Gower Barbara A, Granger Wesley M, Franklin Frank, Shewchuk Richard M, Goran Michael I
Department of Nutrition Sciences and Clinical Nutrition Research Center, University of Alabama at Birmingham 35294-3360, USA.
J Clin Endocrinol Metab. 2002 May;87(5):2218-24. doi: 10.1210/jcem.87.5.8498.
Relative to Caucasians (C), African-American (AA) children and adults have lower indices of insulin sensitivity (S(i)) and a higher acute insulin response to glucose (AIR(g)). Among AA children, AIR(g) is greater than that which would be predicted based on lower S(i). The objectives of the present study were 1) to determine whether insulin secretory parameters differ in AA vs. C children and adolescents using C-peptide modeling, 2) to determine whether hepatic insulin extraction differs with ethnicity/race using the C-peptide to insulin molar ratio, and 3) to determine whether the relatively greater AIR(g) among African-Americans is due to greater insulin secretion or lesser clearance. Subjects (n = 76) were AA and C children (mean age, approximately 11 yr). A 3-h tolbutamide-modified iv glucose tolerance test and minimal modeling were used to determine S(i) and AIR(g). First phase C-peptide/insulin secretion and basal, first, and second phase beta-cell sensitivity to glucose were determined using C-peptide modeling with standard kinetic parameters developed in adults. The incremental C-peptide to insulin molar ratio over the 3-h test period, an index of hepatic insulin extraction, was calculated with the trapezoidal method. S(i) was lower and AIR(g) was higher in AA vs. C children. First phase C-peptide/insulin secretion and first phase beta-cell sensitivity to glucose were approximately 2-fold greater in AA vs. C children (P < 0.001); there were no between-group differences in basal or second phase beta-cell sensitivity to glucose. Hepatic insulin extraction was lower in AA vs. C (3.77 +/- 1.78% vs. 5.99 +/- 2.18%; P < 0.001). Multiple linear regression modeling indicated that first phase C-peptide/insulin secretion and hepatic insulin extraction contributed independently to AIR(g); however, it was only first phase C-peptide/insulin secretion that explained the significant independent contribution of ethnicity/race to AIR(g) after adjusting for S(i). The results of this study suggest that greater AIR(g) among AA is due to both greater insulin secretion and lesser hepatic insulin extraction, and that AIR(g) above that predicted based on lower S(i) is due to greater insulin secretion. The insulin secretion data await verification that the kinetic parameters used apply to children and AA.
与高加索人（C）相比，非裔美国（AA）儿童和成人的胰岛素敏感性指数（S(i)）较低，对葡萄糖的急性胰岛素反应（AIR(g)）较高。在AA儿童中，AIR(g)高于根据较低的S(i)所预测的值。本研究的目的是：1）使用C肽模型确定AA儿童与C儿童及青少年的胰岛素分泌参数是否不同；2）使用C肽与胰岛素的摩尔比确定肝脏胰岛素提取率是否因种族而异；3）确定非裔美国人中相对较高的AIR(g)是由于胰岛素分泌增加还是清除减少。研究对象（n = 76）为AA和C儿童（平均年龄约11岁）。采用3小时甲苯磺丁脲改良静脉葡萄糖耐量试验和最小模型法来测定S(i)和AIR(g)。使用在成人中开发的标准动力学参数的C肽模型来确定第一相C肽/胰岛素分泌以及基础、第一和第二相β细胞对葡萄糖的敏感性。采用梯形法计算3小时试验期内C肽与胰岛素的增量摩尔比，作为肝脏胰岛素提取率的指标。与C儿童相比，AA儿童的S(i)较低，AIR(g)较高。AA儿童的第一相C肽/胰岛素分泌和第一相β细胞对葡萄糖的敏感性比C儿童高约2倍（P < 0.001）；基础或第二相β细胞对葡萄糖的敏感性在组间无差异。与C儿童相比，AA儿童的肝脏胰岛素提取率较低（3.77 +/- 1.78%对5.99 +/- 2.18%；P < 0.001）。多元线性回归模型表明，第一相C肽/胰岛素分泌和肝脏胰岛素提取率独立影响AIR(g)；然而，在调整S(i)后，只有第一相C肽/胰岛素分泌解释了种族对AIR(g)的显著独立贡献。本研究结果表明，AA儿童中较高的AIR(g)是由于胰岛素分泌增加和肝脏胰岛素提取减少，并且基于较低S(i)所预测的AIR(g)之上的部分是由于胰岛素分泌增加。胰岛素分泌数据有待验证所使用的动力学参数是否适用于儿童和AA人群。
