ADA Annual Scientific Sessions 2014

SAN FRANCISCO – Veterans who participated in a lifestyle change program to reduce weight and increase exercise experienced a 17% lower total incidence of cardiovascular disease over 5 years, results from a large analysis demonstrated.

"Two-thirds of U.S. adults are overweight or obese, yet we know little about how to bring help to them," Sandra L. Jackson, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

Lifestyle change is a recommended strategy for prevention of cardiovascular disease, but the evidence of effect of lifestyle change programs on CVD "is mixed, and few studies have had sufficient sample size to study CVD incidence as compared to change in CVD risk factors. In addition, we know little about what lifestyle change programs can achieve in health care settings, where participants are patients and providers recommend a change in lifestyle."

For the current study, she and her associates used data from the U.S. Department of Veterans Affairs’ national weight management program, MOVE! The program has enrolled more than 400,000 veterans since 2005, making it the largest lifestyle change program in the United States. Implementation varies across VA facilities, but most use a standard 10-session core curriculum, with topics that include reading food labels, reducing fat intake, evaluating portion sizes, walking with a pedometer, and setting physical activity goals.

"The program is based on principles of motivational interviewing, so VA patients are encouraged to set their own goals for physical activity and weight loss, rather than follow a set program of prescribed goals," said Dr. Jackson, who conducted the study during her doctoral work in the Nutrition and Health Sciences Program at Emory University, Atlanta. "Nearly three-quarters of patients in the VA health system are overweight or obese and in theory, could benefit from MOVE!"

The researchers evaluated MOVE! participants with data from the National VA Informatics and Computing Infrastructure, which collects data from medical records, including demographics, outpatient visits, inpatient records, diagnoses, procedures, and prescriptions, and also features statistical tools. The study included 1,463,003 eligible patients who did not have CVD at baseline. Their mean age was 52 years, 89% were men, and their mean BMI was 33.6 kg/m². The average follow-up was about 5 years. Of the 1,463,003 patients, 169,248 were MOVE! participants and 1,293,755 were not.

Dr. Jackson reported that MOVE! participants who engaged in at least 8 sessions over 6 months lost about 2.5% of their body weight, and mostly sustained the loss over 3 years. The less active MOVE! participants lost a little over 0.5% of their body weight and maintained the loss over 3 years, while the eligible nonparticipants gained about 0.5% of body weight over the 3 years.

"Even with the substantial differences between the participant and nonparticipant groups, direct comparisons of the risk factors are hard to interpret," Dr. Jackson noted. For this reason, she and her associates used least-square means to compute averages, and adjusted for differences in baseline CVD risk factors, as well as differences in baseline BMI, age, gender, and race/ethnicity between the populations. They also stratified the analyses by diabetes status.

Systolic BP was a little lower among MOVE! participants than among nonparticipants, particularly at 6 and 12 months, "although the effect disappeared over 24 and 36 months," Dr. Jackson said. HDL cholesterol was a little higher among participants, compared with nonparticipants, while non-HDL cholesterol and plasma glucose levels were a little lower among participants, compared with nonparticipants.

Cox proportional hazards modeling revealed that there was a 17% lower incidence of CVD among participants, compared with nonparticipants (hazard ratio, 0.83). "When we looked separately at coronary artery disease, stroke, peripheral vascular disease, and heart failure, the effects remained significant," she said. These models were also adjusted for age, gender, BMI, smoking status, and a propensity score indicating likelihood of MOVE! participation, as well as other demographic and clinical characteristics.

A subgroup analysis revealed that the effect of MOVE! participation was stronger for men than for women (HR 0.83 vs. HR 0.93, respectively; P = .001).

"The VA population does have substantially fewer women than men, and women in the VA tend to be younger and may be at lower CVD risk than men," Dr. Jackson noted. "We also saw a stronger effect of participation among VA patients without diabetes, compared with those with diabetes, and we saw a stronger effect of participation among current smokers compared with nonsmokers."

Dr. Jackson said that she had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN FRANCISCO – Veterans who participated in a lifestyle change program to reduce weight and increase exercise experienced a 17% lower total incidence of cardiovascular disease over 5 years, results from a large analysis demonstrated.

"Two-thirds of U.S. adults are overweight or obese, yet we know little about how to bring help to them," Sandra L. Jackson, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

Lifestyle change is a recommended strategy for prevention of cardiovascular disease, but the evidence of effect of lifestyle change programs on CVD "is mixed, and few studies have had sufficient sample size to study CVD incidence as compared to change in CVD risk factors. In addition, we know little about what lifestyle change programs can achieve in health care settings, where participants are patients and providers recommend a change in lifestyle."

For the current study, she and her associates used data from the U.S. Department of Veterans Affairs’ national weight management program, MOVE! The program has enrolled more than 400,000 veterans since 2005, making it the largest lifestyle change program in the United States. Implementation varies across VA facilities, but most use a standard 10-session core curriculum, with topics that include reading food labels, reducing fat intake, evaluating portion sizes, walking with a pedometer, and setting physical activity goals.

"The program is based on principles of motivational interviewing, so VA patients are encouraged to set their own goals for physical activity and weight loss, rather than follow a set program of prescribed goals," said Dr. Jackson, who conducted the study during her doctoral work in the Nutrition and Health Sciences Program at Emory University, Atlanta. "Nearly three-quarters of patients in the VA health system are overweight or obese and in theory, could benefit from MOVE!"

The researchers evaluated MOVE! participants with data from the National VA Informatics and Computing Infrastructure, which collects data from medical records, including demographics, outpatient visits, inpatient records, diagnoses, procedures, and prescriptions, and also features statistical tools. The study included 1,463,003 eligible patients who did not have CVD at baseline. Their mean age was 52 years, 89% were men, and their mean BMI was 33.6 kg/m². The average follow-up was about 5 years. Of the 1,463,003 patients, 169,248 were MOVE! participants and 1,293,755 were not.

Dr. Jackson reported that MOVE! participants who engaged in at least 8 sessions over 6 months lost about 2.5% of their body weight, and mostly sustained the loss over 3 years. The less active MOVE! participants lost a little over 0.5% of their body weight and maintained the loss over 3 years, while the eligible nonparticipants gained about 0.5% of body weight over the 3 years.

"Even with the substantial differences between the participant and nonparticipant groups, direct comparisons of the risk factors are hard to interpret," Dr. Jackson noted. For this reason, she and her associates used least-square means to compute averages, and adjusted for differences in baseline CVD risk factors, as well as differences in baseline BMI, age, gender, and race/ethnicity between the populations. They also stratified the analyses by diabetes status.

Systolic BP was a little lower among MOVE! participants than among nonparticipants, particularly at 6 and 12 months, "although the effect disappeared over 24 and 36 months," Dr. Jackson said. HDL cholesterol was a little higher among participants, compared with nonparticipants, while non-HDL cholesterol and plasma glucose levels were a little lower among participants, compared with nonparticipants.

Cox proportional hazards modeling revealed that there was a 17% lower incidence of CVD among participants, compared with nonparticipants (hazard ratio, 0.83). "When we looked separately at coronary artery disease, stroke, peripheral vascular disease, and heart failure, the effects remained significant," she said. These models were also adjusted for age, gender, BMI, smoking status, and a propensity score indicating likelihood of MOVE! participation, as well as other demographic and clinical characteristics.

A subgroup analysis revealed that the effect of MOVE! participation was stronger for men than for women (HR 0.83 vs. HR 0.93, respectively; P = .001).

"The VA population does have substantially fewer women than men, and women in the VA tend to be younger and may be at lower CVD risk than men," Dr. Jackson noted. "We also saw a stronger effect of participation among VA patients without diabetes, compared with those with diabetes, and we saw a stronger effect of participation among current smokers compared with nonsmokers."

Dr. Jackson said that she had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN FRANCISCO – Veterans who participated in a lifestyle change program to reduce weight and increase exercise experienced a 17% lower total incidence of cardiovascular disease over 5 years, results from a large analysis demonstrated.

"Two-thirds of U.S. adults are overweight or obese, yet we know little about how to bring help to them," Sandra L. Jackson, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

Lifestyle change is a recommended strategy for prevention of cardiovascular disease, but the evidence of effect of lifestyle change programs on CVD "is mixed, and few studies have had sufficient sample size to study CVD incidence as compared to change in CVD risk factors. In addition, we know little about what lifestyle change programs can achieve in health care settings, where participants are patients and providers recommend a change in lifestyle."

For the current study, she and her associates used data from the U.S. Department of Veterans Affairs’ national weight management program, MOVE! The program has enrolled more than 400,000 veterans since 2005, making it the largest lifestyle change program in the United States. Implementation varies across VA facilities, but most use a standard 10-session core curriculum, with topics that include reading food labels, reducing fat intake, evaluating portion sizes, walking with a pedometer, and setting physical activity goals.

"The program is based on principles of motivational interviewing, so VA patients are encouraged to set their own goals for physical activity and weight loss, rather than follow a set program of prescribed goals," said Dr. Jackson, who conducted the study during her doctoral work in the Nutrition and Health Sciences Program at Emory University, Atlanta. "Nearly three-quarters of patients in the VA health system are overweight or obese and in theory, could benefit from MOVE!"

The researchers evaluated MOVE! participants with data from the National VA Informatics and Computing Infrastructure, which collects data from medical records, including demographics, outpatient visits, inpatient records, diagnoses, procedures, and prescriptions, and also features statistical tools. The study included 1,463,003 eligible patients who did not have CVD at baseline. Their mean age was 52 years, 89% were men, and their mean BMI was 33.6 kg/m². The average follow-up was about 5 years. Of the 1,463,003 patients, 169,248 were MOVE! participants and 1,293,755 were not.

Dr. Jackson reported that MOVE! participants who engaged in at least 8 sessions over 6 months lost about 2.5% of their body weight, and mostly sustained the loss over 3 years. The less active MOVE! participants lost a little over 0.5% of their body weight and maintained the loss over 3 years, while the eligible nonparticipants gained about 0.5% of body weight over the 3 years.

"Even with the substantial differences between the participant and nonparticipant groups, direct comparisons of the risk factors are hard to interpret," Dr. Jackson noted. For this reason, she and her associates used least-square means to compute averages, and adjusted for differences in baseline CVD risk factors, as well as differences in baseline BMI, age, gender, and race/ethnicity between the populations. They also stratified the analyses by diabetes status.

Systolic BP was a little lower among MOVE! participants than among nonparticipants, particularly at 6 and 12 months, "although the effect disappeared over 24 and 36 months," Dr. Jackson said. HDL cholesterol was a little higher among participants, compared with nonparticipants, while non-HDL cholesterol and plasma glucose levels were a little lower among participants, compared with nonparticipants.

Cox proportional hazards modeling revealed that there was a 17% lower incidence of CVD among participants, compared with nonparticipants (hazard ratio, 0.83). "When we looked separately at coronary artery disease, stroke, peripheral vascular disease, and heart failure, the effects remained significant," she said. These models were also adjusted for age, gender, BMI, smoking status, and a propensity score indicating likelihood of MOVE! participation, as well as other demographic and clinical characteristics.

A subgroup analysis revealed that the effect of MOVE! participation was stronger for men than for women (HR 0.83 vs. HR 0.93, respectively; P = .001).

"The VA population does have substantially fewer women than men, and women in the VA tend to be younger and may be at lower CVD risk than men," Dr. Jackson noted. "We also saw a stronger effect of participation among VA patients without diabetes, compared with those with diabetes, and we saw a stronger effect of participation among current smokers compared with nonsmokers."

Dr. Jackson said that she had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN FRANCISCO – Adults with diabetes who started insulin achieved similar levels of glycemic control within 6 months whether they were managed by primary care physicians or specialists, according to a post hoc analysis of data on 17,374 patients.

Primary care physicians had more face-to-face visits and phone contacts with patients and took more time to train patients on insulin use, compared with specialists, which may be why patients seen by primary care physicians had more insulin dose adjustments and were less likely to develop hypoglycemia, Dr. Louise Faerch reported at the annual scientific sessions of the American Diabetes Association.

The data were collected prior to starting insulin and at 12 and 24 weeks after insulin initiation in the 10-country observational SOLVE (Study of Once-Daily Levemir) study (Diabetes Obes. Metab. 2012;14:654-61), which primarily studied the timing of starting insulin.

Hemoglobin A_1c (HbA_1c) levels decreased by a mean of 1.3% in the 13,230 patients managed by specialists and by 1.2% in the 4,144 patients seen in primary care. Fasting blood glucose levels decreased by a mean of 3.1 mmol/L in the specialist group and by 2.9 mmol/L in the primary care group, reported Dr. Faerch of Novo Nordisk, Søborg, Denmark.

Patients seen by primary care providers were 25% less likely to have a hypoglycemic episode after starting insulin, compared with the specialist group, a difference that was significant, she said. The incidences of minor or severe hypoglycemia fell insignificantly in the primary care group, compared with before insulin initiation. In the specialist group, the incidence of minor hypoglycemia increased significantly and the incidence of severe hypoglycemia decreased significantly, compared with before insulin initiation.

The starting dose of insulin increased by 24 weeks in both groups but significantly more in the primary care group than in the specialist group, by a difference of 0.06 units/kg, after adjustment for the effects of confounding characteristics.

Patients in the primary care group lost a mean of 1.1 kg, compared with 0.4 kg in the specialist group, and had a 7% greater odds of losing at least 1 kg than did the specialist group, a significant difference.

