Diabetes

TOPLINE:

Individuals on an intermittent-fasting and protein-pacing (IF-P) diet had fewer gastrointestinal symptoms and increased diversity in gut microbiota than those on a calorie-restricted (CR) Mediterranean-style diet in a small, randomized trial.

METHODOLOGY:

• Researchers compared the effects on gastrointestinal symptoms, the gut microbiome, and circulating cytokines and metabolites of two low-calorie, 8-week dietary interventions: A Mediterranean-style continuous CR diet based on US dietary recommendations and an IF-P diet. The interventions were matched for energy intake.
• Participants included men and women with overweight/obesity who were randomly assigned to one of the two groups: CR diet (n = 20) and IF-P diet (n = 21).
• Researchers used samples and data from an ongoing randomized controlled trial (https://clinicaltrials.gov/study/NCT04327141) comparing the effects of the CR diet vs the IF-P diet on anthropometric and cardiometabolic outcomes.
• In a subanalysis for the current study, researchers compared outcomes in “high” and “low” responders to the IF-P regimen, based on relative weight loss.

TAKEAWAY:

• The IF-P diet resulted in more substantial reductions in patient-reported symptoms of gastrointestinal problems and more pronounced increases in gut microbiota diversity and in the abundance of microbial families and genera associated with favorable metabolic profiles, such as Christensenellaceae, Rikenellaceae, and Marvinbryantia, than the CR diet.
• The IF-P diet significantly increased cytokines linked to lipolysis, weight loss, inflammation, and the immune response.
• With the CR diet, metabolites associated with a longevity-related metabolic pathway increased.
• The subgroup analysis of high and low responders to the IF-P diet showed an increased abundance of certain bacteria associated with metabolic benefits and anti-inflammatory effects among high responders, whereas low responders showed an increased abundance of butyrate-producing and nutritionally adaptive species such as Eubacterium ventriosum and Roseburia inulinivorans.
• A fecal metabolome analysis revealed that high responders showed enrichment of fecal metabolites involved in lipid metabolism, whereas more prominent pathways in low responders were related to the metabolism of amino acids and peptides, as well as tyrosine metabolism and arginine biosynthesis.

IN PRACTICE:

“These findings shed light on the differential effects of IF regimens, including IF-P, as a promising dietary intervention for obesity management and microbiotic and metabolic health.”

SOURCE:

The study, with corresponding author Paul J. Arciero, PhD, of the Human Nutrition and Metabolism Laboratory at Skidmore College, Saratoga Springs, New York, was published online in Nature Communications.

LIMITATIONS:

The reliance on fecal samples to represent the gut microbiome may have overlooked potential microbial populations in the upper gastrointestinal tract. Other limitations include the short, 8-week duration of the trial and small number of patients.

DISCLOSURES:

The study was primarily funded by an unrestricted grant from Isagenix International LLC to Arciero, with secondary funding provided to a coauthor. Dr. Arciero is a consultant for Isagenix International LLC, is an advisory board member of the International Protein Board, and received financial compensation for books and keynote presentations on protein pacing. One coauthor is employed by the funder.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals on an intermittent-fasting and protein-pacing (IF-P) diet had fewer gastrointestinal symptoms and increased diversity in gut microbiota than those on a calorie-restricted (CR) Mediterranean-style diet in a small, randomized trial.

METHODOLOGY:

• Researchers compared the effects on gastrointestinal symptoms, the gut microbiome, and circulating cytokines and metabolites of two low-calorie, 8-week dietary interventions: A Mediterranean-style continuous CR diet based on US dietary recommendations and an IF-P diet. The interventions were matched for energy intake.
• Participants included men and women with overweight/obesity who were randomly assigned to one of the two groups: CR diet (n = 20) and IF-P diet (n = 21).
• Researchers used samples and data from an ongoing randomized controlled trial (https://clinicaltrials.gov/study/NCT04327141) comparing the effects of the CR diet vs the IF-P diet on anthropometric and cardiometabolic outcomes.
• In a subanalysis for the current study, researchers compared outcomes in “high” and “low” responders to the IF-P regimen, based on relative weight loss.

TAKEAWAY:

• The IF-P diet resulted in more substantial reductions in patient-reported symptoms of gastrointestinal problems and more pronounced increases in gut microbiota diversity and in the abundance of microbial families and genera associated with favorable metabolic profiles, such as Christensenellaceae, Rikenellaceae, and Marvinbryantia, than the CR diet.
• The IF-P diet significantly increased cytokines linked to lipolysis, weight loss, inflammation, and the immune response.
• With the CR diet, metabolites associated with a longevity-related metabolic pathway increased.
• The subgroup analysis of high and low responders to the IF-P diet showed an increased abundance of certain bacteria associated with metabolic benefits and anti-inflammatory effects among high responders, whereas low responders showed an increased abundance of butyrate-producing and nutritionally adaptive species such as Eubacterium ventriosum and Roseburia inulinivorans.
• A fecal metabolome analysis revealed that high responders showed enrichment of fecal metabolites involved in lipid metabolism, whereas more prominent pathways in low responders were related to the metabolism of amino acids and peptides, as well as tyrosine metabolism and arginine biosynthesis.

IN PRACTICE:

“These findings shed light on the differential effects of IF regimens, including IF-P, as a promising dietary intervention for obesity management and microbiotic and metabolic health.”

SOURCE:

The study, with corresponding author Paul J. Arciero, PhD, of the Human Nutrition and Metabolism Laboratory at Skidmore College, Saratoga Springs, New York, was published online in Nature Communications.

LIMITATIONS:

The reliance on fecal samples to represent the gut microbiome may have overlooked potential microbial populations in the upper gastrointestinal tract. Other limitations include the short, 8-week duration of the trial and small number of patients.

DISCLOSURES:

The study was primarily funded by an unrestricted grant from Isagenix International LLC to Arciero, with secondary funding provided to a coauthor. Dr. Arciero is a consultant for Isagenix International LLC, is an advisory board member of the International Protein Board, and received financial compensation for books and keynote presentations on protein pacing. One coauthor is employed by the funder.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals on an intermittent-fasting and protein-pacing (IF-P) diet had fewer gastrointestinal symptoms and increased diversity in gut microbiota than those on a calorie-restricted (CR) Mediterranean-style diet in a small, randomized trial.

METHODOLOGY:

• Researchers compared the effects on gastrointestinal symptoms, the gut microbiome, and circulating cytokines and metabolites of two low-calorie, 8-week dietary interventions: A Mediterranean-style continuous CR diet based on US dietary recommendations and an IF-P diet. The interventions were matched for energy intake.
• Participants included men and women with overweight/obesity who were randomly assigned to one of the two groups: CR diet (n = 20) and IF-P diet (n = 21).
• Researchers used samples and data from an ongoing randomized controlled trial (https://clinicaltrials.gov/study/NCT04327141) comparing the effects of the CR diet vs the IF-P diet on anthropometric and cardiometabolic outcomes.
• In a subanalysis for the current study, researchers compared outcomes in “high” and “low” responders to the IF-P regimen, based on relative weight loss.

TAKEAWAY:

• The IF-P diet resulted in more substantial reductions in patient-reported symptoms of gastrointestinal problems and more pronounced increases in gut microbiota diversity and in the abundance of microbial families and genera associated with favorable metabolic profiles, such as Christensenellaceae, Rikenellaceae, and Marvinbryantia, than the CR diet.
• The IF-P diet significantly increased cytokines linked to lipolysis, weight loss, inflammation, and the immune response.
• With the CR diet, metabolites associated with a longevity-related metabolic pathway increased.
• The subgroup analysis of high and low responders to the IF-P diet showed an increased abundance of certain bacteria associated with metabolic benefits and anti-inflammatory effects among high responders, whereas low responders showed an increased abundance of butyrate-producing and nutritionally adaptive species such as Eubacterium ventriosum and Roseburia inulinivorans.
• A fecal metabolome analysis revealed that high responders showed enrichment of fecal metabolites involved in lipid metabolism, whereas more prominent pathways in low responders were related to the metabolism of amino acids and peptides, as well as tyrosine metabolism and arginine biosynthesis.

IN PRACTICE:

“These findings shed light on the differential effects of IF regimens, including IF-P, as a promising dietary intervention for obesity management and microbiotic and metabolic health.”

SOURCE:

The study, with corresponding author Paul J. Arciero, PhD, of the Human Nutrition and Metabolism Laboratory at Skidmore College, Saratoga Springs, New York, was published online in Nature Communications.

