Impaired skin microvascular function in children, adolescents, and young adults with type 1 diabetes.
OBJECTIVE
Vascular disease in type 1 diabetes is a complex and multifactorial process, which probably begins in childhood in association with the onset of diabetes. To determine the possible factors involved, we measured microvascular responses to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilators in 56 patients with type 1 diabetes (aged 9-22 years) and 22 control subjects.


METHODS
Skin perfusion was measured at the dorsum of the foot using laser Doppler flowmetry during low-current iontophoresis of acetylcholine and sodium nitroprusside. Maximum vasodilator function was measured during local 44 degrees C skin heating.


RESULTS
Vascular responses were significantly reduced in patients with type 1 diabetes compared with responses in control subjects: acetylcholine (P<0.01, analysis of variance [ANOVA]), sodium nitroprusside (P<0.01, ANOVA), and local heating (P<0.02. Mann-Whitney U test). Endothelium-dependent responses were related to duration of diabetes (r = -0.38, P<0.01) and to glycemic control (r = 0.37, P<0.01). Significant correlations were found in the patient group between responses to acetylcholine and sodium nitroprusside (r = 0.28, P<0.05) but not to heating, suggesting that a common factor (e.g., nitric oxide activity) may be responsible for the abnormal vascular responses to these chemicals.


CONCLUSIONS
Early changes in microvascular function are present in young patients with type 1 diabetes, long before the initial clinical presentation. These abnormalities may be related to complex interactions between structural abnormalities and functional changes in the endothelium, smooth muscle, and nitric oxide activity.
Khan
F
F
University Department of Medicine, Child Health Ninewells Hospital and Medical School, Dundee, Scotland, UK. f.khan@dundee.ac.uk
Elhadd
T A
TA
Greene
S A
SA
Belch
J J
JJ
D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D001794:Blood Pressure; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D012016:Reference Values; D012044:Regression Analysis; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine