Abdominal obesity with hyperinsulinemia reflects a prediabetic risk state signified by metabolic inflexibility and an overreliance on glucose as a metabolic fuel in skeletal muscle. There is limited information on net metabolic substrate flux across human skeletal muscle under physiological and pathophysiological conditions. Using arteriovenous difference sampling across the forearm in overweight (n = 9) compared with lean men (n = 7), we characterized net metabolic substrate fluxes over three consecutive meals and after an overnight fast during a 24-h cycle. Normoglycemic overweight men had significantly higher fasting and postprandial insulin levels compared with lean men. Overweight men had 3.6-fold higher forearm glucose uptake in the fasted and preprandial state compared with lean men (1.7 ± 0.3 vs. 0.5 ± 0.07 µmol/min/100 mL; P = 0.02), challenging the concept of decreased glucose uptake in skeletal muscle as a consequence of insulin resistance. The dominance of glucose uptake over the 24-h period in overweight men occurred in the context of lower fatty acid uptake. Forearm lactate flux fluctuated from positive to negative in lean men, whereas overweight men displayed lactate uptake across the meal cycles. In contrast, overweight men had 44% higher diurnal mass-adjusted alanine output compared with lean men (312 ± 25 vs. 216 ± 30 nmol/min; P = 0.048). In this cohort, elevated fasting insulin in overweight men was observed alongside greater reliance on glucose relative to fatty acids and increased alanine output from the forearm. These patterns may represent early metabolic adaptations associated with moderate obesity with likely impact on gluconeogenic substrates.
- This study investigated glucose metabolism in the forearm during fasting and postprandial states, comparing overweight men with lean men.
- We sought to understand how glucose is metabolized to prevent hyperglycemia in insulin-resistant men with obesity and the implications of increased basal glucose uptake in this population.
- Our findings reveal that overweight men exhibit elevated basal glucose uptake in the face of increased insulin concentrations and, unlike lean men, very limited basal lactate output.
- The overweight group demonstrated increased alanine release, suggesting a pathway toward enhanced hepatic gluconeogenesis.
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