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.

Conclusion: Factors such as obesity, increased ADMA levels and insulin resistance appear to be strong contributors to endothelial dysfunction observed in women with GDM.