Haffner S M, Stern M P, Hazuda H P, Mitchell B D, Patterson J K
Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
N Engl J Med. 1988 Nov 17;319(20):1297-301. doi: 10.1056/NEJM198811173192001.
Insulin resistance is thought by many to be the primary defect that results in non-insulin-dependent diabetes mellitus (NIDDM). An implication of this theory is that prediabetic persons have higher serum insulin levels than normal subjects. We assessed serum insulin concentrations in a cohort of 1497 nondiabetic Mexican Americans, a population at high risk for NIDDM, according to whether their parents or siblings had diabetes. It was assumed that prediabetic persons would be more likely to have strong family histories of diabetes. We found a stepwise increase in fasting insulin levels in nondiabetics with neither, one, or both parents with diabetes (69.8, 77.8, and 94.6 pmol per liter, respectively; P = 0.002). Similar results were observed for insulin sum (the total of insulin concentrations in the fasting state and at 30, 60, and 120 minutes after a 75-g oral glucose load). The differences in insulin sums according to family history remained statistically significant in analyses of covariance, which controlled for variations in body-mass index, body-fat distribution, and level of blood glucose. Subjects without diabetes who had a diabetic sibling had higher fasting concentrations of insulin than subjects without a diabetic sibling (83.2 vs. 69.6 pmol per liter), but the difference was not statistically significant. We conclude that prediabetic persons, who would be expected to be more numerous in kindreds with progressively stronger family histories of diabetes, have hyperinsulinemia. This supports the insulin-resistance hypothesis.
许多人认为胰岛素抵抗是导致非胰岛素依赖型糖尿病（NIDDM）的主要缺陷。该理论的一个推论是，糖尿病前期患者的血清胰岛素水平高于正常受试者。我们根据1497名非糖尿病墨西哥裔美国人的父母或兄弟姐妹是否患有糖尿病，评估了他们的血清胰岛素浓度。这些人是患NIDDM的高危人群。据推测，糖尿病前期患者更有可能有糖尿病家族史。我们发现，父母均无糖尿病、父母一方有糖尿病、父母双方均有糖尿病的非糖尿病患者的空腹胰岛素水平呈逐步上升趋势（分别为每升69.8、77.8和94.6皮摩尔；P = 0.002）。胰岛素总和（空腹状态以及75克口服葡萄糖负荷后30、60和120分钟时的胰岛素浓度总和）也观察到类似结果。在控制了体重指数、体脂分布和血糖水平变化的协方差分析中，根据家族史得出的胰岛素总和差异仍具有统计学意义。有糖尿病兄弟姐妹的非糖尿病受试者的空腹胰岛素浓度高于没有糖尿病兄弟姐妹的受试者（每升83.2对69.6皮摩尔），但差异无统计学意义。我们得出结论，在糖尿病家族史逐渐增强的亲属中预计会更多的糖尿病前期患者存在高胰岛素血症。这支持了胰岛素抵抗假说。
