Velasquez-Mieyer P A, Cowan P A, Umpierrez G E, Lustig R H, Cashion A K, Burghen G A
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
Int J Obes Relat Metab Disord. 2003 Nov;27(11):1359-64. doi: 10.1038/sj.ijo.0802415.
Obese African-American (AA) subjects have higher resting and stimulated insulin concentrations than obese Caucasians (C), which could not be explained by the severity of obesity or the degree of insulin sensitivity. We investigated whether differences in glucagon-like peptide-1 (GLP-1), the most potent incretin that regulates insulin secretion, might explain racial differences in insulin response. Accordingly, we measured fasting and stimulated glucose, insulin, and GLP-1 levels during a 3-h oral glucose tolerance test (OGTT) in 26 obese C (age 38+/-2 y, body mass index 44+/-1 kg/m(2)) and 16 obese AA (age 36+/-2 y, BMI 46+/-2 kg/m(2)) subjects. Corrected insulin response (CIR(30)), a measure of beta-cell activity, whole body insulin sensitivity index (WBISI), and area under the curve (AUC) for insulin, GLP-1, and C-peptide/insulin ratio were computed from the OGTT. Glucose levels, fasting and during the OGTT, were similar between racial groups; 32% of the C and 31% of the AA subjects had impaired glucose tolerance. With a similar WBISI, AAs had significantly higher CIR(30) (2.3+/-0.4 vs 1.01+/-0.1), insulin response (IAUC: 23 974+/-4828 vs 14 478+/-1463), and lower insulin clearance (0.07+/-0.01 vs 0.11+/-0.01) than C (all, P<0.01). Obese AAs also had higher fasting GLP-1 (6.7+/-2.5 vs 4.5+/-1.1) and GLP-1AUC (1174.7+/-412 vs 822.4+/-191) than C (both, P<0.02). Our results indicate that obese AAs had higher concentrations of GLP-1 both at fasting and during the OGTT than obese C. The increased GLP-1 concentration could explain the greater insulin concentration and the increased prevalence of hyperinsulinemia-associated disorders including obesity and type 2 diabetes in AAs.
肥胖的非裔美国人（AA）受试者的静息和刺激后胰岛素浓度高于肥胖的高加索人（C），这无法用肥胖的严重程度或胰岛素敏感性程度来解释。我们研究了胰高血糖素样肽-1（GLP-1）（调节胰岛素分泌的最有效肠促胰岛素）的差异是否可以解释胰岛素反应的种族差异。因此，我们在26名肥胖的C受试者（年龄38±2岁，体重指数44±1kg/m²）和16名肥胖的AA受试者（年龄36±2岁，BMI 46±2kg/m²）中进行了3小时口服葡萄糖耐量试验（OGTT），测量了空腹和刺激后的血糖、胰岛素和GLP-1水平。根据OGTT计算校正胰岛素反应（CIR(30)）（β细胞活性的指标）、全身胰岛素敏感性指数（WBISI）以及胰岛素、GLP-1和C肽/胰岛素比值的曲线下面积（AUC）。种族组之间的空腹和OGTT期间的血糖水平相似；32%的C受试者和31%的AA受试者有糖耐量受损。在WBISI相似的情况下，AA的CIR(30)显著更高（2.3±0.4对1.01±0.1）、胰岛素反应（IAUC：23974±4828对14478±1463）且胰岛素清除率更低（0.07±0.01对0.11±0.01）（均P<0.01）。肥胖的AA的空腹GLP-1（6.7±2.5对4.5±1.1）和GLP-1 AUC（1174.7±412对822.4±191）也高于C（均P<0.02）。我们的结果表明，肥胖的AA在空腹和OGTT期间的GLP-1浓度均高于肥胖的C。GLP-1浓度的增加可以解释AA中更高的胰岛素浓度以及包括肥胖和2型糖尿病在内的高胰岛素血症相关疾病患病率的增加。
