User login
Intermittent fasting plus early eating may prevent type 2 diabetes
, indicate the results of a randomized controlled trial.
The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.
The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.
However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.
“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.
This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.
“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
Adherence difficult to IF plus early time-restricted eating
Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.
“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”
Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.
She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago. “These regimens make social eating very difficult, which results in high attrition.
“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.
Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”
“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
A novel way to cut calories?
The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.
Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.
To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.
The participants were randomized to one of three groups:
- IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
- Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
- Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.
There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.
A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m2.
In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.
The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).
“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.
IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.
Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).
Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.
IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
Calorie restriction easier to stick to, less likely to cause fatigue
When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.
In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.
At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.
Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.
The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.
No relevant financial relationships were declared.
A version of this article originally appeared on Medscape.com.
, indicate the results of a randomized controlled trial.
The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.
The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.
However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.
“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.
This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.
“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
Adherence difficult to IF plus early time-restricted eating
Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.
“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”
Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.
She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago. “These regimens make social eating very difficult, which results in high attrition.
“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.
Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”
“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
A novel way to cut calories?
The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.
Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.
To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.
The participants were randomized to one of three groups:
- IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
- Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
- Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.
There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.
A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m2.
In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.
The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).
“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.
IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.
Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).
Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.
IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
Calorie restriction easier to stick to, less likely to cause fatigue
When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.
In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.
At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.
Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.
The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.
No relevant financial relationships were declared.
A version of this article originally appeared on Medscape.com.
, indicate the results of a randomized controlled trial.
The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.
The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.
However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.
“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.
This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.
“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
Adherence difficult to IF plus early time-restricted eating
Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.
“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”
Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.
She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago. “These regimens make social eating very difficult, which results in high attrition.
“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.
Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”
“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
A novel way to cut calories?
The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.
Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.
To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.
The participants were randomized to one of three groups:
- IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
- Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
- Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.
There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.
A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m2.
In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.
The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).
“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.
IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.
Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).
Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.
IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
Calorie restriction easier to stick to, less likely to cause fatigue
When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.
In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.
At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.
Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.
The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.
No relevant financial relationships were declared.
A version of this article originally appeared on Medscape.com.
FROM NATURE MEDICINE
Use age, not weight, to screen for diabetes; assess over 35s
Universal screening of all U.S. adults aged 35-70 years for prediabetes and type 2 diabetes, regardless of body mass index, would provide the fairest means of detection, according to a new analysis.
This would better detect prediabetes and diabetes in ethnic groups that have a higher risk of diabetes at lower cutoffs. Compared with White individuals, Black or Hispanic adults have a higher risk of developing type 2 diabetes at a younger age, and Asian, Hispanic, and Black Americans all have a higher risk of developing it at a lower BMI.
In the new study, researchers examined six different screening scenarios in a nationally representative sample without diabetes.
They compared screening for prediabetes and type 2 diabetes using criteria from the 2021 U.S. Preventive Services Task Force (USPSTF) recommendations with the 2015 USPSTF recommendations, as well as four other screening thresholds with lower age or weight.
Universal screening for prediabetes and diabetes at age 35-70, regardless of BMI – which appears to be the sweet spot for most equitable detection in different races – may be easier to put into practice because it will mean clinicians don’t have to remember alternate cutoffs for different patient groups, the researchers suggested.
“All major racial and ethnic minority groups develop diabetes at lower weights than White adults, and it’s most pronounced for Asian Americans,” lead author Matthew J. O’Brien, MD, explained in a press release.
“If we make decisions about diabetes testing based on weight we will miss some people from racial and ethnic minority groups who are developing prediabetes and diabetes at lower weights,” said Dr. O’Brien, of Northwestern University, Chicago.
Going forward, to achieve equity in diagnosing prediabetes and diabetes “also requires addressing structural barriers [facing racial and ethnic minorities], which include not having a usual source of primary care, lacking health insurance, or having copays for screening tests based on insurance coverage,” the authors noted in their paper, published online in the American Journal of Preventive Medicine.
There is also a need for further study to examine the cost-effectiveness of any approach, and to study the impact of screening criteria on diagnosis, treatment, and outcomes in diverse populations.
Nationally representative sample, six screening scenarios
In the overall U.S. population, 81% of adults with prediabetes are unaware they have it, said Dr. O’Brien and colleagues, and 23% of diabetes cases are undiagnosed.
And Black, Hispanic, or Asian individuals have a nearly twofold higher prevalence of diabetes compared with White individuals.
The 2021 USPSTF recommendations state that clinicians should screen asymptomatic adults aged 35-70 years with overweight/obesity (BMI ≥ 25 kg/m2) and “should consider screening at an earlier age in persons from groups with disproportionately high incidence and prevalence (American Indian/Alaska Native, Asian American, Black, Hispanic/Latino, or Native Hawaiian/Pacific Islander persons) or in persons who have a family history of diabetes, a history of gestational diabetes, or a history of polycystic ovarian syndrome, and at a lower BMI in Asian American persons. Data suggest that a BMI of 23 or greater may be an appropriate cut point in Asian American persons.”
Dr. O’Brien and colleagues identified 3,243 nonpregnant adults without diagnosed diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) in 2017-2020 and had an A1c blood test. (Half also had a fasting plasma glucose test.)
First, they compared screening using the more recent and earlier USPSTF criteria: BMI of at least 25 kg/m2 and age 35-70 (2021 criteria) and BMI of at least 25 kg/m2 and age 40-70 (2015 criteria).
They estimated that 13.9 million more adults would be eligible for screening using the 2021 versus the 2015 screening criteria.
The increases in screening eligibility were highest in Hispanic individuals (30.6%), followed by Asian individuals (17.9%), White individuals (14.0%), and Black individuals (13.9%).
Using the USPSTF 2021 versus 2015 screening criteria resulted in marginally higher sensitivity (58.6% vs. 52.9%) but lower specificity (69.3% vs. 76.4%) overall, as well as within each racial group.
Next, the researchers examined screening at two lower age cutoffs and two lower BMI cutoffs: BMI of at least 25 kg/m2 and age 30-70, BMI of at least 25 kg/m2 and age 18-70, age 35-70 and BMI of at least 23 kg/m2, and age 35-70 and any BMI.
Screening at these lower age and weight thresholds resulted in even greater sensitivity and lower specificity than using the 2021 USPSTF criteria, especially among Hispanic, non-Hispanic Black, and Asian adults.
However, screening all adults aged 35-70 years regardless of BMI yielded the most equitable detection of prediabetes and diabetes – with a sensitivity of 67.8% and a specificity of 52.1% in the overall population, and a sensitivity of 70.1%, 70.4%, 68.4%, and 67.6%, and a specificity of 53.8%, 59.9%, 56.2%, and 48.9%, in the Asian, Black, Hispanic, and White subgroups, respectively.
The American Diabetes Association currently recommends screening all adults aged ≥ 35 years, or at any age if they have overweight/obesity and an additional diabetes risk factor, the researchers noted.
The study was partly funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Universal screening of all U.S. adults aged 35-70 years for prediabetes and type 2 diabetes, regardless of body mass index, would provide the fairest means of detection, according to a new analysis.
This would better detect prediabetes and diabetes in ethnic groups that have a higher risk of diabetes at lower cutoffs. Compared with White individuals, Black or Hispanic adults have a higher risk of developing type 2 diabetes at a younger age, and Asian, Hispanic, and Black Americans all have a higher risk of developing it at a lower BMI.
In the new study, researchers examined six different screening scenarios in a nationally representative sample without diabetes.
They compared screening for prediabetes and type 2 diabetes using criteria from the 2021 U.S. Preventive Services Task Force (USPSTF) recommendations with the 2015 USPSTF recommendations, as well as four other screening thresholds with lower age or weight.
Universal screening for prediabetes and diabetes at age 35-70, regardless of BMI – which appears to be the sweet spot for most equitable detection in different races – may be easier to put into practice because it will mean clinicians don’t have to remember alternate cutoffs for different patient groups, the researchers suggested.
“All major racial and ethnic minority groups develop diabetes at lower weights than White adults, and it’s most pronounced for Asian Americans,” lead author Matthew J. O’Brien, MD, explained in a press release.
“If we make decisions about diabetes testing based on weight we will miss some people from racial and ethnic minority groups who are developing prediabetes and diabetes at lower weights,” said Dr. O’Brien, of Northwestern University, Chicago.
Going forward, to achieve equity in diagnosing prediabetes and diabetes “also requires addressing structural barriers [facing racial and ethnic minorities], which include not having a usual source of primary care, lacking health insurance, or having copays for screening tests based on insurance coverage,” the authors noted in their paper, published online in the American Journal of Preventive Medicine.
There is also a need for further study to examine the cost-effectiveness of any approach, and to study the impact of screening criteria on diagnosis, treatment, and outcomes in diverse populations.
Nationally representative sample, six screening scenarios
In the overall U.S. population, 81% of adults with prediabetes are unaware they have it, said Dr. O’Brien and colleagues, and 23% of diabetes cases are undiagnosed.
And Black, Hispanic, or Asian individuals have a nearly twofold higher prevalence of diabetes compared with White individuals.
The 2021 USPSTF recommendations state that clinicians should screen asymptomatic adults aged 35-70 years with overweight/obesity (BMI ≥ 25 kg/m2) and “should consider screening at an earlier age in persons from groups with disproportionately high incidence and prevalence (American Indian/Alaska Native, Asian American, Black, Hispanic/Latino, or Native Hawaiian/Pacific Islander persons) or in persons who have a family history of diabetes, a history of gestational diabetes, or a history of polycystic ovarian syndrome, and at a lower BMI in Asian American persons. Data suggest that a BMI of 23 or greater may be an appropriate cut point in Asian American persons.”
Dr. O’Brien and colleagues identified 3,243 nonpregnant adults without diagnosed diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) in 2017-2020 and had an A1c blood test. (Half also had a fasting plasma glucose test.)
First, they compared screening using the more recent and earlier USPSTF criteria: BMI of at least 25 kg/m2 and age 35-70 (2021 criteria) and BMI of at least 25 kg/m2 and age 40-70 (2015 criteria).
They estimated that 13.9 million more adults would be eligible for screening using the 2021 versus the 2015 screening criteria.
The increases in screening eligibility were highest in Hispanic individuals (30.6%), followed by Asian individuals (17.9%), White individuals (14.0%), and Black individuals (13.9%).
Using the USPSTF 2021 versus 2015 screening criteria resulted in marginally higher sensitivity (58.6% vs. 52.9%) but lower specificity (69.3% vs. 76.4%) overall, as well as within each racial group.
Next, the researchers examined screening at two lower age cutoffs and two lower BMI cutoffs: BMI of at least 25 kg/m2 and age 30-70, BMI of at least 25 kg/m2 and age 18-70, age 35-70 and BMI of at least 23 kg/m2, and age 35-70 and any BMI.
Screening at these lower age and weight thresholds resulted in even greater sensitivity and lower specificity than using the 2021 USPSTF criteria, especially among Hispanic, non-Hispanic Black, and Asian adults.
However, screening all adults aged 35-70 years regardless of BMI yielded the most equitable detection of prediabetes and diabetes – with a sensitivity of 67.8% and a specificity of 52.1% in the overall population, and a sensitivity of 70.1%, 70.4%, 68.4%, and 67.6%, and a specificity of 53.8%, 59.9%, 56.2%, and 48.9%, in the Asian, Black, Hispanic, and White subgroups, respectively.
The American Diabetes Association currently recommends screening all adults aged ≥ 35 years, or at any age if they have overweight/obesity and an additional diabetes risk factor, the researchers noted.
The study was partly funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Universal screening of all U.S. adults aged 35-70 years for prediabetes and type 2 diabetes, regardless of body mass index, would provide the fairest means of detection, according to a new analysis.
This would better detect prediabetes and diabetes in ethnic groups that have a higher risk of diabetes at lower cutoffs. Compared with White individuals, Black or Hispanic adults have a higher risk of developing type 2 diabetes at a younger age, and Asian, Hispanic, and Black Americans all have a higher risk of developing it at a lower BMI.
In the new study, researchers examined six different screening scenarios in a nationally representative sample without diabetes.
They compared screening for prediabetes and type 2 diabetes using criteria from the 2021 U.S. Preventive Services Task Force (USPSTF) recommendations with the 2015 USPSTF recommendations, as well as four other screening thresholds with lower age or weight.
Universal screening for prediabetes and diabetes at age 35-70, regardless of BMI – which appears to be the sweet spot for most equitable detection in different races – may be easier to put into practice because it will mean clinicians don’t have to remember alternate cutoffs for different patient groups, the researchers suggested.
“All major racial and ethnic minority groups develop diabetes at lower weights than White adults, and it’s most pronounced for Asian Americans,” lead author Matthew J. O’Brien, MD, explained in a press release.
“If we make decisions about diabetes testing based on weight we will miss some people from racial and ethnic minority groups who are developing prediabetes and diabetes at lower weights,” said Dr. O’Brien, of Northwestern University, Chicago.
Going forward, to achieve equity in diagnosing prediabetes and diabetes “also requires addressing structural barriers [facing racial and ethnic minorities], which include not having a usual source of primary care, lacking health insurance, or having copays for screening tests based on insurance coverage,” the authors noted in their paper, published online in the American Journal of Preventive Medicine.
There is also a need for further study to examine the cost-effectiveness of any approach, and to study the impact of screening criteria on diagnosis, treatment, and outcomes in diverse populations.
Nationally representative sample, six screening scenarios
In the overall U.S. population, 81% of adults with prediabetes are unaware they have it, said Dr. O’Brien and colleagues, and 23% of diabetes cases are undiagnosed.
And Black, Hispanic, or Asian individuals have a nearly twofold higher prevalence of diabetes compared with White individuals.
The 2021 USPSTF recommendations state that clinicians should screen asymptomatic adults aged 35-70 years with overweight/obesity (BMI ≥ 25 kg/m2) and “should consider screening at an earlier age in persons from groups with disproportionately high incidence and prevalence (American Indian/Alaska Native, Asian American, Black, Hispanic/Latino, or Native Hawaiian/Pacific Islander persons) or in persons who have a family history of diabetes, a history of gestational diabetes, or a history of polycystic ovarian syndrome, and at a lower BMI in Asian American persons. Data suggest that a BMI of 23 or greater may be an appropriate cut point in Asian American persons.”
Dr. O’Brien and colleagues identified 3,243 nonpregnant adults without diagnosed diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) in 2017-2020 and had an A1c blood test. (Half also had a fasting plasma glucose test.)
First, they compared screening using the more recent and earlier USPSTF criteria: BMI of at least 25 kg/m2 and age 35-70 (2021 criteria) and BMI of at least 25 kg/m2 and age 40-70 (2015 criteria).
They estimated that 13.9 million more adults would be eligible for screening using the 2021 versus the 2015 screening criteria.
The increases in screening eligibility were highest in Hispanic individuals (30.6%), followed by Asian individuals (17.9%), White individuals (14.0%), and Black individuals (13.9%).
Using the USPSTF 2021 versus 2015 screening criteria resulted in marginally higher sensitivity (58.6% vs. 52.9%) but lower specificity (69.3% vs. 76.4%) overall, as well as within each racial group.
Next, the researchers examined screening at two lower age cutoffs and two lower BMI cutoffs: BMI of at least 25 kg/m2 and age 30-70, BMI of at least 25 kg/m2 and age 18-70, age 35-70 and BMI of at least 23 kg/m2, and age 35-70 and any BMI.
Screening at these lower age and weight thresholds resulted in even greater sensitivity and lower specificity than using the 2021 USPSTF criteria, especially among Hispanic, non-Hispanic Black, and Asian adults.
However, screening all adults aged 35-70 years regardless of BMI yielded the most equitable detection of prediabetes and diabetes – with a sensitivity of 67.8% and a specificity of 52.1% in the overall population, and a sensitivity of 70.1%, 70.4%, 68.4%, and 67.6%, and a specificity of 53.8%, 59.9%, 56.2%, and 48.9%, in the Asian, Black, Hispanic, and White subgroups, respectively.
The American Diabetes Association currently recommends screening all adults aged ≥ 35 years, or at any age if they have overweight/obesity and an additional diabetes risk factor, the researchers noted.
The study was partly funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF PREVENTIVE MEDICINE
Suicidal thoughts decline in endocrinologists: Survey
Rates of suicidal thoughts and attempted suicide among endocrinologists declined from 2022 and now rank similar to the average rate among physicians overall, but these rates are still higher than the general public, according to survey findings.
The current report about suicide among endocrinologists, titled, “Doctors’ Burden: Endocrinologist Suicide Report 2023,” was recently published.
A report about suicide among physicians overall, based on the same survey, titled, “Doctors’ Burden: Medscape Physician Suicide Report 2023,” was published previously.
Improved rates among 28 medical specialties
In the 2022 survey of a representative national sample of 13,069 U.S. physicians, 10% of endocrinologists reported having suicidal thoughts, ranking the specialty sixth among 29 medical specialties that year.
The 2023 survey found that in a representative national sample of 9,175 U.S. physicians, 8% of endocrinologists reported having suicidal thoughts, roughly the average rate among clinicians overall, ranking it 20th among 29 medical specialties.
The highest rates of thoughts of suicide in the latest survey were reported by physicians in otolaryngology (13%), followed by physicians in psychiatry, family medicine, anesthesiology, obstetrics/gynecology, and emergency medicine (roughly 12% in each specialty).
The rate of attempted suicide was 1% among endocrinologists, which was also the rate among physicians overall.
More female than male endocrinologists reported contemplating suicide (8% versus 5%). In addition, 1% of male endocrinologists reported that they had attempted suicide and 2% of female endocrinologists replied they preferred not to answer the question about attempted suicide.
In contrast, in 2020, an estimated 4.9% of U.S. adults aged 18 and older had serious thoughts about suicide and 0.5% attempted suicide, according to the National Institutes of Health website, the latest report states.
Rates of suicidal thoughts and suicide attempts among physicians overall “are worryingly high numbers,” Peter Yellowlees, MBBS, MD, emeritus professor of psychiatry at University of California, Davis, Health, and chief executive officer, Asynchealth, said in the report.
Confiding in others, good mental health habits, resources
In the 2023 survey, half of the endocrinologists who had thought about suicide had confided in a therapist and 41% had spoken to a family member, but none had told a colleague or a friend, or phoned a suicide hotline.
On the other hand, 7% of male and 10% of female endocrinologists, and 9% of male and 11% of female physicians overall, reported that a colleague had shared suicidal thoughts with them.
“It’s pleasing that physicians overall have shown themselves slightly more likely to bring ideas about suicide to a therapist and less likely to keep their distress entirely to themselves,” Dr. Yellowlees said.
“It’s possible that the need for health care is becoming less stigmatized nationally, with large and increasing emphasis on physician well-being during and after the COVID-19 pandemic,” he suggested.
Endocrinologists reported that to keep happy and have good mental health, they engaged in activities and hobbies (70%), exercised (66%), spent time with family and friends (63%), got enough sleep (56%), ate healthy (48%), went to therapy (11%), or did other things (8%), which was similar to that reported by physicians overall.
The report lists several resources that are specific for physicians having suicidal thoughts (Physician Support Line, 988 Suicide and Crisis Lifeline, Peer RxMed, International Association for Suicide Prevention, and the American Foundation for Suicide Prevention) along with contact information.
The 2023 survey was conducted from June 28, 2022, to Oct. 3, 2022, and the 2022 survey was conducted from June 29, 2021, to Sept. 26, 2021.
A version of this article first appeared on Medscape.com.
Rates of suicidal thoughts and attempted suicide among endocrinologists declined from 2022 and now rank similar to the average rate among physicians overall, but these rates are still higher than the general public, according to survey findings.
The current report about suicide among endocrinologists, titled, “Doctors’ Burden: Endocrinologist Suicide Report 2023,” was recently published.
A report about suicide among physicians overall, based on the same survey, titled, “Doctors’ Burden: Medscape Physician Suicide Report 2023,” was published previously.
Improved rates among 28 medical specialties
In the 2022 survey of a representative national sample of 13,069 U.S. physicians, 10% of endocrinologists reported having suicidal thoughts, ranking the specialty sixth among 29 medical specialties that year.
The 2023 survey found that in a representative national sample of 9,175 U.S. physicians, 8% of endocrinologists reported having suicidal thoughts, roughly the average rate among clinicians overall, ranking it 20th among 29 medical specialties.
The highest rates of thoughts of suicide in the latest survey were reported by physicians in otolaryngology (13%), followed by physicians in psychiatry, family medicine, anesthesiology, obstetrics/gynecology, and emergency medicine (roughly 12% in each specialty).
The rate of attempted suicide was 1% among endocrinologists, which was also the rate among physicians overall.
More female than male endocrinologists reported contemplating suicide (8% versus 5%). In addition, 1% of male endocrinologists reported that they had attempted suicide and 2% of female endocrinologists replied they preferred not to answer the question about attempted suicide.
In contrast, in 2020, an estimated 4.9% of U.S. adults aged 18 and older had serious thoughts about suicide and 0.5% attempted suicide, according to the National Institutes of Health website, the latest report states.
Rates of suicidal thoughts and suicide attempts among physicians overall “are worryingly high numbers,” Peter Yellowlees, MBBS, MD, emeritus professor of psychiatry at University of California, Davis, Health, and chief executive officer, Asynchealth, said in the report.
Confiding in others, good mental health habits, resources
In the 2023 survey, half of the endocrinologists who had thought about suicide had confided in a therapist and 41% had spoken to a family member, but none had told a colleague or a friend, or phoned a suicide hotline.
On the other hand, 7% of male and 10% of female endocrinologists, and 9% of male and 11% of female physicians overall, reported that a colleague had shared suicidal thoughts with them.
“It’s pleasing that physicians overall have shown themselves slightly more likely to bring ideas about suicide to a therapist and less likely to keep their distress entirely to themselves,” Dr. Yellowlees said.
“It’s possible that the need for health care is becoming less stigmatized nationally, with large and increasing emphasis on physician well-being during and after the COVID-19 pandemic,” he suggested.
Endocrinologists reported that to keep happy and have good mental health, they engaged in activities and hobbies (70%), exercised (66%), spent time with family and friends (63%), got enough sleep (56%), ate healthy (48%), went to therapy (11%), or did other things (8%), which was similar to that reported by physicians overall.
The report lists several resources that are specific for physicians having suicidal thoughts (Physician Support Line, 988 Suicide and Crisis Lifeline, Peer RxMed, International Association for Suicide Prevention, and the American Foundation for Suicide Prevention) along with contact information.
The 2023 survey was conducted from June 28, 2022, to Oct. 3, 2022, and the 2022 survey was conducted from June 29, 2021, to Sept. 26, 2021.
A version of this article first appeared on Medscape.com.
Rates of suicidal thoughts and attempted suicide among endocrinologists declined from 2022 and now rank similar to the average rate among physicians overall, but these rates are still higher than the general public, according to survey findings.
The current report about suicide among endocrinologists, titled, “Doctors’ Burden: Endocrinologist Suicide Report 2023,” was recently published.
A report about suicide among physicians overall, based on the same survey, titled, “Doctors’ Burden: Medscape Physician Suicide Report 2023,” was published previously.
Improved rates among 28 medical specialties
In the 2022 survey of a representative national sample of 13,069 U.S. physicians, 10% of endocrinologists reported having suicidal thoughts, ranking the specialty sixth among 29 medical specialties that year.
The 2023 survey found that in a representative national sample of 9,175 U.S. physicians, 8% of endocrinologists reported having suicidal thoughts, roughly the average rate among clinicians overall, ranking it 20th among 29 medical specialties.
The highest rates of thoughts of suicide in the latest survey were reported by physicians in otolaryngology (13%), followed by physicians in psychiatry, family medicine, anesthesiology, obstetrics/gynecology, and emergency medicine (roughly 12% in each specialty).
The rate of attempted suicide was 1% among endocrinologists, which was also the rate among physicians overall.
More female than male endocrinologists reported contemplating suicide (8% versus 5%). In addition, 1% of male endocrinologists reported that they had attempted suicide and 2% of female endocrinologists replied they preferred not to answer the question about attempted suicide.
In contrast, in 2020, an estimated 4.9% of U.S. adults aged 18 and older had serious thoughts about suicide and 0.5% attempted suicide, according to the National Institutes of Health website, the latest report states.
Rates of suicidal thoughts and suicide attempts among physicians overall “are worryingly high numbers,” Peter Yellowlees, MBBS, MD, emeritus professor of psychiatry at University of California, Davis, Health, and chief executive officer, Asynchealth, said in the report.
Confiding in others, good mental health habits, resources
In the 2023 survey, half of the endocrinologists who had thought about suicide had confided in a therapist and 41% had spoken to a family member, but none had told a colleague or a friend, or phoned a suicide hotline.
On the other hand, 7% of male and 10% of female endocrinologists, and 9% of male and 11% of female physicians overall, reported that a colleague had shared suicidal thoughts with them.
“It’s pleasing that physicians overall have shown themselves slightly more likely to bring ideas about suicide to a therapist and less likely to keep their distress entirely to themselves,” Dr. Yellowlees said.
“It’s possible that the need for health care is becoming less stigmatized nationally, with large and increasing emphasis on physician well-being during and after the COVID-19 pandemic,” he suggested.
Endocrinologists reported that to keep happy and have good mental health, they engaged in activities and hobbies (70%), exercised (66%), spent time with family and friends (63%), got enough sleep (56%), ate healthy (48%), went to therapy (11%), or did other things (8%), which was similar to that reported by physicians overall.
The report lists several resources that are specific for physicians having suicidal thoughts (Physician Support Line, 988 Suicide and Crisis Lifeline, Peer RxMed, International Association for Suicide Prevention, and the American Foundation for Suicide Prevention) along with contact information.
The 2023 survey was conducted from June 28, 2022, to Oct. 3, 2022, and the 2022 survey was conducted from June 29, 2021, to Sept. 26, 2021.
A version of this article first appeared on Medscape.com.
Exercise or neuromuscular stimulation in type 2 diabetes?
Studies indicate that physical activity improves glucose metabolism in patients with type 2 diabetes. In addition, other data suggest a decrease in cardiovascular morbidity and mortality through physical activity.
In the consensus report “Management of Hyperglycemia in Type 2 Diabetes, 2022,” the American Diabetes Association and the European Association for the Study of Diabetes, therefore, recommend at least 150 minutes per week of moderate- to vigorous-intensity aerobic activity, supplemented with two to three resistance, flexibility, or balance training sessions per week.
But even when such recommendations are integrated into a therapeutic education program, adherence is often transient or partial.
In this context, Michael Joubert, MD, PhD, and his team at Caen (France) University Hospital wondered about neuromuscular electrical stimulation (NMES), a physical treatment routinely used in functional rehabilitation to improve muscle strength and volume.
To answer this question, they conducted a crossover randomized controlled trial called ELECTRODIAB2. The results were presented at the 2023 Congress of the Francophone Diabetes Society.
A few small pilot studies found that NMES improved insulin sensitivity and glycemic control; therefore, it could indeed be an alternative. The metabolic effect of NMES, however, has not been widely studied.
A total of 40 patients were enrolled in ELECTRODIAB2. Of these participants, 35 were randomly assigned to one of three groups: 6 weeks without NMES (control, no intervention), electrostimulation on 3 days per week for 6 weeks (20-minute ambulatory biquadricipital electrostimulation sessions) (NMES3), and electrostimulation on 5 days per week for 6 weeks (20-minutes ambulatory biquadricipital electrostimulation sessions) (NMES5). The goal was to assess the glucose levels of sedentary patients with type 2 diabetes during these periods. At each session, NMES was applied at the maximum-tolerated intensity.
Data from 32 participants were analyzed. Mean age was 58 ± 10 years, and body mass index was 33.0 ± 4.3 kg/m2. Duration of diabetes was 8.6 ± 5.9 years. Regarding diabetes treatments, 47%, 31%, 9%, and 13% of the patients were taking 0, 1, 2, and 3 oral hypoglycemic agents or glucagonlike peptide–1 agonists, respectively.
No significant differences in glucose levels were observed between the three groups. The primary outcome was mean glucose level based on a 6-day continuous glucose monitoring (CGM) recording. Those levels were 181.4 ± 42.5 mg/dL (control, no intervention), 180.6 ± 45.8 mg/dL (NMES3), and 181.1 ± 48.9 mg/dL (NMES5).
Furthermore, secondary outcomes (rates of hyperglycemia and hypoglycemia) did not differ between the three groups.
The researchers concluded that, “with regard to the CGM criteria, this crossover randomized controlled trial did not show that the 6-week biquadricipital NMES sessions had any benefit. This finding conflicts with the results of preliminary pilot studies but it does not encourage further research on NMES in this population of patients with early-stage diabetes.”
Therefore, at this point, it does not look like NMES can be recommended as an alternative to physical activity for sedentary patients with type 2 diabetes.
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Studies indicate that physical activity improves glucose metabolism in patients with type 2 diabetes. In addition, other data suggest a decrease in cardiovascular morbidity and mortality through physical activity.
In the consensus report “Management of Hyperglycemia in Type 2 Diabetes, 2022,” the American Diabetes Association and the European Association for the Study of Diabetes, therefore, recommend at least 150 minutes per week of moderate- to vigorous-intensity aerobic activity, supplemented with two to three resistance, flexibility, or balance training sessions per week.
But even when such recommendations are integrated into a therapeutic education program, adherence is often transient or partial.
In this context, Michael Joubert, MD, PhD, and his team at Caen (France) University Hospital wondered about neuromuscular electrical stimulation (NMES), a physical treatment routinely used in functional rehabilitation to improve muscle strength and volume.
To answer this question, they conducted a crossover randomized controlled trial called ELECTRODIAB2. The results were presented at the 2023 Congress of the Francophone Diabetes Society.
A few small pilot studies found that NMES improved insulin sensitivity and glycemic control; therefore, it could indeed be an alternative. The metabolic effect of NMES, however, has not been widely studied.
A total of 40 patients were enrolled in ELECTRODIAB2. Of these participants, 35 were randomly assigned to one of three groups: 6 weeks without NMES (control, no intervention), electrostimulation on 3 days per week for 6 weeks (20-minute ambulatory biquadricipital electrostimulation sessions) (NMES3), and electrostimulation on 5 days per week for 6 weeks (20-minutes ambulatory biquadricipital electrostimulation sessions) (NMES5). The goal was to assess the glucose levels of sedentary patients with type 2 diabetes during these periods. At each session, NMES was applied at the maximum-tolerated intensity.
Data from 32 participants were analyzed. Mean age was 58 ± 10 years, and body mass index was 33.0 ± 4.3 kg/m2. Duration of diabetes was 8.6 ± 5.9 years. Regarding diabetes treatments, 47%, 31%, 9%, and 13% of the patients were taking 0, 1, 2, and 3 oral hypoglycemic agents or glucagonlike peptide–1 agonists, respectively.
No significant differences in glucose levels were observed between the three groups. The primary outcome was mean glucose level based on a 6-day continuous glucose monitoring (CGM) recording. Those levels were 181.4 ± 42.5 mg/dL (control, no intervention), 180.6 ± 45.8 mg/dL (NMES3), and 181.1 ± 48.9 mg/dL (NMES5).
Furthermore, secondary outcomes (rates of hyperglycemia and hypoglycemia) did not differ between the three groups.
The researchers concluded that, “with regard to the CGM criteria, this crossover randomized controlled trial did not show that the 6-week biquadricipital NMES sessions had any benefit. This finding conflicts with the results of preliminary pilot studies but it does not encourage further research on NMES in this population of patients with early-stage diabetes.”
Therefore, at this point, it does not look like NMES can be recommended as an alternative to physical activity for sedentary patients with type 2 diabetes.
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Studies indicate that physical activity improves glucose metabolism in patients with type 2 diabetes. In addition, other data suggest a decrease in cardiovascular morbidity and mortality through physical activity.
In the consensus report “Management of Hyperglycemia in Type 2 Diabetes, 2022,” the American Diabetes Association and the European Association for the Study of Diabetes, therefore, recommend at least 150 minutes per week of moderate- to vigorous-intensity aerobic activity, supplemented with two to three resistance, flexibility, or balance training sessions per week.
But even when such recommendations are integrated into a therapeutic education program, adherence is often transient or partial.
In this context, Michael Joubert, MD, PhD, and his team at Caen (France) University Hospital wondered about neuromuscular electrical stimulation (NMES), a physical treatment routinely used in functional rehabilitation to improve muscle strength and volume.
To answer this question, they conducted a crossover randomized controlled trial called ELECTRODIAB2. The results were presented at the 2023 Congress of the Francophone Diabetes Society.
A few small pilot studies found that NMES improved insulin sensitivity and glycemic control; therefore, it could indeed be an alternative. The metabolic effect of NMES, however, has not been widely studied.
A total of 40 patients were enrolled in ELECTRODIAB2. Of these participants, 35 were randomly assigned to one of three groups: 6 weeks without NMES (control, no intervention), electrostimulation on 3 days per week for 6 weeks (20-minute ambulatory biquadricipital electrostimulation sessions) (NMES3), and electrostimulation on 5 days per week for 6 weeks (20-minutes ambulatory biquadricipital electrostimulation sessions) (NMES5). The goal was to assess the glucose levels of sedentary patients with type 2 diabetes during these periods. At each session, NMES was applied at the maximum-tolerated intensity.
Data from 32 participants were analyzed. Mean age was 58 ± 10 years, and body mass index was 33.0 ± 4.3 kg/m2. Duration of diabetes was 8.6 ± 5.9 years. Regarding diabetes treatments, 47%, 31%, 9%, and 13% of the patients were taking 0, 1, 2, and 3 oral hypoglycemic agents or glucagonlike peptide–1 agonists, respectively.
No significant differences in glucose levels were observed between the three groups. The primary outcome was mean glucose level based on a 6-day continuous glucose monitoring (CGM) recording. Those levels were 181.4 ± 42.5 mg/dL (control, no intervention), 180.6 ± 45.8 mg/dL (NMES3), and 181.1 ± 48.9 mg/dL (NMES5).
Furthermore, secondary outcomes (rates of hyperglycemia and hypoglycemia) did not differ between the three groups.
The researchers concluded that, “with regard to the CGM criteria, this crossover randomized controlled trial did not show that the 6-week biquadricipital NMES sessions had any benefit. This finding conflicts with the results of preliminary pilot studies but it does not encourage further research on NMES in this population of patients with early-stage diabetes.”
Therefore, at this point, it does not look like NMES can be recommended as an alternative to physical activity for sedentary patients with type 2 diabetes.
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Spinal cord stimulation may help diabetic neuropathy
according to research that released early, prior to its presentation at the annual meeting of the American Academy of Neurology.
The data represents the longest follow-up available for spinal cord stimulation at a frequency higher than the 60 Hz initially approved for diabetic neuropathy by the Food and Drug Administration, according to lead author Erika A. Petersen, MD, a professor of neurosurgery and the residency program director at the University of Arkansas for Medical Sciences, Little Rock.
“You would expect that somebody who continues to have diabetes for 24 months and has neuropathy would have worse neuropathy after 2 years, and what we’re seeing is that people were stable or better in terms of their nerve function at 2 years,” Dr. Petersen said in an interview. “So that’s really revolutionary.”
Encouraging preliminary findings
The findings are “promising and preliminary,” John D. Markman, MD, a professor in neurology and neurosurgery, vice chair for clinical research, and director of the Translational Pain Research Program at the University of Rochester (N.Y.) Medical Center, said in an interview. Dr. Markman, who was not involved in this study, said that, though the results are encouraging, it’s “less clear how much of [the pain improvement] is due to what we would consider to be on-target, pain-relieving benefit from stimulation versus other factors like expectation.” The crossover rate and amount of reduction in pain intensity are promising, but “I think that excitement is weighed against the fact that this is an open-label study.”
An underused treatment
Although spinal cord stimulation has been around since the late 1960s, its use only picked up steam in the 2000s, when it became more frequently used to treat chronic nerve damage related to neuropathic pain syndromes, Dr. Petersen explained. The FDA approved the treatment’s new indication for diabetic neuropathy in 2015, and data from Abbott and Medtronic have shown benefits from spinal cord stimulation at 60 Hz, but some patients are uncomfortable with the vibration or tingling feelings the devices can cause at that frequency.
“They describe creepy crawlies or ants crawling over the feet, or pins and needles, and painful sensitivity,” Dr. Petersen said. “You create a vibration feeling in the same zone where they already have those feelings of buzzing and pain and vibration, and it’s sometimes actually even more uncomfortable and less satisfying to them in terms of relief” with the spinal cord stimulation at 60 Hz, she said, “so there’s a lot of attrition in terms of who will actually use it.”
At 10 kHz, however, “people don’t feel any vibration or tingling associated with it; it just jams the signal of the pain,” she said. The difference between the frequencies is like that between “a lifeguard whistle and a dog whistle.”
Testing high-frequency stimulation
The new findings included the 24-month follow-up data from a randomized controlled trial that assessed the effectiveness of high-frequency spinal cord stimulation for painful diabetic neuropathy. The original 216 participants enrolled in the trial had diabetic neuropathy symptoms for at least 12 months and either could no not tolerate or did not respond to medications. Enrollment criteria also included lower-limb pain intensity of at least 5 on a 0-10 visual analogy scale and hemoglobin A1c of no more than 10%.
For the first 6 months of the trial – before crossover was offered – participants were randomly assigned to receive either 10 kHz of spinal cord stimulation along with conventional medical management or to receive conventional medical management alone. The 6-month data from 187 patients, as reported in April 2021 in JAMA Neurology, revealed that 79% of those receiving spinal cord stimulation experienced at least 50% improved pain relief without worsening of their baseline neurologic deficits, compared with only 5% of those receiving only conventional treatments.
Average pain levels increased 2% in the control participants compared with a decrease of 76% in those with the spinal cord stimulation devices. In addition, 62% of the patients receiving spinal cord stimulation demonstration neurologic improvement in reflexes, strength, movement and sensation, compared with 3% of those in the control group. The study’s findings led the FDA to approve the device using 10 kHz.
At 6 months, 93% of control patients crossed over to receiving spinal cord stimulation while none with the devices opted to stop their spinal cord stimulation. The 12-month data revealed that 85% of those receiving spinal cord stimulation experienced at least 50% pain relief, with the average pain relief at 74%. Patients also reported statistically significant improved quality of life as well as less interference with sleep, mood, and daily activities from pain.
Two years after baseline, patients’ pain relief was maintained with average 80% improvement, and 66% of patients showed neurologic improvement since baseline. Though no patients had devices removed because of ineffectiveness, five patients’ devices were removed because of infection while infections in three other patients resolved.
“Being able to offer something that is not a pharmaceutical, without the side effects, that shows an even longer durability to that response is a really important finding at this point,” Dr. Petersen said.
Surgical considerations
Among the estimated 37 million Americans with type 1 or 2 diabetes, approximately one quarter of them experience some level of painful diabetic neuropathy, but medication and other medical management strategies are not always adequate in treating their pain. After a 1-week trial of spinal cord stimulation, the devices are implanted under the skin and rechargeable through the skin for up to 10 years, after which they can be replaced.
An appropriate candidate for spinal cord stimulation would be someone for whom existing non-invasive pain relief options, including medications, are ineffective or intolerable, Dr. Petersen and Dr. Markman both said. An adequate trial of medication is not “one size fits all” and will vary by each patient, added Dr. Markman, who is also interested in whether this study’s participants were able to have a reduction in use of pain relief medications.
“I think there’s a significant number of patients out there who can benefit from this, so I think that’s why it’s promising and exciting,” Dr. Markman said. “I do think it’s important to see if this actually allows them to be on less medication or whether stimulation turns out to be another treatment in addition to their baseline treatments.” The challenge is identifying “which patients are most likely to be benefiting from this and which are most likely to be harmed.”
Aside from infection from implantation, other possible risks include pain at the battery site and, in rare cases, a need for reoperation because of migration of the leads, he said.
Improvement in symptom severity and quality of life
After the wound from the implant has completely healed, Dr. Petersen said patients using the devices do not have any activity restrictions outside of magnetic interference, such as MRIs. “I’ve had people go back-country kayaking, scuba diving, fishing with their grandkids, all sorts of all sorts of things. If patients need to go through a scanner of any kind, they should ask whether it’s safe for pacemakers since these devices are like a “pacemaker for pain.
“I had a patient bring solar chargers with him so that he could recharge his battery in the backwoods while kayaking because that’s the level of improvement in pain that he got – from barely being able to walk down the hall to feeling comfortable being off the grid and active again,” Dr. Petersen said. “Those kinds of improvements in quality of life are massive.”
The study findings may also suggest that spinal cord stimulation can benefit a broader population of patients experiencing neuropathic pain, Dr. Markman said.
“There’s an extraordinary unmet need for treatments for neuropathy, and one important question here is the extent to which diabetic peripheral neuropathy and the response that we’re seeing here is a proxy for a broader effect across many neuropathies that are caused by other conditions other than diabetes,” Dr. Markman said. “There’s a lot of reason to think that this will be helpful not just for diabetes-related neuropathic pain, but for other types of neuropathic pain that have similar clinical presentations or clinical symptom patterns to diabetic peripheral neuropathy.”
The study was funded by Nevro, who manufactures the devices. Dr. Petersen and Dr. Markman both reported consulting with, receiving support from, holding stock options with, and serving on the data safety monitoring boards and advisory boards of numerous pharmaceutical companies.
according to research that released early, prior to its presentation at the annual meeting of the American Academy of Neurology.
The data represents the longest follow-up available for spinal cord stimulation at a frequency higher than the 60 Hz initially approved for diabetic neuropathy by the Food and Drug Administration, according to lead author Erika A. Petersen, MD, a professor of neurosurgery and the residency program director at the University of Arkansas for Medical Sciences, Little Rock.
“You would expect that somebody who continues to have diabetes for 24 months and has neuropathy would have worse neuropathy after 2 years, and what we’re seeing is that people were stable or better in terms of their nerve function at 2 years,” Dr. Petersen said in an interview. “So that’s really revolutionary.”
Encouraging preliminary findings
The findings are “promising and preliminary,” John D. Markman, MD, a professor in neurology and neurosurgery, vice chair for clinical research, and director of the Translational Pain Research Program at the University of Rochester (N.Y.) Medical Center, said in an interview. Dr. Markman, who was not involved in this study, said that, though the results are encouraging, it’s “less clear how much of [the pain improvement] is due to what we would consider to be on-target, pain-relieving benefit from stimulation versus other factors like expectation.” The crossover rate and amount of reduction in pain intensity are promising, but “I think that excitement is weighed against the fact that this is an open-label study.”
An underused treatment
Although spinal cord stimulation has been around since the late 1960s, its use only picked up steam in the 2000s, when it became more frequently used to treat chronic nerve damage related to neuropathic pain syndromes, Dr. Petersen explained. The FDA approved the treatment’s new indication for diabetic neuropathy in 2015, and data from Abbott and Medtronic have shown benefits from spinal cord stimulation at 60 Hz, but some patients are uncomfortable with the vibration or tingling feelings the devices can cause at that frequency.
“They describe creepy crawlies or ants crawling over the feet, or pins and needles, and painful sensitivity,” Dr. Petersen said. “You create a vibration feeling in the same zone where they already have those feelings of buzzing and pain and vibration, and it’s sometimes actually even more uncomfortable and less satisfying to them in terms of relief” with the spinal cord stimulation at 60 Hz, she said, “so there’s a lot of attrition in terms of who will actually use it.”
At 10 kHz, however, “people don’t feel any vibration or tingling associated with it; it just jams the signal of the pain,” she said. The difference between the frequencies is like that between “a lifeguard whistle and a dog whistle.”
Testing high-frequency stimulation
The new findings included the 24-month follow-up data from a randomized controlled trial that assessed the effectiveness of high-frequency spinal cord stimulation for painful diabetic neuropathy. The original 216 participants enrolled in the trial had diabetic neuropathy symptoms for at least 12 months and either could no not tolerate or did not respond to medications. Enrollment criteria also included lower-limb pain intensity of at least 5 on a 0-10 visual analogy scale and hemoglobin A1c of no more than 10%.
For the first 6 months of the trial – before crossover was offered – participants were randomly assigned to receive either 10 kHz of spinal cord stimulation along with conventional medical management or to receive conventional medical management alone. The 6-month data from 187 patients, as reported in April 2021 in JAMA Neurology, revealed that 79% of those receiving spinal cord stimulation experienced at least 50% improved pain relief without worsening of their baseline neurologic deficits, compared with only 5% of those receiving only conventional treatments.
Average pain levels increased 2% in the control participants compared with a decrease of 76% in those with the spinal cord stimulation devices. In addition, 62% of the patients receiving spinal cord stimulation demonstration neurologic improvement in reflexes, strength, movement and sensation, compared with 3% of those in the control group. The study’s findings led the FDA to approve the device using 10 kHz.
At 6 months, 93% of control patients crossed over to receiving spinal cord stimulation while none with the devices opted to stop their spinal cord stimulation. The 12-month data revealed that 85% of those receiving spinal cord stimulation experienced at least 50% pain relief, with the average pain relief at 74%. Patients also reported statistically significant improved quality of life as well as less interference with sleep, mood, and daily activities from pain.
