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

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.