said Dr. Weiss.

But outside the lab, FMT is mainly used for one purpose: to treat Clostridioides difficile infection. It works even better than antibiotics, research shows.

But first you need to find a healthy donor, and that’s harder than you might think.
 

Finding healthy stool samples

Banking our bodily substances is nothing new. Blood banks, for example, are common throughout the United States, and cord blood banking – preserving blood from a baby’s umbilical cord to aid possible future medical needs of the child – is becoming more popular. Sperm donors are highly sought after, and doctors regularly transplant kidneys and bone marrow to patients in need.

So why are we so particular about poop?

Part of the reason may be because feces (like blood, for that matter) can harbor disease – which is why it’s so important to find healthy stool donors. Problem is, this can be surprisingly hard to do.

To donate fecal matter, people must go through a rigorous screening process, said Majdi Osman, MD, chief medical officer for OpenBiome, a nonprofit microbiome research organization.

Until recently, OpenBiome operated a stool donation program, though it has since shifted its focus to research. Potential donors were screened for diseases and mental health conditions, pathogens, and antibiotic resistance. The pass rate was less than 3%.

“We take a very cautious approach because the association between diseases and the microbiome is still being understood,” Dr. Osman said.

FMT also carries risks – though so far, they seem mild. Side effects include mild diarrhea, nausea, belly pain, and fatigue. (The reason? Even the healthiest donor stool may not mix perfectly with your own.)

That’s where the idea of using your own stool comes in, said Yang-Yu Liu, PhD, a Harvard researcher who studies the microbiome and the lead author of the paper mentioned above. It’s not just more appealing but may also be a better “match” for your body.
 

Should you bank your stool?

While the researchers say we have reason to be optimistic about the future, it’s important to remember that many challenges remain. FMT is early in development, and there’s a lot about the microbiome we still don’t know.

There’s no guarantee, for example, that restoring a person’s microbiome to its formerly disease-free state will keep diseases at bay forever, said Dr. Weiss. If your genes raise your odds of having Crohn’s, for instance, it’s possible the disease could come back.

We also don’t know how long stool samples can be preserved, said Dr. Liu. Stool banks currently store fecal matter for 1 or 2 years, not decades. To protect the proteins and DNA structures for that long, samples would likely need to be stashed at the liquid nitrogen storage temperature of –196° C. (Currently, samples are stored at about –80° C.) Even then, testing would be needed to confirm if the fragile microorganisms in the stool can survive.

This raises another question: Who’s going to regulate all this?

The FDA regulates the use of FMT as a drug for the treatment of C. diff, but as Dr. Liu pointed out, many gastroenterologists consider the gut microbiota an organ. In that case, human fecal matter could be regulated the same way blood, bone, or even egg cells are.

Cord blood banking may be a helpful model, Dr. Liu said.

“We don’t have to start from scratch.”

Then there’s the question of cost. Cord blood banks could be a point of reference for that too, the researchers say. They charge about $1,500 to $2,820 for the first collection and processing, plus a yearly storage fee of $185 to $370.

Despite the unknowns, one thing is for sure: The interest in fecal banking is real – and growing. At least one microbiome firm, Cordlife Group Limited, based in Singapore, announced that it has started to allow people to bank their stool for future use.

“More people should talk about it and think about it,” said Dr. Liu.

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

Lots of things can disrupt your gut health over the years. A high-sugar diet, stress, antibiotics – all are linked to bad changes in the gut microbiome, the microbes that live in your intestinal tract. And this can raise the risk of diseases.

But what if you could erase all that damage, restoring your gut to a time when you were younger and healthier?

It could be possible, scientists say, by having people take a sample of their own stool when they are young to be put back into their colons when they are older.

While the science to back this up isn’t quite there yet, some researchers are saying we shouldn’t wait. They are calling on existing stool banks to let people start banking their stool now, so it’s there for them to use if the science becomes available.

But how would that work?

First, you’d go to a stool bank and provide a fresh sample of your poop, which would be screened for diseases, washed, processed, and deposited into a long-term storage facility.

Then, down the road, if you get a condition such as inflammatory bowel disease, heart disease, or type 2 diabetes – or if you have a procedure that wipes out your microbiome, like a course of antibiotics or chemotherapy – doctors could use your preserved stool to “re-colonize” your gut, restoring it to its earlier, healthier state, said Scott Weiss, MD, professor of medicine at Harvard Medical School, Boston, and a coauthor of a recent paper on the topic. They would do that using fecal microbiota transplantation, or FMT.

Timing is everything. You’d want a sample from when you’re healthy – say, between the ages of 18 and 35, or before a chronic condition is likely, said Dr. Weiss. But if you’re still healthy into your late 30s, 40s, or even 50s, providing a sample then could still benefit you later in life.

If we could pull off a banking system like this, it could have the potential to treat autoimmune disease, inflammatory bowel disease, diabetes, obesity, and heart disease – or even reverse the effects of aging. How can we make this happen?
 

Stool banks of today

While stool banks do exist today, the samples inside are destined not for the original donors but rather for sick patients hoping to treat an illness. Using FMT, doctors transfer the fecal material to the patient’s colon, restoring helpful gut microbiota.

Some research shows FMT may help treat inflammatory bowel diseases, such as Crohn’s or ulcerative colitis. Animal studies suggest it could help treat obesity, lengthen lifespan, and reverse some effects of aging, such as age-related decline in brain function. Other clinical trials are looking into its potential as a cancer treatment, said Dr. Weiss.

But outside the lab, FMT is mainly used for one purpose: to treat Clostridioides difficile infection. It works even better than antibiotics, research shows.

But first you need to find a healthy donor, and that’s harder than you might think.
 

Finding healthy stool samples

Banking our bodily substances is nothing new. Blood banks, for example, are common throughout the United States, and cord blood banking – preserving blood from a baby’s umbilical cord to aid possible future medical needs of the child – is becoming more popular. Sperm donors are highly sought after, and doctors regularly transplant kidneys and bone marrow to patients in need.

So why are we so particular about poop?

Part of the reason may be because feces (like blood, for that matter) can harbor disease – which is why it’s so important to find healthy stool donors. Problem is, this can be surprisingly hard to do.

To donate fecal matter, people must go through a rigorous screening process, said Majdi Osman, MD, chief medical officer for OpenBiome, a nonprofit microbiome research organization.

Until recently, OpenBiome operated a stool donation program, though it has since shifted its focus to research. Potential donors were screened for diseases and mental health conditions, pathogens, and antibiotic resistance. The pass rate was less than 3%.

“We take a very cautious approach because the association between diseases and the microbiome is still being understood,” Dr. Osman said.

FMT also carries risks – though so far, they seem mild. Side effects include mild diarrhea, nausea, belly pain, and fatigue. (The reason? Even the healthiest donor stool may not mix perfectly with your own.)

That’s where the idea of using your own stool comes in, said Yang-Yu Liu, PhD, a Harvard researcher who studies the microbiome and the lead author of the paper mentioned above. It’s not just more appealing but may also be a better “match” for your body.
 

Should you bank your stool?

While the researchers say we have reason to be optimistic about the future, it’s important to remember that many challenges remain. FMT is early in development, and there’s a lot about the microbiome we still don’t know.

There’s no guarantee, for example, that restoring a person’s microbiome to its formerly disease-free state will keep diseases at bay forever, said Dr. Weiss. If your genes raise your odds of having Crohn’s, for instance, it’s possible the disease could come back.

We also don’t know how long stool samples can be preserved, said Dr. Liu. Stool banks currently store fecal matter for 1 or 2 years, not decades. To protect the proteins and DNA structures for that long, samples would likely need to be stashed at the liquid nitrogen storage temperature of –196° C. (Currently, samples are stored at about –80° C.) Even then, testing would be needed to confirm if the fragile microorganisms in the stool can survive.

This raises another question: Who’s going to regulate all this?

The FDA regulates the use of FMT as a drug for the treatment of C. diff, but as Dr. Liu pointed out, many gastroenterologists consider the gut microbiota an organ. In that case, human fecal matter could be regulated the same way blood, bone, or even egg cells are.

Cord blood banking may be a helpful model, Dr. Liu said.

“We don’t have to start from scratch.”

Then there’s the question of cost. Cord blood banks could be a point of reference for that too, the researchers say. They charge about $1,500 to $2,820 for the first collection and processing, plus a yearly storage fee of $185 to $370.

Despite the unknowns, one thing is for sure: The interest in fecal banking is real – and growing. At least one microbiome firm, Cordlife Group Limited, based in Singapore, announced that it has started to allow people to bank their stool for future use.

“More people should talk about it and think about it,” said Dr. Liu.

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

Obesity in women of reproductive age has emerged as one of the main risk factors associated with neonatal complications and long-term neuropsychiatric consequences in offspring, including attention-deficit/hyperactivity disorder.

Research has also linked pregestational diabetes and gestational diabetes mellitus (GDM) to an increased risk for ADHD in offspring. Now, an observational study of 1,036 singleton births at one hospital between 1998 and 2008 suggests that in the presence of GDM, maternal obesity combined with excessive weight gain during pregnancy may be jointly associated with increased risk of offspring ADHD. The median follow-up was 17.7 years.

Maternal obesity was independently associated with ADHD (adjusted hazard ratio, 1.66; 95% confidence interval: 1.07-2.60), but excessive weight gain during pregnancy and maternal overweight were not, reported Verónica Perea, MD, PhD, of the Hospital Universitari Mútua de Terrassa, Barcelona, and colleagues in the Journal of Clinical Endocrinology & Metabolism.

However, in women with pregestation obesity who gained more weight than recommended by the National Academy of Medicine (NAM), the risk of offspring ADHD was higher, compared with women of normal weight whose pregnancy weight stayed within NAM guidelines (adjusted hazard ratio, 2.13; 95% confidence interval: 1.14-4.01).

“The results of this study suggest that the negative repercussions of excessive weight gain on children within the setting of a high-risk population with GDM and obesity were not only observed during the prenatal period but also years later with a development of ADHD,” the researchers wrote.

The study also showed that when maternal weight gain did not exceed NAM guidelines, maternal obesity was no longer independently associated with ADHD in offspring (aHR, 1.36; 95% CI: 0.78-2.36). This finding conflicts with earlier studies focusing primarily on the role of pregestational maternal weight, the researchers said. A 2018 nationwide Finnish cohort study in newborns showed an increased long-term risk of ADHD in those born to women with GDM, compared with the nondiabetic population. This long-term risk of ADHD increased in the presence of pregestational obesity (HR, 1.64).

Similarly, evidence from systematic reviews and meta-analyses has demonstrated that antenatal lifestyle interventions to prevent excessive weight gain during pregnancy were associated with a reduction in adverse pregnancy outcomes. However, evidence on offspring mental health was lacking, especially in high-risk pregnancies with gestational diabetes, the study authors said.

Although causal inferences can’t be drawn from the current observational study, “it seems that the higher risk [of ADHD] observed would be explained by the role of gestational weight gain during the antenatal period,” Dr. Perea said in an interview. Importantly, the study highlights a window of opportunity for promoting healthy weight gain during pregnancy, Dr. Perea said. ”This should be a priority in the current management of gestation.”

Fatima Cody Stanford, MD, MPH, an associate professor of medicine and pediatrics at Harvard Medical School, Boston, agreed. “I think one of the key issues is that there’s very little attention paid to how weight gain is regulated during pregnancy,” she said in an interview. On many other points, however, Dr. Stanford, who is a specialist in obesity medicine at Massachusetts General Hospital Weight Center, did not agree.

The association between ADHD and obesity has already been well established by a 2019 meta-analysis and systematic review of studies over the last 10 years, she emphasized. “These studies were able to show a much stronger association between maternal obesity and ADHD in offspring because they were powered to detect differences.”

The current study does not say “anything new or novel,” Dr. Stanford added. “Maternal obesity and the association with an increased risk of ADHD in offspring is the main issue. I don’t think there was any appreciable increase when weight gain during pregnancy was factored in. It’s mild at best.”

Eran Bornstein, MD, vice-chair of obstetrics and gynecology at Lenox Hill Hospital, New York, expressed a similar point of view. Although the study findings “add to the current literature,” they should be interpreted “cautiously,” Dr. Bornstein said in an interview.

The size of the effect on ADHD risk attributable to maternal weight gain during pregnancy “was not clear,” he said. “Cohort studies of this sort are excellent for finding associations which help us generate the hypothesis, but this doesn’t demonstrate a cause and effect or a magnitude for this effect.”

Physicians should follow cumulative data suggesting that maternal obesity is associated with a number of pregnancy complications and neonatal outcomes in women with and without diabetes, Dr. Bornstein suggested. “Optimizing maternal weight prior to pregnancy and adhering to recommendations regarding weight gain has the potential to improve some of these outcomes.”

Treating obesity prior to conception mitigates GDM risk, agreed Dr. Stanford. “The issue,” she explained, “is that all of the drugs approved for the treatment of obesity are contraindicated in pregnancy and lifestyle modification fails in 96% of cases, even when there is no pregnancy.” Drugs such as metformin are being used off-label to treat obesity and to safely manage gestational weight gain, she said. “Those of us who practice obesity medicine know that metformin can be safely used throughout pregnancy with no harm to the fetus.”

This study was partially funded by Fundació Docència i Recerca MútuaTerrassa. Dr. Perea and study coauthors reporting have no conflicts of interest. Dr. Stanford disclosed relationships with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Gelesis, Pfizer, Currax, and Rhythm. Dr. Bornstein reported having no conflicts of interest.

This story was updated on 11/7/2022. 

[email protected]

Obesity in women of reproductive age has emerged as one of the main risk factors associated with neonatal complications and long-term neuropsychiatric consequences in offspring, including attention-deficit/hyperactivity disorder.

Research has also linked pregestational diabetes and gestational diabetes mellitus (GDM) to an increased risk for ADHD in offspring. Now, an observational study of 1,036 singleton births at one hospital between 1998 and 2008 suggests that in the presence of GDM, maternal obesity combined with excessive weight gain during pregnancy may be jointly associated with increased risk of offspring ADHD. The median follow-up was 17.7 years.

Maternal obesity was independently associated with ADHD (adjusted hazard ratio, 1.66; 95% confidence interval: 1.07-2.60), but excessive weight gain during pregnancy and maternal overweight were not, reported Verónica Perea, MD, PhD, of the Hospital Universitari Mútua de Terrassa, Barcelona, and colleagues in the Journal of Clinical Endocrinology & Metabolism.

However, in women with pregestation obesity who gained more weight than recommended by the National Academy of Medicine (NAM), the risk of offspring ADHD was higher, compared with women of normal weight whose pregnancy weight stayed within NAM guidelines (adjusted hazard ratio, 2.13; 95% confidence interval: 1.14-4.01).

“The results of this study suggest that the negative repercussions of excessive weight gain on children within the setting of a high-risk population with GDM and obesity were not only observed during the prenatal period but also years later with a development of ADHD,” the researchers wrote.

The study also showed that when maternal weight gain did not exceed NAM guidelines, maternal obesity was no longer independently associated with ADHD in offspring (aHR, 1.36; 95% CI: 0.78-2.36). This finding conflicts with earlier studies focusing primarily on the role of pregestational maternal weight, the researchers said. A 2018 nationwide Finnish cohort study in newborns showed an increased long-term risk of ADHD in those born to women with GDM, compared with the nondiabetic population. This long-term risk of ADHD increased in the presence of pregestational obesity (HR, 1.64).

Similarly, evidence from systematic reviews and meta-analyses has demonstrated that antenatal lifestyle interventions to prevent excessive weight gain during pregnancy were associated with a reduction in adverse pregnancy outcomes. However, evidence on offspring mental health was lacking, especially in high-risk pregnancies with gestational diabetes, the study authors said.

Although causal inferences can’t be drawn from the current observational study, “it seems that the higher risk [of ADHD] observed would be explained by the role of gestational weight gain during the antenatal period,” Dr. Perea said in an interview. Importantly, the study highlights a window of opportunity for promoting healthy weight gain during pregnancy, Dr. Perea said. ”This should be a priority in the current management of gestation.”

Fatima Cody Stanford, MD, MPH, an associate professor of medicine and pediatrics at Harvard Medical School, Boston, agreed. “I think one of the key issues is that there’s very little attention paid to how weight gain is regulated during pregnancy,” she said in an interview. On many other points, however, Dr. Stanford, who is a specialist in obesity medicine at Massachusetts General Hospital Weight Center, did not agree.

The association between ADHD and obesity has already been well established by a 2019 meta-analysis and systematic review of studies over the last 10 years, she emphasized. “These studies were able to show a much stronger association between maternal obesity and ADHD in offspring because they were powered to detect differences.”

The current study does not say “anything new or novel,” Dr. Stanford added. “Maternal obesity and the association with an increased risk of ADHD in offspring is the main issue. I don’t think there was any appreciable increase when weight gain during pregnancy was factored in. It’s mild at best.”

Eran Bornstein, MD, vice-chair of obstetrics and gynecology at Lenox Hill Hospital, New York, expressed a similar point of view. Although the study findings “add to the current literature,” they should be interpreted “cautiously,” Dr. Bornstein said in an interview.

The size of the effect on ADHD risk attributable to maternal weight gain during pregnancy “was not clear,” he said. “Cohort studies of this sort are excellent for finding associations which help us generate the hypothesis, but this doesn’t demonstrate a cause and effect or a magnitude for this effect.”

Physicians should follow cumulative data suggesting that maternal obesity is associated with a number of pregnancy complications and neonatal outcomes in women with and without diabetes, Dr. Bornstein suggested. “Optimizing maternal weight prior to pregnancy and adhering to recommendations regarding weight gain has the potential to improve some of these outcomes.”

Treating obesity prior to conception mitigates GDM risk, agreed Dr. Stanford. “The issue,” she explained, “is that all of the drugs approved for the treatment of obesity are contraindicated in pregnancy and lifestyle modification fails in 96% of cases, even when there is no pregnancy.” Drugs such as metformin are being used off-label to treat obesity and to safely manage gestational weight gain, she said. “Those of us who practice obesity medicine know that metformin can be safely used throughout pregnancy with no harm to the fetus.”

This study was partially funded by Fundació Docència i Recerca MútuaTerrassa. Dr. Perea and study coauthors reporting have no conflicts of interest. Dr. Stanford disclosed relationships with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Gelesis, Pfizer, Currax, and Rhythm. Dr. Bornstein reported having no conflicts of interest.

This story was updated on 11/7/2022. 

[email protected]

Obesity in women of reproductive age has emerged as one of the main risk factors associated with neonatal complications and long-term neuropsychiatric consequences in offspring, including attention-deficit/hyperactivity disorder.

Research has also linked pregestational diabetes and gestational diabetes mellitus (GDM) to an increased risk for ADHD in offspring. Now, an observational study of 1,036 singleton births at one hospital between 1998 and 2008 suggests that in the presence of GDM, maternal obesity combined with excessive weight gain during pregnancy may be jointly associated with increased risk of offspring ADHD. The median follow-up was 17.7 years.

Maternal obesity was independently associated with ADHD (adjusted hazard ratio, 1.66; 95% confidence interval: 1.07-2.60), but excessive weight gain during pregnancy and maternal overweight were not, reported Verónica Perea, MD, PhD, of the Hospital Universitari Mútua de Terrassa, Barcelona, and colleagues in the Journal of Clinical Endocrinology & Metabolism.

However, in women with pregestation obesity who gained more weight than recommended by the National Academy of Medicine (NAM), the risk of offspring ADHD was higher, compared with women of normal weight whose pregnancy weight stayed within NAM guidelines (adjusted hazard ratio, 2.13; 95% confidence interval: 1.14-4.01).

“The results of this study suggest that the negative repercussions of excessive weight gain on children within the setting of a high-risk population with GDM and obesity were not only observed during the prenatal period but also years later with a development of ADHD,” the researchers wrote.

The study also showed that when maternal weight gain did not exceed NAM guidelines, maternal obesity was no longer independently associated with ADHD in offspring (aHR, 1.36; 95% CI: 0.78-2.36). This finding conflicts with earlier studies focusing primarily on the role of pregestational maternal weight, the researchers said. A 2018 nationwide Finnish cohort study in newborns showed an increased long-term risk of ADHD in those born to women with GDM, compared with the nondiabetic population. This long-term risk of ADHD increased in the presence of pregestational obesity (HR, 1.64).

Similarly, evidence from systematic reviews and meta-analyses has demonstrated that antenatal lifestyle interventions to prevent excessive weight gain during pregnancy were associated with a reduction in adverse pregnancy outcomes. However, evidence on offspring mental health was lacking, especially in high-risk pregnancies with gestational diabetes, the study authors said.

Although causal inferences can’t be drawn from the current observational study, “it seems that the higher risk [of ADHD] observed would be explained by the role of gestational weight gain during the antenatal period,” Dr. Perea said in an interview. Importantly, the study highlights a window of opportunity for promoting healthy weight gain during pregnancy, Dr. Perea said. ”This should be a priority in the current management of gestation.”

Fatima Cody Stanford, MD, MPH, an associate professor of medicine and pediatrics at Harvard Medical School, Boston, agreed. “I think one of the key issues is that there’s very little attention paid to how weight gain is regulated during pregnancy,” she said in an interview. On many other points, however, Dr. Stanford, who is a specialist in obesity medicine at Massachusetts General Hospital Weight Center, did not agree.

The association between ADHD and obesity has already been well established by a 2019 meta-analysis and systematic review of studies over the last 10 years, she emphasized. “These studies were able to show a much stronger association between maternal obesity and ADHD in offspring because they were powered to detect differences.”

The current study does not say “anything new or novel,” Dr. Stanford added. “Maternal obesity and the association with an increased risk of ADHD in offspring is the main issue. I don’t think there was any appreciable increase when weight gain during pregnancy was factored in. It’s mild at best.”

Eran Bornstein, MD, vice-chair of obstetrics and gynecology at Lenox Hill Hospital, New York, expressed a similar point of view. Although the study findings “add to the current literature,” they should be interpreted “cautiously,” Dr. Bornstein said in an interview.

The size of the effect on ADHD risk attributable to maternal weight gain during pregnancy “was not clear,” he said. “Cohort studies of this sort are excellent for finding associations which help us generate the hypothesis, but this doesn’t demonstrate a cause and effect or a magnitude for this effect.”

Physicians should follow cumulative data suggesting that maternal obesity is associated with a number of pregnancy complications and neonatal outcomes in women with and without diabetes, Dr. Bornstein suggested. “Optimizing maternal weight prior to pregnancy and adhering to recommendations regarding weight gain has the potential to improve some of these outcomes.”

Treating obesity prior to conception mitigates GDM risk, agreed Dr. Stanford. “The issue,” she explained, “is that all of the drugs approved for the treatment of obesity are contraindicated in pregnancy and lifestyle modification fails in 96% of cases, even when there is no pregnancy.” Drugs such as metformin are being used off-label to treat obesity and to safely manage gestational weight gain, she said. “Those of us who practice obesity medicine know that metformin can be safely used throughout pregnancy with no harm to the fetus.”

This study was partially funded by Fundació Docència i Recerca MútuaTerrassa. Dr. Perea and study coauthors reporting have no conflicts of interest. Dr. Stanford disclosed relationships with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Gelesis, Pfizer, Currax, and Rhythm. Dr. Bornstein reported having no conflicts of interest.

This story was updated on 11/7/2022. 

[email protected]

THE CASE

A 57-year-old man with type 2 diabetes, hyperlipidemia, and obesity presented to the emergency department (ED) for bilateral foot blisters, both of which appeared 1 day prior to evaluation. The patient’s history also included right-side Charcot foot diagnosed 4 years earlier and right foot osteomyelitis diagnosed 2 years prior. He had ongoing neuropathy in both feet but denied any significant pain.

The patient wore orthotics daily and he’d had new orthotics made 6 months prior; however, a recent COVID-19 diagnosis and prolonged hospital stay resulted in a 30-pound weight loss and decreased swelling in his ankles. He acquired new shoes 2 weeks prior to ED presentation.

Physical examination revealed large blisters along the medial aspect of the patient’s feet, with both hemorrhagic and serous fluid-filled bullae. The lesions were flaccid but intact, without drainage or surrounding erythema, warmth, or tenderness. The blister on the left foot measured 8 x 5 cm and extended from the great toe to mid-arch (FIGURE), while the one on the right foot measured 8 x 3 cm and extended from the great toe to the base of the proximal arch. Sensation was decreased in the bilateral first and second digits but unchanged from prior documented exams. Bilateral dorsalis pedis pulses were normal.

Work-up included imaging and lab work. The patient’s complete blood count was normal, as were his erythrocyte sedimentation rate and C-reactive protein level. Radiographs of the right foot were normal, but those of the left foot were concerning, although inconclusive, for osteomyelitis. Further evaluation with magnetic resonance imaging of his left foot revealed a deformity of the first digit with some subchondral signal change that was thought to be posttraumatic or degenerative, but unlikely osteomyelitis.

THE DIAGNOSIS

Podiatry was consulted for blister management. Based on atraumatic history, rapid appearance, location of blisters, unremarkable lab work and imaging, and concurrent diabetes, the patient received a diagnosis of bilateral bullous diabeticorum (BD).

DISCUSSION

Roughly one-third of patients with diabetes will experience some cutaneous adverse effect because of the disease.¹ Common iterations include acanthosis nigricans, rash, or even infection.² BD is a rare bullous skin lesion that occurs in patients with diabetes; it has a reported annual incidence of 0.16% and may be underdiagnosed.¹

Although A1C values do not correlate with blister formation, patients with hypoglycemic episodes and highly varying blood glucose values seem to have higher rates of bullous diabeticorum occurrence.

Cases of BD have been described both in patients with longstanding diabetes and in those newly diagnosed, although the former group is more often affected.¹ BD is reported more frequently in males than females, at a ratio of 2:1.^1,3 Patients ages 17 to 80 years (average age, 55 years) have received a diagnosis of BD.¹ Most affected patients will have a concomitant peripheral neuropathy and sometimes nephropathy or retinopathy.¹

Continue to: The etiology of BD...

The etiology of BD is unclear but appears to be multifactorial. Hypotheses suggest that there’s a link to neuropathy/nephropathy, excessive exposure to ultraviolet light, or a vascular cause secondary to hyaline deposition in the capillary walls.^4,5

What you’ll see at presentation

The typical manifestation of BD is the rapid appearance of tense blisters, which may occur overnight or even within hours.¹ They are usually painless; common locations include the feet, distal legs, hands, and forearms.^1,5 The bullae can be serous or hemorrhagic.¹

Most notable in the patient’s history will be a lack of trauma or injury to the area.¹ Although A1C values do not correlate with blister formation, patients with hypoglycemic episodes and highly varying blood glucose values seem to have higher rates of occurrence.¹

Other sources of blistering must be ruled out

The diagnosis of BD is clinical and based on history, exam, and exclusion of other bullous diagnoses.⁶ A key clue in the history is the spontaneous and rapid onset without associated trauma in a patient with diabetes.⁶ Direct immunofluorescence, although nonspecific, can be helpful to rule out other disorders (such as porphyria cutanea tarda and bullous pemphigoid) if the history and exam are inconclusive. Direct and indirect immunofluorescence is typically negative in BD.^4,6

The differential diagnosis includes other conditions that involve bullae—such as frictional bullae, bullous pemphigoid, and bullous systemic lupus erythematosus—as well as porphyria, erythema multiforme, insect bites, or even fixed drug eruption.^2,7

Continue to: Porphyria

Porphyria tends to develop on the hands, whereas BD most commonly occurs on the feet.⁵

Erythema multiforme typically includes inflammatory skin changes.⁵

Trauma or fixed drug eruption as a cause of blistering lesions would be revealed during history taking.

