Type 2 Diabetes ICYMI

There is a link between cannabis exposure during pregnancy and higher fasting glucose levels and adiposity in the offspring in early childhood, a new study suggests.

Research looking at the effect of prenatal exposure to cannabis on offspring is growing. It is known to affect childhood cognition and behavior; however, there is little work to date on how it affects metabolic outcomes, said lead author Brianna F. Moore, PhD.

“Officially, the American Academy of Obstetricians and Gynecologists recommends that women do not use cannabis during pregnancy or while breastfeeding to limit the effects on offspring. There’s really a lot we don’t know, but researchers across the country are starting to look into this more, and there are signs that it isn’t great for the offspring,” Dr. Moore, assistant professor at the Colorado School of Public Health in Aurora, said in an interview.

And she noted that while some women turn to cannabis to manage the challenging symptoms of pregnancy, “Clinicians should encourage pregnant women to refrain from using cannabis; it is best for these pregnant women to talk to their physicians about alternative ways of managing these symptoms.”

The findings were published online March 31 in the Journal of Clinical Endocrinology & Metabolism.
 

Study of mother and 5-year-old child pairs

The researchers assessed 103 sets of mothers and children from the Healthy Start study. At 27 weeks of gestation, the investigators assessed 12 metabolites of cannabis/cannabinoids in urine samples. Results from these samples were used to categorize fetal exposure to cannabis as either not exposed or exposed. They found that about 15% of the mothers had traceable amounts of cannabinoids, suggesting fetal cannabis exposure.

At follow-up, the study team assessed fat-free mass and fat mass using air displacement plethysmography among the offspring around age 5. They used generalized linear models to approximate the relationship between fetal exposure to cannabis with metabolic measures such as insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA-IR), and adiposity measures such as body mass index, fat-free mass, fat mass, adiposity, and BMI z-scores.

The findings showed that, compared with nonexposed offspring, exposed offspring had greater:

• Fasting glucose (5.6 mg/dL; 95% confidence interval [CI], 0.8-10.3).
• Fat-free mass (1.2 kg; 95% CI, 0.4-2.0).
• Fat mass (1.0 kg; 95% CI, 0.3-1.7).
• Adiposity (2.6%; 95% CI, 0.1-5.2).

“This finding may suggest that fetal exposure to cannabis contributes to higher fasting glucose levels via a direct effect on the pancreatic β-cells. However, we cannot draw conclusions about β-cell response to glucose because we did not perform oral glucose tolerance tests,” the study authors wrote.

Notably, however, there was no relationship between BMI z-scores, BMI, or HOMA-IR and fasting insulin, the study team found.

Study limitations include the small sample size and lack of self-report data on cannabis use to differentiate between direct use and exposure to cannabis, Dr. Moore acknowledged.

Given the small sample size, the researchers were unable to look at dose-response, which future studies will focus on, Dr. Moore noted. Future efforts will also focus on comparing the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), Dr. Moore added.

“This is a relatively new field, so there’s still work to be done. This is just one study, and we need to study this more in other cohorts to confirm our findings,” she concluded.

Dr. Moore has reported no relevant financial relationships.

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

There is a link between cannabis exposure during pregnancy and higher fasting glucose levels and adiposity in the offspring in early childhood, a new study suggests.

Research looking at the effect of prenatal exposure to cannabis on offspring is growing. It is known to affect childhood cognition and behavior; however, there is little work to date on how it affects metabolic outcomes, said lead author Brianna F. Moore, PhD.

“Officially, the American Academy of Obstetricians and Gynecologists recommends that women do not use cannabis during pregnancy or while breastfeeding to limit the effects on offspring. There’s really a lot we don’t know, but researchers across the country are starting to look into this more, and there are signs that it isn’t great for the offspring,” Dr. Moore, assistant professor at the Colorado School of Public Health in Aurora, said in an interview.

And she noted that while some women turn to cannabis to manage the challenging symptoms of pregnancy, “Clinicians should encourage pregnant women to refrain from using cannabis; it is best for these pregnant women to talk to their physicians about alternative ways of managing these symptoms.”

The findings were published online March 31 in the Journal of Clinical Endocrinology & Metabolism.
 

Study of mother and 5-year-old child pairs

The researchers assessed 103 sets of mothers and children from the Healthy Start study. At 27 weeks of gestation, the investigators assessed 12 metabolites of cannabis/cannabinoids in urine samples. Results from these samples were used to categorize fetal exposure to cannabis as either not exposed or exposed. They found that about 15% of the mothers had traceable amounts of cannabinoids, suggesting fetal cannabis exposure.

At follow-up, the study team assessed fat-free mass and fat mass using air displacement plethysmography among the offspring around age 5. They used generalized linear models to approximate the relationship between fetal exposure to cannabis with metabolic measures such as insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA-IR), and adiposity measures such as body mass index, fat-free mass, fat mass, adiposity, and BMI z-scores.

The findings showed that, compared with nonexposed offspring, exposed offspring had greater:

• Fasting glucose (5.6 mg/dL; 95% confidence interval [CI], 0.8-10.3).
• Fat-free mass (1.2 kg; 95% CI, 0.4-2.0).
• Fat mass (1.0 kg; 95% CI, 0.3-1.7).
• Adiposity (2.6%; 95% CI, 0.1-5.2).

“This finding may suggest that fetal exposure to cannabis contributes to higher fasting glucose levels via a direct effect on the pancreatic β-cells. However, we cannot draw conclusions about β-cell response to glucose because we did not perform oral glucose tolerance tests,” the study authors wrote.

Notably, however, there was no relationship between BMI z-scores, BMI, or HOMA-IR and fasting insulin, the study team found.

Study limitations include the small sample size and lack of self-report data on cannabis use to differentiate between direct use and exposure to cannabis, Dr. Moore acknowledged.

Given the small sample size, the researchers were unable to look at dose-response, which future studies will focus on, Dr. Moore noted. Future efforts will also focus on comparing the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), Dr. Moore added.

“This is a relatively new field, so there’s still work to be done. This is just one study, and we need to study this more in other cohorts to confirm our findings,” she concluded.

Dr. Moore has reported no relevant financial relationships.

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

There is a link between cannabis exposure during pregnancy and higher fasting glucose levels and adiposity in the offspring in early childhood, a new study suggests.

Research looking at the effect of prenatal exposure to cannabis on offspring is growing. It is known to affect childhood cognition and behavior; however, there is little work to date on how it affects metabolic outcomes, said lead author Brianna F. Moore, PhD.

“Officially, the American Academy of Obstetricians and Gynecologists recommends that women do not use cannabis during pregnancy or while breastfeeding to limit the effects on offspring. There’s really a lot we don’t know, but researchers across the country are starting to look into this more, and there are signs that it isn’t great for the offspring,” Dr. Moore, assistant professor at the Colorado School of Public Health in Aurora, said in an interview.

And she noted that while some women turn to cannabis to manage the challenging symptoms of pregnancy, “Clinicians should encourage pregnant women to refrain from using cannabis; it is best for these pregnant women to talk to their physicians about alternative ways of managing these symptoms.”

The findings were published online March 31 in the Journal of Clinical Endocrinology & Metabolism.
 

Study of mother and 5-year-old child pairs

The researchers assessed 103 sets of mothers and children from the Healthy Start study. At 27 weeks of gestation, the investigators assessed 12 metabolites of cannabis/cannabinoids in urine samples. Results from these samples were used to categorize fetal exposure to cannabis as either not exposed or exposed. They found that about 15% of the mothers had traceable amounts of cannabinoids, suggesting fetal cannabis exposure.

At follow-up, the study team assessed fat-free mass and fat mass using air displacement plethysmography among the offspring around age 5. They used generalized linear models to approximate the relationship between fetal exposure to cannabis with metabolic measures such as insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA-IR), and adiposity measures such as body mass index, fat-free mass, fat mass, adiposity, and BMI z-scores.

The findings showed that, compared with nonexposed offspring, exposed offspring had greater:

• Fasting glucose (5.6 mg/dL; 95% confidence interval [CI], 0.8-10.3).
• Fat-free mass (1.2 kg; 95% CI, 0.4-2.0).
• Fat mass (1.0 kg; 95% CI, 0.3-1.7).
• Adiposity (2.6%; 95% CI, 0.1-5.2).

“This finding may suggest that fetal exposure to cannabis contributes to higher fasting glucose levels via a direct effect on the pancreatic β-cells. However, we cannot draw conclusions about β-cell response to glucose because we did not perform oral glucose tolerance tests,” the study authors wrote.

Notably, however, there was no relationship between BMI z-scores, BMI, or HOMA-IR and fasting insulin, the study team found.

Study limitations include the small sample size and lack of self-report data on cannabis use to differentiate between direct use and exposure to cannabis, Dr. Moore acknowledged.

Given the small sample size, the researchers were unable to look at dose-response, which future studies will focus on, Dr. Moore noted. Future efforts will also focus on comparing the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), Dr. Moore added.

“This is a relatively new field, so there’s still work to be done. This is just one study, and we need to study this more in other cohorts to confirm our findings,” she concluded.

Dr. Moore has reported no relevant financial relationships.

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

Among patients with diabetes, women are just as likely as men to suffer from sexual dysfunction, but their issues are overlooked, with the narrative focusing mainly on the impact of this issue on men, say experts.

Women with diabetes can experience reduced sexual desire, painful sex, reduced lubrication, and sexual distress, increasing the risk of depression, and such issues often go unnoticed despite treatments being available, said Kirsty Winkley, PhD, diabetes nurse and health psychologist, King’s College London.

There is also the “embarrassment factor” on the side of both the health care professional and the patient, she said in a session she chaired at the Diabetes UK Professional Conference 2022. Many women with diabetes “wouldn’t necessarily know” that their sexual dysfunction “is related to their diabetes,” she told this news organization.

For women, sexual health conversations are “often about contraception and pregnancy,” as well as menstrual disorders, genital infections, and hormone replacement therapy. “As health care professionals, you’re trained to focus on those things, and you’re not really considering there might be sexual dysfunction. If women aren’t aware that it’s related to diabetes, you’ve got the perfect situation where it goes under the radar.”

However, cochair Debbie Cooke, PhD, health psychologist at the University of Surrey in Guildford, explained that having psychotherapy embedded within the diabetes team and “integrated throughout the whole service” means that the problem can be identified and treatment offered.

The issue is that such integration is “very uncommon” and access needs to be improved, Dr. Cooke said in an interview.
 

Sexual dysfunction major predictor of depression in women

Jacqueline Fosbury, psychotherapy lead at Diabetes Care for You, Sussex Community NHS Foundation Trust, said that “intimate activity is clearly beneficial for emotional and physical health,” as it is associated with increased oxytocin release, the burning of calories, better immunity, and improved sleep.

Sexual dysfunction is common in people with diabetes, she noted. Poor glycemic control can “damage” blood vessels and nerves, causing reduced blood flow and loss of sensation in sexual organs.

A recent study led by Belgian researchers found that among more than 750 adults with diabetes, 36% of men and 33% of women reported sexual dysfunction.

Sexual dysfunction was more common in women with type 1 diabetes, at 36%, compared with 26% for those with type 2 diabetes. The most commonly reported issues were decreased sexual desire, lubrication problems, orgasmic dysfunction, and pain. Body image problems and fear of hypoglycemia also affect sexuality and intimacy, leading to “sexual distress.”

Moreover, Ms. Fosbury said female sexual dysfunction has been identified as a “major predictor” of depression, which in turn reduces libido.

Treatments for women can include lubricants, local estrogen, and medications that are prescribed off-label, such as sildenafil. The same is true of testosterone therapy, which can be used to boost libido.
 

Couples therapy?

Next, Trudy Hannington, a psychosexual therapist with Leger Clinic, Doncaster, U.K., talked about how to use an integrated approach to address sexuality overall in people with diabetes.

She said this should be seen in a biopsychosocial context, with emphasis on the couple, on sensation and communication, and sexual growth, as well as changes in daily routines.

