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

Sari Mäkimattila, Antti Virkamäki, Per Henrik Groop, John Cockcroft, Tapio Utriainen, Johan Fagerudd, Hannele Yki-Järvinen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

243 Citations (Scopus)


Background: We explore whether chronic hyperglycemia is associated with defects in endothelium-dependent vasodilatation in vivo and whether defects in the hemodynamics effects of insulin explain insulin resistance. Methods and Results: Vasodilator responses to brachial artery infusions of acetylcholine, sodium nitroprusside, and N(G)-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 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 A(1c) 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 vasodilation 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 vasodilation could contribute to the increased cardiovascular risk in diabetes.

Original languageEnglish
Pages (from-to)1276-1282
Number of pages7
Issue number6
Publication statusPublished - 1996
Externally publishedYes


  • blood flow
  • diabetes mellitus
  • endothelium-derived factors
  • glucose
  • muscles


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