Endothelium-dependent and -independent vascular dysfunction in type 1 diabetes: role of conventional risk factors, sex, and glycemic control.
OBJECTIVE
Defective NO release/response may contribute to increased coronary risk and the loss of sex difference in coronary heart disease in diabetes. We aimed to determine whether NO release/response is impaired in type 1 diabetes and whether any defects are greater in women than men.


RESULTS
Forearm blood flow response to vasoactive drugs was assessed by venous plethysmography in 88 diabetic and 69 control subjects aged 30 to 53 years. In diabetic patients, response was 18% lower for acetylcholine (ACh) (P=0.002), 6% lower for bradykinin (P=0.14), and 17% lower for glyceryl trinitrate (GTN) (P<0.001). Women had a higher response to ACh than men (17%, P=0.006). The diabetes-associated defect in ACh was greater in women (25% lower, P=0.01) than men (13% lower, P=0.08), although not significantly (P=0.26 for the interaction). Poorer glycemic control was associated with ACh response (P=0.003) and contributed to the greater defect in diabetic women than men.


CONCLUSIONS
The diabetes-associated defect in GTN response was similar in men and women. Established coronary heart disease risk factors did not explain any of the defects in ACh or GTN response associated with diabetes. Type 1 diabetes is associated with impaired responsiveness to NO and with an impairment in ACh-stimulated NO release.
Chan
Norman Nor
NN
EURODIAB, Department of Epidemiology, University College London, UK. nnchan@cuhk.edu.hk
Vallance
Patrick
P
Colhoun
Helen Martina
HM
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D001920:Bradykinin / Q000494:pharmacology; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000819:agonists / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D012307:Risk Factors; D012737:Sex Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D001786:Blood Glucose; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin