Abstract

BACKGROUND: It is unclear whether changes in weight affect subsequent adverse events in patients with type 2 diabetes mellitus (T2DM) already at high risk of cardiovascular disease (CVD). METHODS AND RESULTS: This is a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study data to examine the relationship between changes in weight and adverse events. Patients were divided into groups based on changes in body mass index (BMI): stable weight, gain or loss of BMI ≤1.5 kg/m²; moderate weight gain, BMI gain of 1.5-5 kg/m²; pronounced weight gain, BMI gain >5 kg/m²; moderate weight loss, BMI loss of 1.5-5 kg/m²; and pronounced weight loss, BMI loss >5 kg/m². The primary endpoint of the present study was all-cause mortality. Secondary endpoints were cardiac death, non-fatal myocardial infarction (MI), and non-cardiac mortality. A total of 9372 T2DM patients with a mean follow-up of 8.08 ± 3.00 years were included for analysis. The average change in weight across the entire study population was 1.80 ± 9.00%, representing ~0.448 ± 2.98 kg/m². Patients with pronounced weight loss had the highest risk of all-cause mortality (hazard ratio (HR) 2.07, 95% confidence interval (CI): 1.68-2.55), followed by patients with pronounced weight gain (HR 1.23, 95% CI: 1.02-1.56); patients with stable weight had the lowest risk. An asymmetric V-shaped relationship was observed between changes in BMI and all-cause mortality and non-cardiac mortality. Although no statistical significance was observed in terms of cardiac death and non-fatal MI, a flat V-shaped relationship may exist. CONCLUSIONS: Weight was stable in most T2DM patients with high risk of CVD. Weight loss and gain is associated with increased all-cause mortality and non-cardiac mortality. Pronounced weight loss and weight gain is associated with a slight increase in cardiac death and non-fatal MI incidence, which does not reach statistical significance.