Rates of office visits or phone contacts and the number of insulin dose changes were significantly higher in the primary care group at the 12- and 24-week follow-ups, she reported. The insulin dose was adjusted a mean of five times within 12 weeks and three times in the next 12 weeks in the primary care group, compared with three adjustments within 12 weeks and another two adjustments by 24 weeks in the specialist group.

Primary care physicians spent an average of approximately 18 minutes in training each patient on self-injection, 13 minutes on dose adjustments, and 22 minutes on other aspects of insulin treatment (such as diet and glucose monitoring), while specialists spent approximately 14 minutes on self-injection, 11 minutes on dose adjustment, and 16 minutes on other aspects of treatment.

Clinicians in the study were asked to follow the guidelines for diabetes treatment in their countries. Other than that, treatment choices were at the discretion of each physician, Dr. Faerch said.

Before starting insulin, patients in the primary care group were significantly older (64 years) than those in the specialist group (61 years); were heavier (88 kg vs. 79 kg, respectively); and were significantly more likely to have a history of macrovascular complications (30% vs. 26%), hypoglycemia (5.6% vs. 4.7%), and severe hypoglycemia (0.1 events vs. 0 events per person-year). Patients in the primary care group were more likely to be on just one oral antidiabetic drug (40%), compared with the specialist group (27%).

The study controlled for the effects of confounders including age, duration of diabetes, body mass index, history of hypoglycemia or macrovascular disease, number of oral antidiabetic drugs being taken at baseline, change in the number of oral antidiabetics used, time of insulin initiation, HbA_1c levels at baseline, and insulin dose.

Dr. Faerch works for Novo Nordisk, which funded the study and markets diabetes medications.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Adults with diabetes who started insulin achieved similar levels of glycemic control within 6 months whether they were managed by primary care physicians or specialists, according to a post hoc analysis of data on 17,374 patients.

Primary care physicians had more face-to-face visits and phone contacts with patients and took more time to train patients on insulin use, compared with specialists, which may be why patients seen by primary care physicians had more insulin dose adjustments and were less likely to develop hypoglycemia, Dr. Louise Faerch reported at the annual scientific sessions of the American Diabetes Association.

The data were collected prior to starting insulin and at 12 and 24 weeks after insulin initiation in the 10-country observational SOLVE (Study of Once-Daily Levemir) study (Diabetes Obes. Metab. 2012;14:654-61), which primarily studied the timing of starting insulin.

Hemoglobin A_1c (HbA_1c) levels decreased by a mean of 1.3% in the 13,230 patients managed by specialists and by 1.2% in the 4,144 patients seen in primary care. Fasting blood glucose levels decreased by a mean of 3.1 mmol/L in the specialist group and by 2.9 mmol/L in the primary care group, reported Dr. Faerch of Novo Nordisk, Søborg, Denmark.

Patients seen by primary care providers were 25% less likely to have a hypoglycemic episode after starting insulin, compared with the specialist group, a difference that was significant, she said. The incidences of minor or severe hypoglycemia fell insignificantly in the primary care group, compared with before insulin initiation. In the specialist group, the incidence of minor hypoglycemia increased significantly and the incidence of severe hypoglycemia decreased significantly, compared with before insulin initiation.

The starting dose of insulin increased by 24 weeks in both groups but significantly more in the primary care group than in the specialist group, by a difference of 0.06 units/kg, after adjustment for the effects of confounding characteristics.

Patients in the primary care group lost a mean of 1.1 kg, compared with 0.4 kg in the specialist group, and had a 7% greater odds of losing at least 1 kg than did the specialist group, a significant difference.

Rates of office visits or phone contacts and the number of insulin dose changes were significantly higher in the primary care group at the 12- and 24-week follow-ups, she reported. The insulin dose was adjusted a mean of five times within 12 weeks and three times in the next 12 weeks in the primary care group, compared with three adjustments within 12 weeks and another two adjustments by 24 weeks in the specialist group.

Primary care physicians spent an average of approximately 18 minutes in training each patient on self-injection, 13 minutes on dose adjustments, and 22 minutes on other aspects of insulin treatment (such as diet and glucose monitoring), while specialists spent approximately 14 minutes on self-injection, 11 minutes on dose adjustment, and 16 minutes on other aspects of treatment.

Clinicians in the study were asked to follow the guidelines for diabetes treatment in their countries. Other than that, treatment choices were at the discretion of each physician, Dr. Faerch said.

Before starting insulin, patients in the primary care group were significantly older (64 years) than those in the specialist group (61 years); were heavier (88 kg vs. 79 kg, respectively); and were significantly more likely to have a history of macrovascular complications (30% vs. 26%), hypoglycemia (5.6% vs. 4.7%), and severe hypoglycemia (0.1 events vs. 0 events per person-year). Patients in the primary care group were more likely to be on just one oral antidiabetic drug (40%), compared with the specialist group (27%).

The study controlled for the effects of confounders including age, duration of diabetes, body mass index, history of hypoglycemia or macrovascular disease, number of oral antidiabetic drugs being taken at baseline, change in the number of oral antidiabetics used, time of insulin initiation, HbA_1c levels at baseline, and insulin dose.

Dr. Faerch works for Novo Nordisk, which funded the study and markets diabetes medications.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Adults with diabetes who started insulin achieved similar levels of glycemic control within 6 months whether they were managed by primary care physicians or specialists, according to a post hoc analysis of data on 17,374 patients.

Primary care physicians had more face-to-face visits and phone contacts with patients and took more time to train patients on insulin use, compared with specialists, which may be why patients seen by primary care physicians had more insulin dose adjustments and were less likely to develop hypoglycemia, Dr. Louise Faerch reported at the annual scientific sessions of the American Diabetes Association.

The data were collected prior to starting insulin and at 12 and 24 weeks after insulin initiation in the 10-country observational SOLVE (Study of Once-Daily Levemir) study (Diabetes Obes. Metab. 2012;14:654-61), which primarily studied the timing of starting insulin.

Hemoglobin A_1c (HbA_1c) levels decreased by a mean of 1.3% in the 13,230 patients managed by specialists and by 1.2% in the 4,144 patients seen in primary care. Fasting blood glucose levels decreased by a mean of 3.1 mmol/L in the specialist group and by 2.9 mmol/L in the primary care group, reported Dr. Faerch of Novo Nordisk, Søborg, Denmark.

Patients seen by primary care providers were 25% less likely to have a hypoglycemic episode after starting insulin, compared with the specialist group, a difference that was significant, she said. The incidences of minor or severe hypoglycemia fell insignificantly in the primary care group, compared with before insulin initiation. In the specialist group, the incidence of minor hypoglycemia increased significantly and the incidence of severe hypoglycemia decreased significantly, compared with before insulin initiation.

The starting dose of insulin increased by 24 weeks in both groups but significantly more in the primary care group than in the specialist group, by a difference of 0.06 units/kg, after adjustment for the effects of confounding characteristics.

Patients in the primary care group lost a mean of 1.1 kg, compared with 0.4 kg in the specialist group, and had a 7% greater odds of losing at least 1 kg than did the specialist group, a significant difference.

Rates of office visits or phone contacts and the number of insulin dose changes were significantly higher in the primary care group at the 12- and 24-week follow-ups, she reported. The insulin dose was adjusted a mean of five times within 12 weeks and three times in the next 12 weeks in the primary care group, compared with three adjustments within 12 weeks and another two adjustments by 24 weeks in the specialist group.

Primary care physicians spent an average of approximately 18 minutes in training each patient on self-injection, 13 minutes on dose adjustments, and 22 minutes on other aspects of insulin treatment (such as diet and glucose monitoring), while specialists spent approximately 14 minutes on self-injection, 11 minutes on dose adjustment, and 16 minutes on other aspects of treatment.

Clinicians in the study were asked to follow the guidelines for diabetes treatment in their countries. Other than that, treatment choices were at the discretion of each physician, Dr. Faerch said.

Before starting insulin, patients in the primary care group were significantly older (64 years) than those in the specialist group (61 years); were heavier (88 kg vs. 79 kg, respectively); and were significantly more likely to have a history of macrovascular complications (30% vs. 26%), hypoglycemia (5.6% vs. 4.7%), and severe hypoglycemia (0.1 events vs. 0 events per person-year). Patients in the primary care group were more likely to be on just one oral antidiabetic drug (40%), compared with the specialist group (27%).

The study controlled for the effects of confounders including age, duration of diabetes, body mass index, history of hypoglycemia or macrovascular disease, number of oral antidiabetic drugs being taken at baseline, change in the number of oral antidiabetics used, time of insulin initiation, HbA_1c levels at baseline, and insulin dose.

Dr. Faerch works for Novo Nordisk, which funded the study and markets diabetes medications.

[email protected]

On Twitter @sherryboschert

Mobile app interventions for people with diabetes improved glycemic control in separate studies reported at the annual scientific sessions of the American Diabetes Association, San Francisco.

Interim results from a prospective randomized controlled study of 106 patients from a medically underserved Hispanic population with poorly controlled type 2 diabetes found that hemoglobin A_1c (HbA_1c) levels decreased by an average of a relative 12% after 6 months in those who used a text-messaging intervention called Dulce Digital on their mobile phones in addition to receiving usual care, compared with a 2% relative decrease in the control patients who received usual care alone.

Mean HbA_1c levels decreased from 9.4% at baseline in the Dulce Digital group to 8.4% after 3 months and at 6 months. In the control group, mean HbA_1c levels started at 9.5%, decreased to 9.2% at 3 months, and increased to 9.3% at 6 months. The differences between groups were statistically significant, nurse practitioner Maria Isabel Garcia reported.

Changes in other measures, including weight, blood pressure, or lipids, did not differ significantly between groups, said Ms. Garcia of Scripps Health, San Diego.

Patients in the Dulce Digital group who had no cell phone or had limited text-messaging service, received a phone with unlimited messaging. They then received two or three texts per day initially, with the frequency tapering over a 6-month period. Three kinds of texts were sent. Educational messages included a reminder to "Use small plates! Portions will look larger, and you may feel more satisfied after eating." Medication reminders might say, "Tick, tock. Take your medication at the same time every day!" Blood glucose prompts reminded patients, "Time to check your blood sugar! Text back your results."

Nurses monitored blood glucose responses and called the patient if they saw one reported value greater than 250 mg/L or less than 70 mg/dL, three values in the 181- to 250-mg/dL range within 1 month, or no texts back for 1 week.

"Ninety-one percent of the U.S. population already has a cell phone. So let’s use that as a way to circumvent these barriers to access to care," Ms. Garcia said. She and her associates are pursuing funding for further study of Dulce Digital with longer follow-up.

In a separate randomized, controlled French study of 190 adults with type 2 diabetes who were starting insulin, the Telediab2 software system loaded onto patients’ phones nearly doubled the likelihood that patients would achieve HbA_1c levels of less than 7% by 13 months (31%), compared with patients in a control group or a third group who used a simplified software intervention for only the first 4 months (19%), Dr. Sylvia Franc reported in a poster presentation.

The TeleDiab2 system provides automatic basal insulin titration based on blood glucose targets and rules devised by the treating physician, as well as automatic personalized coaching for blood glucose monitoring, diet, and physical activity based on pre- and postprandial blood glucose values. The app enables remote telemonitoring and short teleconsultations, said Dr. Franc of Sud-Francilien Hospital, Corbeil Essones, France.

Physicians initiated and titrated basal insulin at baseline. Patients in the control group then received face-to-face consultations every 3 months. The simplified intervention group received phone consultations through the app for the first 4 months (and had significantly improved HbA_1c levels, compared with the control group, in that period), then had face-to-face visits every 3 months. Patients in the Telediab2 group had no face-to-face visits; they had phone consultations every 2 weeks until month 4, then monthly phone consultations.

Mobile technology also impressed attendees at the meeting in four small studies showing progress in early attempts to develop an "artificial pancreas." In two 5-day crossover studies, 52 U.S. adults and adolescents with type 1 diabetes using a bionic insulin-glucagon pancreas achieved better glycemic control than did patients using insulin pump therapy (N. Engl. J. Med. 2014 June 15 [doi:10.1056/NEJMoa1314474]). The FlorenceD2 closed-loop insulin delivery system seemed to improve glucose control when used by patients at home in two small European randomized crossover studies.

Dr. Garcia and Dr. Franc reported having no financial disclosures. Lifescan, which sells glucose monitoring products, supported Dr. Garcia’s study.

[email protected]

On Twitter @SherryBoschert

Mobile app interventions for people with diabetes improved glycemic control in separate studies reported at the annual scientific sessions of the American Diabetes Association, San Francisco.

Interim results from a prospective randomized controlled study of 106 patients from a medically underserved Hispanic population with poorly controlled type 2 diabetes found that hemoglobin A_1c (HbA_1c) levels decreased by an average of a relative 12% after 6 months in those who used a text-messaging intervention called Dulce Digital on their mobile phones in addition to receiving usual care, compared with a 2% relative decrease in the control patients who received usual care alone.

Mean HbA_1c levels decreased from 9.4% at baseline in the Dulce Digital group to 8.4% after 3 months and at 6 months. In the control group, mean HbA_1c levels started at 9.5%, decreased to 9.2% at 3 months, and increased to 9.3% at 6 months. The differences between groups were statistically significant, nurse practitioner Maria Isabel Garcia reported.

Changes in other measures, including weight, blood pressure, or lipids, did not differ significantly between groups, said Ms. Garcia of Scripps Health, San Diego.

Patients in the Dulce Digital group who had no cell phone or had limited text-messaging service, received a phone with unlimited messaging. They then received two or three texts per day initially, with the frequency tapering over a 6-month period. Three kinds of texts were sent. Educational messages included a reminder to "Use small plates! Portions will look larger, and you may feel more satisfied after eating." Medication reminders might say, "Tick, tock. Take your medication at the same time every day!" Blood glucose prompts reminded patients, "Time to check your blood sugar! Text back your results."

Nurses monitored blood glucose responses and called the patient if they saw one reported value greater than 250 mg/L or less than 70 mg/dL, three values in the 181- to 250-mg/dL range within 1 month, or no texts back for 1 week.

"Ninety-one percent of the U.S. population already has a cell phone. So let’s use that as a way to circumvent these barriers to access to care," Ms. Garcia said. She and her associates are pursuing funding for further study of Dulce Digital with longer follow-up.

In a separate randomized, controlled French study of 190 adults with type 2 diabetes who were starting insulin, the Telediab2 software system loaded onto patients’ phones nearly doubled the likelihood that patients would achieve HbA_1c levels of less than 7% by 13 months (31%), compared with patients in a control group or a third group who used a simplified software intervention for only the first 4 months (19%), Dr. Sylvia Franc reported in a poster presentation.

The TeleDiab2 system provides automatic basal insulin titration based on blood glucose targets and rules devised by the treating physician, as well as automatic personalized coaching for blood glucose monitoring, diet, and physical activity based on pre- and postprandial blood glucose values. The app enables remote telemonitoring and short teleconsultations, said Dr. Franc of Sud-Francilien Hospital, Corbeil Essones, France.

Physicians initiated and titrated basal insulin at baseline. Patients in the control group then received face-to-face consultations every 3 months. The simplified intervention group received phone consultations through the app for the first 4 months (and had significantly improved HbA_1c levels, compared with the control group, in that period), then had face-to-face visits every 3 months. Patients in the Telediab2 group had no face-to-face visits; they had phone consultations every 2 weeks until month 4, then monthly phone consultations.

Mobile technology also impressed attendees at the meeting in four small studies showing progress in early attempts to develop an "artificial pancreas." In two 5-day crossover studies, 52 U.S. adults and adolescents with type 1 diabetes using a bionic insulin-glucagon pancreas achieved better glycemic control than did patients using insulin pump therapy (N. Engl. J. Med. 2014 June 15 [doi:10.1056/NEJMoa1314474]). The FlorenceD2 closed-loop insulin delivery system seemed to improve glucose control when used by patients at home in two small European randomized crossover studies.

Dr. Garcia and Dr. Franc reported having no financial disclosures. Lifescan, which sells glucose monitoring products, supported Dr. Garcia’s study.

[email protected]

On Twitter @SherryBoschert

Mobile app interventions for people with diabetes improved glycemic control in separate studies reported at the annual scientific sessions of the American Diabetes Association, San Francisco.

Interim results from a prospective randomized controlled study of 106 patients from a medically underserved Hispanic population with poorly controlled type 2 diabetes found that hemoglobin A_1c (HbA_1c) levels decreased by an average of a relative 12% after 6 months in those who used a text-messaging intervention called Dulce Digital on their mobile phones in addition to receiving usual care, compared with a 2% relative decrease in the control patients who received usual care alone.

Mean HbA_1c levels decreased from 9.4% at baseline in the Dulce Digital group to 8.4% after 3 months and at 6 months. In the control group, mean HbA_1c levels started at 9.5%, decreased to 9.2% at 3 months, and increased to 9.3% at 6 months. The differences between groups were statistically significant, nurse practitioner Maria Isabel Garcia reported.

Changes in other measures, including weight, blood pressure, or lipids, did not differ significantly between groups, said Ms. Garcia of Scripps Health, San Diego.

Patients in the Dulce Digital group who had no cell phone or had limited text-messaging service, received a phone with unlimited messaging. They then received two or three texts per day initially, with the frequency tapering over a 6-month period. Three kinds of texts were sent. Educational messages included a reminder to "Use small plates! Portions will look larger, and you may feel more satisfied after eating." Medication reminders might say, "Tick, tock. Take your medication at the same time every day!" Blood glucose prompts reminded patients, "Time to check your blood sugar! Text back your results."

Nurses monitored blood glucose responses and called the patient if they saw one reported value greater than 250 mg/L or less than 70 mg/dL, three values in the 181- to 250-mg/dL range within 1 month, or no texts back for 1 week.

"Ninety-one percent of the U.S. population already has a cell phone. So let’s use that as a way to circumvent these barriers to access to care," Ms. Garcia said. She and her associates are pursuing funding for further study of Dulce Digital with longer follow-up.

In a separate randomized, controlled French study of 190 adults with type 2 diabetes who were starting insulin, the Telediab2 software system loaded onto patients’ phones nearly doubled the likelihood that patients would achieve HbA_1c levels of less than 7% by 13 months (31%), compared with patients in a control group or a third group who used a simplified software intervention for only the first 4 months (19%), Dr. Sylvia Franc reported in a poster presentation.

The TeleDiab2 system provides automatic basal insulin titration based on blood glucose targets and rules devised by the treating physician, as well as automatic personalized coaching for blood glucose monitoring, diet, and physical activity based on pre- and postprandial blood glucose values. The app enables remote telemonitoring and short teleconsultations, said Dr. Franc of Sud-Francilien Hospital, Corbeil Essones, France.

Physicians initiated and titrated basal insulin at baseline. Patients in the control group then received face-to-face consultations every 3 months. The simplified intervention group received phone consultations through the app for the first 4 months (and had significantly improved HbA_1c levels, compared with the control group, in that period), then had face-to-face visits every 3 months. Patients in the Telediab2 group had no face-to-face visits; they had phone consultations every 2 weeks until month 4, then monthly phone consultations.

Mobile technology also impressed attendees at the meeting in four small studies showing progress in early attempts to develop an "artificial pancreas." In two 5-day crossover studies, 52 U.S. adults and adolescents with type 1 diabetes using a bionic insulin-glucagon pancreas achieved better glycemic control than did patients using insulin pump therapy (N. Engl. J. Med. 2014 June 15 [doi:10.1056/NEJMoa1314474]). The FlorenceD2 closed-loop insulin delivery system seemed to improve glucose control when used by patients at home in two small European randomized crossover studies.

Dr. Garcia and Dr. Franc reported having no financial disclosures. Lifescan, which sells glucose monitoring products, supported Dr. Garcia’s study.

[email protected]

On Twitter @SherryBoschert

SAN FRANCISCO – Among patients with type 1 diabetes, the ratio of total cholesterol to high-density lipoprotein cholesterol may be a better marker of cardiovascular disease, compared with elevated low-density lipoprotein cholesterol, observational data from a Swedish registry suggest.

"High LDL cholesterol is considered an important risk factor in the general population and in type 2 diabetes," Dr. Christel Hero said at the annual scientific sessions of the American Diabetes Association. "Subgroup and meta-analyses show a reduced risk for CVD with statin treatment in type 1 diabetes, but there is a lack of larger studies in type 1 diabetes concerning treatment of hyperlipidemia."

The aim of the current study was to assess LDL and total cholesterol to HDL cholesterol ratios as predictors of CVD in type 1 diabetes, and to evaluate the risk for CVD at different levels of LDL. To accomplish this, the researchers used different Swedish registries to link patients with type 1 diabetes, including the Swedish National Diabetes Registry, which contains data on more than 96% of individuals with the disease in that country. They also used the hospital discharge register, "from which we can get information about all hospital stays, including medical interventions and discharge diagnosis," said Dr. Hero of Sahlgrenska University Hospital in Gothenburg, Sweden. Reports of death were obtained from Sweden’s cause of death register.

The study population included 30,778 patients with type 1 diabetes who were between the ages of 18 and 79 years. Baseline data were collected during 2003-2006 and the patients were followed until 2011, or until the first event, which resulted in a mean follow-up of 7 years. Outcome events were fatal or nonfatal CVD, which encompassed acute myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft surgery, stroke, and peripheral vascular disease.

The patients were divided into two groups: those on lipid medication (8,172) and those not taking lipid medication (22,608). The researchers formed two subgroups: one from the patients on lipid medication with a history of CVD at baseline (1,973) and one from the overall study population that comprised patients 40 years of age or older who had one CVD risk factor at baseline (9,324).

The researchers used Cox regression analyses with LDL and total cholesterol to HDL ratio as predictors of outcomes, adjusted for CVD risk factors including diabetes duration, body mass index, systolic blood pressure, smoking, and use of antihypertensive and lipid medication.

At baseline, the mean age of patients was 46 years and their mean duration of diabetes was 20 years. Compared with the patients not taking lipid medication, those taking lipid medication were older (56 vs. 43 years, respectively), had longer diabetes duration (26 vs. 19 years), were more commonly treated with hypertensive medication (70% vs. 25%), and had a lower mean estimated glomerular filtration rate (75 vs. 87 mL/min per 1.73 m²), as well as a higher risk of CVD (24% vs. 4%).

Baseline lipid values were similar between the two main groups: a mean LDL of 106 mg/dL and a mean ratio of cholesterol to HDL of 3.2 units.

Dr. Hero reported that there were 13.8 CVD events per 1,000 person-years among patients taking lipid-lowering medications, compared with 51.7 events per 1,000 years among those who were not taking lipid medications. The researchers also found that 67.9% of patients with a history of CVD had a CVD event over 7 years of follow-up.

The adjusted hazard ratios per 1 mmol/L increase in LDL for CVD was 1.02 in those taking lipid medications and 1.08 in those who were not. Both hazard ratios were nonsignificant. A similar association was observed in patients aged 40 years and older who had one CVD risk factor at baseline. In this subgroup "there is a slight but weak significance for the LDL as a predictor of cardiovascular disease, but when looking at the octiles [of LDL] you can see no significance at all," Dr. Hero noted.

The adjusted hazard ratios per 1 mmol/L increase in the cholesterol to HDL ratio were 1.06 in those taking lipid medications and 1.08 in those who were not, both statistically significant differences. "There is a strong correlation between CVD and the cholesterol to HDL ratio as a continuous variable; also, when we look at the ratio divided into octiles, we can see an obvious correlation with a linear trend," Dr. Hero said. "The higher the ratio, the stronger the correlation. The same is true for the patients 40 years and older with one CVD risk factor. There is a strong correlation for the ratio as a continuous variable and also a linear trend for the octiles of the ratio."

The findings suggest "there is no support for an LDL treatment target of 100 mg/dL," Dr. Hero concluded. "The ratio of cholesterol to HDL is a significant predictor of CVD in patients without lipid-lowering medication. The ratio of cholesterol to HDL seems to be a more reliable marker for CVD risk when considering primary prevention."

Dr. Hero said that she had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN FRANCISCO – Among patients with type 1 diabetes, the ratio of total cholesterol to high-density lipoprotein cholesterol may be a better marker of cardiovascular disease, compared with elevated low-density lipoprotein cholesterol, observational data from a Swedish registry suggest.

"High LDL cholesterol is considered an important risk factor in the general population and in type 2 diabetes," Dr. Christel Hero said at the annual scientific sessions of the American Diabetes Association. "Subgroup and meta-analyses show a reduced risk for CVD with statin treatment in type 1 diabetes, but there is a lack of larger studies in type 1 diabetes concerning treatment of hyperlipidemia."

The aim of the current study was to assess LDL and total cholesterol to HDL cholesterol ratios as predictors of CVD in type 1 diabetes, and to evaluate the risk for CVD at different levels of LDL. To accomplish this, the researchers used different Swedish registries to link patients with type 1 diabetes, including the Swedish National Diabetes Registry, which contains data on more than 96% of individuals with the disease in that country. They also used the hospital discharge register, "from which we can get information about all hospital stays, including medical interventions and discharge diagnosis," said Dr. Hero of Sahlgrenska University Hospital in Gothenburg, Sweden. Reports of death were obtained from Sweden’s cause of death register.

The study population included 30,778 patients with type 1 diabetes who were between the ages of 18 and 79 years. Baseline data were collected during 2003-2006 and the patients were followed until 2011, or until the first event, which resulted in a mean follow-up of 7 years. Outcome events were fatal or nonfatal CVD, which encompassed acute myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft surgery, stroke, and peripheral vascular disease.

The patients were divided into two groups: those on lipid medication (8,172) and those not taking lipid medication (22,608). The researchers formed two subgroups: one from the patients on lipid medication with a history of CVD at baseline (1,973) and one from the overall study population that comprised patients 40 years of age or older who had one CVD risk factor at baseline (9,324).

The researchers used Cox regression analyses with LDL and total cholesterol to HDL ratio as predictors of outcomes, adjusted for CVD risk factors including diabetes duration, body mass index, systolic blood pressure, smoking, and use of antihypertensive and lipid medication.

At baseline, the mean age of patients was 46 years and their mean duration of diabetes was 20 years. Compared with the patients not taking lipid medication, those taking lipid medication were older (56 vs. 43 years, respectively), had longer diabetes duration (26 vs. 19 years), were more commonly treated with hypertensive medication (70% vs. 25%), and had a lower mean estimated glomerular filtration rate (75 vs. 87 mL/min per 1.73 m²), as well as a higher risk of CVD (24% vs. 4%).

Baseline lipid values were similar between the two main groups: a mean LDL of 106 mg/dL and a mean ratio of cholesterol to HDL of 3.2 units.