LIMITATIONS:

The reliance on fecal samples to represent the gut microbiome may have overlooked potential microbial populations in the upper gastrointestinal tract. Other limitations include the short, 8-week duration of the trial and small number of patients.

DISCLOSURES:

The study was primarily funded by an unrestricted grant from Isagenix International LLC to Arciero, with secondary funding provided to a coauthor. Dr. Arciero is a consultant for Isagenix International LLC, is an advisory board member of the International Protein Board, and received financial compensation for books and keynote presentations on protein pacing. One coauthor is employed by the funder.
 

A version of this article appeared on Medscape.com.

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

TOPLINE:

Whether they have normal weight, overweight, or obesity, individuals with metabolically healthy (MH) phenotypes show a lower frequency of impaired glucose metabolism than their unhealthy counterparts across all weight categories.

METHODOLOGY:

• The concepts of MH overweight and MH obesity refer to a subset of people who exhibit an absence of cardiometabolic risk factors despite excess body fat, but the prevalence of prediabetes has not been investigated by metabolic phenotype and body mass index (BMI).
• This study first validated the use of estimated glucose disposal rate (eGDR), an index of insulin sensitivity calculated from clinical variables, in 350 individuals without diabetes (mean age, 37 years; 219 women; mean BMI, 30.3) from the EUGENE2 project who had varying glucose tolerance values originally assessed by insulin-stimulated glucose disposal.
• Researchers then stratified 2201 participants without diabetes (mean age, 46 years; White; 1290 women; mean BMI, 31.2) from the CATAMERI study according to BMI into three groups — individuals with normal weight (BMI, 18-24.9), overweight (BMI, 25-29.9), and obesity (BMI, ≥ 30).
• The men and women in each BMI group were separated into quartiles of insulin sensitivity based on eGDR index:
• In the normal weight group, men and women were defined as MH in the top three eGDR quartiles and metabolically unhealthy (MU) in the lowest quartile.
• In the overweight and obesity groups, people were defined as MH in the top eGDR quartile and MU in the lower three quartiles.
• Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG+IGT conditions (from an oral glucose tolerance test) were compared in individuals without diabetes based on MH or unhealthy phenotypes across normal weight, overweight, and obese categories.

TAKEAWAY:

• eGDR demonstrated good accuracy in detecting individuals with higher insulin sensitivity in the EUGENE2 cohort.
• The MH overweight and MH obesity groups showed comparable glycemic parameters as the MH normal weight group, whereas the MU overweight and MU obesity groups exhibited higher A1c levels and fasting and 2-hour post-load glucose than the MH normal weight group.
• The frequencies of IFG, IGT, and IFG+IGT conditions were similar among the MH normal weight, MH overweight, and MH obesity groups but were higher in the MU overweight and MU obesity groups than in the MU normal weight group.
• Furthermore, compared with those in the MH normal weight group, the odds of prediabetes were at least two times higher in the MU obesity (odds ratio [OR], 2.54; P < .001) and MU overweight (OR, 2.06; P < .001) groups but not significantly different in the MU normal weight, MH obesity, and MH overweight groups.

IN PRACTICE:

The authors wrote, “Overall, the results of this cross-sectional study support the notion that metabolically healthy individuals with overweight or obesity have a more favorable metabolic risk profile in comparison to metabolically unhealthy subjects with overweight or obesity.”

SOURCE:

The study was conducted by Chiara M.A. Cefalo, MD, department of clinical and molecular medicine, Sapienza University of Rome, Rome, Italy, and was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

There was no consensus on the parameters and cutoff values for defining metabolic health status, allowing for potential variations in results. The study design suggested an association with prevalent IFG and IGT conditions but not with incident IFG and IGT conditions. All participants in this study were White, limiting the generalizability of its findings.

DISCLOSURES:

The study was supported by Sapienza University of Rome and the Italian Ministry of University. The authors declared no conflicts of interest.

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

TOPLINE:

Whether they have normal weight, overweight, or obesity, individuals with metabolically healthy (MH) phenotypes show a lower frequency of impaired glucose metabolism than their unhealthy counterparts across all weight categories.

METHODOLOGY:

• The concepts of MH overweight and MH obesity refer to a subset of people who exhibit an absence of cardiometabolic risk factors despite excess body fat, but the prevalence of prediabetes has not been investigated by metabolic phenotype and body mass index (BMI).
• This study first validated the use of estimated glucose disposal rate (eGDR), an index of insulin sensitivity calculated from clinical variables, in 350 individuals without diabetes (mean age, 37 years; 219 women; mean BMI, 30.3) from the EUGENE2 project who had varying glucose tolerance values originally assessed by insulin-stimulated glucose disposal.
• Researchers then stratified 2201 participants without diabetes (mean age, 46 years; White; 1290 women; mean BMI, 31.2) from the CATAMERI study according to BMI into three groups — individuals with normal weight (BMI, 18-24.9), overweight (BMI, 25-29.9), and obesity (BMI, ≥ 30).
• The men and women in each BMI group were separated into quartiles of insulin sensitivity based on eGDR index:
• In the normal weight group, men and women were defined as MH in the top three eGDR quartiles and metabolically unhealthy (MU) in the lowest quartile.
• In the overweight and obesity groups, people were defined as MH in the top eGDR quartile and MU in the lower three quartiles.
• Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG+IGT conditions (from an oral glucose tolerance test) were compared in individuals without diabetes based on MH or unhealthy phenotypes across normal weight, overweight, and obese categories.

TAKEAWAY:

• eGDR demonstrated good accuracy in detecting individuals with higher insulin sensitivity in the EUGENE2 cohort.
• The MH overweight and MH obesity groups showed comparable glycemic parameters as the MH normal weight group, whereas the MU overweight and MU obesity groups exhibited higher A1c levels and fasting and 2-hour post-load glucose than the MH normal weight group.
• The frequencies of IFG, IGT, and IFG+IGT conditions were similar among the MH normal weight, MH overweight, and MH obesity groups but were higher in the MU overweight and MU obesity groups than in the MU normal weight group.
• Furthermore, compared with those in the MH normal weight group, the odds of prediabetes were at least two times higher in the MU obesity (odds ratio [OR], 2.54; P < .001) and MU overweight (OR, 2.06; P < .001) groups but not significantly different in the MU normal weight, MH obesity, and MH overweight groups.

IN PRACTICE:

The authors wrote, “Overall, the results of this cross-sectional study support the notion that metabolically healthy individuals with overweight or obesity have a more favorable metabolic risk profile in comparison to metabolically unhealthy subjects with overweight or obesity.”

SOURCE:

The study was conducted by Chiara M.A. Cefalo, MD, department of clinical and molecular medicine, Sapienza University of Rome, Rome, Italy, and was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

There was no consensus on the parameters and cutoff values for defining metabolic health status, allowing for potential variations in results. The study design suggested an association with prevalent IFG and IGT conditions but not with incident IFG and IGT conditions. All participants in this study were White, limiting the generalizability of its findings.

DISCLOSURES:

The study was supported by Sapienza University of Rome and the Italian Ministry of University. The authors declared no conflicts of interest.

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

TOPLINE:

Whether they have normal weight, overweight, or obesity, individuals with metabolically healthy (MH) phenotypes show a lower frequency of impaired glucose metabolism than their unhealthy counterparts across all weight categories.

METHODOLOGY:

• The concepts of MH overweight and MH obesity refer to a subset of people who exhibit an absence of cardiometabolic risk factors despite excess body fat, but the prevalence of prediabetes has not been investigated by metabolic phenotype and body mass index (BMI).
• This study first validated the use of estimated glucose disposal rate (eGDR), an index of insulin sensitivity calculated from clinical variables, in 350 individuals without diabetes (mean age, 37 years; 219 women; mean BMI, 30.3) from the EUGENE2 project who had varying glucose tolerance values originally assessed by insulin-stimulated glucose disposal.
• Researchers then stratified 2201 participants without diabetes (mean age, 46 years; White; 1290 women; mean BMI, 31.2) from the CATAMERI study according to BMI into three groups — individuals with normal weight (BMI, 18-24.9), overweight (BMI, 25-29.9), and obesity (BMI, ≥ 30).
• The men and women in each BMI group were separated into quartiles of insulin sensitivity based on eGDR index:
• In the normal weight group, men and women were defined as MH in the top three eGDR quartiles and metabolically unhealthy (MU) in the lowest quartile.
• In the overweight and obesity groups, people were defined as MH in the top eGDR quartile and MU in the lower three quartiles.
• Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG+IGT conditions (from an oral glucose tolerance test) were compared in individuals without diabetes based on MH or unhealthy phenotypes across normal weight, overweight, and obese categories.

