Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.
BACKGROUND
Endothelium-dependent vasodilation is abnormal in experimental models of diabetes mellitus. We postulated that abnormalities of endothelial function are also present in patients with insulin-dependent diabetes mellitus and may contribute to the pathogenesis of vascular disease in these individuals.


RESULTS
Vascular reactivity was measured in the forearm resistance vessels of 15 patients with insulin-dependent diabetes mellitus and 16 age-matched normal subjects. No patient had hypertension or dyslipidemia. Each subject was pretreated with aspirin to inhibit endogenous production of prostanoids. Methacholine chloride (0.3 to 10 micrograms/min) was administered via the brachial artery to assess endothelium-dependent vasodilation. Sodium nitroprusside (0.3 to 10 micrograms/min) and verapamil (10 to 300 micrograms/min) were infused intra-arterially to assess endothelium-independent vasodilation; phenylephrine (0.3 to 3 micrograms/min) was administered to examine vasoconstrictor responsiveness. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each drug. Basal forearm blood flow in diabetic and normal subjects was comparable (2.6 +/- 0.2 versus 2.1 +/- 0.3 mL x 100 mL-1 x min-1, respectively; P = NS). The forearm vasodilative response to methacholine was less in diabetic than in normal subjects. At the highest dose of methacholine, the forearm blood flow increased 9.5 +/- 1.1 mL x 100 mL-1 x min-1 in diabetic subjects and 15.3 +/- 1.4 mL.100 mL-1 x min-1 in normal subjects (P < .01). The forearm blood flow responses to nitroprusside and verapamil and the forearm vasoconstrictor responses to phenylephrine were similar in diabetic and healthy subjects. In diabetic subjects, endothelium-dependent vasodilation correlated inversely with serum insulin concentration but not with glucose concentration, glycosylated hemoglobin, or duration of diabetes.


CONCLUSIONS
Endothelium-dependent vasodilation is abnormal in forearm resistance vessels of patients with insulin-dependent diabetes mellitus. This abnormality may be relevant to the high prevalence of vascular disease that occurs in these individuals.
Johnstone
M T
MT
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115.
Creager
S J
SJ
Scales
K M
KM
Cusco
J A
JA
Lee
B K
BK
Creager
M A
MA
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000209:etiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D016210:Methacholine Chloride; D009569:Nitric Oxide; D009599:Nitroprusside; D010656:Phenylephrine; D014700:Verapamil