Quantitative Estimation of Sensitivity of Lipolysis to Insulin

血浆游离脂肪酸对葡萄糖和胰岛素反应的种族差异可能有助于了解种族之间可能的健康差异。 在这里，我们比较了白人，非洲裔美国人和归化非洲人之间游离脂肪酸（FFA）清除率的差异。55名女性（17名白色，17名非裔美国人，21名非洲人），年龄35 - 10岁，平均SD，BMI 29.2 - 6.2 kg/m2，进行胰岛素改良频繁采样静脉葡萄糖耐量试验，在3 h内的32个时间点测定血浆葡萄糖、胰岛素和FFA。 以胰岛素为输入，将三室模型拟合至FFA和葡萄糖的时间序列。 该模型是葡萄糖处置的经典最小模型的扩展，经修改以包括由于脂解引起的FFA外观和通过一级动力学的FFA清除。通过远端隔室作用的胰岛素抑制脂解。 该模型发现，非裔美国人的FFA清除率高于白人（0.083 ± 0.05 min-1 v0.13 ± 0.06 min-1，P<0.01），但两者与非洲人（0.10 ± 0.06 min-1）无显著差异。 两组间控制脂解和胰岛素抑制脂解的参数无显著差异。 更大的FFA清除可能会对健康产生影响。 我们正在与米勒博士合作开发一种新的数学方法，用于从测量的C肽血浆浓度推断胰岛素分泌率。 我们正在与Yanovski实验室（NICHD）合作，将我们的研究扩展到奥利司他干预对儿科患者的影响，以及不同种族群体的比较研究（Sumner，NIDDK）。 我们正在研究β受体阻滞剂对模型参数的影响，检验胰岛素对血浆FFA作用的变化可能与这些药物的疗效相关的BF假设（与马里兰州大学Beitelshees合作）。 此外，我们正在检验BF假设，即TZD在肥胖受试者中的疗效与胰岛素对脂解作用的数学模型中参数的变化相关（与Snitker，马里兰州大学合作）。

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).