Diabetes Hub

NASHVILLE – Digital apps for weight loss are ubiquitous, but do they work as a standalone intervention? So far, the evidence is scant, according to a new systematic review.

Beginning with a pool of 1,380 publications, Christina Hopkins and her colleagues at Duke University, Durham, N.C., eventually identified just nine trials of all-digital interventions for weight loss that met their inclusion criteria.

Presenting their findings at a late-breaking poster session during Obesity Week, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery, Ms. Hopkins, a clinical psychology graduate student at Duke, and her colleagues found that three of the nine studies showed statistically significant weight loss, compared with a control state. Absolute weight loss in these three trials ranged from 3 kg to about 7 kg (between-group differences, P less than .001 for all).

Participants in another trial didn’t lose a statistically significant amount of weight, compared with the control arm of the study. However, the mean 5 kg lost by those in the intervention arm was enough to be clinically significant, so Ms. Hopkins and her colleagues included this study in a subanalysis that looked for effective modalities and interventions among the studies with significant results.

The duration of the studies ranged from 6 to 24 months, though five of the trials were less than 1 year long. Women made up the majority of participants in all but one trial.

“There is limited evidence that standalone digital weight-loss interventions produce clinically meaningful outcomes,” wrote Ms. Hopkins and her coauthors. “Absolute magnitude of weight loss was low, and the short intervention lengths call into question the sustainability of these weight losses.”

The systematic review cast a broad net to include digital modalities such as wireless scales, text messaging, email, and web-based interventions, as well as the use of smartphone apps and tracking devices. All interventions used multiple digital modalities.

The most frequently used technologies were the use of a website, used in six (67%) of the trials, followed by text messaging and smartphone apps, each used in five (56%) of the trials. Tracking devices, email, message boards, and gamification of some sort were all used in three (33%) of the trials.

In terms of the specific interventions used in the trials, weight, diet, and activity were all tracked in eight trials (89%). Similarly, all but one trial gave feedback and weight and health education to participants. Behavior change education, as well as calorie goals, were each used in six trials (67%).

Ms. Hopkins and her colleagues looked at which trials incorporated which modalities and interventions, finding that “trials that integrated components unique to digital interventions, such as gamification, podcasts, or interactive features, yielded significantly greater and more clinically meaningful weight losses.”

To be included in the systematic review, trials had to include adult participants with a body mass index of at least 25 kg/m2 and use a standalone digital intervention of at least 6 months’ duration. The primary outcome of interest in the review was the change in participant weight from baseline to the end of the minimum 6-month follow-up period. Randomized, controlled trials and feasibility trials were included, so long as participants were allocated randomly.

Of the 126 trials reviewed at the full text level, the most frequent reason for exclusion was the inclusion of human coaching. Also, 30 of the trials didn’t report weight change as an outcome, the investigators said.

Future directions should include comparing digital interventions that “utilize features unique to digital delivery” with those that more closely resemble in-person weight-loss management interventions, suggested Ms. Hopkins and her collaborators.

The authors reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Hopkins C et al. Obesity Week 2018, Abstract T-P-LB-3640.

NASHVILLE – Digital apps for weight loss are ubiquitous, but do they work as a standalone intervention? So far, the evidence is scant, according to a new systematic review.

Beginning with a pool of 1,380 publications, Christina Hopkins and her colleagues at Duke University, Durham, N.C., eventually identified just nine trials of all-digital interventions for weight loss that met their inclusion criteria.

Presenting their findings at a late-breaking poster session during Obesity Week, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery, Ms. Hopkins, a clinical psychology graduate student at Duke, and her colleagues found that three of the nine studies showed statistically significant weight loss, compared with a control state. Absolute weight loss in these three trials ranged from 3 kg to about 7 kg (between-group differences, P less than .001 for all).

Participants in another trial didn’t lose a statistically significant amount of weight, compared with the control arm of the study. However, the mean 5 kg lost by those in the intervention arm was enough to be clinically significant, so Ms. Hopkins and her colleagues included this study in a subanalysis that looked for effective modalities and interventions among the studies with significant results.

The duration of the studies ranged from 6 to 24 months, though five of the trials were less than 1 year long. Women made up the majority of participants in all but one trial.

“There is limited evidence that standalone digital weight-loss interventions produce clinically meaningful outcomes,” wrote Ms. Hopkins and her coauthors. “Absolute magnitude of weight loss was low, and the short intervention lengths call into question the sustainability of these weight losses.”

The systematic review cast a broad net to include digital modalities such as wireless scales, text messaging, email, and web-based interventions, as well as the use of smartphone apps and tracking devices. All interventions used multiple digital modalities.

The most frequently used technologies were the use of a website, used in six (67%) of the trials, followed by text messaging and smartphone apps, each used in five (56%) of the trials. Tracking devices, email, message boards, and gamification of some sort were all used in three (33%) of the trials.

In terms of the specific interventions used in the trials, weight, diet, and activity were all tracked in eight trials (89%). Similarly, all but one trial gave feedback and weight and health education to participants. Behavior change education, as well as calorie goals, were each used in six trials (67%).

Ms. Hopkins and her colleagues looked at which trials incorporated which modalities and interventions, finding that “trials that integrated components unique to digital interventions, such as gamification, podcasts, or interactive features, yielded significantly greater and more clinically meaningful weight losses.”

To be included in the systematic review, trials had to include adult participants with a body mass index of at least 25 kg/m2 and use a standalone digital intervention of at least 6 months’ duration. The primary outcome of interest in the review was the change in participant weight from baseline to the end of the minimum 6-month follow-up period. Randomized, controlled trials and feasibility trials were included, so long as participants were allocated randomly.

Of the 126 trials reviewed at the full text level, the most frequent reason for exclusion was the inclusion of human coaching. Also, 30 of the trials didn’t report weight change as an outcome, the investigators said.

Future directions should include comparing digital interventions that “utilize features unique to digital delivery” with those that more closely resemble in-person weight-loss management interventions, suggested Ms. Hopkins and her collaborators.

The authors reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Hopkins C et al. Obesity Week 2018, Abstract T-P-LB-3640.

NASHVILLE – Digital apps for weight loss are ubiquitous, but do they work as a standalone intervention? So far, the evidence is scant, according to a new systematic review.

Beginning with a pool of 1,380 publications, Christina Hopkins and her colleagues at Duke University, Durham, N.C., eventually identified just nine trials of all-digital interventions for weight loss that met their inclusion criteria.

Presenting their findings at a late-breaking poster session during Obesity Week, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery, Ms. Hopkins, a clinical psychology graduate student at Duke, and her colleagues found that three of the nine studies showed statistically significant weight loss, compared with a control state. Absolute weight loss in these three trials ranged from 3 kg to about 7 kg (between-group differences, P less than .001 for all).

Participants in another trial didn’t lose a statistically significant amount of weight, compared with the control arm of the study. However, the mean 5 kg lost by those in the intervention arm was enough to be clinically significant, so Ms. Hopkins and her colleagues included this study in a subanalysis that looked for effective modalities and interventions among the studies with significant results.

The duration of the studies ranged from 6 to 24 months, though five of the trials were less than 1 year long. Women made up the majority of participants in all but one trial.

“There is limited evidence that standalone digital weight-loss interventions produce clinically meaningful outcomes,” wrote Ms. Hopkins and her coauthors. “Absolute magnitude of weight loss was low, and the short intervention lengths call into question the sustainability of these weight losses.”

The systematic review cast a broad net to include digital modalities such as wireless scales, text messaging, email, and web-based interventions, as well as the use of smartphone apps and tracking devices. All interventions used multiple digital modalities.

The most frequently used technologies were the use of a website, used in six (67%) of the trials, followed by text messaging and smartphone apps, each used in five (56%) of the trials. Tracking devices, email, message boards, and gamification of some sort were all used in three (33%) of the trials.

In terms of the specific interventions used in the trials, weight, diet, and activity were all tracked in eight trials (89%). Similarly, all but one trial gave feedback and weight and health education to participants. Behavior change education, as well as calorie goals, were each used in six trials (67%).

Ms. Hopkins and her colleagues looked at which trials incorporated which modalities and interventions, finding that “trials that integrated components unique to digital interventions, such as gamification, podcasts, or interactive features, yielded significantly greater and more clinically meaningful weight losses.”

To be included in the systematic review, trials had to include adult participants with a body mass index of at least 25 kg/m2 and use a standalone digital intervention of at least 6 months’ duration. The primary outcome of interest in the review was the change in participant weight from baseline to the end of the minimum 6-month follow-up period. Randomized, controlled trials and feasibility trials were included, so long as participants were allocated randomly.

Of the 126 trials reviewed at the full text level, the most frequent reason for exclusion was the inclusion of human coaching. Also, 30 of the trials didn’t report weight change as an outcome, the investigators said.

Future directions should include comparing digital interventions that “utilize features unique to digital delivery” with those that more closely resemble in-person weight-loss management interventions, suggested Ms. Hopkins and her collaborators.

The authors reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Hopkins C et al. Obesity Week 2018, Abstract T-P-LB-3640.

NASHVILLE – Advising patients in a comprehensive weight loss intervention to moderate their alcohol consumption did not change how much they drank over the long term. At the same time, abstinent patients kept off more weight over time than those who were classified as heavy drinkers, in a new analysis of data from a multicenter trial.

Kari Oakes/MDedge News

Abstinent individuals lost just 1.6% more of their body weight after 4 years than those who drank (P = .003), a figure with “uncertain clinical significance,” Ariana Chao, PhD, said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery. “The results should be taken in the context of the potential – though controversial – benefits of light to moderate alcohol consumption,” she added.

Alcohol contains 7.1 kcal/g, and “calories from alcohol usually add, rather than substitute, for food intake,” said Dr. Chao. Alcohol’s disinhibiting effects are thought to contribute to increased food intake and the making of less healthy food choices. However, existing research has shown inconsistent findings about the relationship between alcohol consumption and body weight, she said.

Reducing or completely cutting out alcoholic beverage consumption is common advice for those trying to lose weight, but whether this advice is followed, and whether it makes a difference over the long term, has been an open question, said Dr. Chao.

She and her collaborators at the University of Pennsylvania, Philadelphia, used data from Look AHEAD, “a multicenter, randomized, clinical trial that compared an intensive lifestyle intervention (ILI) to a diabetes support and education (DSE) control group,” for 5,145 people with overweight or obesity and type 2 diabetes, explained Dr. Chao and her coinvestigators.

Dr. Chao and her colleagues looked at the effect that the lifestyle intervention had on alcohol consumption. Additionally, to see how drinkers and nondrinkers fared over the long term, they examined the interaction between alcohol consumption and weight loss at year 4, hypothesizing that individuals who received ILI would have a greater decrease in their alcohol consumption by year 4 than those who received DSE. The investigators had a second hypothesis that, among the ILI cohort, greater alcohol consumption would be associated with less weight loss over the 4 years studied.

To measure alcohol consumption, participants completed a questionnaire at baseline and annually thereafter. The questionnaire asked whether participants had consumed any alcoholic beverages in the past week, and how many drinks per week of wine, beer, or liquor per week were typical for those who did consume alcohol.

Respondents were grouped into four categories according to their baseline alcohol consumption: nondrinkers, light drinkers (fewer than 7 drinks weekly for men and 4 for women), moderate drinkers (7-14 drinks weekly for men and 4-7 for women), and heavy drinkers (more than 14 drinks weekly for men and 7 for women).

At baseline, 38% of participants reported being abstinent from alcohol, and about 54% reported being light drinkers. Moderate drinkers made up 6%, and 2% reported falling into the heavy drinking category. Females were more likely than males to be nondrinkers.

Heavy drinkers took in significantly more calories than nondrinkers at baseline (2,397 versus 1,907 kcal/day; P less than .001).

Individuals who had consistently been heavy drinkers throughout the study lost less weight than any other group, dropping just 2.4% of their body weight at year 4, compared with their baseline weight. Those who were abstinent from alcohol fared the best, losing 5.1% of their initial body weight (P = .04 for difference). “Heavy drinking is a risk factor for suboptimal long-term weight loss,” said Dr. Chao.

Even those who were consistent light drinkers lost a bit less than those who were abstinent, keeping off 4.2% of their baseline body weight at 4 years (P = .04).

Look AHEAD included individuals aged 45-76 years with type 2 diabetes mellitus and a body mass index of at least 25 kg/m², or 27 kg/m² for those on insulin. Excluded were those with hemoglobin A_1c of at least 11%, blood pressure of at least 160/100 mm Hg, and triglycerides over 600 mg/dL. A total of 4,901 patients had complete data available in the public access data set and were included in the present analysis. Dr. Chao and her colleagues used statistical techniques to adjust for baseline differences among participants.

The three-part ILI in Look AHEAD began by encouraging a low-calorie diet of 1,200-1,500 kcal/day for those weighing under 250 pounds, and 1,500-1,800 kcal/day for those who were heavier at baseline. Advice was to consume a balanced diet with less than 30% fat, less than 10% saturated fat, and at least 15% protein.

Patients were advised to strive for 10,000 steps per day, with 175 minutes of moderate-intensity exercise each week. Exercise was unsupervised.

Behavioral modification techniques included goal-setting, stimulus control, self-monitoring, and ideas for problem solving and relapse prevention. The intervention used motivational interviewing techniques.

With regard to alcohol, the ILI group was given information about the number of calories in various alcoholic beverages and advised to reduce the amount of alcohol consumed, in order to reduce calories.

The DSE group participated in three group sessions annually, and received general information about nutrition, exercise, and general support.

A potentially important limitation of the study was that alcohol consumption was assessed by self-report and a request for annual recall of typical drinking habits. An audience member from the United Kingdom commented that she found the overall rate of reported alcohol consumption to be “shockingly low,” compared with what her patients report drinking in England. The average United States resident drinks 2.3 gallons of alcohol, or 494 standard drinks, annually, according to the National Institute on Alcohol Abuse and Alcoholism, said Dr. Chao.

The midlife age range of participants, their diabetes diagnosis, and the fact that depressive symptoms were overall low limits generalizability of the findings, said Dr. Chao, adding that psychosocial factors, other health conditions, and current or past alcohol use disorder could also cause some residual confounding of the data.

Dr. Chao has received research support from Shire Pharmaceuticals.

[email protected]

SOURCE: Chao A et al. Obesity Week 2018, Abstract T-OR-2017.

NASHVILLE – Advising patients in a comprehensive weight loss intervention to moderate their alcohol consumption did not change how much they drank over the long term. At the same time, abstinent patients kept off more weight over time than those who were classified as heavy drinkers, in a new analysis of data from a multicenter trial.

Kari Oakes/MDedge News

Abstinent individuals lost just 1.6% more of their body weight after 4 years than those who drank (P = .003), a figure with “uncertain clinical significance,” Ariana Chao, PhD, said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery. “The results should be taken in the context of the potential – though controversial – benefits of light to moderate alcohol consumption,” she added.

Alcohol contains 7.1 kcal/g, and “calories from alcohol usually add, rather than substitute, for food intake,” said Dr. Chao. Alcohol’s disinhibiting effects are thought to contribute to increased food intake and the making of less healthy food choices. However, existing research has shown inconsistent findings about the relationship between alcohol consumption and body weight, she said.

Reducing or completely cutting out alcoholic beverage consumption is common advice for those trying to lose weight, but whether this advice is followed, and whether it makes a difference over the long term, has been an open question, said Dr. Chao.

She and her collaborators at the University of Pennsylvania, Philadelphia, used data from Look AHEAD, “a multicenter, randomized, clinical trial that compared an intensive lifestyle intervention (ILI) to a diabetes support and education (DSE) control group,” for 5,145 people with overweight or obesity and type 2 diabetes, explained Dr. Chao and her coinvestigators.

Dr. Chao and her colleagues looked at the effect that the lifestyle intervention had on alcohol consumption. Additionally, to see how drinkers and nondrinkers fared over the long term, they examined the interaction between alcohol consumption and weight loss at year 4, hypothesizing that individuals who received ILI would have a greater decrease in their alcohol consumption by year 4 than those who received DSE. The investigators had a second hypothesis that, among the ILI cohort, greater alcohol consumption would be associated with less weight loss over the 4 years studied.

To measure alcohol consumption, participants completed a questionnaire at baseline and annually thereafter. The questionnaire asked whether participants had consumed any alcoholic beverages in the past week, and how many drinks per week of wine, beer, or liquor per week were typical for those who did consume alcohol.

Respondents were grouped into four categories according to their baseline alcohol consumption: nondrinkers, light drinkers (fewer than 7 drinks weekly for men and 4 for women), moderate drinkers (7-14 drinks weekly for men and 4-7 for women), and heavy drinkers (more than 14 drinks weekly for men and 7 for women).

At baseline, 38% of participants reported being abstinent from alcohol, and about 54% reported being light drinkers. Moderate drinkers made up 6%, and 2% reported falling into the heavy drinking category. Females were more likely than males to be nondrinkers.

Heavy drinkers took in significantly more calories than nondrinkers at baseline (2,397 versus 1,907 kcal/day; P less than .001).

Individuals who had consistently been heavy drinkers throughout the study lost less weight than any other group, dropping just 2.4% of their body weight at year 4, compared with their baseline weight. Those who were abstinent from alcohol fared the best, losing 5.1% of their initial body weight (P = .04 for difference). “Heavy drinking is a risk factor for suboptimal long-term weight loss,” said Dr. Chao.

Even those who were consistent light drinkers lost a bit less than those who were abstinent, keeping off 4.2% of their baseline body weight at 4 years (P = .04).

Look AHEAD included individuals aged 45-76 years with type 2 diabetes mellitus and a body mass index of at least 25 kg/m², or 27 kg/m² for those on insulin. Excluded were those with hemoglobin A_1c of at least 11%, blood pressure of at least 160/100 mm Hg, and triglycerides over 600 mg/dL. A total of 4,901 patients had complete data available in the public access data set and were included in the present analysis. Dr. Chao and her colleagues used statistical techniques to adjust for baseline differences among participants.

The three-part ILI in Look AHEAD began by encouraging a low-calorie diet of 1,200-1,500 kcal/day for those weighing under 250 pounds, and 1,500-1,800 kcal/day for those who were heavier at baseline. Advice was to consume a balanced diet with less than 30% fat, less than 10% saturated fat, and at least 15% protein.

Patients were advised to strive for 10,000 steps per day, with 175 minutes of moderate-intensity exercise each week. Exercise was unsupervised.

Behavioral modification techniques included goal-setting, stimulus control, self-monitoring, and ideas for problem solving and relapse prevention. The intervention used motivational interviewing techniques.

With regard to alcohol, the ILI group was given information about the number of calories in various alcoholic beverages and advised to reduce the amount of alcohol consumed, in order to reduce calories.

The DSE group participated in three group sessions annually, and received general information about nutrition, exercise, and general support.

A potentially important limitation of the study was that alcohol consumption was assessed by self-report and a request for annual recall of typical drinking habits. An audience member from the United Kingdom commented that she found the overall rate of reported alcohol consumption to be “shockingly low,” compared with what her patients report drinking in England. The average United States resident drinks 2.3 gallons of alcohol, or 494 standard drinks, annually, according to the National Institute on Alcohol Abuse and Alcoholism, said Dr. Chao.

The midlife age range of participants, their diabetes diagnosis, and the fact that depressive symptoms were overall low limits generalizability of the findings, said Dr. Chao, adding that psychosocial factors, other health conditions, and current or past alcohol use disorder could also cause some residual confounding of the data.

Dr. Chao has received research support from Shire Pharmaceuticals.

[email protected]

SOURCE: Chao A et al. Obesity Week 2018, Abstract T-OR-2017.

NASHVILLE – Advising patients in a comprehensive weight loss intervention to moderate their alcohol consumption did not change how much they drank over the long term. At the same time, abstinent patients kept off more weight over time than those who were classified as heavy drinkers, in a new analysis of data from a multicenter trial.

Kari Oakes/MDedge News

Abstinent individuals lost just 1.6% more of their body weight after 4 years than those who drank (P = .003), a figure with “uncertain clinical significance,” Ariana Chao, PhD, said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery. “The results should be taken in the context of the potential – though controversial – benefits of light to moderate alcohol consumption,” she added.

Alcohol contains 7.1 kcal/g, and “calories from alcohol usually add, rather than substitute, for food intake,” said Dr. Chao. Alcohol’s disinhibiting effects are thought to contribute to increased food intake and the making of less healthy food choices. However, existing research has shown inconsistent findings about the relationship between alcohol consumption and body weight, she said.

Reducing or completely cutting out alcoholic beverage consumption is common advice for those trying to lose weight, but whether this advice is followed, and whether it makes a difference over the long term, has been an open question, said Dr. Chao.

She and her collaborators at the University of Pennsylvania, Philadelphia, used data from Look AHEAD, “a multicenter, randomized, clinical trial that compared an intensive lifestyle intervention (ILI) to a diabetes support and education (DSE) control group,” for 5,145 people with overweight or obesity and type 2 diabetes, explained Dr. Chao and her coinvestigators.

Dr. Chao and her colleagues looked at the effect that the lifestyle intervention had on alcohol consumption. Additionally, to see how drinkers and nondrinkers fared over the long term, they examined the interaction between alcohol consumption and weight loss at year 4, hypothesizing that individuals who received ILI would have a greater decrease in their alcohol consumption by year 4 than those who received DSE. The investigators had a second hypothesis that, among the ILI cohort, greater alcohol consumption would be associated with less weight loss over the 4 years studied.

To measure alcohol consumption, participants completed a questionnaire at baseline and annually thereafter. The questionnaire asked whether participants had consumed any alcoholic beverages in the past week, and how many drinks per week of wine, beer, or liquor per week were typical for those who did consume alcohol.

Respondents were grouped into four categories according to their baseline alcohol consumption: nondrinkers, light drinkers (fewer than 7 drinks weekly for men and 4 for women), moderate drinkers (7-14 drinks weekly for men and 4-7 for women), and heavy drinkers (more than 14 drinks weekly for men and 7 for women).

At baseline, 38% of participants reported being abstinent from alcohol, and about 54% reported being light drinkers. Moderate drinkers made up 6%, and 2% reported falling into the heavy drinking category. Females were more likely than males to be nondrinkers.

Heavy drinkers took in significantly more calories than nondrinkers at baseline (2,397 versus 1,907 kcal/day; P less than .001).

Individuals who had consistently been heavy drinkers throughout the study lost less weight than any other group, dropping just 2.4% of their body weight at year 4, compared with their baseline weight. Those who were abstinent from alcohol fared the best, losing 5.1% of their initial body weight (P = .04 for difference). “Heavy drinking is a risk factor for suboptimal long-term weight loss,” said Dr. Chao.

Even those who were consistent light drinkers lost a bit less than those who were abstinent, keeping off 4.2% of their baseline body weight at 4 years (P = .04).

Look AHEAD included individuals aged 45-76 years with type 2 diabetes mellitus and a body mass index of at least 25 kg/m², or 27 kg/m² for those on insulin. Excluded were those with hemoglobin A_1c of at least 11%, blood pressure of at least 160/100 mm Hg, and triglycerides over 600 mg/dL. A total of 4,901 patients had complete data available in the public access data set and were included in the present analysis. Dr. Chao and her colleagues used statistical techniques to adjust for baseline differences among participants.

The three-part ILI in Look AHEAD began by encouraging a low-calorie diet of 1,200-1,500 kcal/day for those weighing under 250 pounds, and 1,500-1,800 kcal/day for those who were heavier at baseline. Advice was to consume a balanced diet with less than 30% fat, less than 10% saturated fat, and at least 15% protein.

Patients were advised to strive for 10,000 steps per day, with 175 minutes of moderate-intensity exercise each week. Exercise was unsupervised.

Behavioral modification techniques included goal-setting, stimulus control, self-monitoring, and ideas for problem solving and relapse prevention. The intervention used motivational interviewing techniques.

With regard to alcohol, the ILI group was given information about the number of calories in various alcoholic beverages and advised to reduce the amount of alcohol consumed, in order to reduce calories.

The DSE group participated in three group sessions annually, and received general information about nutrition, exercise, and general support.

A potentially important limitation of the study was that alcohol consumption was assessed by self-report and a request for annual recall of typical drinking habits. An audience member from the United Kingdom commented that she found the overall rate of reported alcohol consumption to be “shockingly low,” compared with what her patients report drinking in England. The average United States resident drinks 2.3 gallons of alcohol, or 494 standard drinks, annually, according to the National Institute on Alcohol Abuse and Alcoholism, said Dr. Chao.

The midlife age range of participants, their diabetes diagnosis, and the fact that depressive symptoms were overall low limits generalizability of the findings, said Dr. Chao, adding that psychosocial factors, other health conditions, and current or past alcohol use disorder could also cause some residual confounding of the data.

Dr. Chao has received research support from Shire Pharmaceuticals.

[email protected]

SOURCE: Chao A et al. Obesity Week 2018, Abstract T-OR-2017.

LOS ANGELES – On any given day, type “statins” in the subject line of your favorite search engine and many results are likely to focus on risks: some based on science, others not so much.

Doug Brunk/MDedge News

“There is all kind of misinformation that are preventing people from taking statins,” Joshua W. Knowles, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The most important side effects of statins are the increased lifespan and decreased risk of heart attacks, but that’s not what our patients are telling us. One of the things that is true is that statins do seem to increase the risk of diabetes. This only emerged after many years and it’s gotten a lot of press.”

In 2016, Dr. Knowles, a cardiologist at the Stanford (Calif.) Center for Inherited Cardiovascular Disease, coauthored a retrospective analysis of data from subjects without diabetes in the Treating to New Targets (TNT) and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) randomized controlled trials (Am J Cardiol 2016;118[9]:1275-81). The authors found that statins particularly increase the risk of type 2 diabetes in those with prediabetes and insulin resistance. “That’s a risk group that we are all treating,” he said. “But that still doesn’t answer the question as to why this happens. Is this because statins increase insulin resistance, because they decrease beta cell function, or because they increase insulin clearance rate?”

In an effort to find out, Dr. Knowles and his colleagues have launched a clinical trial entitled “Relationship Between Insulin Resistance and Statin Induced Type 2 Diabetes, and Integrative Personal Omics Profiling” (NCT 02437084). Candidates do not have diabetes, yet qualify for statin therapy because they have a greater than 7.5% risk of cardiovascular disease over 10 years. To date, the researchers have enrolled 74 patients: 42 to the insulin-sensitive group (defined as having an LDL above 130 mg/dL and a triglyceride level below 150 mg/dL) and 11 to the insulin-resistant group (defined as having an LDL of 130 mg/dL or greater and a triglyceride level of 150 mg/dL or greater). Dr. Knowles said that about two-thirds of patients have been recruited and that full results are expected in late 2019.

At baseline, subjects underwent the insulin suppression test, the graded glucose infusion test, metabolic characterization, and integrated personal omics profiling (iPOP), a monitoring method. After 3 months of atorvastatin therapy 40 mg/day, the researchers repeated these measures and compared the results between groups. “Basically we were looking for changes in insulin resistance, secretion, and clearance between those groups over time,” said Dr. Knowles, who is the study’s principal investigator.

Of the 74 subjects, 13 decided that they did not want to participate and 6 are still undergoing baseline tests. In all, 55 started statin therapy, and 2 have dropped out. This left 42 in the low-triglyceride group and 11 in the high-triglyceride group.

The average age of the 52 individuals who have completed the study so far is 61 years, 30 are male, 35 are non-Hispanic white, their mean body mass index was 27.9 kg/m², and their mean blood pressure was 127/79 mm Hg. By the end of statin therapy, body mass index did not change, but total cholesterol fell from a median of 234 mg/dL to a median of 150 mg/dL, triglycerides fell from a median of 109 mg/dL to a median of 78 mg/dL, LDL cholesterol fell from a median of 153 mg/dL to a median of 71 mg/dL, and mean high-sensitivity C-reactive protein dropped from a median of 1.2 mg/L to a median of 0.8 mg/L. All differences were statistically significant.

Fasting glucose levels have been completed on only 35 patients. “Two-hour glucose is going up, but it’s not yet significant, and on the oral glucose tolerance test, the curves are separating slightly but are not yet significant,” Dr. Knowles said.

On average, insulin resistance among the 35 patients worsened slightly, from 156 mg/dL before statin therapy to 170 mg/dL after initiation. “This is nominally significant (P = 0.03), and we’ll have to see if this holds up over time,” he said. The researchers also observed that statin use was associated with slight decreases in insulin secretion and clearance. Dr. Knowles emphasized that these are preliminary results and need to be further validated.

The study is funded by the Doris Duke Charitable Foundation. Dr. Knowles reported having no disclosures.

[email protected]

LOS ANGELES – On any given day, type “statins” in the subject line of your favorite search engine and many results are likely to focus on risks: some based on science, others not so much.

Doug Brunk/MDedge News

“There is all kind of misinformation that are preventing people from taking statins,” Joshua W. Knowles, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The most important side effects of statins are the increased lifespan and decreased risk of heart attacks, but that’s not what our patients are telling us. One of the things that is true is that statins do seem to increase the risk of diabetes. This only emerged after many years and it’s gotten a lot of press.”

In 2016, Dr. Knowles, a cardiologist at the Stanford (Calif.) Center for Inherited Cardiovascular Disease, coauthored a retrospective analysis of data from subjects without diabetes in the Treating to New Targets (TNT) and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) randomized controlled trials (Am J Cardiol 2016;118[9]:1275-81). The authors found that statins particularly increase the risk of type 2 diabetes in those with prediabetes and insulin resistance. “That’s a risk group that we are all treating,” he said. “But that still doesn’t answer the question as to why this happens. Is this because statins increase insulin resistance, because they decrease beta cell function, or because they increase insulin clearance rate?”

In an effort to find out, Dr. Knowles and his colleagues have launched a clinical trial entitled “Relationship Between Insulin Resistance and Statin Induced Type 2 Diabetes, and Integrative Personal Omics Profiling” (NCT 02437084). Candidates do not have diabetes, yet qualify for statin therapy because they have a greater than 7.5% risk of cardiovascular disease over 10 years. To date, the researchers have enrolled 74 patients: 42 to the insulin-sensitive group (defined as having an LDL above 130 mg/dL and a triglyceride level below 150 mg/dL) and 11 to the insulin-resistant group (defined as having an LDL of 130 mg/dL or greater and a triglyceride level of 150 mg/dL or greater). Dr. Knowles said that about two-thirds of patients have been recruited and that full results are expected in late 2019.

At baseline, subjects underwent the insulin suppression test, the graded glucose infusion test, metabolic characterization, and integrated personal omics profiling (iPOP), a monitoring method. After 3 months of atorvastatin therapy 40 mg/day, the researchers repeated these measures and compared the results between groups. “Basically we were looking for changes in insulin resistance, secretion, and clearance between those groups over time,” said Dr. Knowles, who is the study’s principal investigator.

Of the 74 subjects, 13 decided that they did not want to participate and 6 are still undergoing baseline tests. In all, 55 started statin therapy, and 2 have dropped out. This left 42 in the low-triglyceride group and 11 in the high-triglyceride group.

The average age of the 52 individuals who have completed the study so far is 61 years, 30 are male, 35 are non-Hispanic white, their mean body mass index was 27.9 kg/m², and their mean blood pressure was 127/79 mm Hg. By the end of statin therapy, body mass index did not change, but total cholesterol fell from a median of 234 mg/dL to a median of 150 mg/dL, triglycerides fell from a median of 109 mg/dL to a median of 78 mg/dL, LDL cholesterol fell from a median of 153 mg/dL to a median of 71 mg/dL, and mean high-sensitivity C-reactive protein dropped from a median of 1.2 mg/L to a median of 0.8 mg/L. All differences were statistically significant.

Fasting glucose levels have been completed on only 35 patients. “Two-hour glucose is going up, but it’s not yet significant, and on the oral glucose tolerance test, the curves are separating slightly but are not yet significant,” Dr. Knowles said.

On average, insulin resistance among the 35 patients worsened slightly, from 156 mg/dL before statin therapy to 170 mg/dL after initiation. “This is nominally significant (P = 0.03), and we’ll have to see if this holds up over time,” he said. The researchers also observed that statin use was associated with slight decreases in insulin secretion and clearance. Dr. Knowles emphasized that these are preliminary results and need to be further validated.

The study is funded by the Doris Duke Charitable Foundation. Dr. Knowles reported having no disclosures.

[email protected]

LOS ANGELES – On any given day, type “statins” in the subject line of your favorite search engine and many results are likely to focus on risks: some based on science, others not so much.

Doug Brunk/MDedge News

“There is all kind of misinformation that are preventing people from taking statins,” Joshua W. Knowles, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The most important side effects of statins are the increased lifespan and decreased risk of heart attacks, but that’s not what our patients are telling us. One of the things that is true is that statins do seem to increase the risk of diabetes. This only emerged after many years and it’s gotten a lot of press.”

In 2016, Dr. Knowles, a cardiologist at the Stanford (Calif.) Center for Inherited Cardiovascular Disease, coauthored a retrospective analysis of data from subjects without diabetes in the Treating to New Targets (TNT) and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) randomized controlled trials (Am J Cardiol 2016;118[9]:1275-81). The authors found that statins particularly increase the risk of type 2 diabetes in those with prediabetes and insulin resistance. “That’s a risk group that we are all treating,” he said. “But that still doesn’t answer the question as to why this happens. Is this because statins increase insulin resistance, because they decrease beta cell function, or because they increase insulin clearance rate?”

In an effort to find out, Dr. Knowles and his colleagues have launched a clinical trial entitled “Relationship Between Insulin Resistance and Statin Induced Type 2 Diabetes, and Integrative Personal Omics Profiling” (NCT 02437084). Candidates do not have diabetes, yet qualify for statin therapy because they have a greater than 7.5% risk of cardiovascular disease over 10 years. To date, the researchers have enrolled 74 patients: 42 to the insulin-sensitive group (defined as having an LDL above 130 mg/dL and a triglyceride level below 150 mg/dL) and 11 to the insulin-resistant group (defined as having an LDL of 130 mg/dL or greater and a triglyceride level of 150 mg/dL or greater). Dr. Knowles said that about two-thirds of patients have been recruited and that full results are expected in late 2019.

At baseline, subjects underwent the insulin suppression test, the graded glucose infusion test, metabolic characterization, and integrated personal omics profiling (iPOP), a monitoring method. After 3 months of atorvastatin therapy 40 mg/day, the researchers repeated these measures and compared the results between groups. “Basically we were looking for changes in insulin resistance, secretion, and clearance between those groups over time,” said Dr. Knowles, who is the study’s principal investigator.

Of the 74 subjects, 13 decided that they did not want to participate and 6 are still undergoing baseline tests. In all, 55 started statin therapy, and 2 have dropped out. This left 42 in the low-triglyceride group and 11 in the high-triglyceride group.

The average age of the 52 individuals who have completed the study so far is 61 years, 30 are male, 35 are non-Hispanic white, their mean body mass index was 27.9 kg/m², and their mean blood pressure was 127/79 mm Hg. By the end of statin therapy, body mass index did not change, but total cholesterol fell from a median of 234 mg/dL to a median of 150 mg/dL, triglycerides fell from a median of 109 mg/dL to a median of 78 mg/dL, LDL cholesterol fell from a median of 153 mg/dL to a median of 71 mg/dL, and mean high-sensitivity C-reactive protein dropped from a median of 1.2 mg/L to a median of 0.8 mg/L. All differences were statistically significant.

Fasting glucose levels have been completed on only 35 patients. “Two-hour glucose is going up, but it’s not yet significant, and on the oral glucose tolerance test, the curves are separating slightly but are not yet significant,” Dr. Knowles said.

On average, insulin resistance among the 35 patients worsened slightly, from 156 mg/dL before statin therapy to 170 mg/dL after initiation. “This is nominally significant (P = 0.03), and we’ll have to see if this holds up over time,” he said. The researchers also observed that statin use was associated with slight decreases in insulin secretion and clearance. Dr. Knowles emphasized that these are preliminary results and need to be further validated.

The study is funded by the Doris Duke Charitable Foundation. Dr. Knowles reported having no disclosures.

[email protected]

LOS ANGELES – In the opinion of Paul Zimmet, MD, PhD, the Western 24/7 lifestyle is plagued by chronic sleep insufficiency, continual caloric excess, modernization, and globalization, which all can cause disruption of circadian rhythm.

Doug Brunk/MDedge News

This scenario created the “perfect storm” for rising rates of metabolic syndrome, which is related to low HDL cholesterol levels, central obesity, hypertension, hyperglycemia, and high triglyceride levels, Dr. Zimmet said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. These cardiometabolic risk factors “all seem to cluster together in relation to the changes in our society,” he said. “It’s on that basis and research findings that I think we should understand that most of them, if not all, have been demonstrated to relate to circadian rhythm disturbance.”

In fact, the associated comorbidities sleep apnea, depression, and fatty liver disease should be included in the metabolic syndrome cluster and should be renamed the “circadian syndrome,” according to Dr. Zimmet, professor of diabetes at Monash University, Melbourne.

The term metabolic syndrome is anathema, he said. “There have been numerous different definitions, which finally led to an effort to come up with a harmonized definition” by the International Diabetes Federation Task Force on Epidemiology and Prevention, with involvement from the American Heart Association (Circulation 2009;120[16]:1640-5).

In the early 1970s, Dr. Zimmet and his colleagues at Guys Hospital in London reported on diurnal variation in glucose tolerance. “If you did a glucose tolerance test in the afternoon it could be diabetic, whereas in the morning it was normal,” he noted. “Other researchers reported similar findings. That created in my own mind interest in this area of circadian rhythm. However, I had neglected this until recently, when I was doing background research while trying to find an answer to the elusive question of a central uniting explanation for the cardiometabolic cluster constituting the metabolic syndrome.” So decades later, Dr. Zimmet extended his research to include epigenetics in the quest. Described as the study of heritable changes in gene function that occur without a change in the sequence of the DNA, epigenetic changes “are closely linked to the circadian rhythm, otherwise known as ‘the body clock,’ ” said Dr. Zimmet, who also is codirector with Naftali Stern, MD, of the Sagol Center for Epigenetics of Metabolism and Aging at Tel Aviv Medical Center. “Many aspects of human behavior and metabolism are closely linked to the circadian clock and affected by its rhythm disturbance. We decided that we wanted to further investigate this area: To what extent is circadian rhythm the central feature to explain the clustering of all of these cardiovascular and metabolic risk factors of the metabolic syndrome.”

In recent years, he has been collaborating with Noga Kronfeld-Schor, PhD, of the department of zoology at Tel Aviv (Israel) University. The research focuses on a gerbil from the Negev: Psammomys obesus (otherwise known as the Israeli fat sand rat), which develops elevated blood sugar, obesity, depression, sleep disturbance, fatty liver, and circadian dysrhythmia when removed from the desert environment to the laboratory. “These are all key features of type 2 diabetes in humans,” he said. “This is probably the best animal model of type 2 diabetes, and we felt that it was worth looking more closely to see if there was a similar relationship in humans as to whether circadian dysrhythmia would be causing all or most of these features in humans including obesity.” An epigenetic study of the gerbil in the laboratory of Prof. Sam El-Osta at Monash has shown that parental diet during early life regulated expression of genes associated with DNA methylation in the key FTO gene associated with obesity (Int J Obesity 2016;40:1079-88). It suggests that diet-induced metabolic changes can be transmitted from parent to offspring by mechanisms under epigenetic control.

Published studies from other research groups support the link between other of the cardiometabolic metabolic syndrome characteristics, epigenetic modifications, and circadian dysrhythmia including cardiovascular regulation and disease (Eur Heart J 2018;39[14]:2326-9), sleep loss and alterations in DNA methylation (Science Advances 2018;4[8]:eaar8590), and circadian dysrhythmia and fatty liver (Cell Metab 2012;15[6]:848-60). “In 2009, the FDA approved bromocriptine mesylate, a drug which has effects on circadian rhythm, for treatment of type 2 diabetes, suggesting its use in diabetes may have some role through the alteration of circadian rhythm,” continued Dr. Zimmet, who also is honorary president of the International Diabetes Federation. “Depression is also clearly linked to circadian rhythm and there is evidence from research and human studies that light therapy may be an effective treatment for type 2 diabetes and depression.”

Dr. Zimmet ended his presentation with a strong call for adding sleep apnea, fatty liver, and depression to the existing features of the metabolic syndrome “to encourage clinicians and researchers look at the picture of cardiometabolic risk much more broadly than as just a group of metabolic abnormalities,” he said. “We propose that these comorbidities be embraced within the definition of the cardiometabolic cluster and be renamed the ‘circadian syndrome.’ This cluster is now the main driver of the global chronic disease epidemic and its health burden. This is a disease of civilization – the result of the way we live.”

Dr. Zimmet reported having no disclosures.

[email protected]

LOS ANGELES – In the opinion of Paul Zimmet, MD, PhD, the Western 24/7 lifestyle is plagued by chronic sleep insufficiency, continual caloric excess, modernization, and globalization, which all can cause disruption of circadian rhythm.

Doug Brunk/MDedge News

This scenario created the “perfect storm” for rising rates of metabolic syndrome, which is related to low HDL cholesterol levels, central obesity, hypertension, hyperglycemia, and high triglyceride levels, Dr. Zimmet said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. These cardiometabolic risk factors “all seem to cluster together in relation to the changes in our society,” he said. “It’s on that basis and research findings that I think we should understand that most of them, if not all, have been demonstrated to relate to circadian rhythm disturbance.”

In fact, the associated comorbidities sleep apnea, depression, and fatty liver disease should be included in the metabolic syndrome cluster and should be renamed the “circadian syndrome,” according to Dr. Zimmet, professor of diabetes at Monash University, Melbourne.

The term metabolic syndrome is anathema, he said. “There have been numerous different definitions, which finally led to an effort to come up with a harmonized definition” by the International Diabetes Federation Task Force on Epidemiology and Prevention, with involvement from the American Heart Association (Circulation 2009;120[16]:1640-5).

In the early 1970s, Dr. Zimmet and his colleagues at Guys Hospital in London reported on diurnal variation in glucose tolerance. “If you did a glucose tolerance test in the afternoon it could be diabetic, whereas in the morning it was normal,” he noted. “Other researchers reported similar findings. That created in my own mind interest in this area of circadian rhythm. However, I had neglected this until recently, when I was doing background research while trying to find an answer to the elusive question of a central uniting explanation for the cardiometabolic cluster constituting the metabolic syndrome.” So decades later, Dr. Zimmet extended his research to include epigenetics in the quest. Described as the study of heritable changes in gene function that occur without a change in the sequence of the DNA, epigenetic changes “are closely linked to the circadian rhythm, otherwise known as ‘the body clock,’ ” said Dr. Zimmet, who also is codirector with Naftali Stern, MD, of the Sagol Center for Epigenetics of Metabolism and Aging at Tel Aviv Medical Center. “Many aspects of human behavior and metabolism are closely linked to the circadian clock and affected by its rhythm disturbance. We decided that we wanted to further investigate this area: To what extent is circadian rhythm the central feature to explain the clustering of all of these cardiovascular and metabolic risk factors of the metabolic syndrome.”

In recent years, he has been collaborating with Noga Kronfeld-Schor, PhD, of the department of zoology at Tel Aviv (Israel) University. The research focuses on a gerbil from the Negev: Psammomys obesus (otherwise known as the Israeli fat sand rat), which develops elevated blood sugar, obesity, depression, sleep disturbance, fatty liver, and circadian dysrhythmia when removed from the desert environment to the laboratory. “These are all key features of type 2 diabetes in humans,” he said. “This is probably the best animal model of type 2 diabetes, and we felt that it was worth looking more closely to see if there was a similar relationship in humans as to whether circadian dysrhythmia would be causing all or most of these features in humans including obesity.” An epigenetic study of the gerbil in the laboratory of Prof. Sam El-Osta at Monash has shown that parental diet during early life regulated expression of genes associated with DNA methylation in the key FTO gene associated with obesity (Int J Obesity 2016;40:1079-88). It suggests that diet-induced metabolic changes can be transmitted from parent to offspring by mechanisms under epigenetic control.

Published studies from other research groups support the link between other of the cardiometabolic metabolic syndrome characteristics, epigenetic modifications, and circadian dysrhythmia including cardiovascular regulation and disease (Eur Heart J 2018;39[14]:2326-9), sleep loss and alterations in DNA methylation (Science Advances 2018;4[8]:eaar8590), and circadian dysrhythmia and fatty liver (Cell Metab 2012;15[6]:848-60). “In 2009, the FDA approved bromocriptine mesylate, a drug which has effects on circadian rhythm, for treatment of type 2 diabetes, suggesting its use in diabetes may have some role through the alteration of circadian rhythm,” continued Dr. Zimmet, who also is honorary president of the International Diabetes Federation. “Depression is also clearly linked to circadian rhythm and there is evidence from research and human studies that light therapy may be an effective treatment for type 2 diabetes and depression.”

Dr. Zimmet ended his presentation with a strong call for adding sleep apnea, fatty liver, and depression to the existing features of the metabolic syndrome “to encourage clinicians and researchers look at the picture of cardiometabolic risk much more broadly than as just a group of metabolic abnormalities,” he said. “We propose that these comorbidities be embraced within the definition of the cardiometabolic cluster and be renamed the ‘circadian syndrome.’ This cluster is now the main driver of the global chronic disease epidemic and its health burden. This is a disease of civilization – the result of the way we live.”

Dr. Zimmet reported having no disclosures.

[email protected]

LOS ANGELES – In the opinion of Paul Zimmet, MD, PhD, the Western 24/7 lifestyle is plagued by chronic sleep insufficiency, continual caloric excess, modernization, and globalization, which all can cause disruption of circadian rhythm.

Doug Brunk/MDedge News

This scenario created the “perfect storm” for rising rates of metabolic syndrome, which is related to low HDL cholesterol levels, central obesity, hypertension, hyperglycemia, and high triglyceride levels, Dr. Zimmet said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. These cardiometabolic risk factors “all seem to cluster together in relation to the changes in our society,” he said. “It’s on that basis and research findings that I think we should understand that most of them, if not all, have been demonstrated to relate to circadian rhythm disturbance.”

In fact, the associated comorbidities sleep apnea, depression, and fatty liver disease should be included in the metabolic syndrome cluster and should be renamed the “circadian syndrome,” according to Dr. Zimmet, professor of diabetes at Monash University, Melbourne.

The term metabolic syndrome is anathema, he said. “There have been numerous different definitions, which finally led to an effort to come up with a harmonized definition” by the International Diabetes Federation Task Force on Epidemiology and Prevention, with involvement from the American Heart Association (Circulation 2009;120[16]:1640-5).

In the early 1970s, Dr. Zimmet and his colleagues at Guys Hospital in London reported on diurnal variation in glucose tolerance. “If you did a glucose tolerance test in the afternoon it could be diabetic, whereas in the morning it was normal,” he noted. “Other researchers reported similar findings. That created in my own mind interest in this area of circadian rhythm. However, I had neglected this until recently, when I was doing background research while trying to find an answer to the elusive question of a central uniting explanation for the cardiometabolic cluster constituting the metabolic syndrome.” So decades later, Dr. Zimmet extended his research to include epigenetics in the quest. Described as the study of heritable changes in gene function that occur without a change in the sequence of the DNA, epigenetic changes “are closely linked to the circadian rhythm, otherwise known as ‘the body clock,’ ” said Dr. Zimmet, who also is codirector with Naftali Stern, MD, of the Sagol Center for Epigenetics of Metabolism and Aging at Tel Aviv Medical Center. “Many aspects of human behavior and metabolism are closely linked to the circadian clock and affected by its rhythm disturbance. We decided that we wanted to further investigate this area: To what extent is circadian rhythm the central feature to explain the clustering of all of these cardiovascular and metabolic risk factors of the metabolic syndrome.”

In recent years, he has been collaborating with Noga Kronfeld-Schor, PhD, of the department of zoology at Tel Aviv (Israel) University. The research focuses on a gerbil from the Negev: Psammomys obesus (otherwise known as the Israeli fat sand rat), which develops elevated blood sugar, obesity, depression, sleep disturbance, fatty liver, and circadian dysrhythmia when removed from the desert environment to the laboratory. “These are all key features of type 2 diabetes in humans,” he said. “This is probably the best animal model of type 2 diabetes, and we felt that it was worth looking more closely to see if there was a similar relationship in humans as to whether circadian dysrhythmia would be causing all or most of these features in humans including obesity.” An epigenetic study of the gerbil in the laboratory of Prof. Sam El-Osta at Monash has shown that parental diet during early life regulated expression of genes associated with DNA methylation in the key FTO gene associated with obesity (Int J Obesity 2016;40:1079-88). It suggests that diet-induced metabolic changes can be transmitted from parent to offspring by mechanisms under epigenetic control.

Published studies from other research groups support the link between other of the cardiometabolic metabolic syndrome characteristics, epigenetic modifications, and circadian dysrhythmia including cardiovascular regulation and disease (Eur Heart J 2018;39[14]:2326-9), sleep loss and alterations in DNA methylation (Science Advances 2018;4[8]:eaar8590), and circadian dysrhythmia and fatty liver (Cell Metab 2012;15[6]:848-60). “In 2009, the FDA approved bromocriptine mesylate, a drug which has effects on circadian rhythm, for treatment of type 2 diabetes, suggesting its use in diabetes may have some role through the alteration of circadian rhythm,” continued Dr. Zimmet, who also is honorary president of the International Diabetes Federation. “Depression is also clearly linked to circadian rhythm and there is evidence from research and human studies that light therapy may be an effective treatment for type 2 diabetes and depression.”

Dr. Zimmet ended his presentation with a strong call for adding sleep apnea, fatty liver, and depression to the existing features of the metabolic syndrome “to encourage clinicians and researchers look at the picture of cardiometabolic risk much more broadly than as just a group of metabolic abnormalities,” he said. “We propose that these comorbidities be embraced within the definition of the cardiometabolic cluster and be renamed the ‘circadian syndrome.’ This cluster is now the main driver of the global chronic disease epidemic and its health burden. This is a disease of civilization – the result of the way we live.”

Dr. Zimmet reported having no disclosures.

[email protected]

BERLIN – Diuretics may need to be used cautiously in patients with type 2 diabetes mellitus who are at risk of lower limb amputation, suggest observational study findings presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

A significant and independent increase in the risk of lower limb events, predominantly lower-extremity amputations was seen among patients with type 2 diabetes mellitus (T2DM) who were treated with diuretics versus those who were not. The adjusted hazard ratios in a propensity-matched cohort was 1.60 (95% confidence interval, 1.06-2.42; P = .027) for lower limb events, 2.13 (95% CI, 1.17-3.87; P = .013) for lower limb amputations, and 1.12 (95% CI, 0.70-1.79; P = .6443) for lower limb revascularizations.

“We know diabetes is a leading cause of nontraumatic lower limb amputations in the world,” and thus a very important public health issue, said study investigator Ronan Roussel, MD, PhD, of Hôpital Bichat, Assistance Publique Hôpitaux de Paris. “Many contributing factors are identified, susceptibility to infection, impaired wound healing, peripheral neuropathy; but the most important is the presence of peripheral arterial disease.”

The risk of diabetic amputations is of specific interest because of the recent findings from CANVAS, where treatment with canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was linked to an almost doubled rate of amputations versus placebo (HR, 1.97; 95% CI, 1.41-2.75) in patients with T2DM.

Conflicting results have been seen in observational studies with other SGLT2 inhibitors, however, and it’s not clear if the risk of amputations is just seen with canagliflozin or if it may be a class effect. The underlying mechanism is unknown, but one theory is that hypovolemia may be involved. If this is the case, Dr. Roussel explained, then diuretics would have a similar safety profile as SGLT2 inhibitors in terms of increasing the risk of amputations.

The aim of the present study was to look at the association between lower limb events and diuretic usage in patients with T2DM. Data on 1,459 subjects with T2DM treated with diuretics and data on lower limb events and amputations were obtained from the single-center SURDIAGENE study. Of these, 670 were and 789 were not taking diuretics.

Baseline differences between diuretic and nondiuretic users were seen, such as diuretic users being older (67 vs. 63 years), having longer diabetes duration (16 vs. 13 years), and being more likely to have cardiovascular disease (32.5% vs. 23.4%). A propensity-score approach was used to even out these differences, leaving a population of 1,074 subjects in the final matched cohort.

Over a median follow-up of 7.2 years, 12.7% of diuretic and 7.2% of nondiuretic users experienced lower limb events (P = .001). In multivariate and sensitivity analyses, lower limb amputations remained significantly higher in patients who had been treated with a diuretic than in those who had not.

These are “hypothesis-generating” data, Dr. Roussel pointed out and “we don’t want to be overconclusive, of course.” However, they may explain the risk signal seen with SGLT2 inhibitors in the CANVAS study. Further studies are needed to explore the role of drug-induced hypovolemia in the association between the use of diuretics and lower limb events.

Sara Freeman/MDedge News

EASD delegate Prashanth Vas, MBBS, MRCP, PhD, noted during the discussion that the use of diuretics was ubiquitous. “Nearly everyone uses diuretics,” he said. The potential risk of lower limb amputation and treatment with SGLT2 inhibitors had “been vexing us for some time since the data from CANVAS came out.”

Dr. Vas, who is a consultant diabetologist and diabetic foot specialist at King’s College Hospital NHS Foundation in London, went on to ask why only canagliflozin was found to be associated with amputations and not the other SGLT2 drugs.

Dr. Roussel responded that data were still needed on the other drugs in this class and that they needed to be treated with caution. The literature is not so clear, he admitted.

“It’s important that you noted it’s a single-center study,” Dr. Vas countered. “It’s very important to have multicenter data. An amputation is a decision made by someone. An amputation in one center may not be an amputation in another center.”

The SURDIAGENE study was supported by grants from the French Ministry of Health, the Association Française des Diabétiques, and the Groupement pour l’Etude des Maladies Métaboliques et Systémiques. Dr. Roussel reported relationships with Janssen, Merck, Sanofi-Aventis, AstraZeneca, and Boehringer Ingelheim. Dr. Vas was not involved in the study or analysis.

[email protected]

SOURCE: Roussel R et al. EASD 2018, Abstract 12.

BERLIN – Diuretics may need to be used cautiously in patients with type 2 diabetes mellitus who are at risk of lower limb amputation, suggest observational study findings presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

A significant and independent increase in the risk of lower limb events, predominantly lower-extremity amputations was seen among patients with type 2 diabetes mellitus (T2DM) who were treated with diuretics versus those who were not. The adjusted hazard ratios in a propensity-matched cohort was 1.60 (95% confidence interval, 1.06-2.42; P = .027) for lower limb events, 2.13 (95% CI, 1.17-3.87; P = .013) for lower limb amputations, and 1.12 (95% CI, 0.70-1.79; P = .6443) for lower limb revascularizations.

“We know diabetes is a leading cause of nontraumatic lower limb amputations in the world,” and thus a very important public health issue, said study investigator Ronan Roussel, MD, PhD, of Hôpital Bichat, Assistance Publique Hôpitaux de Paris. “Many contributing factors are identified, susceptibility to infection, impaired wound healing, peripheral neuropathy; but the most important is the presence of peripheral arterial disease.”

The risk of diabetic amputations is of specific interest because of the recent findings from CANVAS, where treatment with canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was linked to an almost doubled rate of amputations versus placebo (HR, 1.97; 95% CI, 1.41-2.75) in patients with T2DM.

Conflicting results have been seen in observational studies with other SGLT2 inhibitors, however, and it’s not clear if the risk of amputations is just seen with canagliflozin or if it may be a class effect. The underlying mechanism is unknown, but one theory is that hypovolemia may be involved. If this is the case, Dr. Roussel explained, then diuretics would have a similar safety profile as SGLT2 inhibitors in terms of increasing the risk of amputations.

The aim of the present study was to look at the association between lower limb events and diuretic usage in patients with T2DM. Data on 1,459 subjects with T2DM treated with diuretics and data on lower limb events and amputations were obtained from the single-center SURDIAGENE study. Of these, 670 were and 789 were not taking diuretics.

Baseline differences between diuretic and nondiuretic users were seen, such as diuretic users being older (67 vs. 63 years), having longer diabetes duration (16 vs. 13 years), and being more likely to have cardiovascular disease (32.5% vs. 23.4%). A propensity-score approach was used to even out these differences, leaving a population of 1,074 subjects in the final matched cohort.

Over a median follow-up of 7.2 years, 12.7% of diuretic and 7.2% of nondiuretic users experienced lower limb events (P = .001). In multivariate and sensitivity analyses, lower limb amputations remained significantly higher in patients who had been treated with a diuretic than in those who had not.

These are “hypothesis-generating” data, Dr. Roussel pointed out and “we don’t want to be overconclusive, of course.” However, they may explain the risk signal seen with SGLT2 inhibitors in the CANVAS study. Further studies are needed to explore the role of drug-induced hypovolemia in the association between the use of diuretics and lower limb events.

Sara Freeman/MDedge News

EASD delegate Prashanth Vas, MBBS, MRCP, PhD, noted during the discussion that the use of diuretics was ubiquitous. “Nearly everyone uses diuretics,” he said. The potential risk of lower limb amputation and treatment with SGLT2 inhibitors had “been vexing us for some time since the data from CANVAS came out.”

Dr. Vas, who is a consultant diabetologist and diabetic foot specialist at King’s College Hospital NHS Foundation in London, went on to ask why only canagliflozin was found to be associated with amputations and not the other SGLT2 drugs.

Dr. Roussel responded that data were still needed on the other drugs in this class and that they needed to be treated with caution. The literature is not so clear, he admitted.

“It’s important that you noted it’s a single-center study,” Dr. Vas countered. “It’s very important to have multicenter data. An amputation is a decision made by someone. An amputation in one center may not be an amputation in another center.”

The SURDIAGENE study was supported by grants from the French Ministry of Health, the Association Française des Diabétiques, and the Groupement pour l’Etude des Maladies Métaboliques et Systémiques. Dr. Roussel reported relationships with Janssen, Merck, Sanofi-Aventis, AstraZeneca, and Boehringer Ingelheim. Dr. Vas was not involved in the study or analysis.

[email protected]

SOURCE: Roussel R et al. EASD 2018, Abstract 12.

BERLIN – Diuretics may need to be used cautiously in patients with type 2 diabetes mellitus who are at risk of lower limb amputation, suggest observational study findings presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

A significant and independent increase in the risk of lower limb events, predominantly lower-extremity amputations was seen among patients with type 2 diabetes mellitus (T2DM) who were treated with diuretics versus those who were not. The adjusted hazard ratios in a propensity-matched cohort was 1.60 (95% confidence interval, 1.06-2.42; P = .027) for lower limb events, 2.13 (95% CI, 1.17-3.87; P = .013) for lower limb amputations, and 1.12 (95% CI, 0.70-1.79; P = .6443) for lower limb revascularizations.

“We know diabetes is a leading cause of nontraumatic lower limb amputations in the world,” and thus a very important public health issue, said study investigator Ronan Roussel, MD, PhD, of Hôpital Bichat, Assistance Publique Hôpitaux de Paris. “Many contributing factors are identified, susceptibility to infection, impaired wound healing, peripheral neuropathy; but the most important is the presence of peripheral arterial disease.”

The risk of diabetic amputations is of specific interest because of the recent findings from CANVAS, where treatment with canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was linked to an almost doubled rate of amputations versus placebo (HR, 1.97; 95% CI, 1.41-2.75) in patients with T2DM.

Conflicting results have been seen in observational studies with other SGLT2 inhibitors, however, and it’s not clear if the risk of amputations is just seen with canagliflozin or if it may be a class effect. The underlying mechanism is unknown, but one theory is that hypovolemia may be involved. If this is the case, Dr. Roussel explained, then diuretics would have a similar safety profile as SGLT2 inhibitors in terms of increasing the risk of amputations.

The aim of the present study was to look at the association between lower limb events and diuretic usage in patients with T2DM. Data on 1,459 subjects with T2DM treated with diuretics and data on lower limb events and amputations were obtained from the single-center SURDIAGENE study. Of these, 670 were and 789 were not taking diuretics.

Baseline differences between diuretic and nondiuretic users were seen, such as diuretic users being older (67 vs. 63 years), having longer diabetes duration (16 vs. 13 years), and being more likely to have cardiovascular disease (32.5% vs. 23.4%). A propensity-score approach was used to even out these differences, leaving a population of 1,074 subjects in the final matched cohort.

Over a median follow-up of 7.2 years, 12.7% of diuretic and 7.2% of nondiuretic users experienced lower limb events (P = .001). In multivariate and sensitivity analyses, lower limb amputations remained significantly higher in patients who had been treated with a diuretic than in those who had not.

These are “hypothesis-generating” data, Dr. Roussel pointed out and “we don’t want to be overconclusive, of course.” However, they may explain the risk signal seen with SGLT2 inhibitors in the CANVAS study. Further studies are needed to explore the role of drug-induced hypovolemia in the association between the use of diuretics and lower limb events.

Sara Freeman/MDedge News

EASD delegate Prashanth Vas, MBBS, MRCP, PhD, noted during the discussion that the use of diuretics was ubiquitous. “Nearly everyone uses diuretics,” he said. The potential risk of lower limb amputation and treatment with SGLT2 inhibitors had “been vexing us for some time since the data from CANVAS came out.”

Dr. Vas, who is a consultant diabetologist and diabetic foot specialist at King’s College Hospital NHS Foundation in London, went on to ask why only canagliflozin was found to be associated with amputations and not the other SGLT2 drugs.

Dr. Roussel responded that data were still needed on the other drugs in this class and that they needed to be treated with caution. The literature is not so clear, he admitted.

“It’s important that you noted it’s a single-center study,” Dr. Vas countered. “It’s very important to have multicenter data. An amputation is a decision made by someone. An amputation in one center may not be an amputation in another center.”

The SURDIAGENE study was supported by grants from the French Ministry of Health, the Association Française des Diabétiques, and the Groupement pour l’Etude des Maladies Métaboliques et Systémiques. Dr. Roussel reported relationships with Janssen, Merck, Sanofi-Aventis, AstraZeneca, and Boehringer Ingelheim. Dr. Vas was not involved in the study or analysis.

[email protected]

SOURCE: Roussel R et al. EASD 2018, Abstract 12.

Comorbid symptoms of anxiety and depression are associated with twice the risk of developing type 2 diabetes, according to a research paper published in the Journal of Affective Disorders.

The researchers sampled 78,025 Dutch adults aged 30-75 years from the Lifelines Cohort Study and assessed them for depressive and anxious symptoms using the Mini-International Neuropsychiatric Interview before sorting them into groups based on whether they had both, depressive symptoms alone, anxious symptoms alone, or neither.

Compared with participants with no symptoms, those with depressive and anxious symptoms had an unadjusted odds ratio of 2.05 (95% confidence interval, 1.40-3.00) of developing type 2 diabetes, reported Sonya S. Deschênes, PhD, of the department of psychiatry at McGill University, Montreal, and her associates. Furthermore, in an analysis that adjusted for sociodemographic and lifestyle factors and a family history of diabetes, Dr. Deschênes and her associates found that the participants with both kinds of symptoms had an OR of 1.93 (95% CI, 1.21-3.07) of developing type 2 diabetes. Those with only depressive or anxious symptoms alone did not have a statistically significant risk of developing type 2 diabetes.

A limitation cited by the researchers is that a screening tool was used to assess depressive and anxiety symptoms. Also, glycosylated hemoglobin data were available only for a subset of the participants.

Nevertheless, Dr. Deschênes and her associates wrote, the “study extends ... prior findings and suggests that having co-occurring symptoms of [depression] and anxiety is most strongly associated with an increased risk of [type 2 diabetes]. This study also provides further support for the notion that depression with comorbid anxiety symptoms might represent a group with distinct features.”

[email protected]

SOURCE: Deschênes SS et al. J Affect Disorder. 2018 Oct 1. doi: 10.1016/j.jad.2018.05.029.

Comorbid symptoms of anxiety and depression are associated with twice the risk of developing type 2 diabetes, according to a research paper published in the Journal of Affective Disorders.

The researchers sampled 78,025 Dutch adults aged 30-75 years from the Lifelines Cohort Study and assessed them for depressive and anxious symptoms using the Mini-International Neuropsychiatric Interview before sorting them into groups based on whether they had both, depressive symptoms alone, anxious symptoms alone, or neither.

Compared with participants with no symptoms, those with depressive and anxious symptoms had an unadjusted odds ratio of 2.05 (95% confidence interval, 1.40-3.00) of developing type 2 diabetes, reported Sonya S. Deschênes, PhD, of the department of psychiatry at McGill University, Montreal, and her associates. Furthermore, in an analysis that adjusted for sociodemographic and lifestyle factors and a family history of diabetes, Dr. Deschênes and her associates found that the participants with both kinds of symptoms had an OR of 1.93 (95% CI, 1.21-3.07) of developing type 2 diabetes. Those with only depressive or anxious symptoms alone did not have a statistically significant risk of developing type 2 diabetes.

A limitation cited by the researchers is that a screening tool was used to assess depressive and anxiety symptoms. Also, glycosylated hemoglobin data were available only for a subset of the participants.

Nevertheless, Dr. Deschênes and her associates wrote, the “study extends ... prior findings and suggests that having co-occurring symptoms of [depression] and anxiety is most strongly associated with an increased risk of [type 2 diabetes]. This study also provides further support for the notion that depression with comorbid anxiety symptoms might represent a group with distinct features.”

[email protected]

SOURCE: Deschênes SS et al. J Affect Disorder. 2018 Oct 1. doi: 10.1016/j.jad.2018.05.029.

Comorbid symptoms of anxiety and depression are associated with twice the risk of developing type 2 diabetes, according to a research paper published in the Journal of Affective Disorders.

The researchers sampled 78,025 Dutch adults aged 30-75 years from the Lifelines Cohort Study and assessed them for depressive and anxious symptoms using the Mini-International Neuropsychiatric Interview before sorting them into groups based on whether they had both, depressive symptoms alone, anxious symptoms alone, or neither.

Compared with participants with no symptoms, those with depressive and anxious symptoms had an unadjusted odds ratio of 2.05 (95% confidence interval, 1.40-3.00) of developing type 2 diabetes, reported Sonya S. Deschênes, PhD, of the department of psychiatry at McGill University, Montreal, and her associates. Furthermore, in an analysis that adjusted for sociodemographic and lifestyle factors and a family history of diabetes, Dr. Deschênes and her associates found that the participants with both kinds of symptoms had an OR of 1.93 (95% CI, 1.21-3.07) of developing type 2 diabetes. Those with only depressive or anxious symptoms alone did not have a statistically significant risk of developing type 2 diabetes.

A limitation cited by the researchers is that a screening tool was used to assess depressive and anxiety symptoms. Also, glycosylated hemoglobin data were available only for a subset of the participants.

Nevertheless, Dr. Deschênes and her associates wrote, the “study extends ... prior findings and suggests that having co-occurring symptoms of [depression] and anxiety is most strongly associated with an increased risk of [type 2 diabetes]. This study also provides further support for the notion that depression with comorbid anxiety symptoms might represent a group with distinct features.”

[email protected]

SOURCE: Deschênes SS et al. J Affect Disorder. 2018 Oct 1. doi: 10.1016/j.jad.2018.05.029.

BERLIN – A significant reduction in severe hypoglycemia was seen within the first year of using continuous glucose monitoring in a registry study of more than 3,000 children with type 1 diabetes mellitus.

Prior to continuous glucose monitoring (CGM) use, 3.9% of 3,171 individuals, aged a median of 12 years, had hypoglycemia events requiring external help. After 6 months of using CGM, however, the rate of severe hypoglycemia had fallen to 1.2% (P = .10), which remained at 1.2% at 12 months (P = .002). The event rate (events per 100 patient-years) was 10.6 at baseline, 7.8 at 6 months, and 6.1 at 12 months.

Fewer hypoglycemia events leading to coma or convulsion were seen with CGM over time, with 1.3%, 0.6%, and 0.7% of patients reporting at least one event at baseline, 6 months (P = .08), and 12 months (P = .15), respectively. Corresponding event rates were 2.5, 1.6, and 1.7 per 100 patient-years.

“The use of continuous glucose monitoring systems has increased considerably in the past years in individuals with type 1 diabetes,” noted Julia Hermann, a PhD student at Ulm University (Germany), at the annual meeting of the European Association for the Study of Diabetes. “In Germany, for example, CGM use rose considerably when reimbursement by health insurance for CGM started in the summer of 2016.”

Ms. Hermann noted that there were studies showing improved metabolic control with CGM but that clinical studies were often limited by the population of patients studied, restricting treatment to selected patients who may have been adhering better to the use of CGM because they were in a trial.

The aim of the present study was to assess metabolic control and acute complications associated with CGM use in children during its first year of use in a real-world population. Anonymized patient records from the prospective German-Austrian-Luxembourg diabetes patient follow-up (DPV) registry were used.

The DPV database is a standardized, computed-based registry of more than 500,000 adult and pediatric patients with all types of diabetes. It was established in 1995 and receives data from 471 diabetes clinics in Germany, Austria, Luxembourg, and Switzerland.

For the current analysis patients had to be aged under 18 years, have had type 1 diabetes mellitus for at least 1 year, have data available for the months prior to starting CGM, and have at least 1 year of follow-up. For inclusion there also had to be documented use of CMG for at least half of the observation time.

The reduction of severe hypoglycemia observed was not accompanied by any deterioration in metabolic control, Ms. Hermann reported. The median baseline glycosylated hemoglobin (HbA1c) was 7.6% (59 mmol/mol) and this did not noticeably change at either the 6- or 12-month follow-up time point. Furthermore, the percentage of patients achieving a target HbA1c of less than 7.5% was 52% at baseline, 55% at 6 months, and 52% at 12 months.

The rate of diabetic ketoacidosis (DKA), defined as a pH of less than 7.3, also did not change significantly from baseline to the two follow-up points, with event rates of 1.5, 1.4, and 1.1, and the percentage of patients with at least one event being 0.8%, 0.5%, and 0.4%.

“We analyzed an overall well-controlled group of pediatric individuals with type 1 diabetes,” Ms. Hermann said. “We observed a significant reduction of severe hypoglycemia. We observed no improvements in HbA1c, but the overall HbA1c remained stable. We observed no statistically significant change in DKA.”

Future research will try to address some of the limitations that the current data may have, such as looking at a longer follow-up period and other endpoints such as hospitalization, Dr. Hermann suggested. Subgroup analyses are also planned.

“Large databases like the DPV registry ... provide a contemporary picture of diabetes treatment and how the use of diabetes technology has changed over the years and also how diabetes outcomes have improved over the years,” Ms. Hermann said. “It has yet to be seen how most recent changes and advances in diabetes technology will affect these long-term trends.”

The work was partially funded by the German Center for Diabetes Research, the German Diabetes Society, Abbott, and Sanofi. Dr. Hermann reported no personal conflicts of interest.
 

SOURCE: Hermann J et al. EASD 2018, Abstract 149.

BERLIN – A significant reduction in severe hypoglycemia was seen within the first year of using continuous glucose monitoring in a registry study of more than 3,000 children with type 1 diabetes mellitus.

Prior to continuous glucose monitoring (CGM) use, 3.9% of 3,171 individuals, aged a median of 12 years, had hypoglycemia events requiring external help. After 6 months of using CGM, however, the rate of severe hypoglycemia had fallen to 1.2% (P = .10), which remained at 1.2% at 12 months (P = .002). The event rate (events per 100 patient-years) was 10.6 at baseline, 7.8 at 6 months, and 6.1 at 12 months.

Fewer hypoglycemia events leading to coma or convulsion were seen with CGM over time, with 1.3%, 0.6%, and 0.7% of patients reporting at least one event at baseline, 6 months (P = .08), and 12 months (P = .15), respectively. Corresponding event rates were 2.5, 1.6, and 1.7 per 100 patient-years.

“The use of continuous glucose monitoring systems has increased considerably in the past years in individuals with type 1 diabetes,” noted Julia Hermann, a PhD student at Ulm University (Germany), at the annual meeting of the European Association for the Study of Diabetes. “In Germany, for example, CGM use rose considerably when reimbursement by health insurance for CGM started in the summer of 2016.”

Ms. Hermann noted that there were studies showing improved metabolic control with CGM but that clinical studies were often limited by the population of patients studied, restricting treatment to selected patients who may have been adhering better to the use of CGM because they were in a trial.

The aim of the present study was to assess metabolic control and acute complications associated with CGM use in children during its first year of use in a real-world population. Anonymized patient records from the prospective German-Austrian-Luxembourg diabetes patient follow-up (DPV) registry were used.

The DPV database is a standardized, computed-based registry of more than 500,000 adult and pediatric patients with all types of diabetes. It was established in 1995 and receives data from 471 diabetes clinics in Germany, Austria, Luxembourg, and Switzerland.

For the current analysis patients had to be aged under 18 years, have had type 1 diabetes mellitus for at least 1 year, have data available for the months prior to starting CGM, and have at least 1 year of follow-up. For inclusion there also had to be documented use of CMG for at least half of the observation time.

The reduction of severe hypoglycemia observed was not accompanied by any deterioration in metabolic control, Ms. Hermann reported. The median baseline glycosylated hemoglobin (HbA1c) was 7.6% (59 mmol/mol) and this did not noticeably change at either the 6- or 12-month follow-up time point. Furthermore, the percentage of patients achieving a target HbA1c of less than 7.5% was 52% at baseline, 55% at 6 months, and 52% at 12 months.

The rate of diabetic ketoacidosis (DKA), defined as a pH of less than 7.3, also did not change significantly from baseline to the two follow-up points, with event rates of 1.5, 1.4, and 1.1, and the percentage of patients with at least one event being 0.8%, 0.5%, and 0.4%.

“We analyzed an overall well-controlled group of pediatric individuals with type 1 diabetes,” Ms. Hermann said. “We observed a significant reduction of severe hypoglycemia. We observed no improvements in HbA1c, but the overall HbA1c remained stable. We observed no statistically significant change in DKA.”

Future research will try to address some of the limitations that the current data may have, such as looking at a longer follow-up period and other endpoints such as hospitalization, Dr. Hermann suggested. Subgroup analyses are also planned.

“Large databases like the DPV registry ... provide a contemporary picture of diabetes treatment and how the use of diabetes technology has changed over the years and also how diabetes outcomes have improved over the years,” Ms. Hermann said. “It has yet to be seen how most recent changes and advances in diabetes technology will affect these long-term trends.”

The work was partially funded by the German Center for Diabetes Research, the German Diabetes Society, Abbott, and Sanofi. Dr. Hermann reported no personal conflicts of interest.
 

SOURCE: Hermann J et al. EASD 2018, Abstract 149.

BERLIN – A significant reduction in severe hypoglycemia was seen within the first year of using continuous glucose monitoring in a registry study of more than 3,000 children with type 1 diabetes mellitus.

Prior to continuous glucose monitoring (CGM) use, 3.9% of 3,171 individuals, aged a median of 12 years, had hypoglycemia events requiring external help. After 6 months of using CGM, however, the rate of severe hypoglycemia had fallen to 1.2% (P = .10), which remained at 1.2% at 12 months (P = .002). The event rate (events per 100 patient-years) was 10.6 at baseline, 7.8 at 6 months, and 6.1 at 12 months.

Fewer hypoglycemia events leading to coma or convulsion were seen with CGM over time, with 1.3%, 0.6%, and 0.7% of patients reporting at least one event at baseline, 6 months (P = .08), and 12 months (P = .15), respectively. Corresponding event rates were 2.5, 1.6, and 1.7 per 100 patient-years.

“The use of continuous glucose monitoring systems has increased considerably in the past years in individuals with type 1 diabetes,” noted Julia Hermann, a PhD student at Ulm University (Germany), at the annual meeting of the European Association for the Study of Diabetes. “In Germany, for example, CGM use rose considerably when reimbursement by health insurance for CGM started in the summer of 2016.”

Ms. Hermann noted that there were studies showing improved metabolic control with CGM but that clinical studies were often limited by the population of patients studied, restricting treatment to selected patients who may have been adhering better to the use of CGM because they were in a trial.

The aim of the present study was to assess metabolic control and acute complications associated with CGM use in children during its first year of use in a real-world population. Anonymized patient records from the prospective German-Austrian-Luxembourg diabetes patient follow-up (DPV) registry were used.

The DPV database is a standardized, computed-based registry of more than 500,000 adult and pediatric patients with all types of diabetes. It was established in 1995 and receives data from 471 diabetes clinics in Germany, Austria, Luxembourg, and Switzerland.

For the current analysis patients had to be aged under 18 years, have had type 1 diabetes mellitus for at least 1 year, have data available for the months prior to starting CGM, and have at least 1 year of follow-up. For inclusion there also had to be documented use of CMG for at least half of the observation time.

The reduction of severe hypoglycemia observed was not accompanied by any deterioration in metabolic control, Ms. Hermann reported. The median baseline glycosylated hemoglobin (HbA1c) was 7.6% (59 mmol/mol) and this did not noticeably change at either the 6- or 12-month follow-up time point. Furthermore, the percentage of patients achieving a target HbA1c of less than 7.5% was 52% at baseline, 55% at 6 months, and 52% at 12 months.

