Impaired microvascular insulin-dependent dilation in women with a history of gestational diabetes.

Schwartz KS, Hernandez PV, Maurer GS, Wetzel EM, Sun M, Jalal DI, Stanhewicz AE. Impaired microvascular insulin-dependent dilation in women with a history of gestational diabetes. American journal of physiology. Heart and circulatory physiology. 2024 Jul 26.

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Abstract:

Women with a history of gestational diabetes mellitus (GDM) have significantly greater lifetime risk of developing cardiovascular disease and type 2 diabetes compared to women who had an uncomplicated pregnancy (HC). Microvascular endothelial dysfunction, mediated via reduced nitric oxide (NO)-dependent dilation secondary to increases in oxidative stress, persists after pregnancy complicated by GDM. We examined whether this microvascular dysfunction reduces insulin-mediated vascular responses in women with a history of GDM. We assessed in vivo microvascular endothelium-dependent vasodilator function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (10 - 10M) and insulin (10 - 10M) in control sites and sites treated with 15mM L-NAME [N-nitro-l-arginine methyl ester; NO-synthase (NOS) inhibitor] or 5mM L-ascorbate. We also measured protein expression of total endothelial NOS (eNOS), insulin-mediated eNOS phosphorylation, and endothelial nitrotyrosine in isolated endothelial cells from GDM and HC. Women with a history of GDM had reduced acetylcholine- (P < 0.001) and insulin- (P < 0.001) mediated dilation and the NO-dependent responses to both acetylcholine (P = 0.006) and insulin (P = 0.006) were reduced in GDM compared to HC. Insulin stimulation increased phosphorylated eNOS content in HC (P = 0.009) but had no effect in GDM (P = 0.306). Ascorbate treatment increased acetylcholine- (P < 0.001) and insulin- (P < 0.001) mediated dilation in GDM, and endothelial cell nitrotyrosine expression was higher in GDM compared to HC (P = 0.014). Women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and this attenuation is mediated, in part, by reduced NO-dependent mechanisms. Our findings implicate increased endothelial oxidative stress in this microvascular insulin resistance.