Campbell P J, Gerich J E
Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232.
J Clin Endocrinol Metab. 1990 Apr;70(4):1114-8. doi: 10.1210/jcem-70-4-1114.
We examined whether obesity must first exceed a critical threshold before it begins to impair insulin action in volunteers with normal glucose tolerance. Forty-nine healthy volunteers, whose ideal body weight ranged from 80-240%, underwent euglycemic clamps during sequential insulin infusions of 0.4, 1.0, and 10 mU/kg.min. Insulin sensitivity was assessed by estimation of the plasma insulin concentration that produced half-maximal glucose disposal (EC50). Glucose disposal during the highest insulin infusion was used as an index of maximal insulin responsiveness. There was a significant correlation between body mass index and insulin sensitivity (EC50) best fitted by a straight line that broke at a body mass index of 26.8 kg/m2 (P less than 0.05). Below this breakpoint (26.8 kg/m2), there was no significant correlation (r = 0.1), whereas above the breakpoint there was a strong positive correlation (r = 0.8; P less than 0.001) between EC50 and body mass index. In contrast, insulin responsiveness was not significantly correlated with body mass index (r = 0.1). We conclude that insulin sensitivity for glucose disposal is impaired in human subjects with normal glucose tolerance who exceed a critical threshold of obesity, which corresponds to an ideal body weight of 120%. This threshold is consistent with the nonlinear (J-shaped) relationship between obesity and its other adverse health consequences, and may have important implications for desirable weight goals.
我们研究了在糖耐量正常的志愿者中，肥胖是否必须先超过一个临界阈值才会开始损害胰岛素作用。49名健康志愿者，其理想体重范围为正常体重的80%-240%，在依次输注0.4、1.0和10 mU/kg·min胰岛素期间进行了正常血糖钳夹试验。通过估算产生半数最大葡萄糖清除率（EC50）的血浆胰岛素浓度来评估胰岛素敏感性。最高胰岛素输注期间的葡萄糖清除率用作最大胰岛素反应性的指标。体重指数与胰岛素敏感性（EC50）之间存在显著相关性，最佳拟合直线在体重指数为26.8 kg/m²处出现转折（P<0.05）。低于该转折点（26.8 kg/m²）时，无显著相关性（r = 0.1），而高于转折点时，EC50与体重指数之间存在强正相关（r = 0.8；P<0.001）。相比之下，胰岛素反应性与体重指数无显著相关性（r = 0.1）。我们得出结论，在糖耐量正常但超过肥胖临界阈值（相当于理想体重的120%）的人类受试者中，葡萄糖清除的胰岛素敏感性受损。该阈值与肥胖及其其他不良健康后果之间的非线性（J形）关系一致，可能对理想体重目标具有重要意义。