Considerations for treatment and follow-up

Without treatment, blisters often self-resolve in 2 to 6 weeks, but there is high likelihood of recurrence.^6,8 There is no consensus on treatment, although a typical course of action is to deroof the blister and examine the area to rule out infection.⁶ The wound is then covered with wet-to-dry gauze that is changed regularly. If there is suspicion for or signs of underlying infection, such as an ulcer or skin necrosis, antibiotics should be included in the treatment plan.⁷

Additional considerations. Patients will often need therapeutic footwear if the blisters are located on the feet. Given the higher prevalence of microvascular complications in patients with diabetes who develop BD, routine ophthalmologic examination and renal function testing to monitor for microalbuminuria are recommended.⁵

Our patient underwent bedside incision and drainage and was discharged home with appropriate wound care and follow-up. 

THE TAKEAWAY

BD cases may be underdiagnosed in clinical practice, perhaps due to patients not seeking help for a seemingly nonthreatening condition or lack of clinician recognition that bullae are related to a patient’s diabetes status. Prompt recognition and proper wound care are important to prevent poor outcomes, such as ulceration or necrosis.

CORRESPONDENCE
Kathleen S. Kinderwater, MD, 101 Heart Drive, Greenville, NC 27834; [email protected]

THE CASE

A 57-year-old man with type 2 diabetes, hyperlipidemia, and obesity presented to the emergency department (ED) for bilateral foot blisters, both of which appeared 1 day prior to evaluation. The patient’s history also included right-side Charcot foot diagnosed 4 years earlier and right foot osteomyelitis diagnosed 2 years prior. He had ongoing neuropathy in both feet but denied any significant pain.

The patient wore orthotics daily and he’d had new orthotics made 6 months prior; however, a recent COVID-19 diagnosis and prolonged hospital stay resulted in a 30-pound weight loss and decreased swelling in his ankles. He acquired new shoes 2 weeks prior to ED presentation.

Physical examination revealed large blisters along the medial aspect of the patient’s feet, with both hemorrhagic and serous fluid-filled bullae. The lesions were flaccid but intact, without drainage or surrounding erythema, warmth, or tenderness. The blister on the left foot measured 8 x 5 cm and extended from the great toe to mid-arch (FIGURE), while the one on the right foot measured 8 x 3 cm and extended from the great toe to the base of the proximal arch. Sensation was decreased in the bilateral first and second digits but unchanged from prior documented exams. Bilateral dorsalis pedis pulses were normal.

Work-up included imaging and lab work. The patient’s complete blood count was normal, as were his erythrocyte sedimentation rate and C-reactive protein level. Radiographs of the right foot were normal, but those of the left foot were concerning, although inconclusive, for osteomyelitis. Further evaluation with magnetic resonance imaging of his left foot revealed a deformity of the first digit with some subchondral signal change that was thought to be posttraumatic or degenerative, but unlikely osteomyelitis.

THE DIAGNOSIS

Podiatry was consulted for blister management. Based on atraumatic history, rapid appearance, location of blisters, unremarkable lab work and imaging, and concurrent diabetes, the patient received a diagnosis of bilateral bullous diabeticorum (BD).

DISCUSSION

Roughly one-third of patients with diabetes will experience some cutaneous adverse effect because of the disease.¹ Common iterations include acanthosis nigricans, rash, or even infection.² BD is a rare bullous skin lesion that occurs in patients with diabetes; it has a reported annual incidence of 0.16% and may be underdiagnosed.¹

Although A1C values do not correlate with blister formation, patients with hypoglycemic episodes and highly varying blood glucose values seem to have higher rates of bullous diabeticorum occurrence.

Cases of BD have been described both in patients with longstanding diabetes and in those newly diagnosed, although the former group is more often affected.¹ BD is reported more frequently in males than females, at a ratio of 2:1.^1,3 Patients ages 17 to 80 years (average age, 55 years) have received a diagnosis of BD.¹ Most affected patients will have a concomitant peripheral neuropathy and sometimes nephropathy or retinopathy.¹

Continue to: The etiology of BD...

The etiology of BD is unclear but appears to be multifactorial. Hypotheses suggest that there’s a link to neuropathy/nephropathy, excessive exposure to ultraviolet light, or a vascular cause secondary to hyaline deposition in the capillary walls.^4,5

What you’ll see at presentation

The typical manifestation of BD is the rapid appearance of tense blisters, which may occur overnight or even within hours.¹ They are usually painless; common locations include the feet, distal legs, hands, and forearms.^1,5 The bullae can be serous or hemorrhagic.¹

Most notable in the patient’s history will be a lack of trauma or injury to the area.¹ Although A1C values do not correlate with blister formation, patients with hypoglycemic episodes and highly varying blood glucose values seem to have higher rates of occurrence.¹

Other sources of blistering must be ruled out

The diagnosis of BD is clinical and based on history, exam, and exclusion of other bullous diagnoses.⁶ A key clue in the history is the spontaneous and rapid onset without associated trauma in a patient with diabetes.⁶ Direct immunofluorescence, although nonspecific, can be helpful to rule out other disorders (such as porphyria cutanea tarda and bullous pemphigoid) if the history and exam are inconclusive. Direct and indirect immunofluorescence is typically negative in BD.^4,6

The differential diagnosis includes other conditions that involve bullae—such as frictional bullae, bullous pemphigoid, and bullous systemic lupus erythematosus—as well as porphyria, erythema multiforme, insect bites, or even fixed drug eruption.^2,7

Continue to: Porphyria

Porphyria tends to develop on the hands, whereas BD most commonly occurs on the feet.⁵

Erythema multiforme typically includes inflammatory skin changes.⁵

Trauma or fixed drug eruption as a cause of blistering lesions would be revealed during history taking.

Considerations for treatment and follow-up

Without treatment, blisters often self-resolve in 2 to 6 weeks, but there is high likelihood of recurrence.^6,8 There is no consensus on treatment, although a typical course of action is to deroof the blister and examine the area to rule out infection.⁶ The wound is then covered with wet-to-dry gauze that is changed regularly. If there is suspicion for or signs of underlying infection, such as an ulcer or skin necrosis, antibiotics should be included in the treatment plan.⁷

Additional considerations. Patients will often need therapeutic footwear if the blisters are located on the feet. Given the higher prevalence of microvascular complications in patients with diabetes who develop BD, routine ophthalmologic examination and renal function testing to monitor for microalbuminuria are recommended.⁵

Our patient underwent bedside incision and drainage and was discharged home with appropriate wound care and follow-up. 

THE TAKEAWAY

BD cases may be underdiagnosed in clinical practice, perhaps due to patients not seeking help for a seemingly nonthreatening condition or lack of clinician recognition that bullae are related to a patient’s diabetes status. Prompt recognition and proper wound care are important to prevent poor outcomes, such as ulceration or necrosis.

CORRESPONDENCE
Kathleen S. Kinderwater, MD, 101 Heart Drive, Greenville, NC 27834; [email protected]

THE CASE

A 57-year-old man with type 2 diabetes, hyperlipidemia, and obesity presented to the emergency department (ED) for bilateral foot blisters, both of which appeared 1 day prior to evaluation. The patient’s history also included right-side Charcot foot diagnosed 4 years earlier and right foot osteomyelitis diagnosed 2 years prior. He had ongoing neuropathy in both feet but denied any significant pain.

The patient wore orthotics daily and he’d had new orthotics made 6 months prior; however, a recent COVID-19 diagnosis and prolonged hospital stay resulted in a 30-pound weight loss and decreased swelling in his ankles. He acquired new shoes 2 weeks prior to ED presentation.

Physical examination revealed large blisters along the medial aspect of the patient’s feet, with both hemorrhagic and serous fluid-filled bullae. The lesions were flaccid but intact, without drainage or surrounding erythema, warmth, or tenderness. The blister on the left foot measured 8 x 5 cm and extended from the great toe to mid-arch (FIGURE), while the one on the right foot measured 8 x 3 cm and extended from the great toe to the base of the proximal arch. Sensation was decreased in the bilateral first and second digits but unchanged from prior documented exams. Bilateral dorsalis pedis pulses were normal.

Work-up included imaging and lab work. The patient’s complete blood count was normal, as were his erythrocyte sedimentation rate and C-reactive protein level. Radiographs of the right foot were normal, but those of the left foot were concerning, although inconclusive, for osteomyelitis. Further evaluation with magnetic resonance imaging of his left foot revealed a deformity of the first digit with some subchondral signal change that was thought to be posttraumatic or degenerative, but unlikely osteomyelitis.

THE DIAGNOSIS

Podiatry was consulted for blister management. Based on atraumatic history, rapid appearance, location of blisters, unremarkable lab work and imaging, and concurrent diabetes, the patient received a diagnosis of bilateral bullous diabeticorum (BD).

DISCUSSION

Roughly one-third of patients with diabetes will experience some cutaneous adverse effect because of the disease.¹ Common iterations include acanthosis nigricans, rash, or even infection.² BD is a rare bullous skin lesion that occurs in patients with diabetes; it has a reported annual incidence of 0.16% and may be underdiagnosed.¹

Although A1C values do not correlate with blister formation, patients with hypoglycemic episodes and highly varying blood glucose values seem to have higher rates of bullous diabeticorum occurrence.

