Lillioja S, Nyomba B L, Saad M F, Ferraro R, Castillo C, Bennett P H, Bogardus C
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix Indian Medical Center/National Institutes of Health, Arizona 85016.
J Clin Endocrinol Metab. 1991 Oct;73(4):866-76. doi: 10.1210/jcem-73-4-866.
Pima Indians have the highest reported prevalence rate of noninsulin-dependent diabetes mellitus (NIDDM) in the world, so that metabolic comparisons with caucasians, who have a much lower rate, should provide insights into the pathogenesis of NIDDM. We have compared 81 caucasians with 211 Pima Indian nondiabetic subjects similar in age, sex, degree of obesity, and glucose tolerance. During a hyperinsulinemic euglycemic clamp at physiological insulin concentrations, Pima Indians were 17% more insulin resistant than caucasians after accounting for any differences in degree of obesity (P less than 0.0001). During oral glucose tolerance testing, mean plasma insulin concentrations were 33% higher in the Pimas (P less than 0.0001), but these differences were largely explained by the greater insulin resistance in the Pimas. Insulin clearance did not differ between the races. However, early insulin responses were exaggerated in the Indians and not explained by insulin resistance. After accounting for differences in insulin action, plasma insulin concentrations in Pima Indians were 50% higher than those in caucasians 3-5 min after iv glucose (P less than 0.0001), 38% higher 10 min after the end of a meal (P less than 0.0001), and 20% higher 30 min after an oral glucose load (P less than 0.006). These data suggest that in addition to insulin resistance, Pima Indians have exaggerated early insulin release and either increased beta-cell mass or enhanced beta-cell sensitivity to glucose. The data argue against low or delayed insulin secretion as primary factors leading to NIDDM in Pima Indians and favor insulin resistance as the underlying and initiating cause of the disease.
皮马印第安人是世界上报告的非胰岛素依赖型糖尿病（NIDDM）患病率最高的人群，因此与患病率低得多的白种人进行代谢比较，应该能为NIDDM的发病机制提供见解。我们将81名白种人与211名年龄、性别、肥胖程度和糖耐量相似的皮马印第安非糖尿病受试者进行了比较。在生理胰岛素浓度下的高胰岛素正常血糖钳夹试验中，在考虑了肥胖程度的任何差异后，皮马印第安人的胰岛素抵抗比白种人高17%（P<0.0001）。在口服葡萄糖耐量试验期间，皮马人的平均血浆胰岛素浓度高33%（P<0.0001），但这些差异在很大程度上是由皮马人更大的胰岛素抵抗所解释的。不同种族之间的胰岛素清除率没有差异。然而，印第安人的早期胰岛素反应被夸大了，且不能用胰岛素抵抗来解释。在考虑了胰岛素作用的差异后，皮马印第安人在静脉注射葡萄糖后3-5分钟的血浆胰岛素浓度比白种人高50%（P<0.0001），餐后10分钟高38%（P<0.0001），口服葡萄糖负荷后30分钟高20%（P<0.006）。这些数据表明，除了胰岛素抵抗外，皮马印第安人还有夸大的早期胰岛素释放，以及要么增加的β细胞量，要么增强的β细胞对葡萄糖的敏感性。这些数据反对低胰岛素分泌或延迟胰岛素分泌是导致皮马印第安人患NIDDM的主要因素，而支持胰岛素抵抗是该疾病的潜在和起始原因。