The rate of diabetic ketoacidosis (DKA), defined as a pH of less than 7.3, also did not change significantly from baseline to the two follow-up points, with event rates of 1.5, 1.4, and 1.1, and the percentage of patients with at least one event being 0.8%, 0.5%, and 0.4%.

“We analyzed an overall well-controlled group of pediatric individuals with type 1 diabetes,” Ms. Hermann said. “We observed a significant reduction of severe hypoglycemia. We observed no improvements in HbA1c, but the overall HbA1c remained stable. We observed no statistically significant change in DKA.”

Future research will try to address some of the limitations that the current data may have, such as looking at a longer follow-up period and other endpoints such as hospitalization, Dr. Hermann suggested. Subgroup analyses are also planned.

“Large databases like the DPV registry ... provide a contemporary picture of diabetes treatment and how the use of diabetes technology has changed over the years and also how diabetes outcomes have improved over the years,” Ms. Hermann said. “It has yet to be seen how most recent changes and advances in diabetes technology will affect these long-term trends.”

The work was partially funded by the German Center for Diabetes Research, the German Diabetes Society, Abbott, and Sanofi. Dr. Hermann reported no personal conflicts of interest.
 

SOURCE: Hermann J et al. EASD 2018, Abstract 149.

BERLIN – A dry-powder nasal formulation of glucagon was as good as intramuscular delivery for the reversal of severe hypoglycemia in patients with type 1 diabetes mellitus (T1DM) in a randomized controlled trial.

Sara Freeman/MDedge News

A 100% treatment success rate (n = 66) was seen for both nasal glucagon and intramuscular glucagon, defined as an increase in plasma glucose to 70 mg/dL (3.9 mmol/L or greater) or more or an increase of 20 mg/L (1.1 mmol/L) or more from the glucose nadir within 30 minutes of administration.

Furthermore, slightly more than 97% of patients achieved treatment success within 15 minutes in both treatment groups, with mean times of 11.4 minutes for the nasal formulation and 9.8 minutes for intramuscular administration.

Similar glucose responses were observed within 40 minutes of glucagon administration, study investigator Leona Plum-Mörschel, MD, PhD, reported at the annual meeting of the European Association for the Study of Diabetes. Dr. Plum-Mörschel is the CEO of the clinical research organization Profil Mainz (Germany), which helped Eli Lilly conduct the trial.

“We are all aware and fully agree that severe hypoglycemia is a serious and potentially life-threatening complication of diabetes treatment with insulin and the sulfonylureas,” said Dr. Plum-Mörschel. At least one in three patients with diabetes reports one hypoglycemic episode per year, she added. While this is quite prevalent in patients with T1DM, it’s not uncommon for those with type 2 diabetes mellitus (T2DM) to experience hypoglycemic episodes.

“Outside of a hospital or emergency room setting, injectable glucagon is currently the only option to treat severe hypoglycemia,” Dr. Plum-Mörschel reminded delegates. “Thankfully, the available injectable glucagon emergency kits are highly effective for the treatment of hypoglycemic events,” she added.

However, for untrained caregivers they can be “really challenging to use,” according to Dr. Plum-Mörschel. This is because the available kits involve multiple steps, including reconstitution, before being ready to inject. A severe hypoglycemic event is stressful enough without them worrying about getting things right, she suggested.

This is where a nasal formulation would be advantageous, and it is something that’s been touted to be on the horizon for a few years. Studies have previously shown that nasal glucagon is comparable to intramuscular glucagon in both adult and pediatric populations. Turning the formulation used in those studies into a commercial product however, has meant more clinical testing before being licensed by the regulatory authorities.

The nasal formulation consists of a dry power containing 3 mg glucagon that is provided in a single-use, compact, and thus, portable, device. It’s been designed to be stored at room temperature and is ready to use immediately. Pressing the plunger on the device releases the fine powder that does not require inhalation to work, which means it can be given easily to an unconscious patient with severe hypoglycemia.

“The aim of the present study was to compare the efficacy and safety of commercially manufactured nasal glucagon with intramuscular glucagon for the treatment of insulin-induced hypoglycemia in adults with type 1 diabetes,” Dr. Plum-Mörschel said.

It was a randomized, single-dose, crossover study involving 70 adult patients with T1DM with hypoglycemia artificially induced by an intravenous insulin infusion during the two dosing visits. Five minutes after stopping insulin, nasal glucagon (3 mg) or intramuscular (1 mg) was given, with multiple plasma glucose measurements taken for up to 90 minutes.

The mean age of participants was 41.7 years old, 61% were male, the mean duration of diabetes was 19.8 years, with a baseline glycated hemoglobin (HbA_1c) of 7.3%.

As for safety, Dr. Plum-Mörschel noted that nasal glucagon had a safety profile that was acceptable for emergency treatment. There was no difference between the nasal or intramuscular glucagon treatment groups in the percentages of patients experiencing treatment-emergent adverse events (at least 5% frequency): nausea was seen in 22% and 29%, vomiting in 10% and 12%, and headache in 12% and 7%, respectively.

Asking patients who had been treated with nasal glucagon about specific symptoms related to nasal administration showed around 63% had watery eyes, 49% nasal itching, 39% nasal congestion, 37% a runny nose, 24% sneezing, 20% itchy eyes, and 12.9% itchy throat. “All of these events were transient, generally mild or moderate in nature, and none were serious. Indeed, there were no deaths in the study and no other serious AEs [adverse events] occurred.”

Dr. Plum-Mörschel concluded: “These results support nasal glucagon as a viable alternative to intramuscular glucagon for the treatment of severe hypoglycemia.

“I personally would expect that, due to its simplicity of use, nasal glucagon will create a greater community who can render quick aid in a rescue situation.”

The study was funded by Eli Lilly. Dr. Plum-Mörschel is an employee of Profil Mainz and has received travel grants and speaker honoraria from Eli Lilly and Novo Nordisk.
 

SOURCE: Suico J et al. EASD 2018, Abstract 150.

BERLIN – A dry-powder nasal formulation of glucagon was as good as intramuscular delivery for the reversal of severe hypoglycemia in patients with type 1 diabetes mellitus (T1DM) in a randomized controlled trial.

Sara Freeman/MDedge News

A 100% treatment success rate (n = 66) was seen for both nasal glucagon and intramuscular glucagon, defined as an increase in plasma glucose to 70 mg/dL (3.9 mmol/L or greater) or more or an increase of 20 mg/L (1.1 mmol/L) or more from the glucose nadir within 30 minutes of administration.

Furthermore, slightly more than 97% of patients achieved treatment success within 15 minutes in both treatment groups, with mean times of 11.4 minutes for the nasal formulation and 9.8 minutes for intramuscular administration.

Similar glucose responses were observed within 40 minutes of glucagon administration, study investigator Leona Plum-Mörschel, MD, PhD, reported at the annual meeting of the European Association for the Study of Diabetes. Dr. Plum-Mörschel is the CEO of the clinical research organization Profil Mainz (Germany), which helped Eli Lilly conduct the trial.

“We are all aware and fully agree that severe hypoglycemia is a serious and potentially life-threatening complication of diabetes treatment with insulin and the sulfonylureas,” said Dr. Plum-Mörschel. At least one in three patients with diabetes reports one hypoglycemic episode per year, she added. While this is quite prevalent in patients with T1DM, it’s not uncommon for those with type 2 diabetes mellitus (T2DM) to experience hypoglycemic episodes.

“Outside of a hospital or emergency room setting, injectable glucagon is currently the only option to treat severe hypoglycemia,” Dr. Plum-Mörschel reminded delegates. “Thankfully, the available injectable glucagon emergency kits are highly effective for the treatment of hypoglycemic events,” she added.

However, for untrained caregivers they can be “really challenging to use,” according to Dr. Plum-Mörschel. This is because the available kits involve multiple steps, including reconstitution, before being ready to inject. A severe hypoglycemic event is stressful enough without them worrying about getting things right, she suggested.

This is where a nasal formulation would be advantageous, and it is something that’s been touted to be on the horizon for a few years. Studies have previously shown that nasal glucagon is comparable to intramuscular glucagon in both adult and pediatric populations. Turning the formulation used in those studies into a commercial product however, has meant more clinical testing before being licensed by the regulatory authorities.

The nasal formulation consists of a dry power containing 3 mg glucagon that is provided in a single-use, compact, and thus, portable, device. It’s been designed to be stored at room temperature and is ready to use immediately. Pressing the plunger on the device releases the fine powder that does not require inhalation to work, which means it can be given easily to an unconscious patient with severe hypoglycemia.

“The aim of the present study was to compare the efficacy and safety of commercially manufactured nasal glucagon with intramuscular glucagon for the treatment of insulin-induced hypoglycemia in adults with type 1 diabetes,” Dr. Plum-Mörschel said.

It was a randomized, single-dose, crossover study involving 70 adult patients with T1DM with hypoglycemia artificially induced by an intravenous insulin infusion during the two dosing visits. Five minutes after stopping insulin, nasal glucagon (3 mg) or intramuscular (1 mg) was given, with multiple plasma glucose measurements taken for up to 90 minutes.

The mean age of participants was 41.7 years old, 61% were male, the mean duration of diabetes was 19.8 years, with a baseline glycated hemoglobin (HbA_1c) of 7.3%.

As for safety, Dr. Plum-Mörschel noted that nasal glucagon had a safety profile that was acceptable for emergency treatment. There was no difference between the nasal or intramuscular glucagon treatment groups in the percentages of patients experiencing treatment-emergent adverse events (at least 5% frequency): nausea was seen in 22% and 29%, vomiting in 10% and 12%, and headache in 12% and 7%, respectively.

Asking patients who had been treated with nasal glucagon about specific symptoms related to nasal administration showed around 63% had watery eyes, 49% nasal itching, 39% nasal congestion, 37% a runny nose, 24% sneezing, 20% itchy eyes, and 12.9% itchy throat. “All of these events were transient, generally mild or moderate in nature, and none were serious. Indeed, there were no deaths in the study and no other serious AEs [adverse events] occurred.”

Dr. Plum-Mörschel concluded: “These results support nasal glucagon as a viable alternative to intramuscular glucagon for the treatment of severe hypoglycemia.

“I personally would expect that, due to its simplicity of use, nasal glucagon will create a greater community who can render quick aid in a rescue situation.”

The study was funded by Eli Lilly. Dr. Plum-Mörschel is an employee of Profil Mainz and has received travel grants and speaker honoraria from Eli Lilly and Novo Nordisk.
 

SOURCE: Suico J et al. EASD 2018, Abstract 150.

BERLIN – A dry-powder nasal formulation of glucagon was as good as intramuscular delivery for the reversal of severe hypoglycemia in patients with type 1 diabetes mellitus (T1DM) in a randomized controlled trial.

Sara Freeman/MDedge News

A 100% treatment success rate (n = 66) was seen for both nasal glucagon and intramuscular glucagon, defined as an increase in plasma glucose to 70 mg/dL (3.9 mmol/L or greater) or more or an increase of 20 mg/L (1.1 mmol/L) or more from the glucose nadir within 30 minutes of administration.

Furthermore, slightly more than 97% of patients achieved treatment success within 15 minutes in both treatment groups, with mean times of 11.4 minutes for the nasal formulation and 9.8 minutes for intramuscular administration.

Similar glucose responses were observed within 40 minutes of glucagon administration, study investigator Leona Plum-Mörschel, MD, PhD, reported at the annual meeting of the European Association for the Study of Diabetes. Dr. Plum-Mörschel is the CEO of the clinical research organization Profil Mainz (Germany), which helped Eli Lilly conduct the trial.

“We are all aware and fully agree that severe hypoglycemia is a serious and potentially life-threatening complication of diabetes treatment with insulin and the sulfonylureas,” said Dr. Plum-Mörschel. At least one in three patients with diabetes reports one hypoglycemic episode per year, she added. While this is quite prevalent in patients with T1DM, it’s not uncommon for those with type 2 diabetes mellitus (T2DM) to experience hypoglycemic episodes.

“Outside of a hospital or emergency room setting, injectable glucagon is currently the only option to treat severe hypoglycemia,” Dr. Plum-Mörschel reminded delegates. “Thankfully, the available injectable glucagon emergency kits are highly effective for the treatment of hypoglycemic events,” she added.

However, for untrained caregivers they can be “really challenging to use,” according to Dr. Plum-Mörschel. This is because the available kits involve multiple steps, including reconstitution, before being ready to inject. A severe hypoglycemic event is stressful enough without them worrying about getting things right, she suggested.

This is where a nasal formulation would be advantageous, and it is something that’s been touted to be on the horizon for a few years. Studies have previously shown that nasal glucagon is comparable to intramuscular glucagon in both adult and pediatric populations. Turning the formulation used in those studies into a commercial product however, has meant more clinical testing before being licensed by the regulatory authorities.

The nasal formulation consists of a dry power containing 3 mg glucagon that is provided in a single-use, compact, and thus, portable, device. It’s been designed to be stored at room temperature and is ready to use immediately. Pressing the plunger on the device releases the fine powder that does not require inhalation to work, which means it can be given easily to an unconscious patient with severe hypoglycemia.

“The aim of the present study was to compare the efficacy and safety of commercially manufactured nasal glucagon with intramuscular glucagon for the treatment of insulin-induced hypoglycemia in adults with type 1 diabetes,” Dr. Plum-Mörschel said.

It was a randomized, single-dose, crossover study involving 70 adult patients with T1DM with hypoglycemia artificially induced by an intravenous insulin infusion during the two dosing visits. Five minutes after stopping insulin, nasal glucagon (3 mg) or intramuscular (1 mg) was given, with multiple plasma glucose measurements taken for up to 90 minutes.

The mean age of participants was 41.7 years old, 61% were male, the mean duration of diabetes was 19.8 years, with a baseline glycated hemoglobin (HbA_1c) of 7.3%.

As for safety, Dr. Plum-Mörschel noted that nasal glucagon had a safety profile that was acceptable for emergency treatment. There was no difference between the nasal or intramuscular glucagon treatment groups in the percentages of patients experiencing treatment-emergent adverse events (at least 5% frequency): nausea was seen in 22% and 29%, vomiting in 10% and 12%, and headache in 12% and 7%, respectively.

Asking patients who had been treated with nasal glucagon about specific symptoms related to nasal administration showed around 63% had watery eyes, 49% nasal itching, 39% nasal congestion, 37% a runny nose, 24% sneezing, 20% itchy eyes, and 12.9% itchy throat. “All of these events were transient, generally mild or moderate in nature, and none were serious. Indeed, there were no deaths in the study and no other serious AEs [adverse events] occurred.”

Dr. Plum-Mörschel concluded: “These results support nasal glucagon as a viable alternative to intramuscular glucagon for the treatment of severe hypoglycemia.

“I personally would expect that, due to its simplicity of use, nasal glucagon will create a greater community who can render quick aid in a rescue situation.”

The study was funded by Eli Lilly. Dr. Plum-Mörschel is an employee of Profil Mainz and has received travel grants and speaker honoraria from Eli Lilly and Novo Nordisk.
 

SOURCE: Suico J et al. EASD 2018, Abstract 150.

SAN DIEGO – Dipeptidyl peptidase–4 (DPP-4) inhibitors appear to delay the progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), a new study has found. Researchers also found that all-cause long-term mortality dropped by an astonishing 78% in patients who took the drugs for an average of more than 3 years.

While the reasons for the impressive mortality results are a mystery, “these medications could have a beneficial effect on the kidneys, and it begins to show after 3 years,” said lead author Mariana Garcia-Touza, MD, of the Kansas City (Missouri) Department of Veterans Affairs Medical Center, in an interview. She presented the results at the meeting, sponsored by the American Society of Nephrology.

DPP-4 inhibitor drugs have been available for more than a decade in the United States. The medications, which include sitagliptin (Januvia) and linagliptin (Tradjenta), are used to treat patients with T2DM who are inadequately controlled by first-line treatments.

The drugs have critics. As UpToDate notes, they’re expensive and their effect on glucose levels is “modest.” In addition, UpToDate says, “some of the DPP-4 inhibitors have been associated with an increased risk of heart failure resulting in hospitalization.”

The authors of the new study sought to understand whether the drugs affect kidney function. As Dr. Garcia-Touza noted, metformin, which is processed in part by the kidneys, is considered harmful to certain patients with kidney disease. However, DPP-4 inhibitors are cleared through the liver. In fact, research has suggested the drugs may actually benefit the liver (Med Sci Monit. 2014 Sep 17;20:1662-7).

For the new study, researchers retrospectively analyzed 20,424 patients with T2DM in the VA system who took DPP-4 inhibitors (average age, 68 years) and compared them with a matched group of 52,118 patients with T2DM who didn’t take the drugs, tracking all patients for a mean of over 3 years.

T2DM control improved slightly in the DPP-4 group but remained worse than the non–DPP-4 group. However, “a significant reduction in progression of CKD was seen” in the DPP-4 group, she said.

The number of patients with creatinine levels above 1.5 mg/dL, 3 mg/dL, and 6 mg/dL was reduced by 7%, 41%, and 47%, respectively, in the DPP-4 group, compared with the other group (P less than .01). And the time to end-stage renal disease (creatinine above 6 mg/dL) was delayed by 144 days in the DPP-4 group (P less than .01).

All-cause mortality also fell by 78% in the DPP-4 group (P less than .0001). “Despite having worse glucose control [than the non–DPP-4 group], these patients have better overall mortality,” Dr. Garcia-Touza said.

The drugs may reduce the burden on the kidneys by decreasing inflammation, she said.

Could DPP-4 drugs be beneficial to patients with CKD even if they don’t have T2DM? Dr. Garcia-Touza wasn’t sure. However, she had a theory about why these kidney benefits didn’t show up in previous research. “My impression is that they didn’t go far enough [in time]. That was the main difference.”

Going forward, Dr. Garcia-Touza said her team plans to study the effects of the drugs on retinopathy and diabetic neuropathy.

The study was funded by the Midwest Biomedical Research Foundation and the VA. The study authors reported no relevant disclosures.
 

SOURCE: Garcia-Tourza M et al. Kidney Week 2018, Abstract TH-OR035.

SAN DIEGO – Dipeptidyl peptidase–4 (DPP-4) inhibitors appear to delay the progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), a new study has found. Researchers also found that all-cause long-term mortality dropped by an astonishing 78% in patients who took the drugs for an average of more than 3 years.

While the reasons for the impressive mortality results are a mystery, “these medications could have a beneficial effect on the kidneys, and it begins to show after 3 years,” said lead author Mariana Garcia-Touza, MD, of the Kansas City (Missouri) Department of Veterans Affairs Medical Center, in an interview. She presented the results at the meeting, sponsored by the American Society of Nephrology.

DPP-4 inhibitor drugs have been available for more than a decade in the United States. The medications, which include sitagliptin (Januvia) and linagliptin (Tradjenta), are used to treat patients with T2DM who are inadequately controlled by first-line treatments.

The drugs have critics. As UpToDate notes, they’re expensive and their effect on glucose levels is “modest.” In addition, UpToDate says, “some of the DPP-4 inhibitors have been associated with an increased risk of heart failure resulting in hospitalization.”

The authors of the new study sought to understand whether the drugs affect kidney function. As Dr. Garcia-Touza noted, metformin, which is processed in part by the kidneys, is considered harmful to certain patients with kidney disease. However, DPP-4 inhibitors are cleared through the liver. In fact, research has suggested the drugs may actually benefit the liver (Med Sci Monit. 2014 Sep 17;20:1662-7).

For the new study, researchers retrospectively analyzed 20,424 patients with T2DM in the VA system who took DPP-4 inhibitors (average age, 68 years) and compared them with a matched group of 52,118 patients with T2DM who didn’t take the drugs, tracking all patients for a mean of over 3 years.

T2DM control improved slightly in the DPP-4 group but remained worse than the non–DPP-4 group. However, “a significant reduction in progression of CKD was seen” in the DPP-4 group, she said.

The number of patients with creatinine levels above 1.5 mg/dL, 3 mg/dL, and 6 mg/dL was reduced by 7%, 41%, and 47%, respectively, in the DPP-4 group, compared with the other group (P less than .01). And the time to end-stage renal disease (creatinine above 6 mg/dL) was delayed by 144 days in the DPP-4 group (P less than .01).

All-cause mortality also fell by 78% in the DPP-4 group (P less than .0001). “Despite having worse glucose control [than the non–DPP-4 group], these patients have better overall mortality,” Dr. Garcia-Touza said.

The drugs may reduce the burden on the kidneys by decreasing inflammation, she said.

Could DPP-4 drugs be beneficial to patients with CKD even if they don’t have T2DM? Dr. Garcia-Touza wasn’t sure. However, she had a theory about why these kidney benefits didn’t show up in previous research. “My impression is that they didn’t go far enough [in time]. That was the main difference.”

Going forward, Dr. Garcia-Touza said her team plans to study the effects of the drugs on retinopathy and diabetic neuropathy.

The study was funded by the Midwest Biomedical Research Foundation and the VA. The study authors reported no relevant disclosures.
 

SOURCE: Garcia-Tourza M et al. Kidney Week 2018, Abstract TH-OR035.

SAN DIEGO – Dipeptidyl peptidase–4 (DPP-4) inhibitors appear to delay the progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), a new study has found. Researchers also found that all-cause long-term mortality dropped by an astonishing 78% in patients who took the drugs for an average of more than 3 years.

While the reasons for the impressive mortality results are a mystery, “these medications could have a beneficial effect on the kidneys, and it begins to show after 3 years,” said lead author Mariana Garcia-Touza, MD, of the Kansas City (Missouri) Department of Veterans Affairs Medical Center, in an interview. She presented the results at the meeting, sponsored by the American Society of Nephrology.

DPP-4 inhibitor drugs have been available for more than a decade in the United States. The medications, which include sitagliptin (Januvia) and linagliptin (Tradjenta), are used to treat patients with T2DM who are inadequately controlled by first-line treatments.

The drugs have critics. As UpToDate notes, they’re expensive and their effect on glucose levels is “modest.” In addition, UpToDate says, “some of the DPP-4 inhibitors have been associated with an increased risk of heart failure resulting in hospitalization.”

The authors of the new study sought to understand whether the drugs affect kidney function. As Dr. Garcia-Touza noted, metformin, which is processed in part by the kidneys, is considered harmful to certain patients with kidney disease. However, DPP-4 inhibitors are cleared through the liver. In fact, research has suggested the drugs may actually benefit the liver (Med Sci Monit. 2014 Sep 17;20:1662-7).

For the new study, researchers retrospectively analyzed 20,424 patients with T2DM in the VA system who took DPP-4 inhibitors (average age, 68 years) and compared them with a matched group of 52,118 patients with T2DM who didn’t take the drugs, tracking all patients for a mean of over 3 years.

T2DM control improved slightly in the DPP-4 group but remained worse than the non–DPP-4 group. However, “a significant reduction in progression of CKD was seen” in the DPP-4 group, she said.

The number of patients with creatinine levels above 1.5 mg/dL, 3 mg/dL, and 6 mg/dL was reduced by 7%, 41%, and 47%, respectively, in the DPP-4 group, compared with the other group (P less than .01). And the time to end-stage renal disease (creatinine above 6 mg/dL) was delayed by 144 days in the DPP-4 group (P less than .01).

All-cause mortality also fell by 78% in the DPP-4 group (P less than .0001). “Despite having worse glucose control [than the non–DPP-4 group], these patients have better overall mortality,” Dr. Garcia-Touza said.

The drugs may reduce the burden on the kidneys by decreasing inflammation, she said.

Could DPP-4 drugs be beneficial to patients with CKD even if they don’t have T2DM? Dr. Garcia-Touza wasn’t sure. However, she had a theory about why these kidney benefits didn’t show up in previous research. “My impression is that they didn’t go far enough [in time]. That was the main difference.”

Going forward, Dr. Garcia-Touza said her team plans to study the effects of the drugs on retinopathy and diabetic neuropathy.

The study was funded by the Midwest Biomedical Research Foundation and the VA. The study authors reported no relevant disclosures.
 

SOURCE: Garcia-Tourza M et al. Kidney Week 2018, Abstract TH-OR035.

BERLIN – Diabetic foot ulcers that were designated as difficult to treat were 58% more likely to heal when they were treated with LeucoPatch than using the best standard care alone in a randomized, controlled study.

With the LeucoPatch – which contained study participants’ own cells (platelets, fibrin, and leukocytes) – 34.1% of ulcers healed within 20 weeks versus 21.6% of ulcers that were treated using the best standard care (unadjusted odds ratio, 1.58; 95% confidence interval, 1.06-2.25; P = .02). Healing was defined as complete epithelialization maintained for 4 weeks, as confirmed by an observer blinded to the treatment group.

SOURCES: Game F et al. EASD 2018, Abstract 9.

BERLIN – Diabetic foot ulcers that were designated as difficult to treat were 58% more likely to heal when they were treated with LeucoPatch than using the best standard care alone in a randomized, controlled study.

With the LeucoPatch – which contained study participants’ own cells (platelets, fibrin, and leukocytes) – 34.1% of ulcers healed within 20 weeks versus 21.6% of ulcers that were treated using the best standard care (unadjusted odds ratio, 1.58; 95% confidence interval, 1.06-2.25; P = .02). Healing was defined as complete epithelialization maintained for 4 weeks, as confirmed by an observer blinded to the treatment group.

SOURCES: Game F et al. EASD 2018, Abstract 9.

BERLIN – Diabetic foot ulcers that were designated as difficult to treat were 58% more likely to heal when they were treated with LeucoPatch than using the best standard care alone in a randomized, controlled study.

With the LeucoPatch – which contained study participants’ own cells (platelets, fibrin, and leukocytes) – 34.1% of ulcers healed within 20 weeks versus 21.6% of ulcers that were treated using the best standard care (unadjusted odds ratio, 1.58; 95% confidence interval, 1.06-2.25; P = .02). Healing was defined as complete epithelialization maintained for 4 weeks, as confirmed by an observer blinded to the treatment group.

SOURCES: Game F et al. EASD 2018, Abstract 9.