Early Microvascular Recruitment Modulates Subsequent Insulin-Mediated Skeletal Muscle Glucose Metabolism During Lipid Infusion

OBJECTIVE: To test whether early, insulin-mediated microvascular recruitment in skeletal muscle predicts steady-state glucose metabolism in the setting of physiological elevation of free fatty acid concentrations. RESEARCH DESIGN AND METHODS: We measured insulin's microvascular and metabolic effects in 14 healthy young adults during a 2-h euglycemic insulin clamp. Plasma free fatty acid concentrations were raised (Intralipid and heparin infusion) for 3 h before the clamp and maintained at postprandial concentrations during the clamp. Microvascular blood volume (MBV) was measured by contrast-enhanced ultrasound (CEU) continuously from baseline through the first 30 min of the insulin clamp. Muscle glucose and insulin uptake were measured by the forearm balance method. RESULTS: The glucose infusion rate (GIR) necessary to maintain euglycemia during the clamp varied by fivefold across subjects (2.5-12.5 mg/min/kg). The early MBV responses to insulin, as indicated by CEU video intensity, ranged widely, from a 39% decline to a 69% increase. During the clamp, steady state forearm muscle glucose uptake and GIR each correlated significantly with the change in forearm MBV (P < 0.01). To explore the basis for the wide range of vascular and metabolic insulin sensitivity observed, we also measured V(O(2max)) in a subset of eight subjects. Fitness (V(O(2max))) correlated significantly with the GIR, the forearm glucose uptake, and the percentage change in MBV during the insulin clamp (P < 0.05 for each). CONCLUSIONS: Early microvascular responses to insulin strongly associate with steady state skeletal muscle insulin-mediated glucose uptake. Physical fitness predicts both metabolic and vascular insulin responsiveness.