Adults with overweight or obesity and type 2 diabetes who lost at least 10% of their body weight or increased their fitness by 2 metabolic equivalents saw a 20% reduction in risk for cardiovascular disease, according to a post-hoc analysis of the Look AHEAD trial.
The original Look AHEAD study, a large, randomized trial of an intensive, lifestyle-based, weight-loss intervention in adults with type 2 diabetes, yielded no significant benefit on morbidity or mortality from CVD for patients assigned to the intervention group, despite other health benefits. In the post-hoc analysis, researchers examined associations between the magnitude of weight loss and changes in physical fitness from baseline to 1 year with the incidence of subsequent CVD, looking at both the full cohort and comparing the occurrence of CVD in the intervention group according to weight change and fitness response vs. controls.
“There are subtle but important differences in interpretation between the two analyses presented here, which complement the original null intention-to-treat findings,” Edward W. Gregg, PhD, chief of the epidemiology and statistics branch at the division of diabetes translation centers for the CDC, and colleagues wrote. “These findings should not be confused with the primary, intention-to-treat analysis, which showed that the weight-loss intervention had no significant effect on either the primary outcome or secondary outcome. Taken together, these analyses suggest that the intensive lifestyle intervention in Look AHEAD did not achieve a large enough weight loss or fitness change among enough people to statistically affect incidence of CVD. However, these findings highlight the variation in responses to lifestyle intervention and resulting outcomes.”
The Look AHEAD study included 5,145 adults with type 2 diabetes and overweight or obesity aged 45 to 76 years randomly assigned to either an intensive lifestyle intervention or diabetes support and education (controls). For analyses related to change in body weight, Gregg and colleagues analyzed data from 4,834 participants; for fitness change, researchers analyzed data from 4,406 participants. Primary outcome was death from CV causes, nonfatal myocardial infarction, stroke or hospital admission for angina; secondary outcome included coronary artery bypass grafting, carotid endarterectomy, percutaneous coronary intervention, congestive heart failure, peripheral vascular disease and total mortality. Median follow-up time was 10.2 years.
In combining both intervention and control groups, researchers found that participants who lost at least 10% of their body weight in 1 year had a 21% reduced risk for the primary outcome and a 24% reduced risk for secondary outcome vs. participants with stable weight or weight gain. Results persisted after adjustment for age, sex, baseline weight and fitness, CVD history, insulin use, diabetes duration, smoking status, cholesterol and blood pressure status.
Increases in fitness were associated with reduced CVD for both the primary and secondary outcomes (P = .03 and .0031 for trend, respectively). Researchers also found that an increase of at least 2 metabolic equivalents in fitness was associated with reduced risk for the secondary, but not primary outcome (P = .023).
Using the control group as reference, researchers found that participants assigned to intensive lifestyle intervention who lost at least 10% body weight over 1 year had a 20% reduced risk for primary outcome after adjustment (adjusted HR = 0.8; 95% CI, 0.65-0.99) and a 21% reduced risk for the secondary outcome (adjusted HR = 0.79; 95% CI, 0.66-0.95). Each standard deviation of weight loss (about 7%) was associated with a 15% reduced risk for the primary outcome (P = .006) and an 18% lower risk for the secondary outcome (P < .0001) vs. controls.
“These findings, combined with evidence for reduced incidence of diabetes, hypertension, disability and other benefits, suggest that approaches to identify individuals most likely to benefit from lifestyle interventions should be refined, and strategies should be developed to improve to improve the magnitude of sustained weight loss with lifestyle interventions,” the researchers wrote. –by Regina Schaffer
Disclosure: Please see the full study for the authors’ relevant financial disclosures.