Two years after baseline, patients’ pain relief was maintained with average 80% improvement, and 66% of patients showed neurologic improvement since baseline. Though no patients had devices removed because of ineffectiveness, five patients’ devices were removed because of infection while infections in three other patients resolved.
“Being able to offer something that is not a pharmaceutical, without the side effects, that shows an even longer durability to that response is a really important finding at this point,” Dr. Petersen said.
Surgical considerations
Among the estimated 37 million Americans with type 1 or 2 diabetes, approximately one quarter of them experience some level of painful diabetic neuropathy, but medication and other medical management strategies are not always adequate in treating their pain. After a 1-week trial of spinal cord stimulation, the devices are implanted under the skin and rechargeable through the skin for up to 10 years, after which they can be replaced.
An appropriate candidate for spinal cord stimulation would be someone for whom existing non-invasive pain relief options, including medications, are ineffective or intolerable, Dr. Petersen and Dr. Markman both said. An adequate trial of medication is not “one size fits all” and will vary by each patient, added Dr. Markman, who is also interested in whether this study’s participants were able to have a reduction in use of pain relief medications.
“I think there’s a significant number of patients out there who can benefit from this, so I think that’s why it’s promising and exciting,” Dr. Markman said. “I do think it’s important to see if this actually allows them to be on less medication or whether stimulation turns out to be another treatment in addition to their baseline treatments.” The challenge is identifying “which patients are most likely to be benefiting from this and which are most likely to be harmed.”
Aside from infection from implantation, other possible risks include pain at the battery site and, in rare cases, a need for reoperation because of migration of the leads, he said.
Improvement in symptom severity and quality of life
After the wound from the implant has completely healed, Dr. Petersen said patients using the devices do not have any activity restrictions outside of magnetic interference, such as MRIs. “I’ve had people go back-country kayaking, scuba diving, fishing with their grandkids, all sorts of all sorts of things. If patients need to go through a scanner of any kind, they should ask whether it’s safe for pacemakers since these devices are like a “pacemaker for pain.
“I had a patient bring solar chargers with him so that he could recharge his battery in the backwoods while kayaking because that’s the level of improvement in pain that he got – from barely being able to walk down the hall to feeling comfortable being off the grid and active again,” Dr. Petersen said. “Those kinds of improvements in quality of life are massive.”
The study findings may also suggest that spinal cord stimulation can benefit a broader population of patients experiencing neuropathic pain, Dr. Markman said.
“There’s an extraordinary unmet need for treatments for neuropathy, and one important question here is the extent to which diabetic peripheral neuropathy and the response that we’re seeing here is a proxy for a broader effect across many neuropathies that are caused by other conditions other than diabetes,” Dr. Markman said. “There’s a lot of reason to think that this will be helpful not just for diabetes-related neuropathic pain, but for other types of neuropathic pain that have similar clinical presentations or clinical symptom patterns to diabetic peripheral neuropathy.”
The study was funded by Nevro, who manufactures the devices. Dr. Petersen and Dr. Markman both reported consulting with, receiving support from, holding stock options with, and serving on the data safety monitoring boards and advisory boards of numerous pharmaceutical companies.
according to research that released early, prior to its presentation at the annual meeting of the American Academy of Neurology.
The data represents the longest follow-up available for spinal cord stimulation at a frequency higher than the 60 Hz initially approved for diabetic neuropathy by the Food and Drug Administration, according to lead author Erika A. Petersen, MD, a professor of neurosurgery and the residency program director at the University of Arkansas for Medical Sciences, Little Rock.
“You would expect that somebody who continues to have diabetes for 24 months and has neuropathy would have worse neuropathy after 2 years, and what we’re seeing is that people were stable or better in terms of their nerve function at 2 years,” Dr. Petersen said in an interview. “So that’s really revolutionary.”
Encouraging preliminary findings
The findings are “promising and preliminary,” John D. Markman, MD, a professor in neurology and neurosurgery, vice chair for clinical research, and director of the Translational Pain Research Program at the University of Rochester (N.Y.) Medical Center, said in an interview. Dr. Markman, who was not involved in this study, said that, though the results are encouraging, it’s “less clear how much of [the pain improvement] is due to what we would consider to be on-target, pain-relieving benefit from stimulation versus other factors like expectation.” The crossover rate and amount of reduction in pain intensity are promising, but “I think that excitement is weighed against the fact that this is an open-label study.”
An underused treatment
Although spinal cord stimulation has been around since the late 1960s, its use only picked up steam in the 2000s, when it became more frequently used to treat chronic nerve damage related to neuropathic pain syndromes, Dr. Petersen explained. The FDA approved the treatment’s new indication for diabetic neuropathy in 2015, and data from Abbott and Medtronic have shown benefits from spinal cord stimulation at 60 Hz, but some patients are uncomfortable with the vibration or tingling feelings the devices can cause at that frequency.
“They describe creepy crawlies or ants crawling over the feet, or pins and needles, and painful sensitivity,” Dr. Petersen said. “You create a vibration feeling in the same zone where they already have those feelings of buzzing and pain and vibration, and it’s sometimes actually even more uncomfortable and less satisfying to them in terms of relief” with the spinal cord stimulation at 60 Hz, she said, “so there’s a lot of attrition in terms of who will actually use it.”
At 10 kHz, however, “people don’t feel any vibration or tingling associated with it; it just jams the signal of the pain,” she said. The difference between the frequencies is like that between “a lifeguard whistle and a dog whistle.”
Testing high-frequency stimulation
The new findings included the 24-month follow-up data from a randomized controlled trial that assessed the effectiveness of high-frequency spinal cord stimulation for painful diabetic neuropathy. The original 216 participants enrolled in the trial had diabetic neuropathy symptoms for at least 12 months and either could no not tolerate or did not respond to medications. Enrollment criteria also included lower-limb pain intensity of at least 5 on a 0-10 visual analogy scale and hemoglobin A1c of no more than 10%.
For the first 6 months of the trial – before crossover was offered – participants were randomly assigned to receive either 10 kHz of spinal cord stimulation along with conventional medical management or to receive conventional medical management alone. The 6-month data from 187 patients, as reported in April 2021 in JAMA Neurology, revealed that 79% of those receiving spinal cord stimulation experienced at least 50% improved pain relief without worsening of their baseline neurologic deficits, compared with only 5% of those receiving only conventional treatments.
Average pain levels increased 2% in the control participants compared with a decrease of 76% in those with the spinal cord stimulation devices. In addition, 62% of the patients receiving spinal cord stimulation demonstration neurologic improvement in reflexes, strength, movement and sensation, compared with 3% of those in the control group. The study’s findings led the FDA to approve the device using 10 kHz.
At 6 months, 93% of control patients crossed over to receiving spinal cord stimulation while none with the devices opted to stop their spinal cord stimulation. The 12-month data revealed that 85% of those receiving spinal cord stimulation experienced at least 50% pain relief, with the average pain relief at 74%. Patients also reported statistically significant improved quality of life as well as less interference with sleep, mood, and daily activities from pain.
Two years after baseline, patients’ pain relief was maintained with average 80% improvement, and 66% of patients showed neurologic improvement since baseline. Though no patients had devices removed because of ineffectiveness, five patients’ devices were removed because of infection while infections in three other patients resolved.
“Being able to offer something that is not a pharmaceutical, without the side effects, that shows an even longer durability to that response is a really important finding at this point,” Dr. Petersen said.
Surgical considerations
Among the estimated 37 million Americans with type 1 or 2 diabetes, approximately one quarter of them experience some level of painful diabetic neuropathy, but medication and other medical management strategies are not always adequate in treating their pain. After a 1-week trial of spinal cord stimulation, the devices are implanted under the skin and rechargeable through the skin for up to 10 years, after which they can be replaced.
An appropriate candidate for spinal cord stimulation would be someone for whom existing non-invasive pain relief options, including medications, are ineffective or intolerable, Dr. Petersen and Dr. Markman both said. An adequate trial of medication is not “one size fits all” and will vary by each patient, added Dr. Markman, who is also interested in whether this study’s participants were able to have a reduction in use of pain relief medications.
“I think there’s a significant number of patients out there who can benefit from this, so I think that’s why it’s promising and exciting,” Dr. Markman said. “I do think it’s important to see if this actually allows them to be on less medication or whether stimulation turns out to be another treatment in addition to their baseline treatments.” The challenge is identifying “which patients are most likely to be benefiting from this and which are most likely to be harmed.”
Aside from infection from implantation, other possible risks include pain at the battery site and, in rare cases, a need for reoperation because of migration of the leads, he said.
Improvement in symptom severity and quality of life
After the wound from the implant has completely healed, Dr. Petersen said patients using the devices do not have any activity restrictions outside of magnetic interference, such as MRIs. “I’ve had people go back-country kayaking, scuba diving, fishing with their grandkids, all sorts of all sorts of things. If patients need to go through a scanner of any kind, they should ask whether it’s safe for pacemakers since these devices are like a “pacemaker for pain.
“I had a patient bring solar chargers with him so that he could recharge his battery in the backwoods while kayaking because that’s the level of improvement in pain that he got – from barely being able to walk down the hall to feeling comfortable being off the grid and active again,” Dr. Petersen said. “Those kinds of improvements in quality of life are massive.”
The study findings may also suggest that spinal cord stimulation can benefit a broader population of patients experiencing neuropathic pain, Dr. Markman said.
“There’s an extraordinary unmet need for treatments for neuropathy, and one important question here is the extent to which diabetic peripheral neuropathy and the response that we’re seeing here is a proxy for a broader effect across many neuropathies that are caused by other conditions other than diabetes,” Dr. Markman said. “There’s a lot of reason to think that this will be helpful not just for diabetes-related neuropathic pain, but for other types of neuropathic pain that have similar clinical presentations or clinical symptom patterns to diabetic peripheral neuropathy.”
The study was funded by Nevro, who manufactures the devices. Dr. Petersen and Dr. Markman both reported consulting with, receiving support from, holding stock options with, and serving on the data safety monitoring boards and advisory boards of numerous pharmaceutical companies.
FROM AAN 2023
NSAID use in diabetes may worsen risk for first HF hospitalization
suggests a prospective, controlled study.
Certain subgroups may account for much of the excess risk, the results suggest, including the very elderly, patients with uncontrolled diabetes, those prescribed an NSAID for the first time, and patients already taking both a renin-angiotensin system inhibitor (RASi) and a diuretic.
Such patients with a firm indication for NSAIDs potentially could “be the ones benefiting most from closer follow-up, reduced dosage, or other mitigation strategies,” Anders Holt, MD, said in an interview.
Dr. Holt, of Copenhagen University Hospital and Herlev-Gentofte Hospital in Hellerup, Denmark, is lead author on the analysis of Danish registry data published in the Journal of the American College of Cardiology. He presented essentially the same results in preliminary form at the 2022 annual congress of the European Society of Cardiology.
HF hospitalizations linked to NSAIDs, the published report notes, are often attributed to symptoms from temporary fluid overload, often without worsening cardiac function, that stem from the drugs’ renal effects.
“One could speculate,” Dr. Holt said, that such HF events might be less severe and even associated with better outcomes, compared with other forms of heart failure.
But the current analysis provides a hint to the contrary, he observed. The 5-year mortality was similar for patients with HF linked to NSAIDs and those with other forms of HF, “which could suggest that NSAID-associated heart failure is more than transient fluid overload.”
The drugs may promote HF through direct effects on the heart by any of several proposed mechanisms, including “induction of arrhythmias and heart fibrosis, vasoconstriction, subclinical inflammation, and blood pressure elevation,” Dr. Holt said.
The current study doesn’t determine whether NSAID-associated HF stems from transient fluid overload or direct cardiac effects, but it’s “most likely both.”
In other limitations, the analysis is unable to “reliably explore” whether promotion of HF is an NSAID class effect, a “clinically relevant” point given the drugs’ varying effects on cardiovascular risk, states an accompanying editorial. Nor was it able to determine whether the drugs exert a dose-response effect on HF risk, noted Hassan Khan, MD, PhD, Norton Healthcare, Louisville, Ky., and Setor K. Kunutsor, MD, PhD, University of Leicester (England).
Still, “given the well-established relationship between the use of NSAIDs and increased HF, these findings are not unexpected because type 2 diabetes is also a major risk factor for HF.”
But it may be “premature to issue guideline recommendations based on a single observational study,” the editorialists wrote. “Further robust clinical trial evidence is needed to replicate these results and investigate the relationship of the type and dose of NSAIDs with HF risk. However, it should be realized that short-term or long-term use of NSAIDs may be detrimental to cardiovascular health.”
The analysis covered 23,308 patients from throughout Denmark with a type 2 diabetes diagnosis and no HF history who experienced a first HF hospitalization; their age averaged 76 years and 39% were women.
They served as their own controls; their NSAID exposures at two 28-day periods preceding the HF event, the one immediately before and the other preceding it by 56 days, were compared as the index and control periods, respectively.
Exposure to NSAIDs was defined as obtaining a prescription for celecoxib, diclofenac, ibuprofen, or naproxen, “as these are NSAIDs used primarily in Denmark,” the report states.
The odds ratios for HF hospitalization associated with NSAID exposure within 28 days preceding the event were 1.43 (95% confidence interval, 1.27-1.63) overall, 1.41 (95% CI, 1.16-1.71) for an NSAID given on top of both RASi and diuretics, 1.68 (95% CI, 1.00-2.88) for patients with elevated hemoglobin A1c, 1.78 (95% CI, 1.39-2.28) for those 80 or older, and 2.71 (95% CI, 1.78-4.23) for those with prior NSAID use.
That NSAID use and diabetes are each associated with increased risk for HF is well established, Dr. Holt observed. Yet the drugs had been prescribed to 16% of patients in the study.
“One of the more surprising findings, to me, was the quite substantial use of prescribed NSAIDs in a population of patients with diabetes, a patient group with a well-established cardiovascular risk,” he said.
“This patient group is only growing, so emphasis on the possible associations between even short-term NSAID use and incident heart failure is probably timely and perhaps needed.”
Dr. Holt and the study were supported by grants from Ib Mogens Kristiansens Almene Fond, Helsefonden, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond, Marie og M.B. Richters Fond, and the Dagmar Marshalls Fond. Dr. Khan and Dr. Kunutsor reported no relevant relationships.
A version of this article first appeared on Medscape.com.
suggests a prospective, controlled study.
Certain subgroups may account for much of the excess risk, the results suggest, including the very elderly, patients with uncontrolled diabetes, those prescribed an NSAID for the first time, and patients already taking both a renin-angiotensin system inhibitor (RASi) and a diuretic.
Such patients with a firm indication for NSAIDs potentially could “be the ones benefiting most from closer follow-up, reduced dosage, or other mitigation strategies,” Anders Holt, MD, said in an interview.
Dr. Holt, of Copenhagen University Hospital and Herlev-Gentofte Hospital in Hellerup, Denmark, is lead author on the analysis of Danish registry data published in the Journal of the American College of Cardiology. He presented essentially the same results in preliminary form at the 2022 annual congress of the European Society of Cardiology.
HF hospitalizations linked to NSAIDs, the published report notes, are often attributed to symptoms from temporary fluid overload, often without worsening cardiac function, that stem from the drugs’ renal effects.
