title: 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.
  
  
  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.
authors.affiliation: Department of Medicine, University of Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Mäkimattila
authors.forename: A
authors.initials: A
authors.lastname: Virkamäki
authors.forename: P H
authors.initials: PH
authors.lastname: Groop
authors.forename: J
authors.initials: J
authors.lastname: Cockcroft
authors.forename: T
authors.initials: T
authors.lastname: Utriainen
authors.forename: J
authors.initials: J
authors.lastname: Fagerudd
authors.forename: H
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000419:Albuminuria / Q000652:urine; D001696:Biomechanical Phenomena; D002908:Chronic Disease; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000652:urine; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007333:Insulin Resistance; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D009599:Nitroprusside; D000109:Acetylcholine