Insulin Status and Vascular Responses to Weight Loss in Obesity

Objectives To determine whether the effects of weight loss on arterial function are differentially modified by insulin status. Background Clinical studies suggest that plasma insulin levels may predict the extent of cardiovascular benefit achieved with weight loss in obese individuals, but mechanisms are unknown. Methods We prospectively followed 208 overweight or obese patients (BMI ≥25 kg/m2) receiving medical/dietary (48%) or bariatric surgical (52%) weight loss treatment during a median period of 11.7 months (inter-quartile range 4.6–13 months). We measured plasma metabolic parameters and vascular endothelial function using ultrasound at baseline and following weight loss intervention, and stratified analyses by median plasma insulin levels. Results Subjects age 45±1 yr, BMI 45±9 kg/m2 experienced 14±14% weight loss during the study period. In individuals with higher baseline plasma insulin levels (above median >12 uIU/ml, n=99), ≥10% weight loss (compared to <10%) significantly improved brachial artery macro-vascular flow-mediated vasodilation and micro-vascular reactive hyperemia (P <0.05 for all). In contrast, vascular function did not change significantly in the lower insulin group (≤12 uIU/mL, n=109) despite similar degree of weight loss. In analyses using a 5% weight loss cut-point, only micro-vascular responses improved in the higher insulin group (P=0.02). Conclusions Insulin status is an important determinant of the positive effect of weight reduction on vascular function with hyperinsulinemic patients deriving the greatest benefit. Integrated improvement in both micro- and macro-vascular function was associated with ≥10% weight loss. Reversal of insulin resistance and endothelial dysfunction may represent key therapeutic targets for cardiovascular risk reduction in obesity.