“One could speculate,” Dr. Holt said, that such HF events might be less severe and even associated with better outcomes, compared with other forms of heart failure.
But the current analysis provides a hint to the contrary, he observed. The 5-year mortality was similar for patients with HF linked to NSAIDs and those with other forms of HF, “which could suggest that NSAID-associated heart failure is more than transient fluid overload.”
The drugs may promote HF through direct effects on the heart by any of several proposed mechanisms, including “induction of arrhythmias and heart fibrosis, vasoconstriction, subclinical inflammation, and blood pressure elevation,” Dr. Holt said.
The current study doesn’t determine whether NSAID-associated HF stems from transient fluid overload or direct cardiac effects, but it’s “most likely both.”
In other limitations, the analysis is unable to “reliably explore” whether promotion of HF is an NSAID class effect, a “clinically relevant” point given the drugs’ varying effects on cardiovascular risk, states an accompanying editorial. Nor was it able to determine whether the drugs exert a dose-response effect on HF risk, noted Hassan Khan, MD, PhD, Norton Healthcare, Louisville, Ky., and Setor K. Kunutsor, MD, PhD, University of Leicester (England).
Still, “given the well-established relationship between the use of NSAIDs and increased HF, these findings are not unexpected because type 2 diabetes is also a major risk factor for HF.”
But it may be “premature to issue guideline recommendations based on a single observational study,” the editorialists wrote. “Further robust clinical trial evidence is needed to replicate these results and investigate the relationship of the type and dose of NSAIDs with HF risk. However, it should be realized that short-term or long-term use of NSAIDs may be detrimental to cardiovascular health.”
The analysis covered 23,308 patients from throughout Denmark with a type 2 diabetes diagnosis and no HF history who experienced a first HF hospitalization; their age averaged 76 years and 39% were women.
They served as their own controls; their NSAID exposures at two 28-day periods preceding the HF event, the one immediately before and the other preceding it by 56 days, were compared as the index and control periods, respectively.
Exposure to NSAIDs was defined as obtaining a prescription for celecoxib, diclofenac, ibuprofen, or naproxen, “as these are NSAIDs used primarily in Denmark,” the report states.
The odds ratios for HF hospitalization associated with NSAID exposure within 28 days preceding the event were 1.43 (95% confidence interval, 1.27-1.63) overall, 1.41 (95% CI, 1.16-1.71) for an NSAID given on top of both RASi and diuretics, 1.68 (95% CI, 1.00-2.88) for patients with elevated hemoglobin A1c, 1.78 (95% CI, 1.39-2.28) for those 80 or older, and 2.71 (95% CI, 1.78-4.23) for those with prior NSAID use.
That NSAID use and diabetes are each associated with increased risk for HF is well established, Dr. Holt observed. Yet the drugs had been prescribed to 16% of patients in the study.
“One of the more surprising findings, to me, was the quite substantial use of prescribed NSAIDs in a population of patients with diabetes, a patient group with a well-established cardiovascular risk,” he said.
“This patient group is only growing, so emphasis on the possible associations between even short-term NSAID use and incident heart failure is probably timely and perhaps needed.”
Dr. Holt and the study were supported by grants from Ib Mogens Kristiansens Almene Fond, Helsefonden, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond, Marie og M.B. Richters Fond, and the Dagmar Marshalls Fond. Dr. Khan and Dr. Kunutsor reported no relevant relationships.
A version of this article first appeared on Medscape.com.
suggests a prospective, controlled study.
Certain subgroups may account for much of the excess risk, the results suggest, including the very elderly, patients with uncontrolled diabetes, those prescribed an NSAID for the first time, and patients already taking both a renin-angiotensin system inhibitor (RASi) and a diuretic.
Such patients with a firm indication for NSAIDs potentially could “be the ones benefiting most from closer follow-up, reduced dosage, or other mitigation strategies,” Anders Holt, MD, said in an interview.
Dr. Holt, of Copenhagen University Hospital and Herlev-Gentofte Hospital in Hellerup, Denmark, is lead author on the analysis of Danish registry data published in the Journal of the American College of Cardiology. He presented essentially the same results in preliminary form at the 2022 annual congress of the European Society of Cardiology.
HF hospitalizations linked to NSAIDs, the published report notes, are often attributed to symptoms from temporary fluid overload, often without worsening cardiac function, that stem from the drugs’ renal effects.
“One could speculate,” Dr. Holt said, that such HF events might be less severe and even associated with better outcomes, compared with other forms of heart failure.
But the current analysis provides a hint to the contrary, he observed. The 5-year mortality was similar for patients with HF linked to NSAIDs and those with other forms of HF, “which could suggest that NSAID-associated heart failure is more than transient fluid overload.”
The drugs may promote HF through direct effects on the heart by any of several proposed mechanisms, including “induction of arrhythmias and heart fibrosis, vasoconstriction, subclinical inflammation, and blood pressure elevation,” Dr. Holt said.
The current study doesn’t determine whether NSAID-associated HF stems from transient fluid overload or direct cardiac effects, but it’s “most likely both.”
In other limitations, the analysis is unable to “reliably explore” whether promotion of HF is an NSAID class effect, a “clinically relevant” point given the drugs’ varying effects on cardiovascular risk, states an accompanying editorial. Nor was it able to determine whether the drugs exert a dose-response effect on HF risk, noted Hassan Khan, MD, PhD, Norton Healthcare, Louisville, Ky., and Setor K. Kunutsor, MD, PhD, University of Leicester (England).
Still, “given the well-established relationship between the use of NSAIDs and increased HF, these findings are not unexpected because type 2 diabetes is also a major risk factor for HF.”
But it may be “premature to issue guideline recommendations based on a single observational study,” the editorialists wrote. “Further robust clinical trial evidence is needed to replicate these results and investigate the relationship of the type and dose of NSAIDs with HF risk. However, it should be realized that short-term or long-term use of NSAIDs may be detrimental to cardiovascular health.”
The analysis covered 23,308 patients from throughout Denmark with a type 2 diabetes diagnosis and no HF history who experienced a first HF hospitalization; their age averaged 76 years and 39% were women.
They served as their own controls; their NSAID exposures at two 28-day periods preceding the HF event, the one immediately before and the other preceding it by 56 days, were compared as the index and control periods, respectively.
Exposure to NSAIDs was defined as obtaining a prescription for celecoxib, diclofenac, ibuprofen, or naproxen, “as these are NSAIDs used primarily in Denmark,” the report states.
The odds ratios for HF hospitalization associated with NSAID exposure within 28 days preceding the event were 1.43 (95% confidence interval, 1.27-1.63) overall, 1.41 (95% CI, 1.16-1.71) for an NSAID given on top of both RASi and diuretics, 1.68 (95% CI, 1.00-2.88) for patients with elevated hemoglobin A1c, 1.78 (95% CI, 1.39-2.28) for those 80 or older, and 2.71 (95% CI, 1.78-4.23) for those with prior NSAID use.
That NSAID use and diabetes are each associated with increased risk for HF is well established, Dr. Holt observed. Yet the drugs had been prescribed to 16% of patients in the study.
“One of the more surprising findings, to me, was the quite substantial use of prescribed NSAIDs in a population of patients with diabetes, a patient group with a well-established cardiovascular risk,” he said.
“This patient group is only growing, so emphasis on the possible associations between even short-term NSAID use and incident heart failure is probably timely and perhaps needed.”
Dr. Holt and the study were supported by grants from Ib Mogens Kristiansens Almene Fond, Helsefonden, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond, Marie og M.B. Richters Fond, and the Dagmar Marshalls Fond. Dr. Khan and Dr. Kunutsor reported no relevant relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Study offers dozens of reasons to cut sugar
A new compilation of nearly all research to date on the health impacts of sugar offers dozens of reasons to cut back.
The studies accounted for decades of research on the topic, stretching back to the beginning of the largest electronic databases for scientific papers.
The result is a list that cites the world’s most common health problems like heart disease, diabetes, obesity, high blood pressure, heart attack, high cholesterol, cancer, and depression. The findings were published in the BMJ. Researchers looked at studies that evaluated the impacts of consuming free sugars, which means any food that contains processed or naturally occurring sugars like table sugar, honey, or maple syrup. Sugar found in whole fruits and vegetables and in milk is not free sugar.
U.S. dietary guidelines recommend getting no more than 10% of daily calories from added sugars. For a typical 2,000-calorie-per-day diet, that equals no more than 200 calories, or about 12 teaspoons. The CDC reports that the average person consumes 17 teaspoons per day, with the largest sources being sugar-sweetened beverages, desserts, and snacks. (For context: one 12-ounce can of soda contains the equivalent of 9 teaspoons of sugar, according to beverage maker Coca-Cola.)
The new analysis also found links between sugary beverage consumption and other diet and lifestyle characteristics that may contribute to health problems.
“People who consumed sugar-sweetened beverages more frequently were likely to ingest more total and saturated fat, carbohydrate, and sodium, and less fruit, fiber, dairy products, and whole grain foods,” the authors wrote. “This dietary pattern was also associated with more frequent smoking and drinking, lower physical activity levels, and more time spent watching television. Therefore, the role of these confounding factors should be taken into consideration when explaining the association between sugar consumption and burden of disease.”
Recommendations for limiting sugar consumption are in place worldwide, the authors noted. They concluded that more needs to be done given the known health dangers of sugar.
“To change sugar consumption patterns, especially for children and adolescents, a combination of widespread public health education and policies worldwide is urgently needed,” they said.
A version of this article first appeared on WebMD.com.
A new compilation of nearly all research to date on the health impacts of sugar offers dozens of reasons to cut back.
The studies accounted for decades of research on the topic, stretching back to the beginning of the largest electronic databases for scientific papers.
The result is a list that cites the world’s most common health problems like heart disease, diabetes, obesity, high blood pressure, heart attack, high cholesterol, cancer, and depression. The findings were published in the BMJ. Researchers looked at studies that evaluated the impacts of consuming free sugars, which means any food that contains processed or naturally occurring sugars like table sugar, honey, or maple syrup. Sugar found in whole fruits and vegetables and in milk is not free sugar.
U.S. dietary guidelines recommend getting no more than 10% of daily calories from added sugars. For a typical 2,000-calorie-per-day diet, that equals no more than 200 calories, or about 12 teaspoons. The CDC reports that the average person consumes 17 teaspoons per day, with the largest sources being sugar-sweetened beverages, desserts, and snacks. (For context: one 12-ounce can of soda contains the equivalent of 9 teaspoons of sugar, according to beverage maker Coca-Cola.)
The new analysis also found links between sugary beverage consumption and other diet and lifestyle characteristics that may contribute to health problems.
“People who consumed sugar-sweetened beverages more frequently were likely to ingest more total and saturated fat, carbohydrate, and sodium, and less fruit, fiber, dairy products, and whole grain foods,” the authors wrote. “This dietary pattern was also associated with more frequent smoking and drinking, lower physical activity levels, and more time spent watching television. Therefore, the role of these confounding factors should be taken into consideration when explaining the association between sugar consumption and burden of disease.”
Recommendations for limiting sugar consumption are in place worldwide, the authors noted. They concluded that more needs to be done given the known health dangers of sugar.
“To change sugar consumption patterns, especially for children and adolescents, a combination of widespread public health education and policies worldwide is urgently needed,” they said.
A version of this article first appeared on WebMD.com.
A new compilation of nearly all research to date on the health impacts of sugar offers dozens of reasons to cut back.
The studies accounted for decades of research on the topic, stretching back to the beginning of the largest electronic databases for scientific papers.
The result is a list that cites the world’s most common health problems like heart disease, diabetes, obesity, high blood pressure, heart attack, high cholesterol, cancer, and depression. The findings were published in the BMJ. Researchers looked at studies that evaluated the impacts of consuming free sugars, which means any food that contains processed or naturally occurring sugars like table sugar, honey, or maple syrup. Sugar found in whole fruits and vegetables and in milk is not free sugar.
U.S. dietary guidelines recommend getting no more than 10% of daily calories from added sugars. For a typical 2,000-calorie-per-day diet, that equals no more than 200 calories, or about 12 teaspoons. The CDC reports that the average person consumes 17 teaspoons per day, with the largest sources being sugar-sweetened beverages, desserts, and snacks. (For context: one 12-ounce can of soda contains the equivalent of 9 teaspoons of sugar, according to beverage maker Coca-Cola.)
The new analysis also found links between sugary beverage consumption and other diet and lifestyle characteristics that may contribute to health problems.
“People who consumed sugar-sweetened beverages more frequently were likely to ingest more total and saturated fat, carbohydrate, and sodium, and less fruit, fiber, dairy products, and whole grain foods,” the authors wrote. “This dietary pattern was also associated with more frequent smoking and drinking, lower physical activity levels, and more time spent watching television. Therefore, the role of these confounding factors should be taken into consideration when explaining the association between sugar consumption and burden of disease.”
Recommendations for limiting sugar consumption are in place worldwide, the authors noted. They concluded that more needs to be done given the known health dangers of sugar.
“To change sugar consumption patterns, especially for children and adolescents, a combination of widespread public health education and policies worldwide is urgently needed,” they said.
A version of this article first appeared on WebMD.com.
FROM THE BMJ
Semaglutide doesn’t improve fibrosis in NASH-related cirrhosis
according to a phase 2 trial.
However, the glucagonlike peptide–1 (GLP-1) receptor agonist led to improvements in liver enzymes, liver steatosis, weight, triglycerides, and very low-density lipoprotein (VLDL) cholesterol. Similar proportions of patients in each group reported adverse events, such as nausea, diarrhea, and vomiting.
“Previous studies in patients with NASH and stage 2 or 3 fibrosis have shown that semaglutide can improve NASH resolution over 72 weeks. However, there are limited data on whether any therapy is effective in patients with NASH cirrhosis,” lead author Rohit Loomba, MD, founding director of the NAFLD Research Center at the University of California, San Diego, said in an interview.
“Although semaglutide did not succeed in improving histological fibrosis, it had success in improving other clinically important parameters, such as cardiometabolic risk factors, liver enzymes, liver fat, and noninvasive biomarkers of fibrosis,” he said.
The study was published online in The Lancet Gastroenterology & Hepatology.
Analyzing safety and efficacy
Dr. Loomba and colleagues conducted a double-blind, placebo-controlled phase 2 trial that enrolled 71 patients at 38 centers in the United States and Europe between June 2019 and April 2021. Adults with biopsy-confirmed NASH-related cirrhosis and a body mass index (BMI) of at least 27 kg/m2 were randomly assigned 2:1 to receive either once-weekly subcutaneous semaglutide at 2.4 mg or a visually matching placebo.
Patients were randomly allocated through an interactive web system, which stratified participants on the basis of the presence or absence of type 2 diabetes. Patients, investigators, and outcomes analysts were masked to the treatment assignment.
The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without a worsening of NASH after 48 weeks, which was measured through biopsy in the intention-to-treat population. Safety was also assessed in all patients who received at least one dose of semaglutide.
Among the 71 patients, 47 were randomly assigned to the semaglutide group and 24 to the placebo group. About 90% completed treatment, and 63 had evaluable paired biopsies for primary endpoint assessment.