Cases of BD have been described both in patients with longstanding diabetes and in those newly diagnosed, although the former group is more often affected.¹ BD is reported more frequently in males than females, at a ratio of 2:1.^1,3 Patients ages 17 to 80 years (average age, 55 years) have received a diagnosis of BD.¹ Most affected patients will have a concomitant peripheral neuropathy and sometimes nephropathy or retinopathy.¹

Continue to: The etiology of BD...

The etiology of BD is unclear but appears to be multifactorial. Hypotheses suggest that there’s a link to neuropathy/nephropathy, excessive exposure to ultraviolet light, or a vascular cause secondary to hyaline deposition in the capillary walls.^4,5

What you’ll see at presentation

The typical manifestation of BD is the rapid appearance of tense blisters, which may occur overnight or even within hours.¹ They are usually painless; common locations include the feet, distal legs, hands, and forearms.^1,5 The bullae can be serous or hemorrhagic.¹

Most notable in the patient’s history will be a lack of trauma or injury to the area.¹ Although A1C values do not correlate with blister formation, patients with hypoglycemic episodes and highly varying blood glucose values seem to have higher rates of occurrence.¹

Other sources of blistering must be ruled out

The diagnosis of BD is clinical and based on history, exam, and exclusion of other bullous diagnoses.⁶ A key clue in the history is the spontaneous and rapid onset without associated trauma in a patient with diabetes.⁶ Direct immunofluorescence, although nonspecific, can be helpful to rule out other disorders (such as porphyria cutanea tarda and bullous pemphigoid) if the history and exam are inconclusive. Direct and indirect immunofluorescence is typically negative in BD.^4,6

The differential diagnosis includes other conditions that involve bullae—such as frictional bullae, bullous pemphigoid, and bullous systemic lupus erythematosus—as well as porphyria, erythema multiforme, insect bites, or even fixed drug eruption.^2,7

Continue to: Porphyria

Porphyria tends to develop on the hands, whereas BD most commonly occurs on the feet.⁵

Erythema multiforme typically includes inflammatory skin changes.⁵

Trauma or fixed drug eruption as a cause of blistering lesions would be revealed during history taking.

Considerations for treatment and follow-up

Without treatment, blisters often self-resolve in 2 to 6 weeks, but there is high likelihood of recurrence.^6,8 There is no consensus on treatment, although a typical course of action is to deroof the blister and examine the area to rule out infection.⁶ The wound is then covered with wet-to-dry gauze that is changed regularly. If there is suspicion for or signs of underlying infection, such as an ulcer or skin necrosis, antibiotics should be included in the treatment plan.⁷

Additional considerations. Patients will often need therapeutic footwear if the blisters are located on the feet. Given the higher prevalence of microvascular complications in patients with diabetes who develop BD, routine ophthalmologic examination and renal function testing to monitor for microalbuminuria are recommended.⁵

Our patient underwent bedside incision and drainage and was discharged home with appropriate wound care and follow-up. 

THE TAKEAWAY

BD cases may be underdiagnosed in clinical practice, perhaps due to patients not seeking help for a seemingly nonthreatening condition or lack of clinician recognition that bullae are related to a patient’s diabetes status. Prompt recognition and proper wound care are important to prevent poor outcomes, such as ulceration or necrosis.

CORRESPONDENCE
Kathleen S. Kinderwater, MD, 101 Heart Drive, Greenville, NC 27834; [email protected]

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

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

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

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

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

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

Imagine that instead of a patient visiting their doctor for blood tests, they could rely on a noninvasive at-home test to predict their risk of diabetes, a disease that affects nearly 15% of U.S. adults (23% of whom are undiagnosed), according to the U.S. Centers for Disease Control and Prevention.

This technology could become a reality thanks to a research team that developed a machine learning algorithm to predict whether people had type 2 diabetes, prediabetes, or no diabetes. In an article published in BMJ Innovations, the researchers describe how their algorithm sorted people into these three categories with 97% accuracy on the basis of measurements of the heart’s electrical activity, determined from an electrocardiogram.

To develop and train their machine learning model – a type of artificial intelligence (AI) that keeps getting smarter over time – researchers used ECG measurements from 1,262 people in Central India. The study participants were part of the Sindhi population, an ethnic group that has been shown in past studies to be at elevated risk for type 2 diabetes.

Why ECG data? Because “cardiovascular abnormalities and diabetes, they go hand in hand,” says study author Manju Mamtani, MD, general manager of M&H Research, San Antonio, and treasurer of the Lata Medical Research Foundation. Subtle cardiovascular changes can occur even early in the development of diabetes.

“ECG has the power to detect these fluctuations, at least in theory, but those fluctuations are so tiny that many times we as humans looking at that might miss it,” says study author Hemant Kulkarni, MD, chief executive officer of M&H Research and president of the Lata Medical Research Foundation. “But the AI, which is powered to detect such specific fluctuations or subtle features, we hypothesized for the study that the AI algorithm might be able to pick those things up. And it did.”

Although this isn’t the first AI algorithm developed to predict diabetes risk, it outperforms previous models, the researchers say.

The team hopes to test and validate the algorithm in a variety of populations so that it can eventually be developed into an accessible, user-friendly technology. They envision that someday their algorithm could be used in smartwatches or other smart devices and could be integrated into telehealth so that people could be screened for diabetes even if they weren’t able to travel to a health care facility for blood testing.

The team is also studying other noninvasive methods of early disease detection and predictive models for adverse outcomes using AI.

“The fact that these algorithms are able to pick up the things of interest and learn on their own and keep learning in the future also adds excitement to their use in these settings,” says Dr. Kulkarni.

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

Imagine that instead of a patient visiting their doctor for blood tests, they could rely on a noninvasive at-home test to predict their risk of diabetes, a disease that affects nearly 15% of U.S. adults (23% of whom are undiagnosed), according to the U.S. Centers for Disease Control and Prevention.

This technology could become a reality thanks to a research team that developed a machine learning algorithm to predict whether people had type 2 diabetes, prediabetes, or no diabetes. In an article published in BMJ Innovations, the researchers describe how their algorithm sorted people into these three categories with 97% accuracy on the basis of measurements of the heart’s electrical activity, determined from an electrocardiogram.

To develop and train their machine learning model – a type of artificial intelligence (AI) that keeps getting smarter over time – researchers used ECG measurements from 1,262 people in Central India. The study participants were part of the Sindhi population, an ethnic group that has been shown in past studies to be at elevated risk for type 2 diabetes.

Why ECG data? Because “cardiovascular abnormalities and diabetes, they go hand in hand,” says study author Manju Mamtani, MD, general manager of M&H Research, San Antonio, and treasurer of the Lata Medical Research Foundation. Subtle cardiovascular changes can occur even early in the development of diabetes.

“ECG has the power to detect these fluctuations, at least in theory, but those fluctuations are so tiny that many times we as humans looking at that might miss it,” says study author Hemant Kulkarni, MD, chief executive officer of M&H Research and president of the Lata Medical Research Foundation. “But the AI, which is powered to detect such specific fluctuations or subtle features, we hypothesized for the study that the AI algorithm might be able to pick those things up. And it did.”

Although this isn’t the first AI algorithm developed to predict diabetes risk, it outperforms previous models, the researchers say.

The team hopes to test and validate the algorithm in a variety of populations so that it can eventually be developed into an accessible, user-friendly technology. They envision that someday their algorithm could be used in smartwatches or other smart devices and could be integrated into telehealth so that people could be screened for diabetes even if they weren’t able to travel to a health care facility for blood testing.

The team is also studying other noninvasive methods of early disease detection and predictive models for adverse outcomes using AI.

“The fact that these algorithms are able to pick up the things of interest and learn on their own and keep learning in the future also adds excitement to their use in these settings,” says Dr. Kulkarni.

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

Imagine that instead of a patient visiting their doctor for blood tests, they could rely on a noninvasive at-home test to predict their risk of diabetes, a disease that affects nearly 15% of U.S. adults (23% of whom are undiagnosed), according to the U.S. Centers for Disease Control and Prevention.

This technology could become a reality thanks to a research team that developed a machine learning algorithm to predict whether people had type 2 diabetes, prediabetes, or no diabetes. In an article published in BMJ Innovations, the researchers describe how their algorithm sorted people into these three categories with 97% accuracy on the basis of measurements of the heart’s electrical activity, determined from an electrocardiogram.

To develop and train their machine learning model – a type of artificial intelligence (AI) that keeps getting smarter over time – researchers used ECG measurements from 1,262 people in Central India. The study participants were part of the Sindhi population, an ethnic group that has been shown in past studies to be at elevated risk for type 2 diabetes.

Why ECG data? Because “cardiovascular abnormalities and diabetes, they go hand in hand,” says study author Manju Mamtani, MD, general manager of M&H Research, San Antonio, and treasurer of the Lata Medical Research Foundation. Subtle cardiovascular changes can occur even early in the development of diabetes.

“ECG has the power to detect these fluctuations, at least in theory, but those fluctuations are so tiny that many times we as humans looking at that might miss it,” says study author Hemant Kulkarni, MD, chief executive officer of M&H Research and president of the Lata Medical Research Foundation. “But the AI, which is powered to detect such specific fluctuations or subtle features, we hypothesized for the study that the AI algorithm might be able to pick those things up. And it did.”

Although this isn’t the first AI algorithm developed to predict diabetes risk, it outperforms previous models, the researchers say.

The team hopes to test and validate the algorithm in a variety of populations so that it can eventually be developed into an accessible, user-friendly technology. They envision that someday their algorithm could be used in smartwatches or other smart devices and could be integrated into telehealth so that people could be screened for diabetes even if they weren’t able to travel to a health care facility for blood testing.

The team is also studying other noninvasive methods of early disease detection and predictive models for adverse outcomes using AI.

“The fact that these algorithms are able to pick up the things of interest and learn on their own and keep learning in the future also adds excitement to their use in these settings,” says Dr. Kulkarni.

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

Many sodium-glucose cotransporter-2 (SGLT2) inhibitors are approved for use at two doses, but there are few clinical data regarding the metabolic impact of uptitrating an SGLT2 inhibitor from the lower to the higher dose in clinical practice. Matsumura and colleagues published the results of a retrospective, longitudinal study at a single institution in Japan. A total of 52 participants who were treated with 10 mg empagliflozin once daily were analyzed at 26 weeks after the dose had been increased to 25 mg once daily. The researchers reported a 0.6 kg weight reduction, a 0.15% reduction in A1c, and a 22.1 mg/dL reduction in triglycerides in the participants on the higher dose of empagliflozin. Although the benefits of the higher dose were rather small, this study does aid the clinician regarding the clinical impact of increasing the dose of empagliflozin.

Outcome studies with SGLT2 inhibitors have shown reductions in major adverse cardiovascular events (MACE), heart failure hospitalization, and mortality. However, clinicians may be reluctant to initiate SGLT2 inhibitors in frail individuals as they are often excluded from randomized trials and may be more likely to have side effects from this class of medications. Wood and colleagues conducted a cohort study in Australia, comparing the effectiveness of SGLT2 inhibitors to that of dipeptidyl peptidase-4 (DPP-4) inhibitors. The study was done with individuals with type 2 diabetes who were initiated on these agents within 60 days of a hospital discharge. It was noted that SGLT2 inhibitors significantly reduced MACE, heart failure hospitalization, and mortality compared with DPP-4 inhibitors, and this benefit was present in both frail and nonfrail individuals. The study did not report on tolerability issues and is limited by the cohort design, but it does suggest a cardiovascular benefit among frail patients with type 2 diabetes who are treated with SGLT2 inhibitors, and it may be reassuring when considering an SGLT2 inhibitor in a frail person.

In my July 2022 commentary, I discussed the results of AWARD-PEDS, which demonstrated a significant A1c reduction but no weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide in youth with type 2 diabetes. Tamborlane and colleagues have now reported the results of a randomized trial that studied the efficacy and safety of 2 mg exenatide once weekly in youth with type 2 diabetes. Similarly to the AWARD-PEDS study, A1c was significantly reduced compared with placebo, with a difference of -0.85% at 24 weeks. Also similarly to AWARD-PEDS, there was no significant difference in body weight between the GLP-1RA and placebo groups. There are now three studies showing glycemic benefits but little weight loss with GLP-1RA treatment in youth with type 2 diabetes, and while the glycemic benefits are encouraging, it remains perplexing why these studies have not demonstrated the weight loss that has consistently been demonstrated in adult studies of GLP-1RA.

Clinicians often choose a second-generation basal insulin analog (glargine U300, degludec) over a first-generation basal analog (glargine U100, detemir) because of lower rates of hypoglycemia. Randomized clinical trials and real-world evidence (RWE) studies comparing glargine U100 vs degludec have shown somewhat inconsistent results. In the newest RWE study comparing these two second-generation analogs, RESTORE-2 NAIVE, Fadini and colleagues reported that 6 months after initiating either glargine U300 or degludec in insulin-naive type 2 diabetes, there was a similar improvement in glycemia, no weight gain, and low hypoglycemia rates in each group. RESTORE-2 is another study demonstrating similar results between the two second-generation insulin analogs and helps build our understanding that these two insulins are more similar than different.

Many sodium-glucose cotransporter-2 (SGLT2) inhibitors are approved for use at two doses, but there are few clinical data regarding the metabolic impact of uptitrating an SGLT2 inhibitor from the lower to the higher dose in clinical practice. Matsumura and colleagues published the results of a retrospective, longitudinal study at a single institution in Japan. A total of 52 participants who were treated with 10 mg empagliflozin once daily were analyzed at 26 weeks after the dose had been increased to 25 mg once daily. The researchers reported a 0.6 kg weight reduction, a 0.15% reduction in A1c, and a 22.1 mg/dL reduction in triglycerides in the participants on the higher dose of empagliflozin. Although the benefits of the higher dose were rather small, this study does aid the clinician regarding the clinical impact of increasing the dose of empagliflozin.

Outcome studies with SGLT2 inhibitors have shown reductions in major adverse cardiovascular events (MACE), heart failure hospitalization, and mortality. However, clinicians may be reluctant to initiate SGLT2 inhibitors in frail individuals as they are often excluded from randomized trials and may be more likely to have side effects from this class of medications. Wood and colleagues conducted a cohort study in Australia, comparing the effectiveness of SGLT2 inhibitors to that of dipeptidyl peptidase-4 (DPP-4) inhibitors. The study was done with individuals with type 2 diabetes who were initiated on these agents within 60 days of a hospital discharge. It was noted that SGLT2 inhibitors significantly reduced MACE, heart failure hospitalization, and mortality compared with DPP-4 inhibitors, and this benefit was present in both frail and nonfrail individuals. The study did not report on tolerability issues and is limited by the cohort design, but it does suggest a cardiovascular benefit among frail patients with type 2 diabetes who are treated with SGLT2 inhibitors, and it may be reassuring when considering an SGLT2 inhibitor in a frail person.

In my July 2022 commentary, I discussed the results of AWARD-PEDS, which demonstrated a significant A1c reduction but no weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide in youth with type 2 diabetes. Tamborlane and colleagues have now reported the results of a randomized trial that studied the efficacy and safety of 2 mg exenatide once weekly in youth with type 2 diabetes. Similarly to the AWARD-PEDS study, A1c was significantly reduced compared with placebo, with a difference of -0.85% at 24 weeks. Also similarly to AWARD-PEDS, there was no significant difference in body weight between the GLP-1RA and placebo groups. There are now three studies showing glycemic benefits but little weight loss with GLP-1RA treatment in youth with type 2 diabetes, and while the glycemic benefits are encouraging, it remains perplexing why these studies have not demonstrated the weight loss that has consistently been demonstrated in adult studies of GLP-1RA.

Clinicians often choose a second-generation basal insulin analog (glargine U300, degludec) over a first-generation basal analog (glargine U100, detemir) because of lower rates of hypoglycemia. Randomized clinical trials and real-world evidence (RWE) studies comparing glargine U100 vs degludec have shown somewhat inconsistent results. In the newest RWE study comparing these two second-generation analogs, RESTORE-2 NAIVE, Fadini and colleagues reported that 6 months after initiating either glargine U300 or degludec in insulin-naive type 2 diabetes, there was a similar improvement in glycemia, no weight gain, and low hypoglycemia rates in each group. RESTORE-2 is another study demonstrating similar results between the two second-generation insulin analogs and helps build our understanding that these two insulins are more similar than different.

Many sodium-glucose cotransporter-2 (SGLT2) inhibitors are approved for use at two doses, but there are few clinical data regarding the metabolic impact of uptitrating an SGLT2 inhibitor from the lower to the higher dose in clinical practice. Matsumura and colleagues published the results of a retrospective, longitudinal study at a single institution in Japan. A total of 52 participants who were treated with 10 mg empagliflozin once daily were analyzed at 26 weeks after the dose had been increased to 25 mg once daily. The researchers reported a 0.6 kg weight reduction, a 0.15% reduction in A1c, and a 22.1 mg/dL reduction in triglycerides in the participants on the higher dose of empagliflozin. Although the benefits of the higher dose were rather small, this study does aid the clinician regarding the clinical impact of increasing the dose of empagliflozin.

Outcome studies with SGLT2 inhibitors have shown reductions in major adverse cardiovascular events (MACE), heart failure hospitalization, and mortality. However, clinicians may be reluctant to initiate SGLT2 inhibitors in frail individuals as they are often excluded from randomized trials and may be more likely to have side effects from this class of medications. Wood and colleagues conducted a cohort study in Australia, comparing the effectiveness of SGLT2 inhibitors to that of dipeptidyl peptidase-4 (DPP-4) inhibitors. The study was done with individuals with type 2 diabetes who were initiated on these agents within 60 days of a hospital discharge. It was noted that SGLT2 inhibitors significantly reduced MACE, heart failure hospitalization, and mortality compared with DPP-4 inhibitors, and this benefit was present in both frail and nonfrail individuals. The study did not report on tolerability issues and is limited by the cohort design, but it does suggest a cardiovascular benefit among frail patients with type 2 diabetes who are treated with SGLT2 inhibitors, and it may be reassuring when considering an SGLT2 inhibitor in a frail person.

In my July 2022 commentary, I discussed the results of AWARD-PEDS, which demonstrated a significant A1c reduction but no weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide in youth with type 2 diabetes. Tamborlane and colleagues have now reported the results of a randomized trial that studied the efficacy and safety of 2 mg exenatide once weekly in youth with type 2 diabetes. Similarly to the AWARD-PEDS study, A1c was significantly reduced compared with placebo, with a difference of -0.85% at 24 weeks. Also similarly to AWARD-PEDS, there was no significant difference in body weight between the GLP-1RA and placebo groups. There are now three studies showing glycemic benefits but little weight loss with GLP-1RA treatment in youth with type 2 diabetes, and while the glycemic benefits are encouraging, it remains perplexing why these studies have not demonstrated the weight loss that has consistently been demonstrated in adult studies of GLP-1RA.

