Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.

TLDR

The study aimed to test whether obesity/insulin resistance impairs endothelium‑dependent vasodilation and its insulin‑mediated augmentation. The authors measured leg blood flow responses to graded intrafemoral infusions of methacholine chloride and sodium nitroprusside during saline infusion and euglycemic hyperinsulinemia in lean controls, obese insulin‑resistant subjects, and NIDDM patients. Obesity/insulin resistance blunted methacholine‑induced leg blood flow and abolished insulin’s augmentation of this response, while nitroprusside responses were unchanged, and maximal methacholine‑induced flow inversely correlated with body fat, indicating endothelial dysfunction that may elevate atherosclerosis risk.

Abstract

To test the hypothesis that obesity/insulin resistance impairs both endothelium-dependent vasodilation and insulin-mediated augmentation of endothelium-dependent vasodilation, we studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP) during saline infusion and euglycemic hyperinsulinemia in lean insulin-sensitive controls (C), in obese insulin-resistant subjects (OB), and in subjects with non-insulin-dependent diabetes mellitus (NIDDM). MCh induced increments in LBF were approximately 40% and 55% lower in OB and NIDDM, respectively, as compared with C (P < 0.05). Euglycemic hyperinsulinemia augmented the LBF response to MCh by - 50% in C (P < 0.05 vs saline) but not in OB and NIDDM. SNP caused comparable increments in LBF in all groups. Regression analysis revealed a significant inverse correlation between the maximal LBF change in response to MCh and body fat content. Thus, obesity/insulin resistance is associated with (a) blunted endothelium-dependent, but normal endothelium-independent vasodilation and (b) failure of euglycemic hyperinsulinemia to augment endothelium-dependent vasodilation. Therefore, obese/insulin-resistant subjects are characterized by endothelial dysfunction and endothelial resistance to insulin's effect on enhancement of endothelium-dependent vasodilation. This endothelial dysfunction could contribute to the increased risk of atherosclerosis in obese insulin-resistant subjects.