Dr. Hero reported that there were 13.8 CVD events per 1,000 person-years among patients taking lipid-lowering medications, compared with 51.7 events per 1,000 years among those who were not taking lipid medications. The researchers also found that 67.9% of patients with a history of CVD had a CVD event over 7 years of follow-up.

The adjusted hazard ratios per 1 mmol/L increase in LDL for CVD was 1.02 in those taking lipid medications and 1.08 in those who were not. Both hazard ratios were nonsignificant. A similar association was observed in patients aged 40 years and older who had one CVD risk factor at baseline. In this subgroup "there is a slight but weak significance for the LDL as a predictor of cardiovascular disease, but when looking at the octiles [of LDL] you can see no significance at all," Dr. Hero noted.

The adjusted hazard ratios per 1 mmol/L increase in the cholesterol to HDL ratio were 1.06 in those taking lipid medications and 1.08 in those who were not, both statistically significant differences. "There is a strong correlation between CVD and the cholesterol to HDL ratio as a continuous variable; also, when we look at the ratio divided into octiles, we can see an obvious correlation with a linear trend," Dr. Hero said. "The higher the ratio, the stronger the correlation. The same is true for the patients 40 years and older with one CVD risk factor. There is a strong correlation for the ratio as a continuous variable and also a linear trend for the octiles of the ratio."

The findings suggest "there is no support for an LDL treatment target of 100 mg/dL," Dr. Hero concluded. "The ratio of cholesterol to HDL is a significant predictor of CVD in patients without lipid-lowering medication. The ratio of cholesterol to HDL seems to be a more reliable marker for CVD risk when considering primary prevention."

Dr. Hero said that she had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN FRANCISCO – Among patients with type 1 diabetes, the ratio of total cholesterol to high-density lipoprotein cholesterol may be a better marker of cardiovascular disease, compared with elevated low-density lipoprotein cholesterol, observational data from a Swedish registry suggest.

"High LDL cholesterol is considered an important risk factor in the general population and in type 2 diabetes," Dr. Christel Hero said at the annual scientific sessions of the American Diabetes Association. "Subgroup and meta-analyses show a reduced risk for CVD with statin treatment in type 1 diabetes, but there is a lack of larger studies in type 1 diabetes concerning treatment of hyperlipidemia."

The aim of the current study was to assess LDL and total cholesterol to HDL cholesterol ratios as predictors of CVD in type 1 diabetes, and to evaluate the risk for CVD at different levels of LDL. To accomplish this, the researchers used different Swedish registries to link patients with type 1 diabetes, including the Swedish National Diabetes Registry, which contains data on more than 96% of individuals with the disease in that country. They also used the hospital discharge register, "from which we can get information about all hospital stays, including medical interventions and discharge diagnosis," said Dr. Hero of Sahlgrenska University Hospital in Gothenburg, Sweden. Reports of death were obtained from Sweden’s cause of death register.

The study population included 30,778 patients with type 1 diabetes who were between the ages of 18 and 79 years. Baseline data were collected during 2003-2006 and the patients were followed until 2011, or until the first event, which resulted in a mean follow-up of 7 years. Outcome events were fatal or nonfatal CVD, which encompassed acute myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft surgery, stroke, and peripheral vascular disease.

The patients were divided into two groups: those on lipid medication (8,172) and those not taking lipid medication (22,608). The researchers formed two subgroups: one from the patients on lipid medication with a history of CVD at baseline (1,973) and one from the overall study population that comprised patients 40 years of age or older who had one CVD risk factor at baseline (9,324).

The researchers used Cox regression analyses with LDL and total cholesterol to HDL ratio as predictors of outcomes, adjusted for CVD risk factors including diabetes duration, body mass index, systolic blood pressure, smoking, and use of antihypertensive and lipid medication.

At baseline, the mean age of patients was 46 years and their mean duration of diabetes was 20 years. Compared with the patients not taking lipid medication, those taking lipid medication were older (56 vs. 43 years, respectively), had longer diabetes duration (26 vs. 19 years), were more commonly treated with hypertensive medication (70% vs. 25%), and had a lower mean estimated glomerular filtration rate (75 vs. 87 mL/min per 1.73 m²), as well as a higher risk of CVD (24% vs. 4%).

Baseline lipid values were similar between the two main groups: a mean LDL of 106 mg/dL and a mean ratio of cholesterol to HDL of 3.2 units.

Dr. Hero reported that there were 13.8 CVD events per 1,000 person-years among patients taking lipid-lowering medications, compared with 51.7 events per 1,000 years among those who were not taking lipid medications. The researchers also found that 67.9% of patients with a history of CVD had a CVD event over 7 years of follow-up.

The adjusted hazard ratios per 1 mmol/L increase in LDL for CVD was 1.02 in those taking lipid medications and 1.08 in those who were not. Both hazard ratios were nonsignificant. A similar association was observed in patients aged 40 years and older who had one CVD risk factor at baseline. In this subgroup "there is a slight but weak significance for the LDL as a predictor of cardiovascular disease, but when looking at the octiles [of LDL] you can see no significance at all," Dr. Hero noted.

The adjusted hazard ratios per 1 mmol/L increase in the cholesterol to HDL ratio were 1.06 in those taking lipid medications and 1.08 in those who were not, both statistically significant differences. "There is a strong correlation between CVD and the cholesterol to HDL ratio as a continuous variable; also, when we look at the ratio divided into octiles, we can see an obvious correlation with a linear trend," Dr. Hero said. "The higher the ratio, the stronger the correlation. The same is true for the patients 40 years and older with one CVD risk factor. There is a strong correlation for the ratio as a continuous variable and also a linear trend for the octiles of the ratio."

The findings suggest "there is no support for an LDL treatment target of 100 mg/dL," Dr. Hero concluded. "The ratio of cholesterol to HDL is a significant predictor of CVD in patients without lipid-lowering medication. The ratio of cholesterol to HDL seems to be a more reliable marker for CVD risk when considering primary prevention."

Dr. Hero said that she had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN FRANCISCO – Among patients with type 1 diabetes, the ratio of total cholesterol to high-density lipoprotein cholesterol may be a better marker of cardiovascular disease, compared with elevated low-density lipoprotein cholesterol, observational data from a Swedish registry suggest.

"High LDL cholesterol is considered an important risk factor in the general population and in type 2 diabetes," Dr. Christel Hero said at the annual scientific sessions of the American Diabetes Association. "Subgroup and meta-analyses show a reduced risk for CVD with statin treatment in type 1 diabetes, but there is a lack of larger studies in type 1 diabetes concerning treatment of hyperlipidemia."

The aim of the current study was to assess LDL and total cholesterol to HDL cholesterol ratios as predictors of CVD in type 1 diabetes, and to evaluate the risk for CVD at different levels of LDL. To accomplish this, the researchers used different Swedish registries to link patients with type 1 diabetes, including the Swedish National Diabetes Registry, which contains data on more than 96% of individuals with the disease in that country. They also used the hospital discharge register, "from which we can get information about all hospital stays, including medical interventions and discharge diagnosis," said Dr. Hero of Sahlgrenska University Hospital in Gothenburg, Sweden. Reports of death were obtained from Sweden’s cause of death register.

The study population included 30,778 patients with type 1 diabetes who were between the ages of 18 and 79 years. Baseline data were collected during 2003-2006 and the patients were followed until 2011, or until the first event, which resulted in a mean follow-up of 7 years. Outcome events were fatal or nonfatal CVD, which encompassed acute myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft surgery, stroke, and peripheral vascular disease.

The patients were divided into two groups: those on lipid medication (8,172) and those not taking lipid medication (22,608). The researchers formed two subgroups: one from the patients on lipid medication with a history of CVD at baseline (1,973) and one from the overall study population that comprised patients 40 years of age or older who had one CVD risk factor at baseline (9,324).

The researchers used Cox regression analyses with LDL and total cholesterol to HDL ratio as predictors of outcomes, adjusted for CVD risk factors including diabetes duration, body mass index, systolic blood pressure, smoking, and use of antihypertensive and lipid medication.

At baseline, the mean age of patients was 46 years and their mean duration of diabetes was 20 years. Compared with the patients not taking lipid medication, those taking lipid medication were older (56 vs. 43 years, respectively), had longer diabetes duration (26 vs. 19 years), were more commonly treated with hypertensive medication (70% vs. 25%), and had a lower mean estimated glomerular filtration rate (75 vs. 87 mL/min per 1.73 m²), as well as a higher risk of CVD (24% vs. 4%).

Baseline lipid values were similar between the two main groups: a mean LDL of 106 mg/dL and a mean ratio of cholesterol to HDL of 3.2 units.

Dr. Hero reported that there were 13.8 CVD events per 1,000 person-years among patients taking lipid-lowering medications, compared with 51.7 events per 1,000 years among those who were not taking lipid medications. The researchers also found that 67.9% of patients with a history of CVD had a CVD event over 7 years of follow-up.

The adjusted hazard ratios per 1 mmol/L increase in LDL for CVD was 1.02 in those taking lipid medications and 1.08 in those who were not. Both hazard ratios were nonsignificant. A similar association was observed in patients aged 40 years and older who had one CVD risk factor at baseline. In this subgroup "there is a slight but weak significance for the LDL as a predictor of cardiovascular disease, but when looking at the octiles [of LDL] you can see no significance at all," Dr. Hero noted.

The adjusted hazard ratios per 1 mmol/L increase in the cholesterol to HDL ratio were 1.06 in those taking lipid medications and 1.08 in those who were not, both statistically significant differences. "There is a strong correlation between CVD and the cholesterol to HDL ratio as a continuous variable; also, when we look at the ratio divided into octiles, we can see an obvious correlation with a linear trend," Dr. Hero said. "The higher the ratio, the stronger the correlation. The same is true for the patients 40 years and older with one CVD risk factor. There is a strong correlation for the ratio as a continuous variable and also a linear trend for the octiles of the ratio."

The findings suggest "there is no support for an LDL treatment target of 100 mg/dL," Dr. Hero concluded. "The ratio of cholesterol to HDL is a significant predictor of CVD in patients without lipid-lowering medication. The ratio of cholesterol to HDL seems to be a more reliable marker for CVD risk when considering primary prevention."

Dr. Hero said that she had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN FRANCISCO – Among patients with type 1 diabetes, the ratio of total cholesterol to high-density lipoprotein cholesterol may be a better marker of cardiovascular disease, compared with elevated low-density lipoprotein cholesterol, observational data from a Swedish registry suggest.

"High LDL cholesterol is considered an important risk factor in the general population and in type 2 diabetes," Dr. Christel Hero said at the annual scientific sessions of the American Diabetes Association. "Subgroup and meta-analyses show a reduced risk for CVD with statin treatment in type 1 diabetes, but there is a lack of larger studies in type 1 diabetes concerning treatment of hyperlipidemia."

The aim of the current study was to assess LDL and total cholesterol to HDL cholesterol ratios as predictors of CVD in type 1 diabetes, and to evaluate the risk for CVD at different levels of LDL. To accomplish this, the researchers used different Swedish registries to link patients with type 1 diabetes, including the Swedish National Diabetes Registry, which contains data on more than 96% of individuals with the disease in that country. They also used the hospital discharge register, "from which we can get information about all hospital stays, including medical interventions and discharge diagnosis," said Dr. Hero of Sahlgrenska University Hospital in Gothenburg, Sweden. Reports of death were obtained from Sweden’s cause of death register.

The study population included 30,778 patients with type 1 diabetes who were between the ages of 18 and 79 years. Baseline data were collected during 2003-2006 and the patients were followed until 2011, or until the first event, which resulted in a mean follow-up of 7 years. Outcome events were fatal or nonfatal CVD, which encompassed acute myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft surgery, stroke, and peripheral vascular disease.

The patients were divided into two groups: those on lipid medication (8,172) and those not taking lipid medication (22,608). The researchers formed two subgroups: one from the patients on lipid medication with a history of CVD at baseline (1,973) and one from the overall study population that comprised patients 40 years of age or older who had one CVD risk factor at baseline (9,324).

The researchers used Cox regression analyses with LDL and total cholesterol to HDL ratio as predictors of outcomes, adjusted for CVD risk factors including diabetes duration, body mass index, systolic blood pressure, smoking, and use of antihypertensive and lipid medication.

At baseline, the mean age of patients was 46 years and their mean duration of diabetes was 20 years. Compared with the patients not taking lipid medication, those taking lipid medication were older (56 vs. 43 years, respectively), had longer diabetes duration (26 vs. 19 years), were more commonly treated with hypertensive medication (70% vs. 25%), and had a lower mean estimated glomerular filtration rate (75 vs. 87 mL/min per 1.73 m²), as well as a higher risk of CVD (24% vs. 4%).

Baseline lipid values were similar between the two main groups: a mean LDL of 106 mg/dL and a mean ratio of cholesterol to HDL of 3.2 units.

Dr. Hero reported that there were 13.8 CVD events per 1,000 person-years among patients taking lipid-lowering medications, compared with 51.7 events per 1,000 years among those who were not taking lipid medications. The researchers also found that 67.9% of patients with a history of CVD had a CVD event over 7 years of follow-up.

The adjusted hazard ratios per 1 mmol/L increase in LDL for CVD was 1.02 in those taking lipid medications and 1.08 in those who were not. Both hazard ratios were nonsignificant. A similar association was observed in patients aged 40 years and older who had one CVD risk factor at baseline. In this subgroup "there is a slight but weak significance for the LDL as a predictor of cardiovascular disease, but when looking at the octiles [of LDL] you can see no significance at all," Dr. Hero noted.