Clinicians often choose a second-generation basal insulin analog (glargine U300, degludec) over a first-generation basal analog (glargine U100, detemir) because of lower rates of hypoglycemia. Randomized clinical trials and real-world evidence (RWE) studies comparing glargine U100 vs degludec have shown somewhat inconsistent results. In the newest RWE study comparing these two second-generation analogs, RESTORE-2 NAIVE, Fadini and colleagues reported that 6 months after initiating either glargine U300 or degludec in insulin-naive type 2 diabetes, there was a similar improvement in glycemia, no weight gain, and low hypoglycemia rates in each group. RESTORE-2 is another study demonstrating similar results between the two second-generation insulin analogs and helps build our understanding that these two insulins are more similar than different.

Women giving birth for the first time have significantly higher odds of developing gestational diabetes if they have a high polygenic risk score (PRS) and low physical activity, new data suggest.

Researchers, led by Kymberleigh A. Pagel, PhD, with the department of computer science, Indiana University, Bloomington, concluded that physical activity early in pregnancy is associated with reduced risk of gestational diabetes and may help women who are at high risk because of genetic predisposition, age, family history of diabetes, and body mass index.

The researchers included 3,533 women in the analysis (average age, 28.6 years) which was a subcohort of a larger study. They found that physical activity’s association with lower gestational diabetes risk “was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history,” the authors wrote.

Women with high PRS and low level of physical activity had three times the odds of developing gestational diabetes (odds ratio, 3.4; 95% confidence interval, 2.3-5.3).

Those with high PRS and moderate to high activity levels in early pregnancy (metabolic equivalents of task [METs] of at least 450) had gestational diabetes risk similar to that of the general population, according to the researchers.

The findings were published in JAMA Network Open.

Maisa Feghali, MD, a maternal-fetal specialist at the University of Pittsburgh Medical Center, who was not part of the study, said in an interview she found the link of physical activity and compensation for high predisposition to gestational diabetes most interesting.

“That’s interesting because a lot of studies that have looked at prevention of gestational diabetes either through limited weight gain or through some form of counseling on physical activity have not really shown any benefit,” she noted. “It might just be it’s not just one size fits all and it may be that physical activity is mostly beneficial in those with a high predisposition.”

Research in this area is particularly important as 7% of pregnancies in the United States each year are affected by gestational diabetes and the risk for developing type 2 diabetes “has doubled in the past decade among patients with GD [gestational diabetes],” the authors wrote.

Researchers looked at risks for gestational diabetes in high-risk subgroups, including women who had a body mass index of more than 25 kg/m² or were at least 35 years old. In that group, women who were either in the in the top 25th percentile for PRS or had low physical activity (METs less than 450) had from 25% to 75% greater risk of developing gestational diabetes.

The findings are consistent with previous research and suggest exercise interventions may be important in improving pregnancy outcomes, the authors wrote.

Christina Han, MD, division director for maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, pointed out several limitations of the study, however.

One of the biggest limitations, she said, was that “they excluded two-thirds of the original study. Essentially, they took only Caucasian [White] patients, which is about one-third of the study.” Additionally, the cohort was made up of people who had never had babies.

“Lots of our gestational diabetes patients are not first-time moms, so this makes the generalizability of the study very limited,” Dr. Han said.

She added that none of the sites where the study was conducted were in the South or Northwest, which also adds questions about generalizability.

Dr. Feghali and Dr. Han reported no relevant financial relationships.

Women giving birth for the first time have significantly higher odds of developing gestational diabetes if they have a high polygenic risk score (PRS) and low physical activity, new data suggest.

Researchers, led by Kymberleigh A. Pagel, PhD, with the department of computer science, Indiana University, Bloomington, concluded that physical activity early in pregnancy is associated with reduced risk of gestational diabetes and may help women who are at high risk because of genetic predisposition, age, family history of diabetes, and body mass index.

The researchers included 3,533 women in the analysis (average age, 28.6 years) which was a subcohort of a larger study. They found that physical activity’s association with lower gestational diabetes risk “was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history,” the authors wrote.

Women with high PRS and low level of physical activity had three times the odds of developing gestational diabetes (odds ratio, 3.4; 95% confidence interval, 2.3-5.3).

Those with high PRS and moderate to high activity levels in early pregnancy (metabolic equivalents of task [METs] of at least 450) had gestational diabetes risk similar to that of the general population, according to the researchers.

The findings were published in JAMA Network Open.

Maisa Feghali, MD, a maternal-fetal specialist at the University of Pittsburgh Medical Center, who was not part of the study, said in an interview she found the link of physical activity and compensation for high predisposition to gestational diabetes most interesting.

“That’s interesting because a lot of studies that have looked at prevention of gestational diabetes either through limited weight gain or through some form of counseling on physical activity have not really shown any benefit,” she noted. “It might just be it’s not just one size fits all and it may be that physical activity is mostly beneficial in those with a high predisposition.”

Research in this area is particularly important as 7% of pregnancies in the United States each year are affected by gestational diabetes and the risk for developing type 2 diabetes “has doubled in the past decade among patients with GD [gestational diabetes],” the authors wrote.

Researchers looked at risks for gestational diabetes in high-risk subgroups, including women who had a body mass index of more than 25 kg/m² or were at least 35 years old. In that group, women who were either in the in the top 25th percentile for PRS or had low physical activity (METs less than 450) had from 25% to 75% greater risk of developing gestational diabetes.

The findings are consistent with previous research and suggest exercise interventions may be important in improving pregnancy outcomes, the authors wrote.

Christina Han, MD, division director for maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, pointed out several limitations of the study, however.

One of the biggest limitations, she said, was that “they excluded two-thirds of the original study. Essentially, they took only Caucasian [White] patients, which is about one-third of the study.” Additionally, the cohort was made up of people who had never had babies.

“Lots of our gestational diabetes patients are not first-time moms, so this makes the generalizability of the study very limited,” Dr. Han said.

She added that none of the sites where the study was conducted were in the South or Northwest, which also adds questions about generalizability.

Dr. Feghali and Dr. Han reported no relevant financial relationships.

Women giving birth for the first time have significantly higher odds of developing gestational diabetes if they have a high polygenic risk score (PRS) and low physical activity, new data suggest.

Researchers, led by Kymberleigh A. Pagel, PhD, with the department of computer science, Indiana University, Bloomington, concluded that physical activity early in pregnancy is associated with reduced risk of gestational diabetes and may help women who are at high risk because of genetic predisposition, age, family history of diabetes, and body mass index.

The researchers included 3,533 women in the analysis (average age, 28.6 years) which was a subcohort of a larger study. They found that physical activity’s association with lower gestational diabetes risk “was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history,” the authors wrote.

Women with high PRS and low level of physical activity had three times the odds of developing gestational diabetes (odds ratio, 3.4; 95% confidence interval, 2.3-5.3).

Those with high PRS and moderate to high activity levels in early pregnancy (metabolic equivalents of task [METs] of at least 450) had gestational diabetes risk similar to that of the general population, according to the researchers.

The findings were published in JAMA Network Open.

Maisa Feghali, MD, a maternal-fetal specialist at the University of Pittsburgh Medical Center, who was not part of the study, said in an interview she found the link of physical activity and compensation for high predisposition to gestational diabetes most interesting.

“That’s interesting because a lot of studies that have looked at prevention of gestational diabetes either through limited weight gain or through some form of counseling on physical activity have not really shown any benefit,” she noted. “It might just be it’s not just one size fits all and it may be that physical activity is mostly beneficial in those with a high predisposition.”

Research in this area is particularly important as 7% of pregnancies in the United States each year are affected by gestational diabetes and the risk for developing type 2 diabetes “has doubled in the past decade among patients with GD [gestational diabetes],” the authors wrote.

Researchers looked at risks for gestational diabetes in high-risk subgroups, including women who had a body mass index of more than 25 kg/m² or were at least 35 years old. In that group, women who were either in the in the top 25th percentile for PRS or had low physical activity (METs less than 450) had from 25% to 75% greater risk of developing gestational diabetes.

The findings are consistent with previous research and suggest exercise interventions may be important in improving pregnancy outcomes, the authors wrote.

Christina Han, MD, division director for maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, pointed out several limitations of the study, however.

One of the biggest limitations, she said, was that “they excluded two-thirds of the original study. Essentially, they took only Caucasian [White] patients, which is about one-third of the study.” Additionally, the cohort was made up of people who had never had babies.

“Lots of our gestational diabetes patients are not first-time moms, so this makes the generalizability of the study very limited,” Dr. Han said.

She added that none of the sites where the study was conducted were in the South or Northwest, which also adds questions about generalizability.

Dr. Feghali and Dr. Han reported no relevant financial relationships.

Key clinical point: Sodium-glucose cotransporter-2 inhibitors (SGLT-2I) offered advantages over dipeptidyl peptidase-4 inhibitors (DPP-4I) for preventing major adverse cardiovascular events (MACE), heart failure (HF) hospitalizations, and all-cause mortality in frail patients with type 2 diabetes (T2D) who were recently hospitalized.

Major finding: The rates of MACE (subdistribution hazard ratio [sHR] 0.51; 95% CI 0.46-0.56), HF hospitalization (sHR 0.42; 95% CI 0.36-0.49), and all-cause mortality (HR 0.38; 95% CI 0.33-0.43) were significantly lower in patients receiving SGLT-2I vs DPP-4I.

Study details: The data come from a cohort study of 32,043 patients aged ≥30 years with T2D who were recently discharged from hospital, of which 5152 received SGLT-2I and 26,891 received DPP-4I.

Disclosures: This study received no specific funding. JS Bell, JE Shaw, J Ilomaki, and M Cesari declared receiving personal fees or research grants from various sources.

Source: Wood SJ et al. Effectiveness of sodium-glucose cotransporter-2 inhibitors vs. dipeptidyl peptidase-4 inhibitors in frail people with diabetes who were recently hospitalized. Front Pharmacol. 2022;13:886834 (Jul 12). Doi: 10.3389/fphar.2022.886834

Key clinical point: Sodium-glucose cotransporter-2 inhibitors (SGLT-2I) offered advantages over dipeptidyl peptidase-4 inhibitors (DPP-4I) for preventing major adverse cardiovascular events (MACE), heart failure (HF) hospitalizations, and all-cause mortality in frail patients with type 2 diabetes (T2D) who were recently hospitalized.

Major finding: The rates of MACE (subdistribution hazard ratio [sHR] 0.51; 95% CI 0.46-0.56), HF hospitalization (sHR 0.42; 95% CI 0.36-0.49), and all-cause mortality (HR 0.38; 95% CI 0.33-0.43) were significantly lower in patients receiving SGLT-2I vs DPP-4I.

Study details: The data come from a cohort study of 32,043 patients aged ≥30 years with T2D who were recently discharged from hospital, of which 5152 received SGLT-2I and 26,891 received DPP-4I.

Disclosures: This study received no specific funding. JS Bell, JE Shaw, J Ilomaki, and M Cesari declared receiving personal fees or research grants from various sources.

Source: Wood SJ et al. Effectiveness of sodium-glucose cotransporter-2 inhibitors vs. dipeptidyl peptidase-4 inhibitors in frail people with diabetes who were recently hospitalized. Front Pharmacol. 2022;13:886834 (Jul 12). Doi: 10.3389/fphar.2022.886834

Key clinical point: Sodium-glucose cotransporter-2 inhibitors (SGLT-2I) offered advantages over dipeptidyl peptidase-4 inhibitors (DPP-4I) for preventing major adverse cardiovascular events (MACE), heart failure (HF) hospitalizations, and all-cause mortality in frail patients with type 2 diabetes (T2D) who were recently hospitalized.

Major finding: The rates of MACE (subdistribution hazard ratio [sHR] 0.51; 95% CI 0.46-0.56), HF hospitalization (sHR 0.42; 95% CI 0.36-0.49), and all-cause mortality (HR 0.38; 95% CI 0.33-0.43) were significantly lower in patients receiving SGLT-2I vs DPP-4I.

Study details: The data come from a cohort study of 32,043 patients aged ≥30 years with T2D who were recently discharged from hospital, of which 5152 received SGLT-2I and 26,891 received DPP-4I.

Disclosures: This study received no specific funding. JS Bell, JE Shaw, J Ilomaki, and M Cesari declared receiving personal fees or research grants from various sources.

Source: Wood SJ et al. Effectiveness of sodium-glucose cotransporter-2 inhibitors vs. dipeptidyl peptidase-4 inhibitors in frail people with diabetes who were recently hospitalized. Front Pharmacol. 2022;13:886834 (Jul 12). Doi: 10.3389/fphar.2022.886834

Key clinical point: Patients with upper gastrointestinal disease (UGID) receiving proton pump inhibitors (PPI) showed a dose-dependent increased risk for type 2 diabetes (T2D) compared with those not receiving PPI.

Major finding: The risk for T2D was significantly higher in patients receiving a cumulative defined daily dose (cDDD) of PPI of 31-120 mg (adjusted odds ratio [aOR] 1.20, 95% CI 1.13-1.26), 121-365 mg (aOR 1.26; 95% CI 1.19-1.33), and >365 mg (aOR 1.34; 95% CI 1.23-1.46) than in those receiving a cDDD of PPI ≤30 mg.

Study details: Findings are from a nested case-control study including 41,880 patients with UGID who received PPI, of which 20,940 who subsequently developed T2D were matched with 20,940 who did not develop T2D.

Disclosures: This study was supported by grants from Taipei Veterans General Hospital, Taiwan, and others. The authors declared no conflicts of interest.

Source: Kuo HY et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: A nationwide nested case–control study. Int J Environ Res Public Health. 2022;19(14):8739 (Jul 18). Doi: 10.3390/ijerph19148739

Key clinical point: Patients with upper gastrointestinal disease (UGID) receiving proton pump inhibitors (PPI) showed a dose-dependent increased risk for type 2 diabetes (T2D) compared with those not receiving PPI.

Major finding: The risk for T2D was significantly higher in patients receiving a cumulative defined daily dose (cDDD) of PPI of 31-120 mg (adjusted odds ratio [aOR] 1.20, 95% CI 1.13-1.26), 121-365 mg (aOR 1.26; 95% CI 1.19-1.33), and >365 mg (aOR 1.34; 95% CI 1.23-1.46) than in those receiving a cDDD of PPI ≤30 mg.

Study details: Findings are from a nested case-control study including 41,880 patients with UGID who received PPI, of which 20,940 who subsequently developed T2D were matched with 20,940 who did not develop T2D.

Disclosures: This study was supported by grants from Taipei Veterans General Hospital, Taiwan, and others. The authors declared no conflicts of interest.

Source: Kuo HY et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: A nationwide nested case–control study. Int J Environ Res Public Health. 2022;19(14):8739 (Jul 18). Doi: 10.3390/ijerph19148739

Key clinical point: Patients with upper gastrointestinal disease (UGID) receiving proton pump inhibitors (PPI) showed a dose-dependent increased risk for type 2 diabetes (T2D) compared with those not receiving PPI.

Major finding: The risk for T2D was significantly higher in patients receiving a cumulative defined daily dose (cDDD) of PPI of 31-120 mg (adjusted odds ratio [aOR] 1.20, 95% CI 1.13-1.26), 121-365 mg (aOR 1.26; 95% CI 1.19-1.33), and >365 mg (aOR 1.34; 95% CI 1.23-1.46) than in those receiving a cDDD of PPI ≤30 mg.

Study details: Findings are from a nested case-control study including 41,880 patients with UGID who received PPI, of which 20,940 who subsequently developed T2D were matched with 20,940 who did not develop T2D.

Disclosures: This study was supported by grants from Taipei Veterans General Hospital, Taiwan, and others. The authors declared no conflicts of interest.

Source: Kuo HY et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: A nationwide nested case–control study. Int J Environ Res Public Health. 2022;19(14):8739 (Jul 18). Doi: 10.3390/ijerph19148739

Key clinical point: Women with type 2 diabetes (T2D) and a history of gestational diabetes (GD) are at a higher risk for myocardial infarction (MI) and coronary artery disease compared with those with T2D and no GD history.

Major finding: Among women with T2D, those with a history of GD had a significantly higher risk for MI (adjusted odds ratio [aOR] 2.53; 95% CI 1.18-5.40) and a borderline increased risk for coronary artery disease (aOR 2.15; 95% CI 1.00-4.66) compared with those without GD history.

Study details: This cross-sectional study included 2494 women aged ≥20 years with T2D, of which 385 (15.4%) had a history of GD.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Cui Y et al. Impact of prior gestational diabetes on long-term type 2 diabetes complications. J Diabetes Complications. 2022;36(9):108282 (Aug 2). Doi: 10.1016/j.jdiacomp.2022.108282

Key clinical point: Women with type 2 diabetes (T2D) and a history of gestational diabetes (GD) are at a higher risk for myocardial infarction (MI) and coronary artery disease compared with those with T2D and no GD history.

Major finding: Among women with T2D, those with a history of GD had a significantly higher risk for MI (adjusted odds ratio [aOR] 2.53; 95% CI 1.18-5.40) and a borderline increased risk for coronary artery disease (aOR 2.15; 95% CI 1.00-4.66) compared with those without GD history.

Study details: This cross-sectional study included 2494 women aged ≥20 years with T2D, of which 385 (15.4%) had a history of GD.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Cui Y et al. Impact of prior gestational diabetes on long-term type 2 diabetes complications. J Diabetes Complications. 2022;36(9):108282 (Aug 2). Doi: 10.1016/j.jdiacomp.2022.108282

Key clinical point: Women with type 2 diabetes (T2D) and a history of gestational diabetes (GD) are at a higher risk for myocardial infarction (MI) and coronary artery disease compared with those with T2D and no GD history.

Major finding: Among women with T2D, those with a history of GD had a significantly higher risk for MI (adjusted odds ratio [aOR] 2.53; 95% CI 1.18-5.40) and a borderline increased risk for coronary artery disease (aOR 2.15; 95% CI 1.00-4.66) compared with those without GD history.

Study details: This cross-sectional study included 2494 women aged ≥20 years with T2D, of which 385 (15.4%) had a history of GD.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Cui Y et al. Impact of prior gestational diabetes on long-term type 2 diabetes complications. J Diabetes Complications. 2022;36(9):108282 (Aug 2). Doi: 10.1016/j.jdiacomp.2022.108282