American Diabetes Association's 73rd Scientific Sessions:

Intensive Lifestyle Intervention Yields Microvascular Benefits, But Not Lower CVD Risk

Intensive lifestyle intervention focused on weight loss did not reduce the risk of heart attack, stroke, or death from heart disease in obese adults with type 2 diabetes as hoped for in the large-scale Look AHEAD (Action for Health in Diabetes) clinical trial, but did lower the risk of microvascular complications such as kidney disease and retinopathy. 

Look AHEAD, a two-armed trial conducted in 16 centers across the U.S., randomized 5,145 participants aged 45 to 76 years to one of two interventions. The lifestyle intervention consisted of a diet of 1,200 to 1,800 calories per day and 175 minutes of moderate-intensity physical activity per week, whereas the diabetes support and education intervention involved three counseling sessions per year on nutrition, physical activity, and social support.

Primary Outcome

The primary outcome was a composite of death from cardiovascular causes, non-fatal heart attack, non-fatal stroke, or hospitalization for angina. Participants were followed for up to 11.5 years, but the trial, which was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), ended after a median follow-up of 9.6 years when it became evident that weight loss did not reduce cardiovascular risk in the lifestyle intervention group. Cardiovascular morbidity and mortality occurred in 403 participants in the lifestyle intervention group compared with 418 participants in the support and education group.

 Participants in the lifestyle intervention group did, however, lose more weight than those in the support and education group. At one year, those in the lifestyle intervention group experienced a mean weight loss of 8.6% of their body weight compared with 0.7% for the support and education group. At study’s end, those in the lifestyle intervention group had a mean weight loss of 6% compared with 3.5% for the support and education group.

 Although the results did not show a cardiovascular benefit for the lifestyle intervention group, this group did reap other rewards for maintaining their lifestyle changes, most notably a 31% lower risk of developing advanced kidney disease.

 Weight Loss Reduced Kidney Disease

“The intensive lifestyle weight-loss intervention substantially reduced the development of advanced kidney disease,” said William Knowler, MD, PhD, MPH, of the diabetes epidemiology and clinical research section at the NIDDK, who presented trial data on microvascular complications. “Based on other studies showing this to be a major factor associated with higher mortality rates in diabetic persons, such an effect, if it persists long-term, might eventually result in improved quality of life and longevity.”

 Dr. Knowler also reported a 14% lower risk of diabetic retinopathy in the lifestyle intervention group.

 Overall, the study demonstrated that dietary changes and exercise work to slim patients down.

 “Look AHEAD showed that participants with diabetes can lose weight and maintain it,” said Rena R. Wing, PhD, professor of psychiatry and human behavior at Brown University’s Alpert Medical School in Providence, RI,  and lead investigator in the trial. “This weight loss has many beneficial effects on glycemic control and cardiovascular disease risk factors. However, it did not affect the [actual] risk of cardiovascular disease.”

 Dr. Wing added that there are several possible explanations for the unexpected results with respect to cardiovascular risk. For example, the participants in the support and education group were more likely to take cholesterol-lowering medications, which may have minimized cardiovascular differences between the two groups.



Dr. Knowler and Dr. Wing disclosed no conflicts of interest.

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