Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.
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.
Steinberg
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Department of Medicine, Indiana University Medical Center, Indianapolis, Indiana 46202, USA.
Chaker
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Leaming
R
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Johnson
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Brechtel
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Baron
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D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance; D007866:Leg / Q000098:blood supply; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects*; D013577:Syndrome; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D016210:Methacholine Chloride; D009599:Nitroprusside; D002784:Cholesterol; D005947:Glucose