(Circulation. 1996;94:1276-1282.)
© 1996 American Heart Association, Inc.
Articles |
Chronic Hyperglycemia Impairs Endothelial Function and Insulin Sensitivity Via Different Mechanisms in Insulin-Dependent Diabetes Mellitus
the Department of Medicine, Divisions of Endocrinology and Diabetology (S.M., A.V., T.U., H.Y.) and Nephrology (P-H.G., J.F.), University of Helsinki, Finland; the Department of Medicine, Division of Therapeutics, University Hospital, Queen's Medical Centre, Nottingham, UK (J.C.); and the University of Texas Health Science Center at San Antonio, Department of Medicine, Division of Diabetes (H.Y.).
Correspondence to Hannele Yki-Jarvinen, MD, University of Helsinki, Department of Medicine, Division of Diabetes, Haartmaninkatu 4, FIN-00290 Helsinki, Finland.
Background We explored whether chronic hyperglycemia is associated with defects in endothelium-dependent vasodilatation in vivo and whether defects in the hemodynamic effects of insulin explain insulin resistance.
Methods and Results Vasodilator responses to brachial artery infusions of acetylcholine, sodium nitroprusside, and NG-monomethyl-L-arginine and, on another occasion, in vivo insulin sensitivity (euglycemic insulin clamp combined with the forearm catheterization technique) were determined in 18 patients with insulin-dependent diabetes mellitus (IDDM) and 9 normal subjects. At identical glucose and insulin levels, insulin stimulation of whole-body and forearm glucose uptake was 57% reduced in the IDDM patients compared with normal subjects (P<.001). The defect in forearm glucose uptake was attributable to a defect in glucose extraction (glucose AV difference, 1.1±0.2 versus 1.9±0.2 mmol/L, P<.001, IDDM versus normal subjects), not blood flow. Within the group of IDDM patients, hemoglobin A1c was inversely correlated with forearm blood flow during administration of acetylcholine (r=-.50, P<.02) but not sodium nitroprusside (r=.07). The ratio of endothelium-dependent to endothelium-independent blood flow was 
40% lower in patients with poor glycemic control than in normal subjects or patients with good or moderate glycemic control.
Conclusions We conclude that chronic hyperglycemia is associated with impaired endothelium-dependent vasodilatation in vivo and with a glucose extraction defect during insulin stimulation. These data imply that chronic hyperglycemia impairs vascular function and insulin action via distinct mechanisms. The defect in endothelium-dependent vasodilatation could contribute to the increased cardiovascular risk in diabetes.
Key Words: endothelium-derived factors • diabetes mellitus • glucose • blood flow • muscles
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