Effect of Intensive Lifestyle Intervention on the Association between Weight Variability and Mortality and Cardiovascular Events in Overweight or Obese Adults with Type 2 Diabetes Mellitus

Abstract Background: The association among intensive lifestyle intervention (ILI), weight variability and the risks of death and cardiovascular events have limited data. We aimed to examine whether the weight variability is associated with all-cause mortality and cardiovascular events, and whether the intensive lifestyle intervention (ILI) will affect these associations in overweight or obese individuals with type 2 diabetes mellitus (T2DM).Methods: Individuals from the Action for Health in Diabetes (Look AHEAD) trial who measured the weight variability based on 5 equally spaced medical measurements of within 4 years were enrolled. A multivariate-adjusted Cox regression models were used to evaluate the associations between weight variability and adverse outcomes including the all-cause mortality and primary cardiovascular disease (CVD) outcome, and the effects of ILI on these associations.Results: Among the 3,859 participants with a median follow-up of 9.6 years, those with the highest quartile of weight variability experienced a double higher risk of death compared with those the lowest quartile (HR 2.25; 95% CI 1.44-3.52), but no difference was found in primary CVD outcome (HR 1.02; 95% CI 0.78-1.33). Moreover, the restricted cubic splines revealed that the risk of death grew with the increased weight variability. Of note, the association between weight variability and all-cause mortality was not observed in ILI arm (the highest vs. lowest quartile group, [HR 1.30; 95% CI 0.67-2.50]) and was just found in diabetes support and education (DSE) arm (the highest vs. lowest quartile group, [HR 3.31; 95% CI 1.84-5.95]).Conclusions: Among the overweight or obese individuals with T2DM, the weight variability was independently associated with increased risks of all-cause mortality, but this association might be removed by ILI.Trial registrations ClinicalTrials.gov identifiers: NCT00017953.