Impaired vascular nitric oxide bioactivity in women with previous gestational diabetes.
BACKGROUND
Dysfunction of the vascular endothelium, preceding vascular morbidity and type 2 diabetes, is present in women with previous gestational diabetes (GDM). However, it is unknown whether excess weight, insulin resistance, and asymmetric dimethylarginine (ADMA)--an endogenous nitric oxide (NO) synthase inhibitor--also contribute to the vascular changes observed in these patients. The aim of this study was therefore to identify factors other than GDM that impair vascular function.


METHODS
Seven overweight and five non-overweight women with previous GDM were included in this study. Vascular function was assessed from forearm blood-flow responses to the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator glyceryltrinitrate, the vasoconstrictor norepinephrine and the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). ADMA was measured in venous blood, and insulin resistance was estimated from a modified intravenous glucose tolerance test. Twenty healthy male volunteers served as a historical control group.


RESULTS
Vasodilation of forearm resistance vessels in response to ACh was impaired in overweight women when compared with non-overweight women (P < 0.05); similarly, vasoconstrictor reactivity tended to be smaller in the overweight group. In addition, there was a significant relationship between vascular responsiveness to ACh and L-NMMA, body-mass index, serum ADMA concentrations and stimulated glucose levels (all P < 0.05). ACh responses and ADMA levels in non-overweight women were similar to those of healthy controls.


CONCLUSIONS
Factors such as obesity, increased ADMA levels and insulin resistance appear to be strong contributors to endothelial dysfunction observed in women with GDM.
Pleiner
Johannes
J
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Mittermayer
Friedrich
F
Langenberger
Herbert
H
Winzer
Christine
C
Schaller
Georg
G
Pacini
Giovanni
G
Kautzky-Willer
Alexandra
A
Tura
Andrea
A
Wolzt
Michael
M
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D016640:Diabetes, Gestational / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology; D011247:Pregnancy; D012016:Reference Values; D012307:Risk Factors; D012737:Sex Factors; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine