Ishikawa M, Pruneda M L, Adams-Huet B, Raskin P
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75235-8858, USA.
Diabetes. 1998 May;47(5):788-92. doi: 10.2337/diabetes.47.5.788.
A close association between obesity and hyperinsulinemia is well recognized, but it is not known whether this relationship is affected by the genetic susceptibility to type 2 diabetes. Insulin response to a 75-g oral glucose load was evaluated in healthy nondiabetic Caucasians with first-degree family history of diabetes (relatives, n = 55) and those without family history (nonrelatives, n = 33). A significant correlation between the BMI and insulin response (area under the curve [AUC] during the 2-h period) was seen in nonrelatives (r = 0.68, P < 0.0001) but not in the relatives (r = 0.12, P = 0.37). Multivariate analysis revealed that obesity (BMI) was the primary determinant of insulin response in nonrelatives (P < 0.001), whereas among the relatives, BMI had no significant impact (P = 0.28). Thus, these distinctions between the relatives and nonrelatives remained after adjusting for glucose level, age, and gender. Among first-degree relatives, the commonly observed association between BMI and insulin response is lost, and hyperinsulinemia is present even in the absence of obesity. First-degree family history of diabetes may confer insulin resistance that is independent of obesity. Alternatively, this could suggest a pathological regulation of an obesity-insulin feedback loop, e.g., a defective recognition of adiposity.
肥胖与高胰岛素血症之间的密切关联已得到充分认识，但尚不清楚这种关系是否受2型糖尿病遗传易感性的影响。对有糖尿病一级家族史的健康非糖尿病白种人（亲属，n = 55）和无家族史的人（非亲属，n = 33）进行了口服75克葡萄糖负荷后的胰岛素反应评估。在非亲属中观察到BMI与胰岛素反应（2小时期间曲线下面积[AUC]）之间存在显著相关性（r = 0.68，P < 0.0001），而在亲属中未观察到（r = 0.12，P = 0.37）。多变量分析显示，肥胖（BMI）是非亲属中胰岛素反应的主要决定因素（P < 0.001），而在亲属中，BMI没有显著影响（P = 0.28）。因此，在调整血糖水平、年龄和性别后，亲属与非亲属之间的这些差异仍然存在。在一级亲属中，通常观察到的BMI与胰岛素反应之间的关联消失，即使没有肥胖也会出现高胰岛素血症。糖尿病一级家族史可能赋予独立于肥胖的胰岛素抵抗。或者，这可能表明肥胖-胰岛素反馈回路的病理调节，例如对肥胖的识别缺陷。
