Quantitative Estimation of Sensitivity of Lipolysis to Insulin

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Racial differences in plasma free fatty acid responses to glucose and insulin could give insights to possible health disparities between races. Here, we compare differences in free fatty acid (FFA) clearance rates between whites, African Americans, and naturalized Africans. Fifty five women (17 white, 17 African Americans, 21 Africans), age 3510y, meanSD, BMI 29.26.2 kg/m2, had insulin modified-frequently sampled intravenous glucose tolerance tests with plasma glucose, insulin and FFA determined at 32 time points in 3h. A three-compartment model was fit to the time series of FFA and glucose with insulin as the input. The model was an extension of the classic minimal model for glucose disposal modified to include FFA appearance due to lipolysis and FFA clearance through first order kinetics. Lipolysis was inhibited by insulin acting through a remote compartment. The model found that African Americans had a higher FFA clearance rate than Whites (0.0830.05 min-1 v 0.130.06 min-1, P<0.01) but both were not significantly different from Africans (0.100.06 min-1). There were no significant differences between the groups for the parameters governing lipolysis and suppression of lipolysis by insulin. Greater FFA clearance may have health implications. We are collaborating with Dr. Miller in developing a new mathematical method for inferring insulin secretion rates from measured C-peptide plasma concentrations. We are collaborating with the Yanovski laboratory (NICHD) in extending our studies to the effects of Orlistat intervention in pediatric patients, and to comparative studies of different ethnic groups (Sumner, NIDDK). We are investigating the effects of beta-blockers on model parameters, testing the bf hypothesis that changes in insulin action on plasma FFA may be correlated with the efficacy of these drugs (collaboration with Beitelshees, University of Maryland). Furthermore, we are testing the bf hypothesis that the efficacy of TZDs in obese subjects is correlated with changes in parameters in the mathematical model of insulin action on lipolysis (collaboration with Snitker, University of Maryland).