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

Abstract：

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 approximately 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.

journal_name

Circulation

journal_title

Circulation

authors

Mäkimattila S,Virkamäki A,Groop PH,Cockcroft J,Utriainen T,Fagerudd J,Yki-Järvinen H

doi

10.1161/01.cir.94.6.1276

subject

Has Abstract

pub_date

1996-09-15 00:00:00

pages

1276-82

issue

eissn

0009-7322

issn

1524-4539

journal_volume

pub_type

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