Effect of intensive lifestyle intervention on the association between weight variability and major adverse cardiovascular events in overweight or obese adults with type 2 diabetes mellitus

Abstract

Aims/introduction: Weight variability is associated with cardiovascular outcomes in diabetic patients. However, whether the guideline-recommended intensive lifestyle intervention (ILI) will affect this association in overweight or obese adults with diabetes is not well established.

Materials and methods: In 3,859 participants from the Action for Health in Diabetes (Look AHEAD) trial, the associations of 4 year weight variability measured by variability independent of the mean (VIM) with major adverse cardiovascular event (MACE) and secondary outcomes in ILI and diabetes support & education (DSE) arm were evaluated.

Results: During a median follow-up of 9.6 years, 255 (12.9%) participants in the ILI arm and 247 (13.2%) participants in the DSE arm developed MACE. Participants with the highest quartile of weight variability (VIM Q4) experienced a 2.23-fold higher risk of MACE compared with the lowest quartile (VIM Q1) in the DSE arm (hazard ratio [HR] 2.23; 95% CI 1.51-3.30). Compared with the lowest weight variability (VIM Q1), participants with the highest weight variability (VIM Q4) were associated with higher risks of secondary cardiovascular composite outcome (HR 1.88; 95% CI 1.20-2.95), all-cause mortality (HR 3.19; 95% CI 1.75-5.82), and myocardial infarction (HR 1.95; 95% CI 1.12-3.37) in the DSE arm.

Conclusions: Among the overweight or obese individuals with type 2 diabetes mellitus, rising weight variability was independently associated with increased MACE risks in the DSE arm. Therefore, a guideline-recommended ILI strategy for weight loss should be adopted to improve cardiovascular outcomes without worrying about the effect of weight fluctuations.

Keywords: Intensive lifestyle intervention; Major adverse cardiovascular events; Weight variability.

Figure 1

Risks of a major adverse cardiovascular event (a) and secondary cardiovascular composite outcome (b) in different quartiles of 4 year weight variability measured by VIM, relative to the lowest quartile (reference group) in overweight or obese adults with type 2 diabetes mellitus. Adjusted HR (95% CI) are derived from Cox proportional hazard regression models adjusted for age, sex, race, education level, smoking status, drinking status, systolic blood pressure, diastolic blood pressure, total cholesterol, high‐density lipoprotein cholesterol, glycosylated hemoglobin, serum creatinine, prevalent hypertension, and cardiovascular disease, insulin use at baseline and mean 4 year weight. MACE was defined as a composite outcome of the first occurrence of all‐cause mortality, death from cardiovascular causes or non‐fatal acute myocardial infarction, stroke. Secondary CV composite outcome was defined as a composite outcome of the first occurrence of death from cardiovascular causes or non‐fatal acute myocardial infarction, stroke. CV, cardiovascular; HR, hazard ratio; MACE, major adverse cardiovascular event; VIM, variability independent of the mean.

Figure 2

Adjusted hazard ratios (95% CI) for the association of 4 year weight variability measured by VIM with MACE in ILI (a) and DSE (b) arms among overweight or obese individuals with type 2 diabetes mellitus. Hazard ratios (indicated by a red solid line) and 95% CIs (red dotted lines) are derived from Cox proportional hazard regression models adjusted for age, sex, race, education level, smoking status, drinking status, systolic blood pressure, diastolic blood pressure, total cholesterol, high‐density lipoprotein cholesterol, glycosylated hemoglobin, serum creatinine, prevalent hypertension and cardiovascular disease, insulin use at baseline and mean 4 year weight. VIM values of weight were centered at the sample median and modeled using a restricted cubic spline with knots at the 5th, 50th, and 95th percentiles. Black solid line is the reference line as hazard ratio = 1. Histograms represent the frequency distribution of 4 year weight variability (VIM). Participants with extreme VIM values (in the bottom first and top 99th percentile) were excluded from these analyses. DSE, diabetes support & education; ILI, intensive lifestyle intervention; MACE, major adverse cardiovascular event; VIM, variability independent of the mean.