Background-The Look AHEAD Study found no significant reduction in cardiovascular disease (CVD) incidence among adults with diabetes enrolled in an intensive weight loss intervention (ILI) compared to those randomized to diabetes support and education (DSE).We examined whether CVD incidence in Look AHEAD varied by weight or fitness change.Methods-Among overweight or obese adults people aged 45-76 with type 2 diabetes in the Look AHEAD study, this observational analysis examined the association of magnitude of weight loss (N=4834) and fitness change (N=4406) over the first year with CVD incidence over a median 10.2 years of follow-up.The primary outcome was a composite of CVD death, myocardial infarction, stroke, or angina hospitalization; the secondary outcome included the same indices plus coronary-artery bypass grafting, carotid endartectomy, percutaneous coronary intervention, hospitalization for congestive heart failure, peripheral vascular disease, or total mortality.Analyses adjusted for baseline differences in weight or fitness, demographics and CVD risk factors.Findings-In analyses of the full cohort combining ILI and DSE, persons who lost > 10% body weight in the first year had 21% lower risk of the primary outcome (HR=0.79,95% CI, 0.64 to 0.98) and a 24% reduced risk of the secondary outcome (HR=0.76,95% CI, 0.63 to 0.91) relative to those with stable weight/weight gain.Achieving a > 2 MET fitness change was associated with a significant reduction in the secondary outcome (HR=0.77,95% CI, 0.61 -0.96) but not the primary outcome (HR=0.78,0.60 -1.03).In analyses treating the DSE as the referent group, ILI participants with > 10% weight losses had a 20% lower risk of the primary outcome (HR=0.80(95% CI, 0.65 -0.99) and a 21% reduced risk of the secondary outcome (0.79 (95% CI, 0.66 -0.95); fitness change was not significantly associated with either outcome.Interpretation-This secondary analysis of Look AHEAD suggests an association between the magnitude of intentional weight loss and CVD incidence.

Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial