Chronic hyperglycemia impairs endothelial function and insulin sensitivity via different mechanisms in insulin-dependent diabetes mellitus

• Published in: Circulation (New York, N.Y.) N.Y.), 1996-09, Vol.94 (6), p.1276-1282
• Main Authors: MÄKIMATTILA, S, VIRKAMÄKI, A, GROOP, P.-H, COCKCROFT, J, UTRIAINEN, T, FAGERUDD, J, YKI-JÄRVINEN, H
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Adult; Albuminuria - urine; Biological and medical sciences; Biomechanical Phenomena; Chronic Disease; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 1 - urine; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Forearm - blood supply; Humans; Hyperglycemia - physiopathology; Insulin Resistance; Male; Medical sciences; Nitroprusside - pharmacology; Regional Blood Flow - drug effects
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.94.6.1276

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. 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 approximately 40% lower in patients with poor glycemic control than in normal subjects or patients with good or moderate glycemic control. 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.