Oxidative stress contributes to attenuated insulin-mediated dilation in the microvasculature of women with a history of gestational diabetes

Abstract

Women with a history of gestational diabetes mellitus (GDM) are at greater risk for cardiovascular disease (CVD) and type II diabetes mellitus (T2DM). Endothelium- and nitric oxide-dependent dilation are attenuated in the microvasculature of otherwise healthy women with a history of GDM and this reduction is mediated, in part, by increased oxidative stress. However, whether this attenuation also reduces insulin-mediated microvascular responses in these women is unknown. We hypothesized that 1) insulin-mediated vasodilation would be attenuated, and that 2) antioxidant treatment would increase these responses, in women with a history of GDM compared to matched women with a history of healthy pregnancy (HC). Nine HC (32±6 yrs.) and 8 GDM (33±6 yrs.) participated in 1 experimental visit. Three microdialysis fibers were placed in the ventral forearm for the local delivery of lactated Ringer’s (control), 15mM N G-nitro-L-arginine methyl ester (L-NAME; NO synthase-inhibition), or 5mM ascorbate (non-specific antioxidant). Following baseline measurements, increasing doses of insulin [10-8 -10-4 M] were added to the site-specific perfusates. Red blood cell flux was measured continuously with laser-Doppler flowmetry, and cutaneous vascular conductance was calculated (CVC=flux/MAP) and standardized to maximum (%CVC max; 28mM SNP + 43°C). Subjects with GDM had attenuated insulin-mediated vasodilation (GDM:16.0 ± 3.0 vs. HC: 31.3 ± 4.7 %CVCmax; p= 0.02) at the control site. L-NAME attenuated insulin-mediated dilation in HC (14.7 ± 3.5 %CVCmax, p=0.004) but not in GDM (12.2 ± 1.9 %CVCmax, p=0.48). Local ascorbate perfusion increased insulin-mediated dilation in GDM (27.6 ± 7.2 %CVCmax; p=0.04) but had no effect in HC (p=0.85). These data suggest that women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and that this attenuation is mediated, in part, by increased oxidative stress. Supported by The UI Fraternal Order of Eagles Diabetes Research Center This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.