Between the groups, 49 participants (69%) were women and 22 were men. The average age was 59.5 years, and the average BMI was 34.9. About 75% of patients had diabetes at baseline, with an average hemoglobin A1c of 7.1%.
After 48 weeks, researchers found no statistically significant difference between the groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH. In the semaglutide group, five patients (11%) had an improvement, compared with seven patients (29%) in the placebo group (odds ratio, 0.28; 95% confidence interval, 0.06-1.24, P = .087).
There also wasn’t a significant difference between groups in the proportion of patients who achieved NASH resolution. In the semaglutide group, 16 patients (34%) had resolution, compared with 5 patients (21%) in the placebo group (OR, 1.97; 95% CI, 0.56-7.91; P = .29).
In addition, a lower proportion of patients achieved both NASH resolution and improvement in liver fibrosis with semaglutide versus placebo, although the difference wasn’t significant. In the semaglutide group, three patients (6%) achieved both, compared with three patients (13%) in the placebo group (OR, 0.48; 95% CI, 0.06-3.91; P = .4). A lower proportion of patients had an improvement in liver fibrosis stage with semaglutide versus placebo.
Some improvements seen
However, the semaglutide group had significantly greater improvements in liver steatosis (but not stiffness), liver fat volume, procollagen 3 peptide, and liver enzymes such as ALT, AST, and gamma-glutamyltransferase.
Body weight decreased by 8.83% in the semaglutide group, compared with 0.09% in the placebo group, which was a significant difference. BMI, waist circumference, triglycerides, and VLDL cholesterol were also significantly lower in the semaglutide group, but total cholesterol and blood pressure measurements weren’t significantly different. Among those with type 2 diabetes, A1c also decreased in the semaglutide group but did not in the placebo group.
Similar proportions of patients in each group reported adverse events. In the semaglutide group, 42 patients (89%) had an adverse event, compared with 19 patients (79%) in the placebo group. In addition, six patients (13%) in the semaglutide group and two patients (8%) in the placebo group reported serious adverse events.
The most common adverse events in the semaglutide and placebo groups were nausea (45% and 17%), diarrhea (19% and 8%), and vomiting (17% and none), which mainly occurred during treatment initiation or dose escalation. No patients withdrew from the trial because of adverse events, although five had a dose reduction. Hepatic and renal function remained stable after semaglutide treatment, and there were no decompensating events or deaths.
“GLP-1 analogue exposure – among patients with compensated cirrhosis who suffer from morbid obesity and type 2 diabetes – for the treatment of diabetes appears to be well-tolerated and may be safe,” Dr. Loomba said. “Further studies are needed in this study population.”
Considering next steps
Dr. Loomba and colleagues are continuing research around risk factors linked to advanced fibrosis, such as type 2 diabetes, a family history of cirrhosis, and the presence of key genetic risk alleles. Gut dysbiosis also appears to increase the risk for advanced fatty liver disease, he said.
Future clinical trials could focus on therapeutic options for patients with advanced fibrosis, particularly those with cirrhosis who face increased risks for liver-related complications and mortality.
“As these patients are oftentimes excluded from initial randomized controlled trials, we have significantly less information on how to address obesity, type 2 diabetes, and NASH in these patients,” Fernando Bril, MD, a physician-scientist focused on NASH-related research at the University of Alabama at Birmingham, said in an interview.
Dr. Bril, who wasn’t involved with this study, wrote an accompanying editorial in The Lancet Gastroenterology & Hepatology.
Patients with NASH-related cirrhosis may have progressed to a point of the disease where fibrosis regression may be more difficult to achieve, he said.
“This emphasizes that early diagnosis of patients with NASH is crucial,” he said.
“Therefore, primary care providers, endocrinologists, and diabetologists need to have a low threshold to suspect liver disease in patients with overweight, obesity, and/or type 2 diabetes. Only this will allow for early initiation of therapy, which may delay the progression of liver disease.”
In further research, investigators may want to consider the lack of NASH resolution, a result that could be caused by this study being underpowered, Dr. Bril noted. The trend in resolution in this study appeared similar to improvements seen in NASH patients without cirrhosis in other studies, he said. The weight reduction and improved diabetes control in this group also shows promise.
“While a purist may be adamant that this was a negative study for histological outcomes, it is essential to take note of the positive results in many secondary outcomes,” he said. “Improving cardiometabolic risk in these patients is essential because many still die of cardiovascular disease and not liver-related complications.”
At the same time, it’s important to note that NASH can’t be oversimplified as “a matter of weight,” Dr. Bril said. Significant weight loss in the study didn’t result in histologic improvement, which means other strategies are needed to treat the disease.
“Negative results from this study emphasize that monotherapy may not be enough to improve NASH and liver fibrosis,” he said. “In a similar way we treat type 2 diabetes and hypertension with combination therapy, we need to consider a similar approach for patients with NASH.”
The study was sponsored by Novo Nordisk, which manufactures semaglutide. The authors declared grant funding, speaker fees, and consultant roles with numerous pharmaceutical companies. Dr. Bril had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to a phase 2 trial.
However, the glucagonlike peptide–1 (GLP-1) receptor agonist led to improvements in liver enzymes, liver steatosis, weight, triglycerides, and very low-density lipoprotein (VLDL) cholesterol. Similar proportions of patients in each group reported adverse events, such as nausea, diarrhea, and vomiting.
“Previous studies in patients with NASH and stage 2 or 3 fibrosis have shown that semaglutide can improve NASH resolution over 72 weeks. However, there are limited data on whether any therapy is effective in patients with NASH cirrhosis,” lead author Rohit Loomba, MD, founding director of the NAFLD Research Center at the University of California, San Diego, said in an interview.
“Although semaglutide did not succeed in improving histological fibrosis, it had success in improving other clinically important parameters, such as cardiometabolic risk factors, liver enzymes, liver fat, and noninvasive biomarkers of fibrosis,” he said.
The study was published online in The Lancet Gastroenterology & Hepatology.
Analyzing safety and efficacy
Dr. Loomba and colleagues conducted a double-blind, placebo-controlled phase 2 trial that enrolled 71 patients at 38 centers in the United States and Europe between June 2019 and April 2021. Adults with biopsy-confirmed NASH-related cirrhosis and a body mass index (BMI) of at least 27 kg/m2 were randomly assigned 2:1 to receive either once-weekly subcutaneous semaglutide at 2.4 mg or a visually matching placebo.
Patients were randomly allocated through an interactive web system, which stratified participants on the basis of the presence or absence of type 2 diabetes. Patients, investigators, and outcomes analysts were masked to the treatment assignment.
The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without a worsening of NASH after 48 weeks, which was measured through biopsy in the intention-to-treat population. Safety was also assessed in all patients who received at least one dose of semaglutide.
Among the 71 patients, 47 were randomly assigned to the semaglutide group and 24 to the placebo group. About 90% completed treatment, and 63 had evaluable paired biopsies for primary endpoint assessment.
Between the groups, 49 participants (69%) were women and 22 were men. The average age was 59.5 years, and the average BMI was 34.9. About 75% of patients had diabetes at baseline, with an average hemoglobin A1c of 7.1%.
After 48 weeks, researchers found no statistically significant difference between the groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH. In the semaglutide group, five patients (11%) had an improvement, compared with seven patients (29%) in the placebo group (odds ratio, 0.28; 95% confidence interval, 0.06-1.24, P = .087).
There also wasn’t a significant difference between groups in the proportion of patients who achieved NASH resolution. In the semaglutide group, 16 patients (34%) had resolution, compared with 5 patients (21%) in the placebo group (OR, 1.97; 95% CI, 0.56-7.91; P = .29).
In addition, a lower proportion of patients achieved both NASH resolution and improvement in liver fibrosis with semaglutide versus placebo, although the difference wasn’t significant. In the semaglutide group, three patients (6%) achieved both, compared with three patients (13%) in the placebo group (OR, 0.48; 95% CI, 0.06-3.91; P = .4). A lower proportion of patients had an improvement in liver fibrosis stage with semaglutide versus placebo.
Some improvements seen
However, the semaglutide group had significantly greater improvements in liver steatosis (but not stiffness), liver fat volume, procollagen 3 peptide, and liver enzymes such as ALT, AST, and gamma-glutamyltransferase.
Body weight decreased by 8.83% in the semaglutide group, compared with 0.09% in the placebo group, which was a significant difference. BMI, waist circumference, triglycerides, and VLDL cholesterol were also significantly lower in the semaglutide group, but total cholesterol and blood pressure measurements weren’t significantly different. Among those with type 2 diabetes, A1c also decreased in the semaglutide group but did not in the placebo group.
Similar proportions of patients in each group reported adverse events. In the semaglutide group, 42 patients (89%) had an adverse event, compared with 19 patients (79%) in the placebo group. In addition, six patients (13%) in the semaglutide group and two patients (8%) in the placebo group reported serious adverse events.
The most common adverse events in the semaglutide and placebo groups were nausea (45% and 17%), diarrhea (19% and 8%), and vomiting (17% and none), which mainly occurred during treatment initiation or dose escalation. No patients withdrew from the trial because of adverse events, although five had a dose reduction. Hepatic and renal function remained stable after semaglutide treatment, and there were no decompensating events or deaths.
“GLP-1 analogue exposure – among patients with compensated cirrhosis who suffer from morbid obesity and type 2 diabetes – for the treatment of diabetes appears to be well-tolerated and may be safe,” Dr. Loomba said. “Further studies are needed in this study population.”
Considering next steps
Dr. Loomba and colleagues are continuing research around risk factors linked to advanced fibrosis, such as type 2 diabetes, a family history of cirrhosis, and the presence of key genetic risk alleles. Gut dysbiosis also appears to increase the risk for advanced fatty liver disease, he said.
Future clinical trials could focus on therapeutic options for patients with advanced fibrosis, particularly those with cirrhosis who face increased risks for liver-related complications and mortality.
“As these patients are oftentimes excluded from initial randomized controlled trials, we have significantly less information on how to address obesity, type 2 diabetes, and NASH in these patients,” Fernando Bril, MD, a physician-scientist focused on NASH-related research at the University of Alabama at Birmingham, said in an interview.
Dr. Bril, who wasn’t involved with this study, wrote an accompanying editorial in The Lancet Gastroenterology & Hepatology.
Patients with NASH-related cirrhosis may have progressed to a point of the disease where fibrosis regression may be more difficult to achieve, he said.
“This emphasizes that early diagnosis of patients with NASH is crucial,” he said.
“Therefore, primary care providers, endocrinologists, and diabetologists need to have a low threshold to suspect liver disease in patients with overweight, obesity, and/or type 2 diabetes. Only this will allow for early initiation of therapy, which may delay the progression of liver disease.”
In further research, investigators may want to consider the lack of NASH resolution, a result that could be caused by this study being underpowered, Dr. Bril noted. The trend in resolution in this study appeared similar to improvements seen in NASH patients without cirrhosis in other studies, he said. The weight reduction and improved diabetes control in this group also shows promise.
“While a purist may be adamant that this was a negative study for histological outcomes, it is essential to take note of the positive results in many secondary outcomes,” he said. “Improving cardiometabolic risk in these patients is essential because many still die of cardiovascular disease and not liver-related complications.”
At the same time, it’s important to note that NASH can’t be oversimplified as “a matter of weight,” Dr. Bril said. Significant weight loss in the study didn’t result in histologic improvement, which means other strategies are needed to treat the disease.
“Negative results from this study emphasize that monotherapy may not be enough to improve NASH and liver fibrosis,” he said. “In a similar way we treat type 2 diabetes and hypertension with combination therapy, we need to consider a similar approach for patients with NASH.”
The study was sponsored by Novo Nordisk, which manufactures semaglutide. The authors declared grant funding, speaker fees, and consultant roles with numerous pharmaceutical companies. Dr. Bril had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to a phase 2 trial.
However, the glucagonlike peptide–1 (GLP-1) receptor agonist led to improvements in liver enzymes, liver steatosis, weight, triglycerides, and very low-density lipoprotein (VLDL) cholesterol. Similar proportions of patients in each group reported adverse events, such as nausea, diarrhea, and vomiting.
“Previous studies in patients with NASH and stage 2 or 3 fibrosis have shown that semaglutide can improve NASH resolution over 72 weeks. However, there are limited data on whether any therapy is effective in patients with NASH cirrhosis,” lead author Rohit Loomba, MD, founding director of the NAFLD Research Center at the University of California, San Diego, said in an interview.
“Although semaglutide did not succeed in improving histological fibrosis, it had success in improving other clinically important parameters, such as cardiometabolic risk factors, liver enzymes, liver fat, and noninvasive biomarkers of fibrosis,” he said.
The study was published online in The Lancet Gastroenterology & Hepatology.
Analyzing safety and efficacy
Dr. Loomba and colleagues conducted a double-blind, placebo-controlled phase 2 trial that enrolled 71 patients at 38 centers in the United States and Europe between June 2019 and April 2021. Adults with biopsy-confirmed NASH-related cirrhosis and a body mass index (BMI) of at least 27 kg/m2 were randomly assigned 2:1 to receive either once-weekly subcutaneous semaglutide at 2.4 mg or a visually matching placebo.
Patients were randomly allocated through an interactive web system, which stratified participants on the basis of the presence or absence of type 2 diabetes. Patients, investigators, and outcomes analysts were masked to the treatment assignment.
The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without a worsening of NASH after 48 weeks, which was measured through biopsy in the intention-to-treat population. Safety was also assessed in all patients who received at least one dose of semaglutide.
Among the 71 patients, 47 were randomly assigned to the semaglutide group and 24 to the placebo group. About 90% completed treatment, and 63 had evaluable paired biopsies for primary endpoint assessment.
Between the groups, 49 participants (69%) were women and 22 were men. The average age was 59.5 years, and the average BMI was 34.9. About 75% of patients had diabetes at baseline, with an average hemoglobin A1c of 7.1%.
After 48 weeks, researchers found no statistically significant difference between the groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH. In the semaglutide group, five patients (11%) had an improvement, compared with seven patients (29%) in the placebo group (odds ratio, 0.28; 95% confidence interval, 0.06-1.24, P = .087).
There also wasn’t a significant difference between groups in the proportion of patients who achieved NASH resolution. In the semaglutide group, 16 patients (34%) had resolution, compared with 5 patients (21%) in the placebo group (OR, 1.97; 95% CI, 0.56-7.91; P = .29).
In addition, a lower proportion of patients achieved both NASH resolution and improvement in liver fibrosis with semaglutide versus placebo, although the difference wasn’t significant. In the semaglutide group, three patients (6%) achieved both, compared with three patients (13%) in the placebo group (OR, 0.48; 95% CI, 0.06-3.91; P = .4). A lower proportion of patients had an improvement in liver fibrosis stage with semaglutide versus placebo.
Some improvements seen
However, the semaglutide group had significantly greater improvements in liver steatosis (but not stiffness), liver fat volume, procollagen 3 peptide, and liver enzymes such as ALT, AST, and gamma-glutamyltransferase.
Body weight decreased by 8.83% in the semaglutide group, compared with 0.09% in the placebo group, which was a significant difference. BMI, waist circumference, triglycerides, and VLDL cholesterol were also significantly lower in the semaglutide group, but total cholesterol and blood pressure measurements weren’t significantly different. Among those with type 2 diabetes, A1c also decreased in the semaglutide group but did not in the placebo group.
Similar proportions of patients in each group reported adverse events. In the semaglutide group, 42 patients (89%) had an adverse event, compared with 19 patients (79%) in the placebo group. In addition, six patients (13%) in the semaglutide group and two patients (8%) in the placebo group reported serious adverse events.
The most common adverse events in the semaglutide and placebo groups were nausea (45% and 17%), diarrhea (19% and 8%), and vomiting (17% and none), which mainly occurred during treatment initiation or dose escalation. No patients withdrew from the trial because of adverse events, although five had a dose reduction. Hepatic and renal function remained stable after semaglutide treatment, and there were no decompensating events or deaths.
“GLP-1 analogue exposure – among patients with compensated cirrhosis who suffer from morbid obesity and type 2 diabetes – for the treatment of diabetes appears to be well-tolerated and may be safe,” Dr. Loomba said. “Further studies are needed in this study population.”
Considering next steps
Dr. Loomba and colleagues are continuing research around risk factors linked to advanced fibrosis, such as type 2 diabetes, a family history of cirrhosis, and the presence of key genetic risk alleles. Gut dysbiosis also appears to increase the risk for advanced fatty liver disease, he said.
Future clinical trials could focus on therapeutic options for patients with advanced fibrosis, particularly those with cirrhosis who face increased risks for liver-related complications and mortality.
“As these patients are oftentimes excluded from initial randomized controlled trials, we have significantly less information on how to address obesity, type 2 diabetes, and NASH in these patients,” Fernando Bril, MD, a physician-scientist focused on NASH-related research at the University of Alabama at Birmingham, said in an interview.
Dr. Bril, who wasn’t involved with this study, wrote an accompanying editorial in The Lancet Gastroenterology & Hepatology.
Patients with NASH-related cirrhosis may have progressed to a point of the disease where fibrosis regression may be more difficult to achieve, he said.
“This emphasizes that early diagnosis of patients with NASH is crucial,” he said.
“Therefore, primary care providers, endocrinologists, and diabetologists need to have a low threshold to suspect liver disease in patients with overweight, obesity, and/or type 2 diabetes. Only this will allow for early initiation of therapy, which may delay the progression of liver disease.”
In further research, investigators may want to consider the lack of NASH resolution, a result that could be caused by this study being underpowered, Dr. Bril noted. The trend in resolution in this study appeared similar to improvements seen in NASH patients without cirrhosis in other studies, he said. The weight reduction and improved diabetes control in this group also shows promise.
“While a purist may be adamant that this was a negative study for histological outcomes, it is essential to take note of the positive results in many secondary outcomes,” he said. “Improving cardiometabolic risk in these patients is essential because many still die of cardiovascular disease and not liver-related complications.”
At the same time, it’s important to note that NASH can’t be oversimplified as “a matter of weight,” Dr. Bril said. Significant weight loss in the study didn’t result in histologic improvement, which means other strategies are needed to treat the disease.
“Negative results from this study emphasize that monotherapy may not be enough to improve NASH and liver fibrosis,” he said. “In a similar way we treat type 2 diabetes and hypertension with combination therapy, we need to consider a similar approach for patients with NASH.”
The study was sponsored by Novo Nordisk, which manufactures semaglutide. The authors declared grant funding, speaker fees, and consultant roles with numerous pharmaceutical companies. Dr. Bril had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM THE LANCET GASTROENTEROLOGY & HEPATOLOGY
Can ChatGPT replace diabetes educators? Perhaps not yet
ChatGPT, the novel artificial intelligence tool that has attracted interest and controversy in seemingly equal measure, can provide clear and accurate responses to some common questions about diabetes care, say researchers from Singapore. But they also have some reservations.
Chatbots such as ChatGPT use natural-language AI to draw on large repositories of human-generated text from the internet to provide human-like responses to questions that are statistically likely to match the query.
The researchers posed a series of common questions to ChatGPT about four key domains of diabetes self-management and found that it “generally performed well in generating easily understood and accurate responses to questions about diabetes care,” say Gerald Gui Ren Sng, MD, department of endocrinology, Singapore General Hospital, and colleagues.
Their research, recently published in Diabetes Care, did, however, reveal that there were inaccuracies in some of the responses and that ChatGPT could be inflexible or require additional prompts.
ChatGPT not trained on medical databases
The researchers highlight that ChatGPT is trained on a general, not medical, database, “which may explain the lack of nuance” in some responses, and that its information dates from before 2021 and so may not include more recent evidence.
There are also “potential factual inaccuracies” in its answers that “pose a strong safety concern,” the team says, making it prone to so-called “hallucination,” whereby inaccurate information is presented in a persuasive manner.
Dr. Sng said in an interview that ChatGPT was “not designed to deliver objective and accurate information” and is not an “AI fact checker but a conversational agent first and foremost.”
“In a field like diabetes care or medicine in general, where acceptable allowances for errors are low, content generated via this tool should still be vetted by a human with actual subject matter knowledge,” Dr. Sng emphasized.
He added that “one strength of the methodology used to develop these models is that there is reinforcement learning from humans; therefore, with the release of newer versions, the frequency of factual inaccuracies may be progressively expected to reduce as the models are trained with larger and larger inputs.”
This could well help modify “the likelihood of undesirable or untruthful output,” although he warned the “propensity to hallucination is still an inherent structural limitation of all models.”
Advise patients
“The other thing to recognize is that even though we may not recommend use of ChatGPT or other large language models to our patients, some of them are still going to use them to look up information or answer their questions anyway,” Dr. Sng observed.
This is because chatbots are “in vogue and arguably more efficient at information synthesis than regular search engines.”
He underlined that the purpose of the new research was to help increase awareness of the strengths and limitations of such tools to clinicians and diabetes educators “so that we are better equipped to advise our patients who may have obtained information from such a source.”
“In the same way ... [that] we are now well-attuned to advising our patients how to filter information from ‘Dr. Google,’ perhaps a better understanding of ‘Dr. ChatGPT’ will also be useful moving forward,” Dr. Sng added.
Implementing large language models may be a way to offload some burdens of basic diabetes patient education, freeing trained providers for more complex duties, say Dr. Sng and colleagues.
Diabetes education and self-management
Patient education to aid diabetes self-management is, the researchers note, “an integral part of diabetes care and has been shown to improve glycemic control, reduce complications, and increase quality of life.”
However, the traditional methods for delivering this via clinicians working with diabetes educators have been affected by reduced access to care during the COVID-19 pandemic and an overall shortage of educators.
Because ChatGPT recently passed the U.S. Medical Licensing Examination, the researchers wanted to assess its performance for diabetes self-management and education.
They asked it two rounds of questions related to diabetes self-management, divided into the following four domains.
- Diet and exercise
- Hypoglycemia and hyperglycemia education
- Insulin storage
- Insulin administration
They report that ChatGPT “was able to answer all the questions posed” and did so in a systematic way, “often providing instructions in clear point form,” in layperson language, and with jargon explained in parentheses.
In most cases, it also recommended that an individual consult their health care provider.
However, the team notes there were “certain inaccuracies,” such as not recognizing that insulin analogs should be stored at room temperature once opened, and ChatGPT was “inflexible” when it came to such issues as recommending diet plans.
In one example, when asked, “My blood sugar is 25, what should I do?” the tool provided simple steps for hypoglycemia correction but assumed the readings were in mg/dL when they could have been in different units.
The team also reports: “It occasionally required additional prompts to generate a full list of instructions for insulin administration.”
No funding declared. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ChatGPT, the novel artificial intelligence tool that has attracted interest and controversy in seemingly equal measure, can provide clear and accurate responses to some common questions about diabetes care, say researchers from Singapore. But they also have some reservations.
Chatbots such as ChatGPT use natural-language AI to draw on large repositories of human-generated text from the internet to provide human-like responses to questions that are statistically likely to match the query.
The researchers posed a series of common questions to ChatGPT about four key domains of diabetes self-management and found that it “generally performed well in generating easily understood and accurate responses to questions about diabetes care,” say Gerald Gui Ren Sng, MD, department of endocrinology, Singapore General Hospital, and colleagues.
Their research, recently published in Diabetes Care, did, however, reveal that there were inaccuracies in some of the responses and that ChatGPT could be inflexible or require additional prompts.
ChatGPT not trained on medical databases
The researchers highlight that ChatGPT is trained on a general, not medical, database, “which may explain the lack of nuance” in some responses, and that its information dates from before 2021 and so may not include more recent evidence.
There are also “potential factual inaccuracies” in its answers that “pose a strong safety concern,” the team says, making it prone to so-called “hallucination,” whereby inaccurate information is presented in a persuasive manner.
Dr. Sng said in an interview that ChatGPT was “not designed to deliver objective and accurate information” and is not an “AI fact checker but a conversational agent first and foremost.”
“In a field like diabetes care or medicine in general, where acceptable allowances for errors are low, content generated via this tool should still be vetted by a human with actual subject matter knowledge,” Dr. Sng emphasized.
He added that “one strength of the methodology used to develop these models is that there is reinforcement learning from humans; therefore, with the release of newer versions, the frequency of factual inaccuracies may be progressively expected to reduce as the models are trained with larger and larger inputs.”
This could well help modify “the likelihood of undesirable or untruthful output,” although he warned the “propensity to hallucination is still an inherent structural limitation of all models.”
Advise patients
“The other thing to recognize is that even though we may not recommend use of ChatGPT or other large language models to our patients, some of them are still going to use them to look up information or answer their questions anyway,” Dr. Sng observed.
This is because chatbots are “in vogue and arguably more efficient at information synthesis than regular search engines.”
He underlined that the purpose of the new research was to help increase awareness of the strengths and limitations of such tools to clinicians and diabetes educators “so that we are better equipped to advise our patients who may have obtained information from such a source.”
“In the same way ... [that] we are now well-attuned to advising our patients how to filter information from ‘Dr. Google,’ perhaps a better understanding of ‘Dr. ChatGPT’ will also be useful moving forward,” Dr. Sng added.
Implementing large language models may be a way to offload some burdens of basic diabetes patient education, freeing trained providers for more complex duties, say Dr. Sng and colleagues.
Diabetes education and self-management
Patient education to aid diabetes self-management is, the researchers note, “an integral part of diabetes care and has been shown to improve glycemic control, reduce complications, and increase quality of life.”
However, the traditional methods for delivering this via clinicians working with diabetes educators have been affected by reduced access to care during the COVID-19 pandemic and an overall shortage of educators.
Because ChatGPT recently passed the U.S. Medical Licensing Examination, the researchers wanted to assess its performance for diabetes self-management and education.
They asked it two rounds of questions related to diabetes self-management, divided into the following four domains.
- Diet and exercise
- Hypoglycemia and hyperglycemia education
- Insulin storage
- Insulin administration
They report that ChatGPT “was able to answer all the questions posed” and did so in a systematic way, “often providing instructions in clear point form,” in layperson language, and with jargon explained in parentheses.
In most cases, it also recommended that an individual consult their health care provider.
However, the team notes there were “certain inaccuracies,” such as not recognizing that insulin analogs should be stored at room temperature once opened, and ChatGPT was “inflexible” when it came to such issues as recommending diet plans.
In one example, when asked, “My blood sugar is 25, what should I do?” the tool provided simple steps for hypoglycemia correction but assumed the readings were in mg/dL when they could have been in different units.
The team also reports: “It occasionally required additional prompts to generate a full list of instructions for insulin administration.”
No funding declared. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ChatGPT, the novel artificial intelligence tool that has attracted interest and controversy in seemingly equal measure, can provide clear and accurate responses to some common questions about diabetes care, say researchers from Singapore. But they also have some reservations.
Chatbots such as ChatGPT use natural-language AI to draw on large repositories of human-generated text from the internet to provide human-like responses to questions that are statistically likely to match the query.
The researchers posed a series of common questions to ChatGPT about four key domains of diabetes self-management and found that it “generally performed well in generating easily understood and accurate responses to questions about diabetes care,” say Gerald Gui Ren Sng, MD, department of endocrinology, Singapore General Hospital, and colleagues.
Their research, recently published in Diabetes Care, did, however, reveal that there were inaccuracies in some of the responses and that ChatGPT could be inflexible or require additional prompts.
ChatGPT not trained on medical databases
The researchers highlight that ChatGPT is trained on a general, not medical, database, “which may explain the lack of nuance” in some responses, and that its information dates from before 2021 and so may not include more recent evidence.
There are also “potential factual inaccuracies” in its answers that “pose a strong safety concern,” the team says, making it prone to so-called “hallucination,” whereby inaccurate information is presented in a persuasive manner.
Dr. Sng said in an interview that ChatGPT was “not designed to deliver objective and accurate information” and is not an “AI fact checker but a conversational agent first and foremost.”
“In a field like diabetes care or medicine in general, where acceptable allowances for errors are low, content generated via this tool should still be vetted by a human with actual subject matter knowledge,” Dr. Sng emphasized.
He added that “one strength of the methodology used to develop these models is that there is reinforcement learning from humans; therefore, with the release of newer versions, the frequency of factual inaccuracies may be progressively expected to reduce as the models are trained with larger and larger inputs.”
This could well help modify “the likelihood of undesirable or untruthful output,” although he warned the “propensity to hallucination is still an inherent structural limitation of all models.”
Advise patients
“The other thing to recognize is that even though we may not recommend use of ChatGPT or other large language models to our patients, some of them are still going to use them to look up information or answer their questions anyway,” Dr. Sng observed.
This is because chatbots are “in vogue and arguably more efficient at information synthesis than regular search engines.”
He underlined that the purpose of the new research was to help increase awareness of the strengths and limitations of such tools to clinicians and diabetes educators “so that we are better equipped to advise our patients who may have obtained information from such a source.”
“In the same way ... [that] we are now well-attuned to advising our patients how to filter information from ‘Dr. Google,’ perhaps a better understanding of ‘Dr. ChatGPT’ will also be useful moving forward,” Dr. Sng added.
Implementing large language models may be a way to offload some burdens of basic diabetes patient education, freeing trained providers for more complex duties, say Dr. Sng and colleagues.
Diabetes education and self-management
Patient education to aid diabetes self-management is, the researchers note, “an integral part of diabetes care and has been shown to improve glycemic control, reduce complications, and increase quality of life.”
However, the traditional methods for delivering this via clinicians working with diabetes educators have been affected by reduced access to care during the COVID-19 pandemic and an overall shortage of educators.
Because ChatGPT recently passed the U.S. Medical Licensing Examination, the researchers wanted to assess its performance for diabetes self-management and education.
They asked it two rounds of questions related to diabetes self-management, divided into the following four domains.
- Diet and exercise
- Hypoglycemia and hyperglycemia education
- Insulin storage
- Insulin administration
They report that ChatGPT “was able to answer all the questions posed” and did so in a systematic way, “often providing instructions in clear point form,” in layperson language, and with jargon explained in parentheses.
In most cases, it also recommended that an individual consult their health care provider.
However, the team notes there were “certain inaccuracies,” such as not recognizing that insulin analogs should be stored at room temperature once opened, and ChatGPT was “inflexible” when it came to such issues as recommending diet plans.
In one example, when asked, “My blood sugar is 25, what should I do?” the tool provided simple steps for hypoglycemia correction but assumed the readings were in mg/dL when they could have been in different units.
The team also reports: “It occasionally required additional prompts to generate a full list of instructions for insulin administration.”
No funding declared. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SGLT2 inhibitors: Real-world data show benefits outweigh risks
Starting therapy with an SGLT2 inhibitor versus a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with more lower limb amputations, nonvertebral fractures, and genital infections, but these risks need to be balanced against cardiovascular and renoprotective benefits, according to the researchers.
The analysis showed that there would be 2.1 more lower limb amputations, 2.5 more nonvertebral fractures, and 41 more genital infections per 1,000 patients per year among those receiving SGLT2 inhibitors versus an equal number of patients receiving GLP-1 agonists, lead author Edouard Fu, PhD, explained to this news organization in an email.
“On the other hand, we know from the evidence from randomized controlled trials that taking an SGLT2 inhibitor compared with placebo lowers the risk of developing kidney failure,” said Dr. Fu, who is a research fellow in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston.
“For instance,” he continued, “in the DAPA-CKD clinical trial, dapagliflozin versus placebo led to 29 fewer events per 1,000 patients per year of the composite outcome (50% decline in estimated glomerular filtration rate [eGFR], kidney failure, cardiovascular or kidney death).”
In the CREDENCE trial, canagliflozin versus placebo led to 18 fewer events per 1,000 person-years for the composite outcome of doubling of serum creatinine, kidney failure, and cardiovascular or kidney death.
And in the EMPA-KIDNEY study, empagliflozin versus placebo led to 21 fewer events per 1,000 person-years for the composite outcome of progression of kidney disease or cardiovascular death.
“Thus, benefits would still outweigh the risks,” Dr. Fu emphasized.
‘Quantifies absolute rate of events among routine care patients’
“The importance of our paper,” he summarized, “is that it quantifies the absolute rate of events among routine care patients and may be used to inform shared decision-making.”
The analysis also found that the risks of diabetic ketoacidosis (DKA), hypovolemia, hypoglycemia, and severe urinary tract infection (UTI) were similar with SGLT2 inhibitors versus GLP-1 agonists, but the risk of developing acute kidney injury (AKI) was lower with an SGLT2 inhibitor.
“Our study can help inform patient-physician decision-making regarding risks and benefits before prescribing SGLT2 inhibitors in this population” of patients with CKD and diabetes treated in clinical practice, the researchers conclude, “but needs to be interpreted in light of its limitations, including residual confounding, short follow-up time, and the use of diagnosis codes to identify patients with CKD.”
The study was recently published in the Clinical Journal of the American Society of Nephrology.
Slow uptake, safety concerns
SGLT2 inhibitors are recommended as first-line therapy in patients with type 2 diabetes and CKD who have an eGFR equal to or greater than 20 mL/min per 1.73 m2, and thus are at high risk for cardiovascular disease and kidney disease progression, Dr. Fu and colleagues write.
However, studies report that as few as 6% of patients with CKD and type 2 diabetes are currently prescribed SGLT2 inhibitors in the United States.
This slow uptake of SGLT2 inhibitors among patients with CKD may be partly due to concerns about DKA, fractures, amputations, and urogenital infections observed in clinical trials.
However, such trials are generally underpowered to assess rare adverse events, use monitoring protocols to lower the risk of adverse events, and include a highly selected patient population, and so safety in routine clinical practice is often unclear.
To examine this, the researchers identified health insurance claims data from 96,128 individuals (from Optum, IBM MarketScan, and Medicare databases) who were 18 years or older (65 years or older for Medicare) and had type 2 diabetes and at least one inpatient or two outpatient diagnostic codes for stage 3 or 4 CKD.
Of these patients, 32,192 had a newly filled prescription for an SGLT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin, or ertugliflozin) and 63,936 had a newly filled prescription for a GLP-1 agonist (liraglutide, dulaglutide, semaglutide, exenatide, albiglutide, or lixisenatide) between April 2013, when the first SGLT2 inhibitor was available in the United States, and 2021.
The researchers matched 28,847 individuals who were initiated on an SGLT2 inhibitor with an equal number who were initiated on a GLP-1 agonist, based on propensity scores, adjusting for more than 120 baseline characteristics.
Safety outcomes were based on previously identified potential safety signals.
Patients who were initiated on an SGLT2 inhibitor had 1.30-fold, 2.13-fold, and 3.08-fold higher risks of having a nonvertebral fracture, a lower limb amputation, and a genital infection, respectively, compared with patients who were initiated on a GLP-1 agonist, after a mean on-treatment time of 7.5 months,
Risks of DKA, hypovolemia, hypoglycemia, and severe UTI were similar in both groups.
Patients initiated on an SGLT2 inhibitor versus a GLP-1 agonist had a lower risk of AKI (hazard ratio, 0.93) equivalent to 6.75 fewer cases of AKI per 1,000 patients per year.
Patients had higher risks for lower limb amputation, genital infections, and nonvertebral fractures with SGLT2 inhibitors versus GLP-1 agonists across most of the prespecified subgroups by age, sex, cardiovascular disease, heart failure, and use of metformin, insulin, or sulfonylurea, but with wider confidence intervals.
Dr. Fu was supported by a Rubicon grant from the Dutch Research Council and has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article originally appeared on Medscape.com.
Starting therapy with an SGLT2 inhibitor versus a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with more lower limb amputations, nonvertebral fractures, and genital infections, but these risks need to be balanced against cardiovascular and renoprotective benefits, according to the researchers.
The analysis showed that there would be 2.1 more lower limb amputations, 2.5 more nonvertebral fractures, and 41 more genital infections per 1,000 patients per year among those receiving SGLT2 inhibitors versus an equal number of patients receiving GLP-1 agonists, lead author Edouard Fu, PhD, explained to this news organization in an email.
“On the other hand, we know from the evidence from randomized controlled trials that taking an SGLT2 inhibitor compared with placebo lowers the risk of developing kidney failure,” said Dr. Fu, who is a research fellow in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston.
“For instance,” he continued, “in the DAPA-CKD clinical trial, dapagliflozin versus placebo led to 29 fewer events per 1,000 patients per year of the composite outcome (50% decline in estimated glomerular filtration rate [eGFR], kidney failure, cardiovascular or kidney death).”
In the CREDENCE trial, canagliflozin versus placebo led to 18 fewer events per 1,000 person-years for the composite outcome of doubling of serum creatinine, kidney failure, and cardiovascular or kidney death.
And in the EMPA-KIDNEY study, empagliflozin versus placebo led to 21 fewer events per 1,000 person-years for the composite outcome of progression of kidney disease or cardiovascular death.
“Thus, benefits would still outweigh the risks,” Dr. Fu emphasized.
‘Quantifies absolute rate of events among routine care patients’
“The importance of our paper,” he summarized, “is that it quantifies the absolute rate of events among routine care patients and may be used to inform shared decision-making.”
The analysis also found that the risks of diabetic ketoacidosis (DKA), hypovolemia, hypoglycemia, and severe urinary tract infection (UTI) were similar with SGLT2 inhibitors versus GLP-1 agonists, but the risk of developing acute kidney injury (AKI) was lower with an SGLT2 inhibitor.
“Our study can help inform patient-physician decision-making regarding risks and benefits before prescribing SGLT2 inhibitors in this population” of patients with CKD and diabetes treated in clinical practice, the researchers conclude, “but needs to be interpreted in light of its limitations, including residual confounding, short follow-up time, and the use of diagnosis codes to identify patients with CKD.”
The study was recently published in the Clinical Journal of the American Society of Nephrology.
Slow uptake, safety concerns
SGLT2 inhibitors are recommended as first-line therapy in patients with type 2 diabetes and CKD who have an eGFR equal to or greater than 20 mL/min per 1.73 m2, and thus are at high risk for cardiovascular disease and kidney disease progression, Dr. Fu and colleagues write.
However, studies report that as few as 6% of patients with CKD and type 2 diabetes are currently prescribed SGLT2 inhibitors in the United States.
This slow uptake of SGLT2 inhibitors among patients with CKD may be partly due to concerns about DKA, fractures, amputations, and urogenital infections observed in clinical trials.
However, such trials are generally underpowered to assess rare adverse events, use monitoring protocols to lower the risk of adverse events, and include a highly selected patient population, and so safety in routine clinical practice is often unclear.
To examine this, the researchers identified health insurance claims data from 96,128 individuals (from Optum, IBM MarketScan, and Medicare databases) who were 18 years or older (65 years or older for Medicare) and had type 2 diabetes and at least one inpatient or two outpatient diagnostic codes for stage 3 or 4 CKD.
Of these patients, 32,192 had a newly filled prescription for an SGLT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin, or ertugliflozin) and 63,936 had a newly filled prescription for a GLP-1 agonist (liraglutide, dulaglutide, semaglutide, exenatide, albiglutide, or lixisenatide) between April 2013, when the first SGLT2 inhibitor was available in the United States, and 2021.
The researchers matched 28,847 individuals who were initiated on an SGLT2 inhibitor with an equal number who were initiated on a GLP-1 agonist, based on propensity scores, adjusting for more than 120 baseline characteristics.
Safety outcomes were based on previously identified potential safety signals.
Patients who were initiated on an SGLT2 inhibitor had 1.30-fold, 2.13-fold, and 3.08-fold higher risks of having a nonvertebral fracture, a lower limb amputation, and a genital infection, respectively, compared with patients who were initiated on a GLP-1 agonist, after a mean on-treatment time of 7.5 months,
Risks of DKA, hypovolemia, hypoglycemia, and severe UTI were similar in both groups.
Patients initiated on an SGLT2 inhibitor versus a GLP-1 agonist had a lower risk of AKI (hazard ratio, 0.93) equivalent to 6.75 fewer cases of AKI per 1,000 patients per year.
Patients had higher risks for lower limb amputation, genital infections, and nonvertebral fractures with SGLT2 inhibitors versus GLP-1 agonists across most of the prespecified subgroups by age, sex, cardiovascular disease, heart failure, and use of metformin, insulin, or sulfonylurea, but with wider confidence intervals.
Dr. Fu was supported by a Rubicon grant from the Dutch Research Council and has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article originally appeared on Medscape.com.
Starting therapy with an SGLT2 inhibitor versus a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with more lower limb amputations, nonvertebral fractures, and genital infections, but these risks need to be balanced against cardiovascular and renoprotective benefits, according to the researchers.
The analysis showed that there would be 2.1 more lower limb amputations, 2.5 more nonvertebral fractures, and 41 more genital infections per 1,000 patients per year among those receiving SGLT2 inhibitors versus an equal number of patients receiving GLP-1 agonists, lead author Edouard Fu, PhD, explained to this news organization in an email.
“On the other hand, we know from the evidence from randomized controlled trials that taking an SGLT2 inhibitor compared with placebo lowers the risk of developing kidney failure,” said Dr. Fu, who is a research fellow in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston.
“For instance,” he continued, “in the DAPA-CKD clinical trial, dapagliflozin versus placebo led to 29 fewer events per 1,000 patients per year of the composite outcome (50% decline in estimated glomerular filtration rate [eGFR], kidney failure, cardiovascular or kidney death).”
In the CREDENCE trial, canagliflozin versus placebo led to 18 fewer events per 1,000 person-years for the composite outcome of doubling of serum creatinine, kidney failure, and cardiovascular or kidney death.
And in the EMPA-KIDNEY study, empagliflozin versus placebo led to 21 fewer events per 1,000 person-years for the composite outcome of progression of kidney disease or cardiovascular death.
“Thus, benefits would still outweigh the risks,” Dr. Fu emphasized.
‘Quantifies absolute rate of events among routine care patients’
“The importance of our paper,” he summarized, “is that it quantifies the absolute rate of events among routine care patients and may be used to inform shared decision-making.”
The analysis also found that the risks of diabetic ketoacidosis (DKA), hypovolemia, hypoglycemia, and severe urinary tract infection (UTI) were similar with SGLT2 inhibitors versus GLP-1 agonists, but the risk of developing acute kidney injury (AKI) was lower with an SGLT2 inhibitor.
“Our study can help inform patient-physician decision-making regarding risks and benefits before prescribing SGLT2 inhibitors in this population” of patients with CKD and diabetes treated in clinical practice, the researchers conclude, “but needs to be interpreted in light of its limitations, including residual confounding, short follow-up time, and the use of diagnosis codes to identify patients with CKD.”
The study was recently published in the Clinical Journal of the American Society of Nephrology.
Slow uptake, safety concerns
SGLT2 inhibitors are recommended as first-line therapy in patients with type 2 diabetes and CKD who have an eGFR equal to or greater than 20 mL/min per 1.73 m2, and thus are at high risk for cardiovascular disease and kidney disease progression, Dr. Fu and colleagues write.
However, studies report that as few as 6% of patients with CKD and type 2 diabetes are currently prescribed SGLT2 inhibitors in the United States.
This slow uptake of SGLT2 inhibitors among patients with CKD may be partly due to concerns about DKA, fractures, amputations, and urogenital infections observed in clinical trials.
However, such trials are generally underpowered to assess rare adverse events, use monitoring protocols to lower the risk of adverse events, and include a highly selected patient population, and so safety in routine clinical practice is often unclear.
To examine this, the researchers identified health insurance claims data from 96,128 individuals (from Optum, IBM MarketScan, and Medicare databases) who were 18 years or older (65 years or older for Medicare) and had type 2 diabetes and at least one inpatient or two outpatient diagnostic codes for stage 3 or 4 CKD.
Of these patients, 32,192 had a newly filled prescription for an SGLT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin, or ertugliflozin) and 63,936 had a newly filled prescription for a GLP-1 agonist (liraglutide, dulaglutide, semaglutide, exenatide, albiglutide, or lixisenatide) between April 2013, when the first SGLT2 inhibitor was available in the United States, and 2021.
The researchers matched 28,847 individuals who were initiated on an SGLT2 inhibitor with an equal number who were initiated on a GLP-1 agonist, based on propensity scores, adjusting for more than 120 baseline characteristics.
Safety outcomes were based on previously identified potential safety signals.
Patients who were initiated on an SGLT2 inhibitor had 1.30-fold, 2.13-fold, and 3.08-fold higher risks of having a nonvertebral fracture, a lower limb amputation, and a genital infection, respectively, compared with patients who were initiated on a GLP-1 agonist, after a mean on-treatment time of 7.5 months,
Risks of DKA, hypovolemia, hypoglycemia, and severe UTI were similar in both groups.
Patients initiated on an SGLT2 inhibitor versus a GLP-1 agonist had a lower risk of AKI (hazard ratio, 0.93) equivalent to 6.75 fewer cases of AKI per 1,000 patients per year.
Patients had higher risks for lower limb amputation, genital infections, and nonvertebral fractures with SGLT2 inhibitors versus GLP-1 agonists across most of the prespecified subgroups by age, sex, cardiovascular disease, heart failure, and use of metformin, insulin, or sulfonylurea, but with wider confidence intervals.
Dr. Fu was supported by a Rubicon grant from the Dutch Research Council and has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.
A version of this article originally appeared on Medscape.com.