Body Mass Index Variability and Cardiovascular Risk: Contemporary Evidence and Clinical Implications for Diabetes...

To synthesize contemporary evidence on body mass index (BMI) variability as a determinant of cardiovascular risk, integrate mechanistic insights, and clarify its clinical relevance in individuals with and without diabetes.

Large cohort studies demonstrate that greater BMI or weight variability is associated with increased risks of all-cause mortality, atherosclerotic cardiovascular disease, heart failure and atrial fibrillation, independent of mean BMI. Mechanistic evidence to explain the observed association implicates adipose tissue dysfunction, ectopic fat deposition, metabolic instability, systemic inflammation, and autonomic imbalance. Diabetes may amplify these pathways through impaired metabolic flexibility and treatment-related weight fluctuations. Evidence from diabetes-specific cohorts suggests that structured, intentional weight loss may attenuate the adverse associations seen with unstructured weight cycling. BMI variability is an emerging marker of cardiometabolic instability with implications for cardiovascular risk, particularly in diabetes. Defining actionable thresholds and determining whether stabilizing weight improves outcomes are key future research priorities.