The adjusted hazard ratios per 1 mmol/L increase in the cholesterol to HDL ratio were 1.06 in those taking lipid medications and 1.08 in those who were not, both statistically significant differences. "There is a strong correlation between CVD and the cholesterol to HDL ratio as a continuous variable; also, when we look at the ratio divided into octiles, we can see an obvious correlation with a linear trend," Dr. Hero said. "The higher the ratio, the stronger the correlation. The same is true for the patients 40 years and older with one CVD risk factor. There is a strong correlation for the ratio as a continuous variable and also a linear trend for the octiles of the ratio."

The findings suggest "there is no support for an LDL treatment target of 100 mg/dL," Dr. Hero concluded. "The ratio of cholesterol to HDL is a significant predictor of CVD in patients without lipid-lowering medication. The ratio of cholesterol to HDL seems to be a more reliable marker for CVD risk when considering primary prevention."

Dr. Hero said that she had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN FRANCISCO – Among patients with type 1 diabetes, the ratio of total cholesterol to high-density lipoprotein cholesterol may be a better marker of cardiovascular disease, compared with elevated low-density lipoprotein cholesterol, observational data from a Swedish registry suggest.

"High LDL cholesterol is considered an important risk factor in the general population and in type 2 diabetes," Dr. Christel Hero said at the annual scientific sessions of the American Diabetes Association. "Subgroup and meta-analyses show a reduced risk for CVD with statin treatment in type 1 diabetes, but there is a lack of larger studies in type 1 diabetes concerning treatment of hyperlipidemia."

The aim of the current study was to assess LDL and total cholesterol to HDL cholesterol ratios as predictors of CVD in type 1 diabetes, and to evaluate the risk for CVD at different levels of LDL. To accomplish this, the researchers used different Swedish registries to link patients with type 1 diabetes, including the Swedish National Diabetes Registry, which contains data on more than 96% of individuals with the disease in that country. They also used the hospital discharge register, "from which we can get information about all hospital stays, including medical interventions and discharge diagnosis," said Dr. Hero of Sahlgrenska University Hospital in Gothenburg, Sweden. Reports of death were obtained from Sweden’s cause of death register.

The study population included 30,778 patients with type 1 diabetes who were between the ages of 18 and 79 years. Baseline data were collected during 2003-2006 and the patients were followed until 2011, or until the first event, which resulted in a mean follow-up of 7 years. Outcome events were fatal or nonfatal CVD, which encompassed acute myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft surgery, stroke, and peripheral vascular disease.

The patients were divided into two groups: those on lipid medication (8,172) and those not taking lipid medication (22,608). The researchers formed two subgroups: one from the patients on lipid medication with a history of CVD at baseline (1,973) and one from the overall study population that comprised patients 40 years of age or older who had one CVD risk factor at baseline (9,324).

The researchers used Cox regression analyses with LDL and total cholesterol to HDL ratio as predictors of outcomes, adjusted for CVD risk factors including diabetes duration, body mass index, systolic blood pressure, smoking, and use of antihypertensive and lipid medication.

At baseline, the mean age of patients was 46 years and their mean duration of diabetes was 20 years. Compared with the patients not taking lipid medication, those taking lipid medication were older (56 vs. 43 years, respectively), had longer diabetes duration (26 vs. 19 years), were more commonly treated with hypertensive medication (70% vs. 25%), and had a lower mean estimated glomerular filtration rate (75 vs. 87 mL/min per 1.73 m²), as well as a higher risk of CVD (24% vs. 4%).

Baseline lipid values were similar between the two main groups: a mean LDL of 106 mg/dL and a mean ratio of cholesterol to HDL of 3.2 units.

Dr. Hero reported that there were 13.8 CVD events per 1,000 person-years among patients taking lipid-lowering medications, compared with 51.7 events per 1,000 years among those who were not taking lipid medications. The researchers also found that 67.9% of patients with a history of CVD had a CVD event over 7 years of follow-up.

The adjusted hazard ratios per 1 mmol/L increase in LDL for CVD was 1.02 in those taking lipid medications and 1.08 in those who were not. Both hazard ratios were nonsignificant. A similar association was observed in patients aged 40 years and older who had one CVD risk factor at baseline. In this subgroup "there is a slight but weak significance for the LDL as a predictor of cardiovascular disease, but when looking at the octiles [of LDL] you can see no significance at all," Dr. Hero noted.

The adjusted hazard ratios per 1 mmol/L increase in the cholesterol to HDL ratio were 1.06 in those taking lipid medications and 1.08 in those who were not, both statistically significant differences. "There is a strong correlation between CVD and the cholesterol to HDL ratio as a continuous variable; also, when we look at the ratio divided into octiles, we can see an obvious correlation with a linear trend," Dr. Hero said. "The higher the ratio, the stronger the correlation. The same is true for the patients 40 years and older with one CVD risk factor. There is a strong correlation for the ratio as a continuous variable and also a linear trend for the octiles of the ratio."

The findings suggest "there is no support for an LDL treatment target of 100 mg/dL," Dr. Hero concluded. "The ratio of cholesterol to HDL is a significant predictor of CVD in patients without lipid-lowering medication. The ratio of cholesterol to HDL seems to be a more reliable marker for CVD risk when considering primary prevention."

Dr. Hero said that she had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN FRANCISCO – The American Diabetes Association has unified the pediatric hemoglobin A_1c target values to less than 7.5% for all pediatric age groups, moving away from breaking down glycemic control targets by age. This will also harmonize the HbA_1c goals with those of international groups such as the International Society of Pediatric and Adolescent Diabetes (ISPAD).

The change is part of a new position statement released on June 16 during the annual scientific sessions of the American Diabetes Association (Diabetes Care 2014;37:2034-54). The document also for the first time brings together recommendations for care of individuals with type 1 diabetes across all age groups.

In a video interview, Dr. Lori M.B. Laffel, one of the statement’s coauthors and chief of the pediatric, adolescent, and young adult section at Joslin Diabetes Center, Boston, explains the rationale behind this decision. Dr. David Maahs of the University of Colorado, Aurora, discusses the potential concern regarding the risk of hypoglycemia.

[email protected]

On Twitter @naseemmiller

SAN FRANCISCO – The American Diabetes Association has unified the pediatric hemoglobin A_1c target values to less than 7.5% for all pediatric age groups, moving away from breaking down glycemic control targets by age. This will also harmonize the HbA_1c goals with those of international groups such as the International Society of Pediatric and Adolescent Diabetes (ISPAD).

The change is part of a new position statement released on June 16 during the annual scientific sessions of the American Diabetes Association (Diabetes Care 2014;37:2034-54). The document also for the first time brings together recommendations for care of individuals with type 1 diabetes across all age groups.

In a video interview, Dr. Lori M.B. Laffel, one of the statement’s coauthors and chief of the pediatric, adolescent, and young adult section at Joslin Diabetes Center, Boston, explains the rationale behind this decision. Dr. David Maahs of the University of Colorado, Aurora, discusses the potential concern regarding the risk of hypoglycemia.

[email protected]

On Twitter @naseemmiller

SAN FRANCISCO – The American Diabetes Association has unified the pediatric hemoglobin A_1c target values to less than 7.5% for all pediatric age groups, moving away from breaking down glycemic control targets by age. This will also harmonize the HbA_1c goals with those of international groups such as the International Society of Pediatric and Adolescent Diabetes (ISPAD).

The change is part of a new position statement released on June 16 during the annual scientific sessions of the American Diabetes Association (Diabetes Care 2014;37:2034-54). The document also for the first time brings together recommendations for care of individuals with type 1 diabetes across all age groups.

In a video interview, Dr. Lori M.B. Laffel, one of the statement’s coauthors and chief of the pediatric, adolescent, and young adult section at Joslin Diabetes Center, Boston, explains the rationale behind this decision. Dr. David Maahs of the University of Colorado, Aurora, discusses the potential concern regarding the risk of hypoglycemia.

[email protected]

On Twitter @naseemmiller

SAN FRANCISCO – The American Diabetes Association has unified the pediatric hemoglobin A_1c target values to less than 7.5% for all pediatric age groups, moving away from breaking down glycemic control targets by age. This will also harmonize the HbA_1c goals with those of international groups such as the International Society of Pediatric and Adolescent Diabetes (ISPAD).

The change is part of a new position statement released on June 16 during the annual scientific sessions of the American Diabetes Association (Diabetes Care 2014;37:2034-54). The document also for the first time brings together recommendations for care of individuals with type 1 diabetes across all age groups.

In a video interview, Dr. Lori M.B. Laffel, one of the statement’s coauthors and chief of the pediatric, adolescent, and young adult section at Joslin Diabetes Center, Boston, explains the rationale behind this decision. Dr. David Maahs of the University of Colorado, Aurora, discusses the potential concern regarding the risk of hypoglycemia.

[email protected]

On Twitter @naseemmiller

SAN FRANCISCO – The American Diabetes Association has unified the pediatric hemoglobin A_1c target values to less than 7.5% for all pediatric age groups, moving away from breaking down glycemic control targets by age. This will also harmonize the HbA_1c goals with those of international groups such as the International Society of Pediatric and Adolescent Diabetes (ISPAD).

The change is part of a new position statement released on June 16 during the annual scientific sessions of the American Diabetes Association (Diabetes Care 2014;37:2034-54). The document also for the first time brings together recommendations for care of individuals with type 1 diabetes across all age groups.

In a video interview, Dr. Lori M.B. Laffel, one of the statement’s coauthors and chief of the pediatric, adolescent, and young adult section at Joslin Diabetes Center, Boston, explains the rationale behind this decision. Dr. David Maahs of the University of Colorado, Aurora, discusses the potential concern regarding the risk of hypoglycemia.

[email protected]

On Twitter @naseemmiller

SAN FRANCISCO – The American Diabetes Association has unified the pediatric hemoglobin A_1c target values to less than 7.5% for all pediatric age groups, moving away from breaking down glycemic control targets by age. This will also harmonize the HbA_1c goals with those of international groups such as the International Society of Pediatric and Adolescent Diabetes (ISPAD).

The change is part of a new position statement released on June 16 during the annual scientific sessions of the American Diabetes Association (Diabetes Care 2014;37:2034-54). The document also for the first time brings together recommendations for care of individuals with type 1 diabetes across all age groups.

In a video interview, Dr. Lori M.B. Laffel, one of the statement’s coauthors and chief of the pediatric, adolescent, and young adult section at Joslin Diabetes Center, Boston, explains the rationale behind this decision. Dr. David Maahs of the University of Colorado, Aurora, discusses the potential concern regarding the risk of hypoglycemia.

[email protected]

On Twitter @naseemmiller

SAN FRANCISCO – The developing adolescent brain may be responding differently to sugary drinks, leading to higher consumption of sugars and feeding the childhood obesity epidemic, according to researchers.

The findings come from a small, preliminary study that compared cerebral blood flow in 14 lean adolescents and 20 lean adults brains after the study subjects ingested 75 g of glucose.

Functional MRI scans revealed that glucose ingestion increased cerebral blood flow in the reward and executive function areas of the teens’ brains.

"This study is the first step in understanding what is occurring in the developing adolescent brain in response to drinking sugar," said Dr. Ania M. Jastreboff of Yale University, New Haven, Conn.

Several areas of the brain regulate food intake. They include the hypothalamus; the striatal region, which includes the putamen and caudate and is in charge of motivation and reward; the limbic region, where emotion and memory reside; and the cortical region, which includes the prefrontal cortex, insula, and the anterior cingulate cortex and handles the integration and processing of the brain.

In a previous study, Dr. Jastreboff and colleagues showed that "obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food" (Diabetes Care 2013;36:394-402).

The group also has shown that glucose ingestion in lean adults reduced cerebral blood flow in appetite-regulation and reward-processing regions of the brain, Dr. Jastreboff said at the annual scientific sessions of the American Diabetes Association.

Subsequently, they wanted to find out if lean adolescent brains, compared with brains of lean adults, responded differently to glucose.

Among the subjects, the average body mass index was 22 kg/m², and the mean age was 16 years for adolescents and 31 years for adults.

They came in at 8 a.m. after overnight fasting. They had a baseline MRI, drank 75 g of glucose, and had a functional MRI scan. Their labs were drawn every 10 minutes throughout the 1-hour scanning procedures.

Results showed that in lean adolescents, glucose ingestion increased cerebral blood flow in the striatum, insula, anterior cingulate cortex and the prefrontal cortex, all of which are regions of the brain that reside in the corticostriatal-limbic circuitry undergoing significant developmental changes during adolescence, said Dr. Jastreboff. There were no changes in hypothalamus and thalamus blood flow.

In contrast, consumption of the sugary drink in lean adults decreased cerebral blood flow in the hypothalamus, thalamus, striatum, insula, and the anterior cingulate cortex. There was no change in the prefrontal cortex.

"We hypothesize that these striking differences in brain response to glucose ingestion might contribute to adolescents’ higher consumption of added sugars," said Dr. Jastreboff.

She said that her group also conducted the study in obese adolescents and the results should be published soon. "What I can say is that the responses were different," she said.

The findings are far from definitive.

"I’m always skeptical that any test, if repeated the next day, will show the same thing," said Dr. Silva Arslanian, professor of pediatrics at the University of Pittsburgh. "The question is, is it an innate difference, or is it an environmental-driven difference?"

"But it’s definitely new data that needs to be pursued further to see what its translation is," said Dr. Arslanian, who was not involved in the study.

Dr. Jastreboff and Dr. Arslanian had no relevant disclosures.

[email protected]

On Twitter @naseemmiller

SAN FRANCISCO – The developing adolescent brain may be responding differently to sugary drinks, leading to higher consumption of sugars and feeding the childhood obesity epidemic, according to researchers.

The findings come from a small, preliminary study that compared cerebral blood flow in 14 lean adolescents and 20 lean adults brains after the study subjects ingested 75 g of glucose.

Functional MRI scans revealed that glucose ingestion increased cerebral blood flow in the reward and executive function areas of the teens’ brains.

"This study is the first step in understanding what is occurring in the developing adolescent brain in response to drinking sugar," said Dr. Ania M. Jastreboff of Yale University, New Haven, Conn.

Several areas of the brain regulate food intake. They include the hypothalamus; the striatal region, which includes the putamen and caudate and is in charge of motivation and reward; the limbic region, where emotion and memory reside; and the cortical region, which includes the prefrontal cortex, insula, and the anterior cingulate cortex and handles the integration and processing of the brain.

In a previous study, Dr. Jastreboff and colleagues showed that "obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food" (Diabetes Care 2013;36:394-402).

The group also has shown that glucose ingestion in lean adults reduced cerebral blood flow in appetite-regulation and reward-processing regions of the brain, Dr. Jastreboff said at the annual scientific sessions of the American Diabetes Association.

Subsequently, they wanted to find out if lean adolescent brains, compared with brains of lean adults, responded differently to glucose.

Among the subjects, the average body mass index was 22 kg/m², and the mean age was 16 years for adolescents and 31 years for adults.

They came in at 8 a.m. after overnight fasting. They had a baseline MRI, drank 75 g of glucose, and had a functional MRI scan. Their labs were drawn every 10 minutes throughout the 1-hour scanning procedures.

Results showed that in lean adolescents, glucose ingestion increased cerebral blood flow in the striatum, insula, anterior cingulate cortex and the prefrontal cortex, all of which are regions of the brain that reside in the corticostriatal-limbic circuitry undergoing significant developmental changes during adolescence, said Dr. Jastreboff. There were no changes in hypothalamus and thalamus blood flow.

In contrast, consumption of the sugary drink in lean adults decreased cerebral blood flow in the hypothalamus, thalamus, striatum, insula, and the anterior cingulate cortex. There was no change in the prefrontal cortex.

"We hypothesize that these striking differences in brain response to glucose ingestion might contribute to adolescents’ higher consumption of added sugars," said Dr. Jastreboff.

She said that her group also conducted the study in obese adolescents and the results should be published soon. "What I can say is that the responses were different," she said.

The findings are far from definitive.

"I’m always skeptical that any test, if repeated the next day, will show the same thing," said Dr. Silva Arslanian, professor of pediatrics at the University of Pittsburgh. "The question is, is it an innate difference, or is it an environmental-driven difference?"

"But it’s definitely new data that needs to be pursued further to see what its translation is," said Dr. Arslanian, who was not involved in the study.

Dr. Jastreboff and Dr. Arslanian had no relevant disclosures.

[email protected]

On Twitter @naseemmiller

SAN FRANCISCO – The developing adolescent brain may be responding differently to sugary drinks, leading to higher consumption of sugars and feeding the childhood obesity epidemic, according to researchers.

The findings come from a small, preliminary study that compared cerebral blood flow in 14 lean adolescents and 20 lean adults brains after the study subjects ingested 75 g of glucose.

Functional MRI scans revealed that glucose ingestion increased cerebral blood flow in the reward and executive function areas of the teens’ brains.

"This study is the first step in understanding what is occurring in the developing adolescent brain in response to drinking sugar," said Dr. Ania M. Jastreboff of Yale University, New Haven, Conn.

Several areas of the brain regulate food intake. They include the hypothalamus; the striatal region, which includes the putamen and caudate and is in charge of motivation and reward; the limbic region, where emotion and memory reside; and the cortical region, which includes the prefrontal cortex, insula, and the anterior cingulate cortex and handles the integration and processing of the brain.

In a previous study, Dr. Jastreboff and colleagues showed that "obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food" (Diabetes Care 2013;36:394-402).

The group also has shown that glucose ingestion in lean adults reduced cerebral blood flow in appetite-regulation and reward-processing regions of the brain, Dr. Jastreboff said at the annual scientific sessions of the American Diabetes Association.

Subsequently, they wanted to find out if lean adolescent brains, compared with brains of lean adults, responded differently to glucose.

Among the subjects, the average body mass index was 22 kg/m², and the mean age was 16 years for adolescents and 31 years for adults.

They came in at 8 a.m. after overnight fasting. They had a baseline MRI, drank 75 g of glucose, and had a functional MRI scan. Their labs were drawn every 10 minutes throughout the 1-hour scanning procedures.

Results showed that in lean adolescents, glucose ingestion increased cerebral blood flow in the striatum, insula, anterior cingulate cortex and the prefrontal cortex, all of which are regions of the brain that reside in the corticostriatal-limbic circuitry undergoing significant developmental changes during adolescence, said Dr. Jastreboff. There were no changes in hypothalamus and thalamus blood flow.

In contrast, consumption of the sugary drink in lean adults decreased cerebral blood flow in the hypothalamus, thalamus, striatum, insula, and the anterior cingulate cortex. There was no change in the prefrontal cortex.

"We hypothesize that these striking differences in brain response to glucose ingestion might contribute to adolescents’ higher consumption of added sugars," said Dr. Jastreboff.

She said that her group also conducted the study in obese adolescents and the results should be published soon. "What I can say is that the responses were different," she said.

The findings are far from definitive.

"I’m always skeptical that any test, if repeated the next day, will show the same thing," said Dr. Silva Arslanian, professor of pediatrics at the University of Pittsburgh. "The question is, is it an innate difference, or is it an environmental-driven difference?"

"But it’s definitely new data that needs to be pursued further to see what its translation is," said Dr. Arslanian, who was not involved in the study.

Dr. Jastreboff and Dr. Arslanian had no relevant disclosures.

[email protected]

On Twitter @naseemmiller

SAN FRANCISCO – Unsupervised home use of a closed-loop insulin delivery system by patients with type 1 diabetes proved to be feasible and acceptable to patients and seemed to improve glucose control in two small prospective, randomized crossover studies.

The results move development of a potential artificial pancreas one step forward, though much work remains before one ever becomes commercially available.

Courtesy Dr. Lalantha Leelarathna

Both of the multicenter European studies of insulin-dependent adults with type 1 diabetes – one with 24 participants and the other with 17 participants – compared the same experimental closed-loop insulin delivery system (the FlorenceD2 system) with a control treatment that used sensor-augmented insulin pump therapy.

Courtesy Dr. Lalantha Leelarathna

In one study of overnight use, patients using the closed-loop system spent a mean of 53% of nights (midnight to 7 a.m.) with their glucose levels in the target range of 3.9-8.0 mmol/L (70-144 mg/dL), compared with 39% of nights while on the control therapy, a significant difference. In the other study of both day and night use, glucose levels were in the target ranges (3.9-10 mmol/L during the day or 3.9-8 mmol/L at night) for 73% of days and 48% of nights on the closed-loop system, significantly longer than with the control treatment (65% and 35%, respectively).

Investigators reported the findings in separate presentations at the annual scientific sessions of the American Diabetes Association.

The 24-patient night-use study randomized patients to the intervention or control therapy for 4 weeks, then had them switch to the other therapy for 4 weeks. Before taking the closed-loop system home, patients spent one night at a clinical research center for training and to assess their competency to use the automated system.

The proportion of nighttime with hyperglycemia (glucose levels above the 144 mg/dL upper limit of the target range) was significantly lower while on the closed-loop system (44%) than on the control therapy (57%), reported Dr. Hood Thabit of the University of Cambridge (England) and his associates. The proportion of nighttime with hypoglycemia did not differ significantly between groups.

Mean overnight glucose levels were significantly lower while on the closed-loop system (148 mg/dL) than on the control therapy (162 mg/dL), as were mean 24-hour glucose levels (157 mg/dL vs. 167 mg/dL, respectively), the intention-to-treat analysis showed.

Two episodes of severe hypoglycemia occurred while on the closed-loop system, one due to user error and the other for unknown reasons. Both patients made a full recovery, Dr. Thabit said.

The closed-loop system was interrupted unintentionally an average of once every 5 nights, which one physician in the audience called "very impressive."

The separate day-and-night study of 17 adults randomized them to 8 days of either therapy followed by a 1- to 3-week washout period and then 8 days on the other therapy. Again, patients received a day of training at a research facility before using the closed-loop system at home.

During the 7 days of home use with the closed-loop system, patients spent significantly less time in hyperglycemia (levels above 10 mmol/L), compared with the control therapy (21% vs. 30% of the time, respectively), reported Dr. Lalantha Leelarathna, also of the University of Cambridge. Time spent in hypoglycemia did not differ significantly between groups.

Mean glucose levels were significantly lower while patients were on the closed-loop system (8.1 mmol/L) than on the sensor-augmented pump (8.8 mmol/L), he said.

The closed-loop system was interrupted unintentionally every 12 hours on average, mainly because the pump was not connected, the continuous glucose monitor was unavailable, or the user changed pump settings. Two severe hypoglycemic episodes occurred, one during use of the closed-loop system and one during the crossover period. Both patients recovered fully. Four episodes of high glucose because of failure of the insulin infusion set did not lead to ketosis or hospitalization.

"We need to improve portability and connectivity between devices," Dr. Leelarathna said.

The Artificial Pancreas at Home (AP@home) consortium next will test the system in a 3-monthy study of day-and-night use by 30 adults with type 1 diabetes, compared with optimized sensor-augmented pump therapy, Dr. Leelarathna said.

Previous studies conducted exclusively in clinical research facilities have shown that closed-loop insulin delivery systems can improve glucose control, but these are among the first studies to show that they may do the same when used by patients at home.

Dr. Leelarathna and Dr. Thabit reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Unsupervised home use of a closed-loop insulin delivery system by patients with type 1 diabetes proved to be feasible and acceptable to patients and seemed to improve glucose control in two small prospective, randomized crossover studies.

The results move development of a potential artificial pancreas one step forward, though much work remains before one ever becomes commercially available.

Courtesy Dr. Lalantha Leelarathna

Both of the multicenter European studies of insulin-dependent adults with type 1 diabetes – one with 24 participants and the other with 17 participants – compared the same experimental closed-loop insulin delivery system (the FlorenceD2 system) with a control treatment that used sensor-augmented insulin pump therapy.

Courtesy Dr. Lalantha Leelarathna

In one study of overnight use, patients using the closed-loop system spent a mean of 53% of nights (midnight to 7 a.m.) with their glucose levels in the target range of 3.9-8.0 mmol/L (70-144 mg/dL), compared with 39% of nights while on the control therapy, a significant difference. In the other study of both day and night use, glucose levels were in the target ranges (3.9-10 mmol/L during the day or 3.9-8 mmol/L at night) for 73% of days and 48% of nights on the closed-loop system, significantly longer than with the control treatment (65% and 35%, respectively).

Investigators reported the findings in separate presentations at the annual scientific sessions of the American Diabetes Association.

The 24-patient night-use study randomized patients to the intervention or control therapy for 4 weeks, then had them switch to the other therapy for 4 weeks. Before taking the closed-loop system home, patients spent one night at a clinical research center for training and to assess their competency to use the automated system.

The proportion of nighttime with hyperglycemia (glucose levels above the 144 mg/dL upper limit of the target range) was significantly lower while on the closed-loop system (44%) than on the control therapy (57%), reported Dr. Hood Thabit of the University of Cambridge (England) and his associates. The proportion of nighttime with hypoglycemia did not differ significantly between groups.

Mean overnight glucose levels were significantly lower while on the closed-loop system (148 mg/dL) than on the control therapy (162 mg/dL), as were mean 24-hour glucose levels (157 mg/dL vs. 167 mg/dL, respectively), the intention-to-treat analysis showed.

Two episodes of severe hypoglycemia occurred while on the closed-loop system, one due to user error and the other for unknown reasons. Both patients made a full recovery, Dr. Thabit said.

The closed-loop system was interrupted unintentionally an average of once every 5 nights, which one physician in the audience called "very impressive."

The separate day-and-night study of 17 adults randomized them to 8 days of either therapy followed by a 1- to 3-week washout period and then 8 days on the other therapy. Again, patients received a day of training at a research facility before using the closed-loop system at home.

During the 7 days of home use with the closed-loop system, patients spent significantly less time in hyperglycemia (levels above 10 mmol/L), compared with the control therapy (21% vs. 30% of the time, respectively), reported Dr. Lalantha Leelarathna, also of the University of Cambridge. Time spent in hypoglycemia did not differ significantly between groups.

Mean glucose levels were significantly lower while patients were on the closed-loop system (8.1 mmol/L) than on the sensor-augmented pump (8.8 mmol/L), he said.

The closed-loop system was interrupted unintentionally every 12 hours on average, mainly because the pump was not connected, the continuous glucose monitor was unavailable, or the user changed pump settings. Two severe hypoglycemic episodes occurred, one during use of the closed-loop system and one during the crossover period. Both patients recovered fully. Four episodes of high glucose because of failure of the insulin infusion set did not lead to ketosis or hospitalization.

"We need to improve portability and connectivity between devices," Dr. Leelarathna said.

The Artificial Pancreas at Home (AP@home) consortium next will test the system in a 3-monthy study of day-and-night use by 30 adults with type 1 diabetes, compared with optimized sensor-augmented pump therapy, Dr. Leelarathna said.

Previous studies conducted exclusively in clinical research facilities have shown that closed-loop insulin delivery systems can improve glucose control, but these are among the first studies to show that they may do the same when used by patients at home.

Dr. Leelarathna and Dr. Thabit reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Unsupervised home use of a closed-loop insulin delivery system by patients with type 1 diabetes proved to be feasible and acceptable to patients and seemed to improve glucose control in two small prospective, randomized crossover studies.

The results move development of a potential artificial pancreas one step forward, though much work remains before one ever becomes commercially available.

Courtesy Dr. Lalantha Leelarathna

Both of the multicenter European studies of insulin-dependent adults with type 1 diabetes – one with 24 participants and the other with 17 participants – compared the same experimental closed-loop insulin delivery system (the FlorenceD2 system) with a control treatment that used sensor-augmented insulin pump therapy.

Courtesy Dr. Lalantha Leelarathna

In one study of overnight use, patients using the closed-loop system spent a mean of 53% of nights (midnight to 7 a.m.) with their glucose levels in the target range of 3.9-8.0 mmol/L (70-144 mg/dL), compared with 39% of nights while on the control therapy, a significant difference. In the other study of both day and night use, glucose levels were in the target ranges (3.9-10 mmol/L during the day or 3.9-8 mmol/L at night) for 73% of days and 48% of nights on the closed-loop system, significantly longer than with the control treatment (65% and 35%, respectively).

Investigators reported the findings in separate presentations at the annual scientific sessions of the American Diabetes Association.

The 24-patient night-use study randomized patients to the intervention or control therapy for 4 weeks, then had them switch to the other therapy for 4 weeks. Before taking the closed-loop system home, patients spent one night at a clinical research center for training and to assess their competency to use the automated system.

The proportion of nighttime with hyperglycemia (glucose levels above the 144 mg/dL upper limit of the target range) was significantly lower while on the closed-loop system (44%) than on the control therapy (57%), reported Dr. Hood Thabit of the University of Cambridge (England) and his associates. The proportion of nighttime with hypoglycemia did not differ significantly between groups.

Mean overnight glucose levels were significantly lower while on the closed-loop system (148 mg/dL) than on the control therapy (162 mg/dL), as were mean 24-hour glucose levels (157 mg/dL vs. 167 mg/dL, respectively), the intention-to-treat analysis showed.

Two episodes of severe hypoglycemia occurred while on the closed-loop system, one due to user error and the other for unknown reasons. Both patients made a full recovery, Dr. Thabit said.

The closed-loop system was interrupted unintentionally an average of once every 5 nights, which one physician in the audience called "very impressive."

The separate day-and-night study of 17 adults randomized them to 8 days of either therapy followed by a 1- to 3-week washout period and then 8 days on the other therapy. Again, patients received a day of training at a research facility before using the closed-loop system at home.

During the 7 days of home use with the closed-loop system, patients spent significantly less time in hyperglycemia (levels above 10 mmol/L), compared with the control therapy (21% vs. 30% of the time, respectively), reported Dr. Lalantha Leelarathna, also of the University of Cambridge. Time spent in hypoglycemia did not differ significantly between groups.

Mean glucose levels were significantly lower while patients were on the closed-loop system (8.1 mmol/L) than on the sensor-augmented pump (8.8 mmol/L), he said.

The closed-loop system was interrupted unintentionally every 12 hours on average, mainly because the pump was not connected, the continuous glucose monitor was unavailable, or the user changed pump settings. Two severe hypoglycemic episodes occurred, one during use of the closed-loop system and one during the crossover period. Both patients recovered fully. Four episodes of high glucose because of failure of the insulin infusion set did not lead to ketosis or hospitalization.

"We need to improve portability and connectivity between devices," Dr. Leelarathna said.

The Artificial Pancreas at Home (AP@home) consortium next will test the system in a 3-monthy study of day-and-night use by 30 adults with type 1 diabetes, compared with optimized sensor-augmented pump therapy, Dr. Leelarathna said.

Previous studies conducted exclusively in clinical research facilities have shown that closed-loop insulin delivery systems can improve glucose control, but these are among the first studies to show that they may do the same when used by patients at home.

Dr. Leelarathna and Dr. Thabit reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Glycemic control has remained stable for an average of 15 years after initial randomization for patients in the Diabetes Prevention Program.

No significant differences in early microvascular complications were seen among interventions on intention to treat analysis, although intensive lifestyle intervention was effective in reducing microvascular complications in women.

Those are two key findings from an analysis of long-term outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS), which were presented at the annual scientific sessions of the American Diabetes Association.

Doug Brunk/Frontline Medical News

DPPOS is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial of intensive lifestyle and metformin, compared with placebo for the prevention of diabetes. Launched in 1996, the trial took place at 27 centers in the United States and was designed to determine whether the development of diabetes could be prevented or delayed in high-risk patients. A total of 3,234 patients were randomized to either an intensive lifestyle intervention to reduce their weight by 7% through a low-fat diet and increased physical activity, or standard advice on diet and exercise plus metformin, or standard advice on diet and exercise plus placebo.

The DPP ended 1 year ahead of schedule after an average of 3 years of study. The lifestyle intervention program, which had accomplished its goal of 7% weight loss at 1 year, and then maintained about a 5% weight loss over the remaining time of the study, resulted in a 58% reduction in diabetes. The metformin group reduced diabetes development by 31%.

"To put these reductions in perspective, approximately 11% per year of participants in the placebo group developed diabetes," Dr. David M. Nathan, chair of the DPP and DPPOS and professor of medicine at Harvard Medical School, Boston, said during a press briefing. "That was reduced to about 8%/year in the metformin group, and less than 5%/year in the lifestyle group."

The DPP results were "widely heralded and reported," Dr. Nathan continued, "but they only covered a very brief period: Three years in what is in fact a life-long disease or risk state." DPPOS was designed to examine "whether the diabetes development that we demonstrated was delayed over a brief period of time, would continue to be delayed or prevented over a longer period of time."

Of the original 3,234 DPP participants, 2,776 (86%) continued in DPPOS. Their average age at the first visit was 56 years and 68% were women. Their average age is now 67 years and 31% have developed diabetes since enrollment in DPP.

The annual diabetes incidence rates among the original DPP placebo and metformin groups have declined to approximately equal the rate in the lifestyle group, "which have remained remarkably stable, at approximately 5% per year over time," said Dr. William C. Knowler, chief of diabetes epidemiology and clinical research at the National Institute of Diabetes and Digestive and Kidney Diseases. While the reasons for this decline were not clear, one possibility is that an effective lifestyle intervention was offered to all study participants, he said.

Despite the convergence of the annual diabetes rates in long-term follow-up, the differences between groups obtained in the first 3 years of DPP "resulted in continued lower overall long-term incidence of diabetes over the 15 years of follow-up, during which the diabetes incidence rate overall was 18% lower in the metformin group and 27% lower in the original lifestyle group, than in the original placebo group."

Even though diabetes prevention or delay was substantial with lifestyle or metformin over 15 years, all three treatment groups maintained good glycemic control on average. HbA_1c averages over follow-up were 6.1%, 6.0%, and 6.0% in the original placebo, metformin, and lifestyle groups, respectively.

"While these differences are statistically significant, they are very small and of questionable clinical importance," Dr. Knowler said. "The good news is that all three groups maintained good glycemic control on average, perhaps as a result not only of our interventions, but [also as] a result of rapid diagnosis and intensive treatment of diabetes once it developed."

As for microvascular outcomes such as retinopathy and neuropathy, Dr. Kieren J. Mather, professor of medicine at Indiana University, Indianapolis, reported that the average prevalence of microvascular disease at year 15 following DPP randomization was 12.4% in the placebo group, 13% in the metformin group, and 11.3% in the lifestyle group. While these differences between groups did not reach statistical significance, the mean prevalence of microvascular outcomes was about 50% higher in men than in women.

"This is not something we expected, and we have not had an opportunity to explain that," Dr. Mather said.

He went on to note that the intensive lifestyle intervention was associated with a lower prevalence of microvascular complications in women (21% vs. placebo; P = .03, and 22% vs. metformin; P = .02), but not in men. The DPPOS researchers also observed a significant difference in microvascular disease prevalence at year 15 in those who progressed to diabetes, compared with those who did not progress to diabetes (13% vs. about 10%, respectively). This equated to about a 28% lower prevalence in those who had not progressed to diabetes, an effect was present in all three treatment groups.

"This equates to a paradox. We have diabetes reduction and we have a reduced prevalence of complications in those who did not develop diabetes, compared to those who did, but we don’t have a treatment effect to prevent diabetes at this point," Dr. Mather said. "We interpret these findings in the context of the achieved levels of glycemia. Despite the rising prevalence of diabetes in our population, we started following them quite early, and even at year 15, all three treatment groups have very low mean hemoglobin A_1cs, in the 6% range."

Dr. Nathan noted that even though the study is currently insufficiently powered to test the effects of interventions on CVD events, CVD risk factors improved in all subjects.

"This is a good news message, the fact that we had too few cardiac events to analyze and that CVD risk factors fell in the entire population speaks to the high level of care they were getting outside of the study."

At the same time, development of diabetes was accompanied by a worsening CVD risk factor profile and increased coronary artery calcification severity, compared with those who did not develop diabetes. The reduction in conventional CVD risk factors such as blood pressure and lipids, and in the novel CVD risk factors, such as C-reactive protein and other indices of inflammation, "was generally greater in the lifestyle group than the placebo group, and it was generally intermediate (somewhere between lifestyle and placebo) in the metformin group," Dr. Nathan explained. "Notably, it was not an increase in use of blood pressure– or lipid-lowering drugs that explained the differences among the treatment groups. In fact, during much of DPP and much of DPPOS, the lifestyle group was using fewer statins, using fewer blood pressure lowering medications. During DPPOS the development of diabetes and higher glucose levels was associated with higher levels of CVD risk factors."

Dr. Nathan added that there were no differences in the level of coronary calcification among the treatment groups. However, metformin reduced coronary artery calcification in men, which suggests that metformin has cardioprotective effects.

Dr. Jill P. Crandall, director of the diabetes clinical trials unit at the Albert Einstein College of Medicine, N.Y., discussed side effects and other consequences of long-term metformin therapy as well as the health impact implications of diabetes prevention. After an estimated 10,000 patient-years of follow-up with metformin use, there have been no reported cases of lactic acidosis or severe hypoglycemia requiring hospitalization. The prevalence of B₁₂ deficiency was about 9% in original DPP participants randomized to the metformin group.

"Our data also show that metformin-associated vitamin B₁₂ deficiency often occurs in the absence of anemia, leading us to recommend that B₁₂ testing be considered for patients taking metformin," Dr. Crandall said.

The researchers also observed a "modest but surprisingly durable weight loss" among participants in the metformin group. "The most highly adherent patients in the metformin group lost or maintained about 5% of their initial body weight over 10 years of follow-up," she said. "To our knowledge, the DPP/DPPOS represents the longest pharmacologic weight-loss study ever conducted."

When considering the measured cost of the DPP/DPPOS interventions and the aggregate cost of medical care received by the participants outside of the study, metformin was actually cost saving, and both the intensive lifestyle intervention and metformin were cost effective. "The net cost of the lifestyle intervention was approximately $1,700 more than placebo over the 10 years of follow-up," Dr. Crandall said. "Since the nature of the costs associated with diabetes is related to its complications, additional cost benefits of the interventions may accrue over time if these complications are prevented or delayed."

The study was funded by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.

The researchers stated that they had no relevant financial conflicts to disclose.

[email protected]

* An earlier version of this story misspelled Dr. Mather's name.

SAN FRANCISCO – Glycemic control has remained stable for an average of 15 years after initial randomization for patients in the Diabetes Prevention Program.

No significant differences in early microvascular complications were seen among interventions on intention to treat analysis, although intensive lifestyle intervention was effective in reducing microvascular complications in women.

Those are two key findings from an analysis of long-term outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS), which were presented at the annual scientific sessions of the American Diabetes Association.

Doug Brunk/Frontline Medical News

DPPOS is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial of intensive lifestyle and metformin, compared with placebo for the prevention of diabetes. Launched in 1996, the trial took place at 27 centers in the United States and was designed to determine whether the development of diabetes could be prevented or delayed in high-risk patients. A total of 3,234 patients were randomized to either an intensive lifestyle intervention to reduce their weight by 7% through a low-fat diet and increased physical activity, or standard advice on diet and exercise plus metformin, or standard advice on diet and exercise plus placebo.

The DPP ended 1 year ahead of schedule after an average of 3 years of study. The lifestyle intervention program, which had accomplished its goal of 7% weight loss at 1 year, and then maintained about a 5% weight loss over the remaining time of the study, resulted in a 58% reduction in diabetes. The metformin group reduced diabetes development by 31%.

"To put these reductions in perspective, approximately 11% per year of participants in the placebo group developed diabetes," Dr. David M. Nathan, chair of the DPP and DPPOS and professor of medicine at Harvard Medical School, Boston, said during a press briefing. "That was reduced to about 8%/year in the metformin group, and less than 5%/year in the lifestyle group."

The DPP results were "widely heralded and reported," Dr. Nathan continued, "but they only covered a very brief period: Three years in what is in fact a life-long disease or risk state." DPPOS was designed to examine "whether the diabetes development that we demonstrated was delayed over a brief period of time, would continue to be delayed or prevented over a longer period of time."

Of the original 3,234 DPP participants, 2,776 (86%) continued in DPPOS. Their average age at the first visit was 56 years and 68% were women. Their average age is now 67 years and 31% have developed diabetes since enrollment in DPP.

The annual diabetes incidence rates among the original DPP placebo and metformin groups have declined to approximately equal the rate in the lifestyle group, "which have remained remarkably stable, at approximately 5% per year over time," said Dr. William C. Knowler, chief of diabetes epidemiology and clinical research at the National Institute of Diabetes and Digestive and Kidney Diseases. While the reasons for this decline were not clear, one possibility is that an effective lifestyle intervention was offered to all study participants, he said.

Despite the convergence of the annual diabetes rates in long-term follow-up, the differences between groups obtained in the first 3 years of DPP "resulted in continued lower overall long-term incidence of diabetes over the 15 years of follow-up, during which the diabetes incidence rate overall was 18% lower in the metformin group and 27% lower in the original lifestyle group, than in the original placebo group."

Even though diabetes prevention or delay was substantial with lifestyle or metformin over 15 years, all three treatment groups maintained good glycemic control on average. HbA_1c averages over follow-up were 6.1%, 6.0%, and 6.0% in the original placebo, metformin, and lifestyle groups, respectively.

"While these differences are statistically significant, they are very small and of questionable clinical importance," Dr. Knowler said. "The good news is that all three groups maintained good glycemic control on average, perhaps as a result not only of our interventions, but [also as] a result of rapid diagnosis and intensive treatment of diabetes once it developed."

As for microvascular outcomes such as retinopathy and neuropathy, Dr. Kieren J. Mather, professor of medicine at Indiana University, Indianapolis, reported that the average prevalence of microvascular disease at year 15 following DPP randomization was 12.4% in the placebo group, 13% in the metformin group, and 11.3% in the lifestyle group. While these differences between groups did not reach statistical significance, the mean prevalence of microvascular outcomes was about 50% higher in men than in women.

"This is not something we expected, and we have not had an opportunity to explain that," Dr. Mather said.

He went on to note that the intensive lifestyle intervention was associated with a lower prevalence of microvascular complications in women (21% vs. placebo; P = .03, and 22% vs. metformin; P = .02), but not in men. The DPPOS researchers also observed a significant difference in microvascular disease prevalence at year 15 in those who progressed to diabetes, compared with those who did not progress to diabetes (13% vs. about 10%, respectively). This equated to about a 28% lower prevalence in those who had not progressed to diabetes, an effect was present in all three treatment groups.

"This equates to a paradox. We have diabetes reduction and we have a reduced prevalence of complications in those who did not develop diabetes, compared to those who did, but we don’t have a treatment effect to prevent diabetes at this point," Dr. Mather said. "We interpret these findings in the context of the achieved levels of glycemia. Despite the rising prevalence of diabetes in our population, we started following them quite early, and even at year 15, all three treatment groups have very low mean hemoglobin A_1cs, in the 6% range."

Dr. Nathan noted that even though the study is currently insufficiently powered to test the effects of interventions on CVD events, CVD risk factors improved in all subjects.

"This is a good news message, the fact that we had too few cardiac events to analyze and that CVD risk factors fell in the entire population speaks to the high level of care they were getting outside of the study."

At the same time, development of diabetes was accompanied by a worsening CVD risk factor profile and increased coronary artery calcification severity, compared with those who did not develop diabetes. The reduction in conventional CVD risk factors such as blood pressure and lipids, and in the novel CVD risk factors, such as C-reactive protein and other indices of inflammation, "was generally greater in the lifestyle group than the placebo group, and it was generally intermediate (somewhere between lifestyle and placebo) in the metformin group," Dr. Nathan explained. "Notably, it was not an increase in use of blood pressure– or lipid-lowering drugs that explained the differences among the treatment groups. In fact, during much of DPP and much of DPPOS, the lifestyle group was using fewer statins, using fewer blood pressure lowering medications. During DPPOS the development of diabetes and higher glucose levels was associated with higher levels of CVD risk factors."

Dr. Nathan added that there were no differences in the level of coronary calcification among the treatment groups. However, metformin reduced coronary artery calcification in men, which suggests that metformin has cardioprotective effects.

Dr. Jill P. Crandall, director of the diabetes clinical trials unit at the Albert Einstein College of Medicine, N.Y., discussed side effects and other consequences of long-term metformin therapy as well as the health impact implications of diabetes prevention. After an estimated 10,000 patient-years of follow-up with metformin use, there have been no reported cases of lactic acidosis or severe hypoglycemia requiring hospitalization. The prevalence of B₁₂ deficiency was about 9% in original DPP participants randomized to the metformin group.

"Our data also show that metformin-associated vitamin B₁₂ deficiency often occurs in the absence of anemia, leading us to recommend that B₁₂ testing be considered for patients taking metformin," Dr. Crandall said.

The researchers also observed a "modest but surprisingly durable weight loss" among participants in the metformin group. "The most highly adherent patients in the metformin group lost or maintained about 5% of their initial body weight over 10 years of follow-up," she said. "To our knowledge, the DPP/DPPOS represents the longest pharmacologic weight-loss study ever conducted."

When considering the measured cost of the DPP/DPPOS interventions and the aggregate cost of medical care received by the participants outside of the study, metformin was actually cost saving, and both the intensive lifestyle intervention and metformin were cost effective. "The net cost of the lifestyle intervention was approximately $1,700 more than placebo over the 10 years of follow-up," Dr. Crandall said. "Since the nature of the costs associated with diabetes is related to its complications, additional cost benefits of the interventions may accrue over time if these complications are prevented or delayed."

The study was funded by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.

The researchers stated that they had no relevant financial conflicts to disclose.

[email protected]

* An earlier version of this story misspelled Dr. Mather's name.

SAN FRANCISCO – Glycemic control has remained stable for an average of 15 years after initial randomization for patients in the Diabetes Prevention Program.

No significant differences in early microvascular complications were seen among interventions on intention to treat analysis, although intensive lifestyle intervention was effective in reducing microvascular complications in women.

Those are two key findings from an analysis of long-term outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS), which were presented at the annual scientific sessions of the American Diabetes Association.

Doug Brunk/Frontline Medical News

DPPOS is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial of intensive lifestyle and metformin, compared with placebo for the prevention of diabetes. Launched in 1996, the trial took place at 27 centers in the United States and was designed to determine whether the development of diabetes could be prevented or delayed in high-risk patients. A total of 3,234 patients were randomized to either an intensive lifestyle intervention to reduce their weight by 7% through a low-fat diet and increased physical activity, or standard advice on diet and exercise plus metformin, or standard advice on diet and exercise plus placebo.

The DPP ended 1 year ahead of schedule after an average of 3 years of study. The lifestyle intervention program, which had accomplished its goal of 7% weight loss at 1 year, and then maintained about a 5% weight loss over the remaining time of the study, resulted in a 58% reduction in diabetes. The metformin group reduced diabetes development by 31%.

"To put these reductions in perspective, approximately 11% per year of participants in the placebo group developed diabetes," Dr. David M. Nathan, chair of the DPP and DPPOS and professor of medicine at Harvard Medical School, Boston, said during a press briefing. "That was reduced to about 8%/year in the metformin group, and less than 5%/year in the lifestyle group."

The DPP results were "widely heralded and reported," Dr. Nathan continued, "but they only covered a very brief period: Three years in what is in fact a life-long disease or risk state." DPPOS was designed to examine "whether the diabetes development that we demonstrated was delayed over a brief period of time, would continue to be delayed or prevented over a longer period of time."

Of the original 3,234 DPP participants, 2,776 (86%) continued in DPPOS. Their average age at the first visit was 56 years and 68% were women. Their average age is now 67 years and 31% have developed diabetes since enrollment in DPP.

The annual diabetes incidence rates among the original DPP placebo and metformin groups have declined to approximately equal the rate in the lifestyle group, "which have remained remarkably stable, at approximately 5% per year over time," said Dr. William C. Knowler, chief of diabetes epidemiology and clinical research at the National Institute of Diabetes and Digestive and Kidney Diseases. While the reasons for this decline were not clear, one possibility is that an effective lifestyle intervention was offered to all study participants, he said.

Despite the convergence of the annual diabetes rates in long-term follow-up, the differences between groups obtained in the first 3 years of DPP "resulted in continued lower overall long-term incidence of diabetes over the 15 years of follow-up, during which the diabetes incidence rate overall was 18% lower in the metformin group and 27% lower in the original lifestyle group, than in the original placebo group."

Even though diabetes prevention or delay was substantial with lifestyle or metformin over 15 years, all three treatment groups maintained good glycemic control on average. HbA_1c averages over follow-up were 6.1%, 6.0%, and 6.0% in the original placebo, metformin, and lifestyle groups, respectively.

"While these differences are statistically significant, they are very small and of questionable clinical importance," Dr. Knowler said. "The good news is that all three groups maintained good glycemic control on average, perhaps as a result not only of our interventions, but [also as] a result of rapid diagnosis and intensive treatment of diabetes once it developed."

As for microvascular outcomes such as retinopathy and neuropathy, Dr. Kieren J. Mather, professor of medicine at Indiana University, Indianapolis, reported that the average prevalence of microvascular disease at year 15 following DPP randomization was 12.4% in the placebo group, 13% in the metformin group, and 11.3% in the lifestyle group. While these differences between groups did not reach statistical significance, the mean prevalence of microvascular outcomes was about 50% higher in men than in women.

"This is not something we expected, and we have not had an opportunity to explain that," Dr. Mather said.

He went on to note that the intensive lifestyle intervention was associated with a lower prevalence of microvascular complications in women (21% vs. placebo; P = .03, and 22% vs. metformin; P = .02), but not in men. The DPPOS researchers also observed a significant difference in microvascular disease prevalence at year 15 in those who progressed to diabetes, compared with those who did not progress to diabetes (13% vs. about 10%, respectively). This equated to about a 28% lower prevalence in those who had not progressed to diabetes, an effect was present in all three treatment groups.

"This equates to a paradox. We have diabetes reduction and we have a reduced prevalence of complications in those who did not develop diabetes, compared to those who did, but we don’t have a treatment effect to prevent diabetes at this point," Dr. Mather said. "We interpret these findings in the context of the achieved levels of glycemia. Despite the rising prevalence of diabetes in our population, we started following them quite early, and even at year 15, all three treatment groups have very low mean hemoglobin A_1cs, in the 6% range."

Dr. Nathan noted that even though the study is currently insufficiently powered to test the effects of interventions on CVD events, CVD risk factors improved in all subjects.

"This is a good news message, the fact that we had too few cardiac events to analyze and that CVD risk factors fell in the entire population speaks to the high level of care they were getting outside of the study."

At the same time, development of diabetes was accompanied by a worsening CVD risk factor profile and increased coronary artery calcification severity, compared with those who did not develop diabetes. The reduction in conventional CVD risk factors such as blood pressure and lipids, and in the novel CVD risk factors, such as C-reactive protein and other indices of inflammation, "was generally greater in the lifestyle group than the placebo group, and it was generally intermediate (somewhere between lifestyle and placebo) in the metformin group," Dr. Nathan explained. "Notably, it was not an increase in use of blood pressure– or lipid-lowering drugs that explained the differences among the treatment groups. In fact, during much of DPP and much of DPPOS, the lifestyle group was using fewer statins, using fewer blood pressure lowering medications. During DPPOS the development of diabetes and higher glucose levels was associated with higher levels of CVD risk factors."

Dr. Nathan added that there were no differences in the level of coronary calcification among the treatment groups. However, metformin reduced coronary artery calcification in men, which suggests that metformin has cardioprotective effects.

Dr. Jill P. Crandall, director of the diabetes clinical trials unit at the Albert Einstein College of Medicine, N.Y., discussed side effects and other consequences of long-term metformin therapy as well as the health impact implications of diabetes prevention. After an estimated 10,000 patient-years of follow-up with metformin use, there have been no reported cases of lactic acidosis or severe hypoglycemia requiring hospitalization. The prevalence of B₁₂ deficiency was about 9% in original DPP participants randomized to the metformin group.

"Our data also show that metformin-associated vitamin B₁₂ deficiency often occurs in the absence of anemia, leading us to recommend that B₁₂ testing be considered for patients taking metformin," Dr. Crandall said.

The researchers also observed a "modest but surprisingly durable weight loss" among participants in the metformin group. "The most highly adherent patients in the metformin group lost or maintained about 5% of their initial body weight over 10 years of follow-up," she said. "To our knowledge, the DPP/DPPOS represents the longest pharmacologic weight-loss study ever conducted."

When considering the measured cost of the DPP/DPPOS interventions and the aggregate cost of medical care received by the participants outside of the study, metformin was actually cost saving, and both the intensive lifestyle intervention and metformin were cost effective. "The net cost of the lifestyle intervention was approximately $1,700 more than placebo over the 10 years of follow-up," Dr. Crandall said. "Since the nature of the costs associated with diabetes is related to its complications, additional cost benefits of the interventions may accrue over time if these complications are prevented or delayed."

The study was funded by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.

The researchers stated that they had no relevant financial conflicts to disclose.

[email protected]

* An earlier version of this story misspelled Dr. Mather's name.