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

Abstract

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 Vo2max in a subset of eight subjects. Fitness (Vo2max) 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.