Intense Lifestyle Intervention in Type 2 Diabetes

It has been well documented that overweight or obese patients with type 2 diabetes benefit from weight loss, with numerous short-term studies demonstrating such benefits as improved glycemic control, reduction of cardiovascular disease risk factors, increased quality of life, and reduction of other comorbidities related to obesity.

According to researchers, the long-term effects on cardiovascular disease have not been widely studied; it is unknown whether weight loss reduces the risk of cardiovascular morbidity and mortality in patients with type 2 diabetes. Researchers at Look AHEAD (Action for Health in Diabetes) recently conducted a multicenter, randomized clinical trial to determine whether an intensive lifestyle intervention designed to achieve weight loss through caloric restriction and increased physical activity would decrease cardiovascular morbidity and mortality among overweight or obese adults with type 2 diabetes.

The primary end point was the first occurrence of a composite cardiovascular outcome (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for angina). Results were reported in the New England Journal of Medicine [2013;369(2):145-154].

The study was conducted at 16 centers in the United States from August 2001 through April 2004 and was sponsored by the National Institutes of Health, with additional support from other federal partners and the clinical research centers of several participating institutions. After applying inclusion and exclusion criteria, the final study cohort included 5145 overweight or obese patients with type 2 diabetes who were randomly assigned to participate in the intensive lifestyle intervention (n=2570) or to receive diabetes support and education (control; n=2575).

Baseline characteristics were similar between the 2 groups. Average age was 58.7 years, 60% were female, and mean body mass index was 36.0. Median duration of diabetes was 5 years, and 14% of patients reported a history of cardiovascular disease.

At the median follow-up of 9.6 years, the trial was stopped on the basis of a futility analysis. At 1 year of follow-up, and throughout the study, weight loss was greater in the intervention group than in the control group (8.6% vs 0.7%). Although the differences in mean weight loss were largest at the 1-year point, they remained significant throughout the study (6.0% vs 3.5% at study end).

Patients in the intervention group also had significantly greater reductions in waist circumference and greater improvements in fitness compared with those in the control group. The intensive lifestyle intervention also resulted in greater reductions in glycated hemoglobin compared with the control group.

With the exception of levels of low-density lipoprotein, the intervention group had greater improvements in all cardiovascular risk factors. The between-group difference in cardiovascular risk factors diminished over time; glycated hemoglobin and systolic blood pressure had the most sustained differences.

The composite primary outcome occurred in 403 patients in the intervention group and 418 in the control group, with no significant between-group difference. There were no significant differences between the groups in the prespecified composite secondary outcomes.

The researchers stated, “An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults.”