Improving nitric oxide bioavailability to treat endothelial dysfunction in women with type 1 diabetes: impact of race

BACKGROUND: Type 1 diabetes (T1D) is associated with a greater risk of cardiovascular disease (CVD), mediated in part, by impaired nitric oxide (NO) bioavailability and endothelial dysfunction. In fact, women with T1D have a greater risk of CVD compared to men, and although the incidence of T1D is greater in Caucasians (Cs), African Americans (AAs) with T1D have significantly worse health outcomes. In healthy women, both resveratrol (RES) and antioxidants have been used to improve NO bioavailability and endothelial function by reducing oxidative stress. Accordingly, the present investigation sought to determine the role of resveratrol and antioxidants on vascular function in C and AA women with T1D. METHODS: 15 C women with T1D and 6 AA women with T1D were enrolled. Participants were randomized to either an acute dose of RES or an antioxidant cocktail (AOC) containing Vitamin C, Vitamin E, and Alpha-Lipoic Acid. The flow-mediated dilation (FMD) test, a bioassay of NO bioavailability, was utilized to assess endothelial function normalized for shear (FMD/Shear) before and after treatment. In addition, a venous blood sample was collected to assess baseline clinical laboratory values and plasma concentrations of oxidative stress (8-isoprostane (8-iso) and superoxide dismutase (SOD)) before and after treatment. Data are reported as mean ± SD. RESULTS: No differences in baseline demographics were observed between Cs and AAs. Clinical laboratory values were similar between groups, except HbA 1c was higher ( p=0.013) in AAs (9.6±1.2%) compared to Cs (7.7±1.5%). Using a mixed model repeated measures design, a significant race x treatment x time interaction ( p=0.050) was observed for FMD/Shear. Treatment with AOC in AAs resulted in a significant increase ( p=0.002) in FMD/Shear. In addition, FMD/Shear was higher ( p=0.019) in AAs following treatment with AOC (0.370±0.128) compared to RES (0.212±0.049). Further, the % increase in FMD/Shear following treatment with AOC was greater ( p<0.001) in AAs (48±32%) compared to Cs (-1±42%). Independent of treatment, SOD was higher at both baseline ( p<0.001) and after treatment ( p=0.015) in AAs compared to Cs. Additionally, there was a decrease in SOD over time in AAs, collapsing treatment ( p=0.005). No differences in 8-iso were observed. CONCLUSION: Findings from the present investigation have identified that treatment to improve endothelial function in T1D can be race dependent. Compared to RES, treatment with AOC in AA women with T1D may be more effective at improving endothelial function. Neither treatment was effective at improving endothelial function in C women with T1D. Differences in oxidative stress may play a role; however, future studies are needed to understand how race impacts the treatment response in women with T1D. 1R01HL137087 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.