There should be a move away from “penetrative sex,” Ms. Hannington said, with the goal being “enjoyment, not orgasm.” Pleasure should be facilitated and the opportunities for “performance pressure and/or anxiety” reduced.

She discussed the case of Marie, a 27-year-old woman with type 1 diabetes who had been referred with painful sex and vaginal dryness. Marie had “never experienced orgasm,” despite being in a same-sex relationship with Emily.

Marie’s treatment involved a sexual growth program, to which Emily was invited, as well as recommendations to use lubricants, vibrators, and to try sildenafil.
 

Prioritize women

Ms. Fosbury reiterated that, in men, sexual dysfunction is “readily identified as a complication of diabetes” and is described as “traumatic” and “crucial to well-being.” It is also seen as “easy to treat” with medication, such as that for erectile dysfunction.

It is therefore crucial to talk to women with diabetes about possible sexual dysfunction, and the scene must be set before the appointment to explain that the subject will be broached. In addition, handouts and leaflets should be available for patients in the clinic so they can read about female sexual health and to lower the stigma around discussing it.

“Cultural stereotypes diminish the importance of female sexuality and prevent us from providing equal consideration to the sexual difficulties of our patients,” she concluded.

No funding declared. No relevant financial relationships declared.

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

Among patients with diabetes, women are just as likely as men to suffer from sexual dysfunction, but their issues are overlooked, with the narrative focusing mainly on the impact of this issue on men, say experts.

Women with diabetes can experience reduced sexual desire, painful sex, reduced lubrication, and sexual distress, increasing the risk of depression, and such issues often go unnoticed despite treatments being available, said Kirsty Winkley, PhD, diabetes nurse and health psychologist, King’s College London.

There is also the “embarrassment factor” on the side of both the health care professional and the patient, she said in a session she chaired at the Diabetes UK Professional Conference 2022. Many women with diabetes “wouldn’t necessarily know” that their sexual dysfunction “is related to their diabetes,” she told this news organization.

For women, sexual health conversations are “often about contraception and pregnancy,” as well as menstrual disorders, genital infections, and hormone replacement therapy. “As health care professionals, you’re trained to focus on those things, and you’re not really considering there might be sexual dysfunction. If women aren’t aware that it’s related to diabetes, you’ve got the perfect situation where it goes under the radar.”

However, cochair Debbie Cooke, PhD, health psychologist at the University of Surrey in Guildford, explained that having psychotherapy embedded within the diabetes team and “integrated throughout the whole service” means that the problem can be identified and treatment offered.

The issue is that such integration is “very uncommon” and access needs to be improved, Dr. Cooke said in an interview.
 

Sexual dysfunction major predictor of depression in women

Jacqueline Fosbury, psychotherapy lead at Diabetes Care for You, Sussex Community NHS Foundation Trust, said that “intimate activity is clearly beneficial for emotional and physical health,” as it is associated with increased oxytocin release, the burning of calories, better immunity, and improved sleep.

Sexual dysfunction is common in people with diabetes, she noted. Poor glycemic control can “damage” blood vessels and nerves, causing reduced blood flow and loss of sensation in sexual organs.

A recent study led by Belgian researchers found that among more than 750 adults with diabetes, 36% of men and 33% of women reported sexual dysfunction.

Sexual dysfunction was more common in women with type 1 diabetes, at 36%, compared with 26% for those with type 2 diabetes. The most commonly reported issues were decreased sexual desire, lubrication problems, orgasmic dysfunction, and pain. Body image problems and fear of hypoglycemia also affect sexuality and intimacy, leading to “sexual distress.”

Moreover, Ms. Fosbury said female sexual dysfunction has been identified as a “major predictor” of depression, which in turn reduces libido.

Treatments for women can include lubricants, local estrogen, and medications that are prescribed off-label, such as sildenafil. The same is true of testosterone therapy, which can be used to boost libido.
 

Couples therapy?

Next, Trudy Hannington, a psychosexual therapist with Leger Clinic, Doncaster, U.K., talked about how to use an integrated approach to address sexuality overall in people with diabetes.

She said this should be seen in a biopsychosocial context, with emphasis on the couple, on sensation and communication, and sexual growth, as well as changes in daily routines.

There should be a move away from “penetrative sex,” Ms. Hannington said, with the goal being “enjoyment, not orgasm.” Pleasure should be facilitated and the opportunities for “performance pressure and/or anxiety” reduced.

She discussed the case of Marie, a 27-year-old woman with type 1 diabetes who had been referred with painful sex and vaginal dryness. Marie had “never experienced orgasm,” despite being in a same-sex relationship with Emily.

Marie’s treatment involved a sexual growth program, to which Emily was invited, as well as recommendations to use lubricants, vibrators, and to try sildenafil.
 

Prioritize women

Ms. Fosbury reiterated that, in men, sexual dysfunction is “readily identified as a complication of diabetes” and is described as “traumatic” and “crucial to well-being.” It is also seen as “easy to treat” with medication, such as that for erectile dysfunction.

It is therefore crucial to talk to women with diabetes about possible sexual dysfunction, and the scene must be set before the appointment to explain that the subject will be broached. In addition, handouts and leaflets should be available for patients in the clinic so they can read about female sexual health and to lower the stigma around discussing it.

“Cultural stereotypes diminish the importance of female sexuality and prevent us from providing equal consideration to the sexual difficulties of our patients,” she concluded.

No funding declared. No relevant financial relationships declared.

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

Among patients with diabetes, women are just as likely as men to suffer from sexual dysfunction, but their issues are overlooked, with the narrative focusing mainly on the impact of this issue on men, say experts.

Women with diabetes can experience reduced sexual desire, painful sex, reduced lubrication, and sexual distress, increasing the risk of depression, and such issues often go unnoticed despite treatments being available, said Kirsty Winkley, PhD, diabetes nurse and health psychologist, King’s College London.

There is also the “embarrassment factor” on the side of both the health care professional and the patient, she said in a session she chaired at the Diabetes UK Professional Conference 2022. Many women with diabetes “wouldn’t necessarily know” that their sexual dysfunction “is related to their diabetes,” she told this news organization.

For women, sexual health conversations are “often about contraception and pregnancy,” as well as menstrual disorders, genital infections, and hormone replacement therapy. “As health care professionals, you’re trained to focus on those things, and you’re not really considering there might be sexual dysfunction. If women aren’t aware that it’s related to diabetes, you’ve got the perfect situation where it goes under the radar.”

However, cochair Debbie Cooke, PhD, health psychologist at the University of Surrey in Guildford, explained that having psychotherapy embedded within the diabetes team and “integrated throughout the whole service” means that the problem can be identified and treatment offered.

The issue is that such integration is “very uncommon” and access needs to be improved, Dr. Cooke said in an interview.
 

Sexual dysfunction major predictor of depression in women

Jacqueline Fosbury, psychotherapy lead at Diabetes Care for You, Sussex Community NHS Foundation Trust, said that “intimate activity is clearly beneficial for emotional and physical health,” as it is associated with increased oxytocin release, the burning of calories, better immunity, and improved sleep.

Sexual dysfunction is common in people with diabetes, she noted. Poor glycemic control can “damage” blood vessels and nerves, causing reduced blood flow and loss of sensation in sexual organs.

A recent study led by Belgian researchers found that among more than 750 adults with diabetes, 36% of men and 33% of women reported sexual dysfunction.

Sexual dysfunction was more common in women with type 1 diabetes, at 36%, compared with 26% for those with type 2 diabetes. The most commonly reported issues were decreased sexual desire, lubrication problems, orgasmic dysfunction, and pain. Body image problems and fear of hypoglycemia also affect sexuality and intimacy, leading to “sexual distress.”

Moreover, Ms. Fosbury said female sexual dysfunction has been identified as a “major predictor” of depression, which in turn reduces libido.

Treatments for women can include lubricants, local estrogen, and medications that are prescribed off-label, such as sildenafil. The same is true of testosterone therapy, which can be used to boost libido.
 

Couples therapy?

Next, Trudy Hannington, a psychosexual therapist with Leger Clinic, Doncaster, U.K., talked about how to use an integrated approach to address sexuality overall in people with diabetes.

She said this should be seen in a biopsychosocial context, with emphasis on the couple, on sensation and communication, and sexual growth, as well as changes in daily routines.

There should be a move away from “penetrative sex,” Ms. Hannington said, with the goal being “enjoyment, not orgasm.” Pleasure should be facilitated and the opportunities for “performance pressure and/or anxiety” reduced.

She discussed the case of Marie, a 27-year-old woman with type 1 diabetes who had been referred with painful sex and vaginal dryness. Marie had “never experienced orgasm,” despite being in a same-sex relationship with Emily.

Marie’s treatment involved a sexual growth program, to which Emily was invited, as well as recommendations to use lubricants, vibrators, and to try sildenafil.
 

Prioritize women

Ms. Fosbury reiterated that, in men, sexual dysfunction is “readily identified as a complication of diabetes” and is described as “traumatic” and “crucial to well-being.” It is also seen as “easy to treat” with medication, such as that for erectile dysfunction.

It is therefore crucial to talk to women with diabetes about possible sexual dysfunction, and the scene must be set before the appointment to explain that the subject will be broached. In addition, handouts and leaflets should be available for patients in the clinic so they can read about female sexual health and to lower the stigma around discussing it.

“Cultural stereotypes diminish the importance of female sexuality and prevent us from providing equal consideration to the sexual difficulties of our patients,” she concluded.

No funding declared. No relevant financial relationships declared.

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

The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.

The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.

The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

“Our data reinforce this and give some quantitative measures of when we should start to consider that.”

A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.

The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.

That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.

Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.

The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.

They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:

• 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
• 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
• 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
• 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000

The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.

Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.

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

The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.

The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.

The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

“Our data reinforce this and give some quantitative measures of when we should start to consider that.”

A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.

The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.

That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.

Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.

The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.

They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:

• 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
• 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
• 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
• 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000

The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.

Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.

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

The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.

The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.

The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

“Our data reinforce this and give some quantitative measures of when we should start to consider that.”

A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.

The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.

That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.

Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.

The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.

They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:

• 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
• 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
• 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
• 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000

The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.

Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.

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

Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.

The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.

However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.

“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.

The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.

In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”

“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”

“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.

The study authors also note that few of the trials reported biliary-related events.

“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.   

Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.

Controversial link

The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.

Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.

Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.

To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).

Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).

The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6). 

Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m² and 36.9 kg/m² in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.  

Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).

Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).

Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.     

Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.

Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.       

The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.

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

Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.

The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.

However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.

“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.

The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.

In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”

“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”

“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.

The study authors also note that few of the trials reported biliary-related events.

“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.   

Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.

Controversial link

The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.

Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.

Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.

To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).

Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).

The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6). 

Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m² and 36.9 kg/m² in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.  

Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).

Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).

Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.     

Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.

Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.       

The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.

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

Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.

The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.

However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.

“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.

The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.

In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”

“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”

“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.

The study authors also note that few of the trials reported biliary-related events.

“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.   

Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.

Controversial link

The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.

Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.

Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.

To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).

Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).

The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6). 

Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m² and 36.9 kg/m² in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.  

Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).

Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).

Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.     

Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.

Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.       

The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

The U.S. Food and Drug Administration has approved a higher 2-mg dose of the GLP-1 agonist semaglutide (Ozempic, Novo Nordisk) for adults with type 2 diabetes, giving a higher-dose alternative to the previous maximum 1-mg dose of semaglutide, administered by subcutaneous injection once weekly.

Semaglutide is currently available as 0.5-mg and 1-mg doses.

Results from the pivotal SUSTAIN FORTE study of the 2-mg dose (which, like lower-dose semaglutide for type 2 diabetes, comes in a single-use pen injector) showed that when compared head-to-head with a 1-mg/week dose in a 40-week study with 961 randomized patients, the 2-mg regimen led to a significant average incremental reduction in A1c levels of 0.23 percentage points. The 2-mg dose also produced a significant incremental increase in weight loss, with patients losing 0.93 kg more on the higher dose.

The 2-mg dose gives patients with type 2 diabetes and clinicians an “additional option” when a bigger “shift” in blood glucose is needed, said Juan Pablo Frias, MD, National Research Institute, Los Angeles, California, who was lead investigator for SUSTAIN FORTE, in a written statement.

As well as reducing glucose levels, semaglutide has been shown to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known cardiovascular disease.

Semaglutide was approved as a 2.4-mg injectable dose, as Wegovy, in 2021 for weight loss in patients with overweight or obesity.

SUSTAIN FORTE and other trials of semaglutide were sponsored by Novo Nordisk. SURPASS-2 and other trials of tirzepatide were sponsored by Lilly. Dr. Frias was lead investigator for both SUSTAIN FORTE and SURPASS-2, as well as an investigator for other trials sponsored by Lilly, Novo Nordisk, and other companies.

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

The U.S. Food and Drug Administration has approved a higher 2-mg dose of the GLP-1 agonist semaglutide (Ozempic, Novo Nordisk) for adults with type 2 diabetes, giving a higher-dose alternative to the previous maximum 1-mg dose of semaglutide, administered by subcutaneous injection once weekly.

Semaglutide is currently available as 0.5-mg and 1-mg doses.

Results from the pivotal SUSTAIN FORTE study of the 2-mg dose (which, like lower-dose semaglutide for type 2 diabetes, comes in a single-use pen injector) showed that when compared head-to-head with a 1-mg/week dose in a 40-week study with 961 randomized patients, the 2-mg regimen led to a significant average incremental reduction in A1c levels of 0.23 percentage points. The 2-mg dose also produced a significant incremental increase in weight loss, with patients losing 0.93 kg more on the higher dose.

The 2-mg dose gives patients with type 2 diabetes and clinicians an “additional option” when a bigger “shift” in blood glucose is needed, said Juan Pablo Frias, MD, National Research Institute, Los Angeles, California, who was lead investigator for SUSTAIN FORTE, in a written statement.

As well as reducing glucose levels, semaglutide has been shown to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known cardiovascular disease.

Semaglutide was approved as a 2.4-mg injectable dose, as Wegovy, in 2021 for weight loss in patients with overweight or obesity.

SUSTAIN FORTE and other trials of semaglutide were sponsored by Novo Nordisk. SURPASS-2 and other trials of tirzepatide were sponsored by Lilly. Dr. Frias was lead investigator for both SUSTAIN FORTE and SURPASS-2, as well as an investigator for other trials sponsored by Lilly, Novo Nordisk, and other companies.

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

The U.S. Food and Drug Administration has approved a higher 2-mg dose of the GLP-1 agonist semaglutide (Ozempic, Novo Nordisk) for adults with type 2 diabetes, giving a higher-dose alternative to the previous maximum 1-mg dose of semaglutide, administered by subcutaneous injection once weekly.

Semaglutide is currently available as 0.5-mg and 1-mg doses.

Results from the pivotal SUSTAIN FORTE study of the 2-mg dose (which, like lower-dose semaglutide for type 2 diabetes, comes in a single-use pen injector) showed that when compared head-to-head with a 1-mg/week dose in a 40-week study with 961 randomized patients, the 2-mg regimen led to a significant average incremental reduction in A1c levels of 0.23 percentage points. The 2-mg dose also produced a significant incremental increase in weight loss, with patients losing 0.93 kg more on the higher dose.

The 2-mg dose gives patients with type 2 diabetes and clinicians an “additional option” when a bigger “shift” in blood glucose is needed, said Juan Pablo Frias, MD, National Research Institute, Los Angeles, California, who was lead investigator for SUSTAIN FORTE, in a written statement.

As well as reducing glucose levels, semaglutide has been shown to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known cardiovascular disease.

Semaglutide was approved as a 2.4-mg injectable dose, as Wegovy, in 2021 for weight loss in patients with overweight or obesity.

SUSTAIN FORTE and other trials of semaglutide were sponsored by Novo Nordisk. SURPASS-2 and other trials of tirzepatide were sponsored by Lilly. Dr. Frias was lead investigator for both SUSTAIN FORTE and SURPASS-2, as well as an investigator for other trials sponsored by Lilly, Novo Nordisk, and other companies.

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

The widely used antidiabetic drug metformin may cause genital birth defects such as undescended testicles and urethral problems in the male offspring of men who take the medication, researchers have found.

The association appears to involve the effects of metformin on the development of sperm during a critical window prior to conception. Female offspring were not affected. Although previous studies have linked diabetes with fertility problems in men, the latest study is the first to show that these problems can result from treatment rather than the disease itself, according to the researchers, whose findings appear in Annals of Internal Medicine.

“This is the first data to suggest that paternal metformin [use] may be associated with birth defects in children. As such, it would be early to begin to alter clinical practice,” Michael Eisenberg, MD, director of male reproductive medicine and surgery, department of urology, Stanford (Calif.) University, who is a coauthor of the study, said in an interview. “However, if it is confirmed in other populations, then it may begin to enter counseling discussions.”

Dr. Eisenberg added that eating a nutritious diet, exercising, and maintaining a healthy body weight “can improve a man’s health and likely his fertility as well.”

For the new study, Dr. Eisenberg and colleagues analyzed records in a registry of all 1.25 million births that occurred in Denmark between 1997 and 2016. The registry included information on birth defects and parental drug prescriptions.

Offspring were considered exposed to a diabetes drug if a father had filled one or more prescriptions for the medications during the 3 months prior to conception, when the fertilizing sperm would have been produced.

The final analysis included 1,116,779 offspring – all singleton births to women without a history of diabetes or essential hypertension – of whom 7,029 were exposed to diabetes drugs via the father, and 3.3% (n = 36,585) had one or more major birth defects.

Among male offspring whose fathers had taken metformin (n = 1,451), there was a 3.4-fold greater incidence of major genitourinary birth defects, according to the researchers. The study failed to find associations between birth defects and the use of insulin. Although a signal did emerge for sulfonylurea-based drugs, it did not reach statistical significance.

The risk associated with metformin did not appear for men who were prescribed the drug in the year before or after sperm development. Nor was it evident in siblings of the boys with birth defects who were not considered to have been exposed to the medication, the researchers reported.

In an editorial accompanying the journal article, Germaine Buck Louis, PhD, a reproductive and perinatal epidemiologist, wrote: “Given the prevalence of metformin use as first-line therapy for type 2 diabetes, corroboration of these findings is urgently needed.”

Dr. Louis, dean of the College of Health and Human Services at George Mason University, Washington, said a key limitation of the research is the lack of data on how well men in the study adhered to their diabetes treatment. Nevertheless, “clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications.”

The researchers received funding from the National Institutes of Health and the Centers for Disease Control and Prevention.

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

The widely used antidiabetic drug metformin may cause genital birth defects such as undescended testicles and urethral problems in the male offspring of men who take the medication, researchers have found.

The association appears to involve the effects of metformin on the development of sperm during a critical window prior to conception. Female offspring were not affected. Although previous studies have linked diabetes with fertility problems in men, the latest study is the first to show that these problems can result from treatment rather than the disease itself, according to the researchers, whose findings appear in Annals of Internal Medicine.

“This is the first data to suggest that paternal metformin [use] may be associated with birth defects in children. As such, it would be early to begin to alter clinical practice,” Michael Eisenberg, MD, director of male reproductive medicine and surgery, department of urology, Stanford (Calif.) University, who is a coauthor of the study, said in an interview. “However, if it is confirmed in other populations, then it may begin to enter counseling discussions.”

Dr. Eisenberg added that eating a nutritious diet, exercising, and maintaining a healthy body weight “can improve a man’s health and likely his fertility as well.”

For the new study, Dr. Eisenberg and colleagues analyzed records in a registry of all 1.25 million births that occurred in Denmark between 1997 and 2016. The registry included information on birth defects and parental drug prescriptions.

Offspring were considered exposed to a diabetes drug if a father had filled one or more prescriptions for the medications during the 3 months prior to conception, when the fertilizing sperm would have been produced.

The final analysis included 1,116,779 offspring – all singleton births to women without a history of diabetes or essential hypertension – of whom 7,029 were exposed to diabetes drugs via the father, and 3.3% (n = 36,585) had one or more major birth defects.

Among male offspring whose fathers had taken metformin (n = 1,451), there was a 3.4-fold greater incidence of major genitourinary birth defects, according to the researchers. The study failed to find associations between birth defects and the use of insulin. Although a signal did emerge for sulfonylurea-based drugs, it did not reach statistical significance.

The risk associated with metformin did not appear for men who were prescribed the drug in the year before or after sperm development. Nor was it evident in siblings of the boys with birth defects who were not considered to have been exposed to the medication, the researchers reported.

In an editorial accompanying the journal article, Germaine Buck Louis, PhD, a reproductive and perinatal epidemiologist, wrote: “Given the prevalence of metformin use as first-line therapy for type 2 diabetes, corroboration of these findings is urgently needed.”

Dr. Louis, dean of the College of Health and Human Services at George Mason University, Washington, said a key limitation of the research is the lack of data on how well men in the study adhered to their diabetes treatment. Nevertheless, “clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications.”

The researchers received funding from the National Institutes of Health and the Centers for Disease Control and Prevention.

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

The widely used antidiabetic drug metformin may cause genital birth defects such as undescended testicles and urethral problems in the male offspring of men who take the medication, researchers have found.

The association appears to involve the effects of metformin on the development of sperm during a critical window prior to conception. Female offspring were not affected. Although previous studies have linked diabetes with fertility problems in men, the latest study is the first to show that these problems can result from treatment rather than the disease itself, according to the researchers, whose findings appear in Annals of Internal Medicine.

“This is the first data to suggest that paternal metformin [use] may be associated with birth defects in children. As such, it would be early to begin to alter clinical practice,” Michael Eisenberg, MD, director of male reproductive medicine and surgery, department of urology, Stanford (Calif.) University, who is a coauthor of the study, said in an interview. “However, if it is confirmed in other populations, then it may begin to enter counseling discussions.”

Dr. Eisenberg added that eating a nutritious diet, exercising, and maintaining a healthy body weight “can improve a man’s health and likely his fertility as well.”

For the new study, Dr. Eisenberg and colleagues analyzed records in a registry of all 1.25 million births that occurred in Denmark between 1997 and 2016. The registry included information on birth defects and parental drug prescriptions.

Offspring were considered exposed to a diabetes drug if a father had filled one or more prescriptions for the medications during the 3 months prior to conception, when the fertilizing sperm would have been produced.

The final analysis included 1,116,779 offspring – all singleton births to women without a history of diabetes or essential hypertension – of whom 7,029 were exposed to diabetes drugs via the father, and 3.3% (n = 36,585) had one or more major birth defects.

Among male offspring whose fathers had taken metformin (n = 1,451), there was a 3.4-fold greater incidence of major genitourinary birth defects, according to the researchers. The study failed to find associations between birth defects and the use of insulin. Although a signal did emerge for sulfonylurea-based drugs, it did not reach statistical significance.

The risk associated with metformin did not appear for men who were prescribed the drug in the year before or after sperm development. Nor was it evident in siblings of the boys with birth defects who were not considered to have been exposed to the medication, the researchers reported.

In an editorial accompanying the journal article, Germaine Buck Louis, PhD, a reproductive and perinatal epidemiologist, wrote: “Given the prevalence of metformin use as first-line therapy for type 2 diabetes, corroboration of these findings is urgently needed.”

Dr. Louis, dean of the College of Health and Human Services at George Mason University, Washington, said a key limitation of the research is the lack of data on how well men in the study adhered to their diabetes treatment. Nevertheless, “clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications.”

The researchers received funding from the National Institutes of Health and the Centers for Disease Control and Prevention.

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

The infants of obese pregnant women had a 55% higher adjusted perinatal death rate, compared with those of normal-weight pregnant women, but lower gestational age had a mediating effect, based on data from nearly 400,000 women-infant pairs.

“While some obesity-related causes of fetal death are known, the exact pathophysiology behind the effects of obesity on perinatal death are not completely understood,” Jeffrey N. Bone, MD, of the University of British Columbia, Vancouver, and colleagues wrote. Higher body mass index prior to pregnancy also is associated with preterm delivery, but the effect of gestational age on the association between BMI and infant mortality has not been well explored.

In a study published in PLOS ONE, the researchers reviewed data from nearly 400,000 women obtained through the British Columbia Perinatal Database Registry, which collects obstetric and neonatal data from hospital charts and from delivery records of home births. Births at less than 20 weeks’ gestation and late pregnancy terminations were excluded.

BMI was based on self-reported prepregnancy height and weight; of the 392,820 included women, 12.8% were classified as obese, 20.6% were overweight, 60.6% were normal weight, and 6.0% were underweight. Infants of women with higher BMI had a lower gestational age at delivery. Perinatal mortality occurred in 1,834 pregnancies (0.5%). In adjusted analysis, infant perinatal death was significantly more likely for obese women (adjusted odds ratio, 1.55) and overweight women (aOR, 1.22).

However, 63.1% of this association in obese women was mediated by gestational age of the infant at delivery, with aORs of 1.32 and 1.18 for natural indirect and natural direct effects, respectively, compared with that of normal-weight women. Similar, but lesser effects were noted for overweight women, with aORs of 1.11 and 1.10, respectively. “Direct effects were higher, and mediation was lower for stillbirth than for neonatal death, where the total effect was entirely indirect,” but the confidence intervals remained consistent with the primary analyses, the researchers noted.

The increased perinatal death rates of infants of obese and overweight women reflect data from previous studies, but the current study’s use of mediation analysis offers new insight on the mechanism by which perinatal death rates increase with higher maternal BMI, the researchers wrote.

The study findings were limited by several factors including the need to consider potential common risk factors for both perinatal death and early delivery that would be affected by maternal obesity, the researchers noted. Other limitations included the use of gestational age at stillbirth, which represents an approximation of fetal death in some cases, and the use of self-reports for prepregnancy maternal BMI.

However, the results were strengthened by the large, population-based design and information on potential confounding variables, and suggest that early gestational age at delivery may play a role in maternal obesity-related perinatal death risk.

“To better inform the pregnancy management in obese women, further studies should continue to disentangle the causal pathways under which obesity increases the risk of perinatal death, including, for example, gestational diabetes and other obesity-related pregnancy complications,” they concluded.
 

More testing and counseling are needed

The current study is important because obesity rates continue to increase in the reproductive-age population, Marissa Platner, MD, of Emory University, Atlanta, said in an interview. “Obesity has become a known risk factor for adverse pregnancy outcomes, specifically the risk of stillbirth and perinatal death. However, the authors correctly point out that the underlying cause of these perinatal deaths in women with obesity is unclear. Additionally, ACOG recently updated their clinical guidelines to recommend routine antenatal testing for women with obesity due to these increased rates of stillbirth.

“I was not surprised by these findings; similar to previous literature, the risks of perinatal death seem to have a dose-response relationship with increasing BMI. We know that women with prepregnancy obesity are also at higher risk of perinatal complications in the preterm period, which would increase the risk of perinatal death,” Dr. Platner said

“I think the take-home message for clinicians is twofold,” Dr. Platner said. First, “we need to take the updated antenatal testing guidelines from ACOG very seriously and implement these in our practices.” Second, “in the preconception or early antepartum period, these patients should be thoroughly counseled on the associated risks of pregnancy and discuss appropriate gestational weight gain guidelines and lifestyle modifications.”

However, “additional research is needed in a U.S. population with higher rates of obesity to determine the true effects of obesity on perinatal deaths and to further elucidate the underlying pathophysiology and disease processes that may lead to increased risk of both stillbirth and perinatal deaths,” Dr. Platner emphasized.

*This story was updated on March 23, 2022.

The study was supported by the Sick Kids Foundation and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

The infants of obese pregnant women had a 55% higher adjusted perinatal death rate, compared with those of normal-weight pregnant women, but lower gestational age had a mediating effect, based on data from nearly 400,000 women-infant pairs.

“While some obesity-related causes of fetal death are known, the exact pathophysiology behind the effects of obesity on perinatal death are not completely understood,” Jeffrey N. Bone, MD, of the University of British Columbia, Vancouver, and colleagues wrote. Higher body mass index prior to pregnancy also is associated with preterm delivery, but the effect of gestational age on the association between BMI and infant mortality has not been well explored.

In a study published in PLOS ONE, the researchers reviewed data from nearly 400,000 women obtained through the British Columbia Perinatal Database Registry, which collects obstetric and neonatal data from hospital charts and from delivery records of home births. Births at less than 20 weeks’ gestation and late pregnancy terminations were excluded.

BMI was based on self-reported prepregnancy height and weight; of the 392,820 included women, 12.8% were classified as obese, 20.6% were overweight, 60.6% were normal weight, and 6.0% were underweight. Infants of women with higher BMI had a lower gestational age at delivery. Perinatal mortality occurred in 1,834 pregnancies (0.5%). In adjusted analysis, infant perinatal death was significantly more likely for obese women (adjusted odds ratio, 1.55) and overweight women (aOR, 1.22).

However, 63.1% of this association in obese women was mediated by gestational age of the infant at delivery, with aORs of 1.32 and 1.18 for natural indirect and natural direct effects, respectively, compared with that of normal-weight women. Similar, but lesser effects were noted for overweight women, with aORs of 1.11 and 1.10, respectively. “Direct effects were higher, and mediation was lower for stillbirth than for neonatal death, where the total effect was entirely indirect,” but the confidence intervals remained consistent with the primary analyses, the researchers noted.

The increased perinatal death rates of infants of obese and overweight women reflect data from previous studies, but the current study’s use of mediation analysis offers new insight on the mechanism by which perinatal death rates increase with higher maternal BMI, the researchers wrote.

The study findings were limited by several factors including the need to consider potential common risk factors for both perinatal death and early delivery that would be affected by maternal obesity, the researchers noted. Other limitations included the use of gestational age at stillbirth, which represents an approximation of fetal death in some cases, and the use of self-reports for prepregnancy maternal BMI.

