The relationship between glucose disposal in response to physiological hyperinsulinemia and basal glucose and free fatty acid concentrations in healthy volunteers

This study was initiated to see if defects in the ability of physiological hyperinsulinemia (similar to 60 mu U/mL) to stimulate glucose uptake in hea lthy, nondiabetic volunteers are associated with increases in concentration s of plasma glucose and free fatty acid (FFA) when measured at basal insuli n concentrations (similar to 10 mu U/mL). We recruited 22 volunteers (12 wo men and 10 men) for these studies, with a (mean +/- SEM) body mass index of 24.8 +/- 0.5 kg/m(2). Resistance to insulin-mediated glucose disposal duri ng physiological hyperinsulinemia was determined by suppressing endogenous insulin and determining the steady-state plasma glucose (SSPG) and steady-s tate plasma insulin (SSPI) concentrations at the end of a 3-h infusion, per iod during which glucose (267 mg/m(2).min) and insulin (32 mU/m(2).min) wer e infused at a constant rate. Glucose, insulin and FFA concentrations were also measured in response to infusion rates of glucose (50 mg/m(2)min) and insulin (6 mU/m(2).min). The SSPI concentration (mean +/- SEM) during physi ological hyperinsulinemia was 64 +/- 3 mu U/mL), in contrast to 12 +/- 0.4 mu U/mL during the basal insulin study. The results demonstrated a signific ant relationship between SSPG concentration in response to physiological hy perinsulinemia (SSPG(60)) and SSPG(Basal) (r = 0.57, P < 0.01) and FFA(Basa l) (r = 0.73, P < 0.001). Furthermore, FFA(Basal) and SSPG(Basal) were sign ificantly correlated (r = 0.47, P < 0.05). Comparison of the seven most ins ulin resistant and seven most insulin sensitive individuals (SSPG,, values of 209 +/- 16 vs. 64 +/- 8 mg/dL) revealed that the insulin-resistant group also had significantly higher SSPG(Basal) (105 +/- 5 vs. 78 +/- 7 mg/dL, P < 0.01) and FFA(Basal) (394 +/- 91 vs. 104 +/- 41, P < 0.02) concentration s. However, random fasting plasma glucose and FFA concentrations of the two groups were not different. The results presented demonstrate that individu al differences in the ability of elevated insulin concentrations to stimula te muscle glucose disposal are significantly correlated with variations in insulin regulation of plasma glucose and FFA concentrations at basal insuli n concentrations.