Impact of Insulin-Induced Relative Hypoglycemia on Vascular Insulin Sensitivity and Central Hemodynamics in Prediabetes

Abstract

Abstract Context Relative hypoglycemia (RH) is linked to sympathetic responses that can alter vascular function in individuals with type 2 diabetes. However, less is known about the role of RH on hemodynamics or metabolic insulin sensitivity in prediabetes. Objective Determine if RH alters peripheral endothelial function or central hemodynamics to a greater extent in those with prediabetes vs normoglycemia. Methods Seventy adults with obesity were classified using ADA criteria as prediabetes (n = 34 (28 F); HbA1c = 6.02% ± 0.1%) or normoglycemia (n = 36 (30 F); HbA1c = 5.4% ± 0.0%). Brachial artery endothelial function, skeletal muscle capillary perfusion, and aortic waveforms were assessed at 0 and 120 minutes of a euglycemic clamp (40 mU/m2/min, 90 mg/dL). Plasma nitrate/nitrite and endothelin-1 were measured as surrogates of nitric oxide–mediated vasodilation and vasoconstriction, respectively. RH was defined as the drop in glucose (%) from fasting to clamp steady state. Results There were no differences in age, weight, or VO2max between groups. The prediabetes group had higher HbA1c (P < .01) and a greater drop in glucose in response to insulin (14% vs 8%; P = .03). Further, heart rate increased in normoglycemia compared to prediabetes (P < .01), while forward wave (Pf) decreased in prediabetes (P = .04). Insulin also tended to reduce arterial stiffness in normoglycemia vs prediabetes (P = .07), despite similar increases in preocclusion diameter (P = .02), blood flow (P = .02), and lower augmentation index (P ≤ .05). Conclusion Compared with normoglycemia, insulin-induced RH corresponded with a blunted rise in heart rate and drop in Pf during insulin infusion in adults with prediabetes, independent of changes in peripheral endothelial function.