Association of cognition with leptin and vascular endothelial growth factor in individuals with type 2 diabetes mellitus

OBJECTIVE: The 10‐year intensive lifestyle intervention (ILI) of the Look AHEAD study left a legacy of relative deficits in cognitive function among participants who entered the clinical trial with obesity or a history of cardiovascular disease. We hypothesized that altered levels of two weight‐sensitive proangiogenic cytokines, leptin and vascular endothelial growth factor (VEGF), accounted for this concerning finding. METHODS: Serum leptin and VEGF concentrations were determined in 1,279 Look AHEAD participants at baseline, proximal to cessation of the interventions (Epoch 1), and an average of 4 years later (Epoch 2). Up to four standardized assessments of attention, executive function, and memory were collected during follow‐up. Mixed effects models were used to assess relative differences in leptin and VEGF concentrations between intervention groups and whether these accounted for changes in cognitive composite scores. RESULTS: ILI and diabetes support and education differences in VEGF, but not leptin, concentrations varied depending on baseline history of cardiovascular disease and obesity, but neither leptin nor VEGF concentrations accounted for the relative decrements in cognitive function in participants assigned to ILI. CONCLUSIONS: Alterations in two weight‐sensitive proangiogenic cytokines did not account for the long‐term adverse effects of ILI on cognitive function among adults with diabetes and either obesity or cardiovascular disease.