TAKEAWAY:

• eGDR demonstrated good accuracy in detecting individuals with higher insulin sensitivity in the EUGENE2 cohort.
• The MH overweight and MH obesity groups showed comparable glycemic parameters as the MH normal weight group, whereas the MU overweight and MU obesity groups exhibited higher A1c levels and fasting and 2-hour post-load glucose than the MH normal weight group.
• The frequencies of IFG, IGT, and IFG+IGT conditions were similar among the MH normal weight, MH overweight, and MH obesity groups but were higher in the MU overweight and MU obesity groups than in the MU normal weight group.
• Furthermore, compared with those in the MH normal weight group, the odds of prediabetes were at least two times higher in the MU obesity (odds ratio [OR], 2.54; P < .001) and MU overweight (OR, 2.06; P < .001) groups but not significantly different in the MU normal weight, MH obesity, and MH overweight groups.

IN PRACTICE:

The authors wrote, “Overall, the results of this cross-sectional study support the notion that metabolically healthy individuals with overweight or obesity have a more favorable metabolic risk profile in comparison to metabolically unhealthy subjects with overweight or obesity.”

SOURCE:

The study was conducted by Chiara M.A. Cefalo, MD, department of clinical and molecular medicine, Sapienza University of Rome, Rome, Italy, and was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

There was no consensus on the parameters and cutoff values for defining metabolic health status, allowing for potential variations in results. The study design suggested an association with prevalent IFG and IGT conditions but not with incident IFG and IGT conditions. All participants in this study were White, limiting the generalizability of its findings.

DISCLOSURES:

The study was supported by Sapienza University of Rome and the Italian Ministry of University. The authors declared no conflicts of interest.

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

TOPLINE:

Mortality and disability-adjusted life years (DALYs) among people with type 1 diabetes (T1D) aged ≥ 65 years dropped significantly from 1990 to 2019. Both were lower among women and those living in higher sociodemographic areas.

METHODOLOGY:

• A population-based study of adults aged ≥ 65 years from 21 regions and 204 countries and territories, 1990-2019, was conducted.

TAKEAWAY:

• Globally, the prevalence of T1D among people aged ≥ 65 years increased by 180% between 1990 and 2019, from 1.3 million to 3.7 million.
• The proportion of older people with T1D has consistently trended upward, from 12% of all people with T1D in 1990 to 17% in 2019.
• Age-standardized mortality from T1D among this age group significantly decreased by 25%, from 4.7/100,000 population in 1990 to 3.5/100,000 in 2019.
• Age-standardized increases in T1D prevalence have occurred in both men and women worldwide, while the increase was more rapid among men (average annual percent change, 1.00% vs 0.74%).
• Globally, T1D prevalence at least tripled in every age subgroup of those aged ≥ 65 years, and even fivefold to sixfold for those ≥ 90-95 years (0.02-0.11 million for ages 90-94 years; 0.005-0.03 million for ages ≥ 95 years).
• No decreases occurred in T1D prevalence among those aged ≥ 65 years in any of the 21 global regions.
• Three primary risk factors associated with DALYs for T1D among people aged ≥ 65 years were high fasting plasma glucose levels, low temperature, and high temperature, accounting for 103 DALYs per 100,000 people, 3/100,000 people, and 1/100,000 people, respectively, in 2019.

IN PRACTICE:

“The results suggest that T1DM is no longer a contributory factor in decreased life expectancy owing to improvements in medical care over the three decades,” the authors wrote. “Management of high fasting plasma glucose levels remains a major challenge for older people with T1D, and targeted clinical guidelines are needed.”

SOURCE:

The study was conducted by Kaijie Yang, the Department of Endocrinology and Metabolism, the Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China, and colleagues. The study was published online in the BMJ.

LIMITATIONS:

Data were extrapolated from countries that have epidemiologic data. Health information systems and reporting mechanisms vary across countries and regions. Disease burden data include a time lag. Diagnosing T1D in older people can be challenging.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. The authors reported no additional financial relationships.

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

TOPLINE:

Mortality and disability-adjusted life years (DALYs) among people with type 1 diabetes (T1D) aged ≥ 65 years dropped significantly from 1990 to 2019. Both were lower among women and those living in higher sociodemographic areas.

METHODOLOGY:

• A population-based study of adults aged ≥ 65 years from 21 regions and 204 countries and territories, 1990-2019, was conducted.

TAKEAWAY:

• Globally, the prevalence of T1D among people aged ≥ 65 years increased by 180% between 1990 and 2019, from 1.3 million to 3.7 million.
• The proportion of older people with T1D has consistently trended upward, from 12% of all people with T1D in 1990 to 17% in 2019.
• Age-standardized mortality from T1D among this age group significantly decreased by 25%, from 4.7/100,000 population in 1990 to 3.5/100,000 in 2019.
• Age-standardized increases in T1D prevalence have occurred in both men and women worldwide, while the increase was more rapid among men (average annual percent change, 1.00% vs 0.74%).
• Globally, T1D prevalence at least tripled in every age subgroup of those aged ≥ 65 years, and even fivefold to sixfold for those ≥ 90-95 years (0.02-0.11 million for ages 90-94 years; 0.005-0.03 million for ages ≥ 95 years).
• No decreases occurred in T1D prevalence among those aged ≥ 65 years in any of the 21 global regions.
• Three primary risk factors associated with DALYs for T1D among people aged ≥ 65 years were high fasting plasma glucose levels, low temperature, and high temperature, accounting for 103 DALYs per 100,000 people, 3/100,000 people, and 1/100,000 people, respectively, in 2019.

IN PRACTICE:

“The results suggest that T1DM is no longer a contributory factor in decreased life expectancy owing to improvements in medical care over the three decades,” the authors wrote. “Management of high fasting plasma glucose levels remains a major challenge for older people with T1D, and targeted clinical guidelines are needed.”

SOURCE:

The study was conducted by Kaijie Yang, the Department of Endocrinology and Metabolism, the Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China, and colleagues. The study was published online in the BMJ.

LIMITATIONS:

Data were extrapolated from countries that have epidemiologic data. Health information systems and reporting mechanisms vary across countries and regions. Disease burden data include a time lag. Diagnosing T1D in older people can be challenging.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. The authors reported no additional financial relationships.

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

TOPLINE:

Mortality and disability-adjusted life years (DALYs) among people with type 1 diabetes (T1D) aged ≥ 65 years dropped significantly from 1990 to 2019. Both were lower among women and those living in higher sociodemographic areas.

METHODOLOGY:

• A population-based study of adults aged ≥ 65 years from 21 regions and 204 countries and territories, 1990-2019, was conducted.

TAKEAWAY:

• Globally, the prevalence of T1D among people aged ≥ 65 years increased by 180% between 1990 and 2019, from 1.3 million to 3.7 million.
• The proportion of older people with T1D has consistently trended upward, from 12% of all people with T1D in 1990 to 17% in 2019.
• Age-standardized mortality from T1D among this age group significantly decreased by 25%, from 4.7/100,000 population in 1990 to 3.5/100,000 in 2019.
• Age-standardized increases in T1D prevalence have occurred in both men and women worldwide, while the increase was more rapid among men (average annual percent change, 1.00% vs 0.74%).
• Globally, T1D prevalence at least tripled in every age subgroup of those aged ≥ 65 years, and even fivefold to sixfold for those ≥ 90-95 years (0.02-0.11 million for ages 90-94 years; 0.005-0.03 million for ages ≥ 95 years).
• No decreases occurred in T1D prevalence among those aged ≥ 65 years in any of the 21 global regions.
• Three primary risk factors associated with DALYs for T1D among people aged ≥ 65 years were high fasting plasma glucose levels, low temperature, and high temperature, accounting for 103 DALYs per 100,000 people, 3/100,000 people, and 1/100,000 people, respectively, in 2019.

IN PRACTICE:

“The results suggest that T1DM is no longer a contributory factor in decreased life expectancy owing to improvements in medical care over the three decades,” the authors wrote. “Management of high fasting plasma glucose levels remains a major challenge for older people with T1D, and targeted clinical guidelines are needed.”

SOURCE:

The study was conducted by Kaijie Yang, the Department of Endocrinology and Metabolism, the Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China, and colleagues. The study was published online in the BMJ.

LIMITATIONS:

Data were extrapolated from countries that have epidemiologic data. Health information systems and reporting mechanisms vary across countries and regions. Disease burden data include a time lag. Diagnosing T1D in older people can be challenging.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. The authors reported no additional financial relationships.

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

TOPLINE:

Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.

METHODOLOGY:

• There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
• This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
• Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
• The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.

TAKEAWAY:

• Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
• Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
• The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
• Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
• The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.

IN PRACTICE:

“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.

SOURCE:

The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.

LIMITATIONS:

The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.

DISCLOSURES:

The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.

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

TOPLINE:

Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.

METHODOLOGY:

• There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
• This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
• Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
• The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.

TAKEAWAY:

• Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
• Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
• The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
• Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
• The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.

IN PRACTICE:

“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.

SOURCE:

The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.

LIMITATIONS:

The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.

DISCLOSURES:

The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.

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

TOPLINE:

Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.

METHODOLOGY:

• There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
• This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
• Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
• The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.

TAKEAWAY:

• Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
• Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
• The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
• Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
• The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.

IN PRACTICE:

“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.

SOURCE:

The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.

LIMITATIONS:

The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.

DISCLOSURES:

The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.

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

It seems intuitive that, because people with type 2 diabetes (T2D) generally need to avoid sugar, clinicians should recommend eating foods and using recipes containing artificial sweeteners such as sucralose instead.

Splenda, which produces sucralose and other non-sugar sweeteners (NSS), is a sponsor of the American Diabetes Association (ADA) Diabetes Food Hub. Earlier in 2024, the ADA settled a lawsuit regarding its former director of nutrition’s refusal to approve recipes containing sucralose (Splenda), which she believed “flew in the face of the ADA’s mission.” 

Experts agree that, while artificial sweeteners may help in certain scenarios, they can also be harmful.

“There’s not a lot of evidence that sweeteners like sucralose provide significant benefits, especially over the long term,” said Susan Swithers, PhD, professor, department of psychological sciences and associate dean for faculty affairs at Purdue University, West Lafayette, Indiana.

Dr. Swithers authored an article several years ago cautioning that consuming nonnutritive sweeteners in beverages not only fails to prevent disease but also is associated with an increase in risks for the same health outcomes associated with sugar-sweetened beverages, including T2D, cardiovascular disease, hypertension, and stroke.

“At this point, we have pretty good evidence that these chemicals that were once touted as being completely inert are, in fact, not inert,” she said. “We know that they’re unlikely to be toxic in the short term, but they are not benign, and they have consequences. Right now, we have little understanding of the outcomes of consumption of these products chronically.”
 

What the Science Says

In 2023, the World Health Organization (WHO) released a guideline on NSS that recommended against their use for weight control or to reduce the risk for noncommunicable diseases.

The systematic review and meta-analysis upon which the guideline is based found that high intakes of NSS were associated with increases in body mass index and, as Dr. Swithers found, risks of developing T2D, cardiovascular events, and any type of stroke, as well as hypertension, bladder cancer, and all-cause mortality.

In a press release announcing the guideline, Francesco Branca, WHO director for Nutrition and Food Safety, said, “NSS are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.” 

The “common” NSS named by WHO included sucralose, as well as acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, stevia, and stevia derivatives.

If NSS consumption can increase T2D risk, what about people who already have T2D? 

Some research suggests that NSS may affect people with and without T2D differently, said Dr. Swithers. For example, one small study showed that sucralose enhanced glucagon-like peptide 1 release and lowered blood glucose in healthy patients but not in patients with newly diagnosed T2D.

Similarly, Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, said in an interview that his group “showed for the first time in 2014 that disruption of the microbiome by artificial sweeteners is causally linked to disrupted glycemic control.” 

Recently, the team studied the impact of sucralose, aspartame, saccharin, and stevia in healthy adults and “were surprised to discover that all four sweeteners altered gut bacteria and the molecules they secrete,” he said. However, subsequent glucose tolerance tests in healthy humans showed varying results, “suggesting that human microbiome responses to the nonnutritive sweeteners we assessed are highly personalized and may lead to glycemic alterations in some, but not all, consumers depending on their microbes and the sweeteners they consume.” 

Nevertheless, a recent review led by researchers in Mexico concluded that sucralose consumption “is associated with various adverse health effects. Despite being considered safe following previous studies, recent research suggests possible links to systemic inflammation, metabolic diseases, disruptions in gut microbiota, liver damage, and toxic effects at the cellular level.” 

In addition, they wrote, “it is crucial to highlight the persistence of sucralose in the body, its ability to cross the placenta, and its presence in breast milk, raising concerns about prenatal and neonatal exposure.” 

Sabyasachi Sen, MD, a professor of biochemistry and molecular medicine at George Washington School of Medicine & Health Sciences, Washington, DC, has led and coauthored preclinical and clinical studies demonstrating the potential ill effects of sucralose and other artificial sweeteners. One showed that sucralose and acesulfame potassium–containing diet soda altered microbial taxa in two pilot studies in healthy young adults; another showed a connection between artificial sweeteners and inflammation.

But Dr. Sen’s current work is directed at his team’s finding that sucralose promotes the accumulation of reactive oxygen species and adipogenesis in human stem cells, he said in an interview. “It is essentially an additive that is clearly harmful to cells. Our concern is that stem cells are going to remain in the system for a long period of time. If it is causing inflammation in these cells, then that may lead to adverse outcomes.”

Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment & Education Center at Cedars-Sinai in Los Angeles, California, is the principal investigator of a recent study suggesting that non-aspartame NSS and aspartame alone may alter the structure and function of the stool and duodenal microbiomes. Levels of circulating inflammatory markers were also altered in participants who consumed artificial sweeteners, compared with control participants who did not.

In addition to these potential adverse effects, “we have to think about the fact that patients with diabetes often have other comorbidities like obesity and are at higher risk for cardiovascular disease and other conditions,” she said in an interview. “If you’re taking a patient who’s already at risk for those things and you don’t have a detailed discussion with them about pros and cons, you’re doing them a disservice.” 
 

Industry Interests

Addressing the largely negative but varying findings, Dr. Swithers said, “one of the difficulties with getting clear answers about the science is that the food and beverage industry has an interest in confusing the picture. If people are selling or using a product, the best thing is for them not have a clear reason to change their behavior. All that needs to happen is for them to be able say, ‘well, it’s not clear, and we don’t really know what’s going on, so I’m just going to keep doing what I’m doing.’ Then the producers and sellers of that product have won.” 

“As Upton Sinclair said,” she added, “‘It is difficult to get a man to understand something when his salary depends on his not understanding it.’ When organizations like ADA appear to be promoting a product like sucralose, and they’re not always being clear about disclosing the funding, I think that’s problematic.”

In fact, some recipes in the ADA’s hub that contain Splenda are marked sponsored, such as the four-ingredient peanut butter cookies; others, such as gluten-free brownies, are not — even though the latter contains “1/4 cup plus 1 tbsp” of Splenda Sugar Blend (Splenda produces several nonnutritive sweeteners, not all of which contain sucralose). Splenda is a sponsor of the ADA’s hub.
 

Consume in Moderation?

Regarding the use of Splenda products, Robert Gabbay, MD, PhD, the ADA’s chief scientific and medical officer, said in an interview that “some people with diabetes are accustomed to regularly consuming sugar-sweetened products, which can make management of their diabetes more challenging. As highlighted in the ADA’s Standards of Care, nonnutritive sweeteners (containing few or no calories) may be an acceptable substitute for sweeteners that contain sugar and calories when consumed in moderation. By providing a diabetes-friendly way to prepare foods people are used to eating, we can meet people where they are in offering support to effectively manage their diabetes.”

Of course, “moderation” means different things to different people. “With sucralose in particular, you can bake with it, you can cook with it, and beverages and packaged foods contain it, so it’s easy to end up overconsuming foods that may be fine if they’re occasional treats but aren’t healthy choices to have every single day,” Dr. Swithers said. “If you’re having a cookie containing sucralose once a week, it’s not a big deal, but if you’re having a cookie or a brownie every day, that’s something different.”

“I think ‘everything in moderation’ is a very reasonable approach here,” Dr. Mathur said. “Anything too much is probably not good, and that includes sweeteners like sucralose and others.”

Dr. Suez, whose team is currently exploring the mechanisms through which gut bacteria interact with nonnutritive sweeteners in the pathogenesis of cardiometabolic diseases, was more circumspect.

“We believe that additional, long-term, and non–industry-sponsored studies in humans are needed before we can make a recommendation in favor or against the use of nonnutritive sweeteners,” he said.

“However, our results demonstrating that nonnutritive sweeteners are not inert, when taken together with a growing body of evidence on potential harms of these sweeteners, merit caution until additional studies are completed,” he added. “Our findings do not imply in any way that sugar consumption, shown to be harmful to human health in many studies, is superior to nonnutritive sweeteners. Sugar consumption should be minimized, especially in individuals with obesity or diabetes. Of all the options, unsweetened beverages, specifically water, seem to be the safest and best options.”

Dr. Sen, who also “tries to convince patients to have sparkling or cold bottled water,” instead of artificially sweetened soda, agreed. “If a diabetes patient is trying to choose between sugar and sucralose, I’m not sure which one is worse.”

Dr. Swithers, Dr. Mathur, Dr. Sen, and Dr. Suez declared no competing interests.

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

It seems intuitive that, because people with type 2 diabetes (T2D) generally need to avoid sugar, clinicians should recommend eating foods and using recipes containing artificial sweeteners such as sucralose instead.

Splenda, which produces sucralose and other non-sugar sweeteners (NSS), is a sponsor of the American Diabetes Association (ADA) Diabetes Food Hub. Earlier in 2024, the ADA settled a lawsuit regarding its former director of nutrition’s refusal to approve recipes containing sucralose (Splenda), which she believed “flew in the face of the ADA’s mission.” 

Experts agree that, while artificial sweeteners may help in certain scenarios, they can also be harmful.

“There’s not a lot of evidence that sweeteners like sucralose provide significant benefits, especially over the long term,” said Susan Swithers, PhD, professor, department of psychological sciences and associate dean for faculty affairs at Purdue University, West Lafayette, Indiana.

Dr. Swithers authored an article several years ago cautioning that consuming nonnutritive sweeteners in beverages not only fails to prevent disease but also is associated with an increase in risks for the same health outcomes associated with sugar-sweetened beverages, including T2D, cardiovascular disease, hypertension, and stroke.

“At this point, we have pretty good evidence that these chemicals that were once touted as being completely inert are, in fact, not inert,” she said. “We know that they’re unlikely to be toxic in the short term, but they are not benign, and they have consequences. Right now, we have little understanding of the outcomes of consumption of these products chronically.”
 

What the Science Says

In 2023, the World Health Organization (WHO) released a guideline on NSS that recommended against their use for weight control or to reduce the risk for noncommunicable diseases.

The systematic review and meta-analysis upon which the guideline is based found that high intakes of NSS were associated with increases in body mass index and, as Dr. Swithers found, risks of developing T2D, cardiovascular events, and any type of stroke, as well as hypertension, bladder cancer, and all-cause mortality.

In a press release announcing the guideline, Francesco Branca, WHO director for Nutrition and Food Safety, said, “NSS are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.” 

The “common” NSS named by WHO included sucralose, as well as acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, stevia, and stevia derivatives.

If NSS consumption can increase T2D risk, what about people who already have T2D? 

Some research suggests that NSS may affect people with and without T2D differently, said Dr. Swithers. For example, one small study showed that sucralose enhanced glucagon-like peptide 1 release and lowered blood glucose in healthy patients but not in patients with newly diagnosed T2D.

Similarly, Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, said in an interview that his group “showed for the first time in 2014 that disruption of the microbiome by artificial sweeteners is causally linked to disrupted glycemic control.” 

Recently, the team studied the impact of sucralose, aspartame, saccharin, and stevia in healthy adults and “were surprised to discover that all four sweeteners altered gut bacteria and the molecules they secrete,” he said. However, subsequent glucose tolerance tests in healthy humans showed varying results, “suggesting that human microbiome responses to the nonnutritive sweeteners we assessed are highly personalized and may lead to glycemic alterations in some, but not all, consumers depending on their microbes and the sweeteners they consume.” 

Nevertheless, a recent review led by researchers in Mexico concluded that sucralose consumption “is associated with various adverse health effects. Despite being considered safe following previous studies, recent research suggests possible links to systemic inflammation, metabolic diseases, disruptions in gut microbiota, liver damage, and toxic effects at the cellular level.” 

In addition, they wrote, “it is crucial to highlight the persistence of sucralose in the body, its ability to cross the placenta, and its presence in breast milk, raising concerns about prenatal and neonatal exposure.” 

Sabyasachi Sen, MD, a professor of biochemistry and molecular medicine at George Washington School of Medicine & Health Sciences, Washington, DC, has led and coauthored preclinical and clinical studies demonstrating the potential ill effects of sucralose and other artificial sweeteners. One showed that sucralose and acesulfame potassium–containing diet soda altered microbial taxa in two pilot studies in healthy young adults; another showed a connection between artificial sweeteners and inflammation.

But Dr. Sen’s current work is directed at his team’s finding that sucralose promotes the accumulation of reactive oxygen species and adipogenesis in human stem cells, he said in an interview. “It is essentially an additive that is clearly harmful to cells. Our concern is that stem cells are going to remain in the system for a long period of time. If it is causing inflammation in these cells, then that may lead to adverse outcomes.”

Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment & Education Center at Cedars-Sinai in Los Angeles, California, is the principal investigator of a recent study suggesting that non-aspartame NSS and aspartame alone may alter the structure and function of the stool and duodenal microbiomes. Levels of circulating inflammatory markers were also altered in participants who consumed artificial sweeteners, compared with control participants who did not.

In addition to these potential adverse effects, “we have to think about the fact that patients with diabetes often have other comorbidities like obesity and are at higher risk for cardiovascular disease and other conditions,” she said in an interview. “If you’re taking a patient who’s already at risk for those things and you don’t have a detailed discussion with them about pros and cons, you’re doing them a disservice.” 
 

Industry Interests

Addressing the largely negative but varying findings, Dr. Swithers said, “one of the difficulties with getting clear answers about the science is that the food and beverage industry has an interest in confusing the picture. If people are selling or using a product, the best thing is for them not have a clear reason to change their behavior. All that needs to happen is for them to be able say, ‘well, it’s not clear, and we don’t really know what’s going on, so I’m just going to keep doing what I’m doing.’ Then the producers and sellers of that product have won.” 

“As Upton Sinclair said,” she added, “‘It is difficult to get a man to understand something when his salary depends on his not understanding it.’ When organizations like ADA appear to be promoting a product like sucralose, and they’re not always being clear about disclosing the funding, I think that’s problematic.”

In fact, some recipes in the ADA’s hub that contain Splenda are marked sponsored, such as the four-ingredient peanut butter cookies; others, such as gluten-free brownies, are not — even though the latter contains “1/4 cup plus 1 tbsp” of Splenda Sugar Blend (Splenda produces several nonnutritive sweeteners, not all of which contain sucralose). Splenda is a sponsor of the ADA’s hub.
 

Consume in Moderation?

Regarding the use of Splenda products, Robert Gabbay, MD, PhD, the ADA’s chief scientific and medical officer, said in an interview that “some people with diabetes are accustomed to regularly consuming sugar-sweetened products, which can make management of their diabetes more challenging. As highlighted in the ADA’s Standards of Care, nonnutritive sweeteners (containing few or no calories) may be an acceptable substitute for sweeteners that contain sugar and calories when consumed in moderation. By providing a diabetes-friendly way to prepare foods people are used to eating, we can meet people where they are in offering support to effectively manage their diabetes.”

Of course, “moderation” means different things to different people. “With sucralose in particular, you can bake with it, you can cook with it, and beverages and packaged foods contain it, so it’s easy to end up overconsuming foods that may be fine if they’re occasional treats but aren’t healthy choices to have every single day,” Dr. Swithers said. “If you’re having a cookie containing sucralose once a week, it’s not a big deal, but if you’re having a cookie or a brownie every day, that’s something different.”

“I think ‘everything in moderation’ is a very reasonable approach here,” Dr. Mathur said. “Anything too much is probably not good, and that includes sweeteners like sucralose and others.”

Dr. Suez, whose team is currently exploring the mechanisms through which gut bacteria interact with nonnutritive sweeteners in the pathogenesis of cardiometabolic diseases, was more circumspect.

“We believe that additional, long-term, and non–industry-sponsored studies in humans are needed before we can make a recommendation in favor or against the use of nonnutritive sweeteners,” he said.

“However, our results demonstrating that nonnutritive sweeteners are not inert, when taken together with a growing body of evidence on potential harms of these sweeteners, merit caution until additional studies are completed,” he added. “Our findings do not imply in any way that sugar consumption, shown to be harmful to human health in many studies, is superior to nonnutritive sweeteners. Sugar consumption should be minimized, especially in individuals with obesity or diabetes. Of all the options, unsweetened beverages, specifically water, seem to be the safest and best options.”

Dr. Sen, who also “tries to convince patients to have sparkling or cold bottled water,” instead of artificially sweetened soda, agreed. “If a diabetes patient is trying to choose between sugar and sucralose, I’m not sure which one is worse.”

Dr. Swithers, Dr. Mathur, Dr. Sen, and Dr. Suez declared no competing interests.

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

It seems intuitive that, because people with type 2 diabetes (T2D) generally need to avoid sugar, clinicians should recommend eating foods and using recipes containing artificial sweeteners such as sucralose instead.

Splenda, which produces sucralose and other non-sugar sweeteners (NSS), is a sponsor of the American Diabetes Association (ADA) Diabetes Food Hub. Earlier in 2024, the ADA settled a lawsuit regarding its former director of nutrition’s refusal to approve recipes containing sucralose (Splenda), which she believed “flew in the face of the ADA’s mission.” 

Experts agree that, while artificial sweeteners may help in certain scenarios, they can also be harmful.

“There’s not a lot of evidence that sweeteners like sucralose provide significant benefits, especially over the long term,” said Susan Swithers, PhD, professor, department of psychological sciences and associate dean for faculty affairs at Purdue University, West Lafayette, Indiana.

Dr. Swithers authored an article several years ago cautioning that consuming nonnutritive sweeteners in beverages not only fails to prevent disease but also is associated with an increase in risks for the same health outcomes associated with sugar-sweetened beverages, including T2D, cardiovascular disease, hypertension, and stroke.

“At this point, we have pretty good evidence that these chemicals that were once touted as being completely inert are, in fact, not inert,” she said. “We know that they’re unlikely to be toxic in the short term, but they are not benign, and they have consequences. Right now, we have little understanding of the outcomes of consumption of these products chronically.”
 

What the Science Says

In 2023, the World Health Organization (WHO) released a guideline on NSS that recommended against their use for weight control or to reduce the risk for noncommunicable diseases.

The systematic review and meta-analysis upon which the guideline is based found that high intakes of NSS were associated with increases in body mass index and, as Dr. Swithers found, risks of developing T2D, cardiovascular events, and any type of stroke, as well as hypertension, bladder cancer, and all-cause mortality.

In a press release announcing the guideline, Francesco Branca, WHO director for Nutrition and Food Safety, said, “NSS are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.” 

The “common” NSS named by WHO included sucralose, as well as acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, stevia, and stevia derivatives.

If NSS consumption can increase T2D risk, what about people who already have T2D? 

Some research suggests that NSS may affect people with and without T2D differently, said Dr. Swithers. For example, one small study showed that sucralose enhanced glucagon-like peptide 1 release and lowered blood glucose in healthy patients but not in patients with newly diagnosed T2D.

Similarly, Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, said in an interview that his group “showed for the first time in 2014 that disruption of the microbiome by artificial sweeteners is causally linked to disrupted glycemic control.” 

Recently, the team studied the impact of sucralose, aspartame, saccharin, and stevia in healthy adults and “were surprised to discover that all four sweeteners altered gut bacteria and the molecules they secrete,” he said. However, subsequent glucose tolerance tests in healthy humans showed varying results, “suggesting that human microbiome responses to the nonnutritive sweeteners we assessed are highly personalized and may lead to glycemic alterations in some, but not all, consumers depending on their microbes and the sweeteners they consume.” 

Nevertheless, a recent review led by researchers in Mexico concluded that sucralose consumption “is associated with various adverse health effects. Despite being considered safe following previous studies, recent research suggests possible links to systemic inflammation, metabolic diseases, disruptions in gut microbiota, liver damage, and toxic effects at the cellular level.” 

In addition, they wrote, “it is crucial to highlight the persistence of sucralose in the body, its ability to cross the placenta, and its presence in breast milk, raising concerns about prenatal and neonatal exposure.” 

Sabyasachi Sen, MD, a professor of biochemistry and molecular medicine at George Washington School of Medicine & Health Sciences, Washington, DC, has led and coauthored preclinical and clinical studies demonstrating the potential ill effects of sucralose and other artificial sweeteners. One showed that sucralose and acesulfame potassium–containing diet soda altered microbial taxa in two pilot studies in healthy young adults; another showed a connection between artificial sweeteners and inflammation.

But Dr. Sen’s current work is directed at his team’s finding that sucralose promotes the accumulation of reactive oxygen species and adipogenesis in human stem cells, he said in an interview. “It is essentially an additive that is clearly harmful to cells. Our concern is that stem cells are going to remain in the system for a long period of time. If it is causing inflammation in these cells, then that may lead to adverse outcomes.”

Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment & Education Center at Cedars-Sinai in Los Angeles, California, is the principal investigator of a recent study suggesting that non-aspartame NSS and aspartame alone may alter the structure and function of the stool and duodenal microbiomes. Levels of circulating inflammatory markers were also altered in participants who consumed artificial sweeteners, compared with control participants who did not.

In addition to these potential adverse effects, “we have to think about the fact that patients with diabetes often have other comorbidities like obesity and are at higher risk for cardiovascular disease and other conditions,” she said in an interview. “If you’re taking a patient who’s already at risk for those things and you don’t have a detailed discussion with them about pros and cons, you’re doing them a disservice.” 
 

Industry Interests

Addressing the largely negative but varying findings, Dr. Swithers said, “one of the difficulties with getting clear answers about the science is that the food and beverage industry has an interest in confusing the picture. If people are selling or using a product, the best thing is for them not have a clear reason to change their behavior. All that needs to happen is for them to be able say, ‘well, it’s not clear, and we don’t really know what’s going on, so I’m just going to keep doing what I’m doing.’ Then the producers and sellers of that product have won.” 

“As Upton Sinclair said,” she added, “‘It is difficult to get a man to understand something when his salary depends on his not understanding it.’ When organizations like ADA appear to be promoting a product like sucralose, and they’re not always being clear about disclosing the funding, I think that’s problematic.”

In fact, some recipes in the ADA’s hub that contain Splenda are marked sponsored, such as the four-ingredient peanut butter cookies; others, such as gluten-free brownies, are not — even though the latter contains “1/4 cup plus 1 tbsp” of Splenda Sugar Blend (Splenda produces several nonnutritive sweeteners, not all of which contain sucralose). Splenda is a sponsor of the ADA’s hub.
 

Consume in Moderation?

Regarding the use of Splenda products, Robert Gabbay, MD, PhD, the ADA’s chief scientific and medical officer, said in an interview that “some people with diabetes are accustomed to regularly consuming sugar-sweetened products, which can make management of their diabetes more challenging. As highlighted in the ADA’s Standards of Care, nonnutritive sweeteners (containing few or no calories) may be an acceptable substitute for sweeteners that contain sugar and calories when consumed in moderation. By providing a diabetes-friendly way to prepare foods people are used to eating, we can meet people where they are in offering support to effectively manage their diabetes.”

Of course, “moderation” means different things to different people. “With sucralose in particular, you can bake with it, you can cook with it, and beverages and packaged foods contain it, so it’s easy to end up overconsuming foods that may be fine if they’re occasional treats but aren’t healthy choices to have every single day,” Dr. Swithers said. “If you’re having a cookie containing sucralose once a week, it’s not a big deal, but if you’re having a cookie or a brownie every day, that’s something different.”

“I think ‘everything in moderation’ is a very reasonable approach here,” Dr. Mathur said. “Anything too much is probably not good, and that includes sweeteners like sucralose and others.”

Dr. Suez, whose team is currently exploring the mechanisms through which gut bacteria interact with nonnutritive sweeteners in the pathogenesis of cardiometabolic diseases, was more circumspect.

“We believe that additional, long-term, and non–industry-sponsored studies in humans are needed before we can make a recommendation in favor or against the use of nonnutritive sweeteners,” he said.

“However, our results demonstrating that nonnutritive sweeteners are not inert, when taken together with a growing body of evidence on potential harms of these sweeteners, merit caution until additional studies are completed,” he added. “Our findings do not imply in any way that sugar consumption, shown to be harmful to human health in many studies, is superior to nonnutritive sweeteners. Sugar consumption should be minimized, especially in individuals with obesity or diabetes. Of all the options, unsweetened beverages, specifically water, seem to be the safest and best options.”

Dr. Sen, who also “tries to convince patients to have sparkling or cold bottled water,” instead of artificially sweetened soda, agreed. “If a diabetes patient is trying to choose between sugar and sucralose, I’m not sure which one is worse.”

Dr. Swithers, Dr. Mathur, Dr. Sen, and Dr. Suez declared no competing interests.

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

WASHINGTON – Women with autoimmune liver diseases (AILD) may face increased risks for major adverse cardiovascular outcomes, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.

“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.

“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”

Dr. Redfield

Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.

Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.

The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.

The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.

Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).

Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).

There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).

When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).

Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.

“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”

Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.

As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.

“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”

Dr. Redfield and Dr. Kelson reported no relevant disclosures.

WASHINGTON – Women with autoimmune liver diseases (AILD) may face increased risks for major adverse cardiovascular outcomes, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.

“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.

“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”

Dr. Redfield

Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.

Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.

The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.

The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.

Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).

Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).

There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).

When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).

Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.

“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”

Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.

As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.

“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”

Dr. Redfield and Dr. Kelson reported no relevant disclosures.

WASHINGTON – Women with autoimmune liver diseases (AILD) may face increased risks for major adverse cardiovascular outcomes, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.

“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.

“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”

Dr. Redfield

Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.

Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.

The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.

The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.

Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).

Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).

There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).

When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).

Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.

“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”

Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.

As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.

“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”

Dr. Redfield and Dr. Kelson reported no relevant disclosures.

Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.

The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.

Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
 

New Drugs

The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).

Recommendations

The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.

SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.

Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.

Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.

Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.

The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).

Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
 

Considerations for Practice

Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.

The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.

The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.

The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.

The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.

Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
 

New Drugs

The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).

Recommendations

The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.

SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.

Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.

Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.

Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.

The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).

Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
 

Considerations for Practice

Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.

The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.

The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.

The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.

The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.

Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
 

New Drugs

The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).

Recommendations

The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.

SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.

Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.

Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.

Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.

The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).

Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
 

Considerations for Practice

Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.

The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.

The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.

The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Should we now recommend continuous glucose monitoring to all our patients, even those without diabetes? Most of us would instinctively say “no” to this question, but we are seeing opinions from doctors recommending it, and in recent years, scientific literature has focused on the subject. 

Today, anyone can get an arm patch that continuously measures interstitial glucose, which is closely related to blood sugar. The information can be read on a dedicated reader or on a mobile phone by scanning the patch or, with some models, without even doing anything.

There is a consensus for prescribing continuous glucose monitoring for patients with type 1 or type 2 diabetes who are treated with at least three insulin injections. Not only is the use of continuous glucose monitoring much more comfortable than self-monitoring with finger sticks, but continuous monitoring also helps reduce glycosylated hemoglobin while decreasing the risk for hypoglycemia. Recently, another indication has begun to be reimbursed in France: Type 2 diabetes under mono-insulin injection when the diabetes is not well controlled.

But alongside these situations, there are two questions that are worth considering.
 

Untreated Type 2 Diabetes 

First, is continuous glucose monitoring desirable for all patients with diabetes, even those not treated with insulin and even when blood sugar levels are well managed? Intuitively, one might think that it can’t hurt and that continuous monitoring of blood sugar can only improve things. We have some evidence supporting this idea, but the level of proof is quite weak. It is not clear that continuous monitoring can improve patients’ awareness of the impact of dietary choices or physical activity on blood sugar. Obviously, one can imagine that continuously monitoring glucose will encourage a shift toward more beneficial behaviors. But honestly, today, we do not have proof that wearing a continuous glucose monitor can improve behaviors in patients with type 2 diabetes who are treated with noninsulin antidiabetic medications.

Furthermore, a significant study has shown that while the effectiveness is more evident in patients treated with insulin, strong evidence suggests that continuous glucose monitoring could also reduce glycosylated hemoglobin in patients with type 2 diabetes who are not treated with insulin. A close examination of the results suggests that the benefits generally are less than those observed in insulin-treated patients with diabetes.

When we look at the scientific literature, two factors seem particularly important to consider if choosing to prescribe a continuous glucose monitoring sensor. The first is the method used, because the results can vary depending on the method. It appears that only self-monitoring that allows the patient to follow glucose in real time is effective, unlike blind monitoring that allows only a retrospective analysis of blood sugar levels. In the latter case, the patient wears the sensor, and after a week, 10 days, or 15 days, the results are analyzed, possibly with a health care provider. It seems that this is not very effective in improving glycosylated hemoglobin and dietary and physical activity behavior.

The second essential factor to consider is the need for an education program for the use of these sensors to be helpful. If sensors are used but nothing else is done, it does not seem logical. Seeing blood sugar levels without being able to understand them and act accordingly seems of little use. Scientific literature seems to confirm this idea. 
 

Patients Without Diabetes

Now there is another question. We have discussed patients with type 2 diabetes without insulin. It’s trendy to talk about the potential benefits of continuous glucose monitors in patients without diabetes. The idea is emerging that these monitors could be used to refine the diagnosis of diabetes or to better predict the onset of diabetes in the subsequent years.

Others claim that continuous glucose monitors are an effective way to induce a change in dietary and physical activity behaviors in patients with prediabetes. One can, for example, tell a patient, “You are at risk of developing diabetes, so by monitoring your glucose, you will change your behavior.” Honestly, the scientific data we have today do not support these ideas, and I sincerely believe that it is not advisable today to recommend, as some would like, the mass use of monitors, whether in patients with overweight or obesity, or in patients with prediabetes. This goes for suggestions for using the monitor for 7-10 days per year, in the form of a session to try to reduce the risk for diabetes by motivating patients to change their behavior. We have no evidence at all that this can work. And in my opinion, with this kind of discourse, we ultimately risk, as usual, encouraging patients who are already “fans” of self-checks and self-monitoring to get health data, even if they do not know how to interpret it. Maybe even the doctor they ask for interpretation will not be trained to interpret the results of these monitors.

Spreading the idea that monitors are useful for preventing diabetes has a side effect: It hinders progress on the essential issue. Today, one of the problems in diabetes and prediabetes is that screening is not done often enough, and 20% of patients with diabetes are still unaware of their diagnosis. The management of early diabetes or prediabetes, in my opinion, is not optimal in routine care today. So, I think that adding the idea that using monitors could be beneficial dilutes the main information.

Having said that, I sometimes offer continuous glucose monitoring to some of my patients on a case-by-case basis. I believe that with proper support and an educational program, it can be beneficial for certain patients.
 

In Practice

In summary, I am totally opposed to the normalization of the use of monitors. I think it is our role as health care professionals to warn the public that even if it is accessible — anyone can buy a reader, a sensor — it is not necessarily beneficial, and it may even distract us from what is essential. But as a specialist, I think that using a monitor within a genuine care plan seems reasonable. Ultimately, it’s just personalized medicine.

Dr. Hansel is an endocrinologist-diabetologist and nutritionist, Department of Diabetology-Endocrinology-Nutrition, Hôpital Bichat, and a university lecturer and hospital practitioner, Université Paris-Diderot, France. He discloses ties with Iriade, Sanofi-Aventis, and Amgen.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Should we now recommend continuous glucose monitoring to all our patients, even those without diabetes? Most of us would instinctively say “no” to this question, but we are seeing opinions from doctors recommending it, and in recent years, scientific literature has focused on the subject. 

Today, anyone can get an arm patch that continuously measures interstitial glucose, which is closely related to blood sugar. The information can be read on a dedicated reader or on a mobile phone by scanning the patch or, with some models, without even doing anything.

There is a consensus for prescribing continuous glucose monitoring for patients with type 1 or type 2 diabetes who are treated with at least three insulin injections. Not only is the use of continuous glucose monitoring much more comfortable than self-monitoring with finger sticks, but continuous monitoring also helps reduce glycosylated hemoglobin while decreasing the risk for hypoglycemia. Recently, another indication has begun to be reimbursed in France: Type 2 diabetes under mono-insulin injection when the diabetes is not well controlled.

But alongside these situations, there are two questions that are worth considering.
 

Untreated Type 2 Diabetes 

First, is continuous glucose monitoring desirable for all patients with diabetes, even those not treated with insulin and even when blood sugar levels are well managed? Intuitively, one might think that it can’t hurt and that continuous monitoring of blood sugar can only improve things. We have some evidence supporting this idea, but the level of proof is quite weak. It is not clear that continuous monitoring can improve patients’ awareness of the impact of dietary choices or physical activity on blood sugar. Obviously, one can imagine that continuously monitoring glucose will encourage a shift toward more beneficial behaviors. But honestly, today, we do not have proof that wearing a continuous glucose monitor can improve behaviors in patients with type 2 diabetes who are treated with noninsulin antidiabetic medications.

Furthermore, a significant study has shown that while the effectiveness is more evident in patients treated with insulin, strong evidence suggests that continuous glucose monitoring could also reduce glycosylated hemoglobin in patients with type 2 diabetes who are not treated with insulin. A close examination of the results suggests that the benefits generally are less than those observed in insulin-treated patients with diabetes.

When we look at the scientific literature, two factors seem particularly important to consider if choosing to prescribe a continuous glucose monitoring sensor. The first is the method used, because the results can vary depending on the method. It appears that only self-monitoring that allows the patient to follow glucose in real time is effective, unlike blind monitoring that allows only a retrospective analysis of blood sugar levels. In the latter case, the patient wears the sensor, and after a week, 10 days, or 15 days, the results are analyzed, possibly with a health care provider. It seems that this is not very effective in improving glycosylated hemoglobin and dietary and physical activity behavior.

The second essential factor to consider is the need for an education program for the use of these sensors to be helpful. If sensors are used but nothing else is done, it does not seem logical. Seeing blood sugar levels without being able to understand them and act accordingly seems of little use. Scientific literature seems to confirm this idea. 
 

Patients Without Diabetes

Now there is another question. We have discussed patients with type 2 diabetes without insulin. It’s trendy to talk about the potential benefits of continuous glucose monitors in patients without diabetes. The idea is emerging that these monitors could be used to refine the diagnosis of diabetes or to better predict the onset of diabetes in the subsequent years.

Others claim that continuous glucose monitors are an effective way to induce a change in dietary and physical activity behaviors in patients with prediabetes. One can, for example, tell a patient, “You are at risk of developing diabetes, so by monitoring your glucose, you will change your behavior.” Honestly, the scientific data we have today do not support these ideas, and I sincerely believe that it is not advisable today to recommend, as some would like, the mass use of monitors, whether in patients with overweight or obesity, or in patients with prediabetes. This goes for suggestions for using the monitor for 7-10 days per year, in the form of a session to try to reduce the risk for diabetes by motivating patients to change their behavior. We have no evidence at all that this can work. And in my opinion, with this kind of discourse, we ultimately risk, as usual, encouraging patients who are already “fans” of self-checks and self-monitoring to get health data, even if they do not know how to interpret it. Maybe even the doctor they ask for interpretation will not be trained to interpret the results of these monitors.

Spreading the idea that monitors are useful for preventing diabetes has a side effect: It hinders progress on the essential issue. Today, one of the problems in diabetes and prediabetes is that screening is not done often enough, and 20% of patients with diabetes are still unaware of their diagnosis. The management of early diabetes or prediabetes, in my opinion, is not optimal in routine care today. So, I think that adding the idea that using monitors could be beneficial dilutes the main information.

Having said that, I sometimes offer continuous glucose monitoring to some of my patients on a case-by-case basis. I believe that with proper support and an educational program, it can be beneficial for certain patients.
 

In Practice

In summary, I am totally opposed to the normalization of the use of monitors. I think it is our role as health care professionals to warn the public that even if it is accessible — anyone can buy a reader, a sensor — it is not necessarily beneficial, and it may even distract us from what is essential. But as a specialist, I think that using a monitor within a genuine care plan seems reasonable. Ultimately, it’s just personalized medicine.

Dr. Hansel is an endocrinologist-diabetologist and nutritionist, Department of Diabetology-Endocrinology-Nutrition, Hôpital Bichat, and a university lecturer and hospital practitioner, Université Paris-Diderot, France. He discloses ties with Iriade, Sanofi-Aventis, and Amgen.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Should we now recommend continuous glucose monitoring to all our patients, even those without diabetes? Most of us would instinctively say “no” to this question, but we are seeing opinions from doctors recommending it, and in recent years, scientific literature has focused on the subject. 

Today, anyone can get an arm patch that continuously measures interstitial glucose, which is closely related to blood sugar. The information can be read on a dedicated reader or on a mobile phone by scanning the patch or, with some models, without even doing anything.

There is a consensus for prescribing continuous glucose monitoring for patients with type 1 or type 2 diabetes who are treated with at least three insulin injections. Not only is the use of continuous glucose monitoring much more comfortable than self-monitoring with finger sticks, but continuous monitoring also helps reduce glycosylated hemoglobin while decreasing the risk for hypoglycemia. Recently, another indication has begun to be reimbursed in France: Type 2 diabetes under mono-insulin injection when the diabetes is not well controlled.

But alongside these situations, there are two questions that are worth considering.
 

Untreated Type 2 Diabetes 

First, is continuous glucose monitoring desirable for all patients with diabetes, even those not treated with insulin and even when blood sugar levels are well managed? Intuitively, one might think that it can’t hurt and that continuous monitoring of blood sugar can only improve things. We have some evidence supporting this idea, but the level of proof is quite weak. It is not clear that continuous monitoring can improve patients’ awareness of the impact of dietary choices or physical activity on blood sugar. Obviously, one can imagine that continuously monitoring glucose will encourage a shift toward more beneficial behaviors. But honestly, today, we do not have proof that wearing a continuous glucose monitor can improve behaviors in patients with type 2 diabetes who are treated with noninsulin antidiabetic medications.

Furthermore, a significant study has shown that while the effectiveness is more evident in patients treated with insulin, strong evidence suggests that continuous glucose monitoring could also reduce glycosylated hemoglobin in patients with type 2 diabetes who are not treated with insulin. A close examination of the results suggests that the benefits generally are less than those observed in insulin-treated patients with diabetes.

When we look at the scientific literature, two factors seem particularly important to consider if choosing to prescribe a continuous glucose monitoring sensor. The first is the method used, because the results can vary depending on the method. It appears that only self-monitoring that allows the patient to follow glucose in real time is effective, unlike blind monitoring that allows only a retrospective analysis of blood sugar levels. In the latter case, the patient wears the sensor, and after a week, 10 days, or 15 days, the results are analyzed, possibly with a health care provider. It seems that this is not very effective in improving glycosylated hemoglobin and dietary and physical activity behavior.

The second essential factor to consider is the need for an education program for the use of these sensors to be helpful. If sensors are used but nothing else is done, it does not seem logical. Seeing blood sugar levels without being able to understand them and act accordingly seems of little use. Scientific literature seems to confirm this idea. 
 

Patients Without Diabetes

Now there is another question. We have discussed patients with type 2 diabetes without insulin. It’s trendy to talk about the potential benefits of continuous glucose monitors in patients without diabetes. The idea is emerging that these monitors could be used to refine the diagnosis of diabetes or to better predict the onset of diabetes in the subsequent years.

Others claim that continuous glucose monitors are an effective way to induce a change in dietary and physical activity behaviors in patients with prediabetes. One can, for example, tell a patient, “You are at risk of developing diabetes, so by monitoring your glucose, you will change your behavior.” Honestly, the scientific data we have today do not support these ideas, and I sincerely believe that it is not advisable today to recommend, as some would like, the mass use of monitors, whether in patients with overweight or obesity, or in patients with prediabetes. This goes for suggestions for using the monitor for 7-10 days per year, in the form of a session to try to reduce the risk for diabetes by motivating patients to change their behavior. We have no evidence at all that this can work. And in my opinion, with this kind of discourse, we ultimately risk, as usual, encouraging patients who are already “fans” of self-checks and self-monitoring to get health data, even if they do not know how to interpret it. Maybe even the doctor they ask for interpretation will not be trained to interpret the results of these monitors.

Spreading the idea that monitors are useful for preventing diabetes has a side effect: It hinders progress on the essential issue. Today, one of the problems in diabetes and prediabetes is that screening is not done often enough, and 20% of patients with diabetes are still unaware of their diagnosis. The management of early diabetes or prediabetes, in my opinion, is not optimal in routine care today. So, I think that adding the idea that using monitors could be beneficial dilutes the main information.

Having said that, I sometimes offer continuous glucose monitoring to some of my patients on a case-by-case basis. I believe that with proper support and an educational program, it can be beneficial for certain patients.
 

In Practice

In summary, I am totally opposed to the normalization of the use of monitors. I think it is our role as health care professionals to warn the public that even if it is accessible — anyone can buy a reader, a sensor — it is not necessarily beneficial, and it may even distract us from what is essential. But as a specialist, I think that using a monitor within a genuine care plan seems reasonable. Ultimately, it’s just personalized medicine.

Dr. Hansel is an endocrinologist-diabetologist and nutritionist, Department of Diabetology-Endocrinology-Nutrition, Hôpital Bichat, and a university lecturer and hospital practitioner, Université Paris-Diderot, France. He discloses ties with Iriade, Sanofi-Aventis, and Amgen.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.