However, the results were strengthened by the large, population-based design and information on potential confounding variables, and suggest that early gestational age at delivery may play a role in maternal obesity-related perinatal death risk.

“To better inform the pregnancy management in obese women, further studies should continue to disentangle the causal pathways under which obesity increases the risk of perinatal death, including, for example, gestational diabetes and other obesity-related pregnancy complications,” they concluded.
 

More testing and counseling are needed

The current study is important because obesity rates continue to increase in the reproductive-age population, Marissa Platner, MD, of Emory University, Atlanta, said in an interview. “Obesity has become a known risk factor for adverse pregnancy outcomes, specifically the risk of stillbirth and perinatal death. However, the authors correctly point out that the underlying cause of these perinatal deaths in women with obesity is unclear. Additionally, ACOG recently updated their clinical guidelines to recommend routine antenatal testing for women with obesity due to these increased rates of stillbirth.

“I was not surprised by these findings; similar to previous literature, the risks of perinatal death seem to have a dose-response relationship with increasing BMI. We know that women with prepregnancy obesity are also at higher risk of perinatal complications in the preterm period, which would increase the risk of perinatal death,” Dr. Platner said

“I think the take-home message for clinicians is twofold,” Dr. Platner said. First, “we need to take the updated antenatal testing guidelines from ACOG very seriously and implement these in our practices.” Second, “in the preconception or early antepartum period, these patients should be thoroughly counseled on the associated risks of pregnancy and discuss appropriate gestational weight gain guidelines and lifestyle modifications.”

However, “additional research is needed in a U.S. population with higher rates of obesity to determine the true effects of obesity on perinatal deaths and to further elucidate the underlying pathophysiology and disease processes that may lead to increased risk of both stillbirth and perinatal deaths,” Dr. Platner emphasized.

*This story was updated on March 23, 2022.

The study was supported by the Sick Kids Foundation and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

The infants of obese pregnant women had a 55% higher adjusted perinatal death rate, compared with those of normal-weight pregnant women, but lower gestational age had a mediating effect, based on data from nearly 400,000 women-infant pairs.

“While some obesity-related causes of fetal death are known, the exact pathophysiology behind the effects of obesity on perinatal death are not completely understood,” Jeffrey N. Bone, MD, of the University of British Columbia, Vancouver, and colleagues wrote. Higher body mass index prior to pregnancy also is associated with preterm delivery, but the effect of gestational age on the association between BMI and infant mortality has not been well explored.

In a study published in PLOS ONE, the researchers reviewed data from nearly 400,000 women obtained through the British Columbia Perinatal Database Registry, which collects obstetric and neonatal data from hospital charts and from delivery records of home births. Births at less than 20 weeks’ gestation and late pregnancy terminations were excluded.

BMI was based on self-reported prepregnancy height and weight; of the 392,820 included women, 12.8% were classified as obese, 20.6% were overweight, 60.6% were normal weight, and 6.0% were underweight. Infants of women with higher BMI had a lower gestational age at delivery. Perinatal mortality occurred in 1,834 pregnancies (0.5%). In adjusted analysis, infant perinatal death was significantly more likely for obese women (adjusted odds ratio, 1.55) and overweight women (aOR, 1.22).

However, 63.1% of this association in obese women was mediated by gestational age of the infant at delivery, with aORs of 1.32 and 1.18 for natural indirect and natural direct effects, respectively, compared with that of normal-weight women. Similar, but lesser effects were noted for overweight women, with aORs of 1.11 and 1.10, respectively. “Direct effects were higher, and mediation was lower for stillbirth than for neonatal death, where the total effect was entirely indirect,” but the confidence intervals remained consistent with the primary analyses, the researchers noted.

The increased perinatal death rates of infants of obese and overweight women reflect data from previous studies, but the current study’s use of mediation analysis offers new insight on the mechanism by which perinatal death rates increase with higher maternal BMI, the researchers wrote.

The study findings were limited by several factors including the need to consider potential common risk factors for both perinatal death and early delivery that would be affected by maternal obesity, the researchers noted. Other limitations included the use of gestational age at stillbirth, which represents an approximation of fetal death in some cases, and the use of self-reports for prepregnancy maternal BMI.

However, the results were strengthened by the large, population-based design and information on potential confounding variables, and suggest that early gestational age at delivery may play a role in maternal obesity-related perinatal death risk.

“To better inform the pregnancy management in obese women, further studies should continue to disentangle the causal pathways under which obesity increases the risk of perinatal death, including, for example, gestational diabetes and other obesity-related pregnancy complications,” they concluded.
 

More testing and counseling are needed

The current study is important because obesity rates continue to increase in the reproductive-age population, Marissa Platner, MD, of Emory University, Atlanta, said in an interview. “Obesity has become a known risk factor for adverse pregnancy outcomes, specifically the risk of stillbirth and perinatal death. However, the authors correctly point out that the underlying cause of these perinatal deaths in women with obesity is unclear. Additionally, ACOG recently updated their clinical guidelines to recommend routine antenatal testing for women with obesity due to these increased rates of stillbirth.

“I was not surprised by these findings; similar to previous literature, the risks of perinatal death seem to have a dose-response relationship with increasing BMI. We know that women with prepregnancy obesity are also at higher risk of perinatal complications in the preterm period, which would increase the risk of perinatal death,” Dr. Platner said

“I think the take-home message for clinicians is twofold,” Dr. Platner said. First, “we need to take the updated antenatal testing guidelines from ACOG very seriously and implement these in our practices.” Second, “in the preconception or early antepartum period, these patients should be thoroughly counseled on the associated risks of pregnancy and discuss appropriate gestational weight gain guidelines and lifestyle modifications.”

However, “additional research is needed in a U.S. population with higher rates of obesity to determine the true effects of obesity on perinatal deaths and to further elucidate the underlying pathophysiology and disease processes that may lead to increased risk of both stillbirth and perinatal deaths,” Dr. Platner emphasized.

*This story was updated on March 23, 2022.

The study was supported by the Sick Kids Foundation and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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