Utzschneider Kristina M, Prigeon Ronald L, Carr Darcy B, Hull Rebecca L, Tong Jenny, Shofer Jane B, Retzlaff Barbara M, Knopp Robert H, Kahn Steven E
Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System (151), 1660 S. Columbian Way, Seattle, WA 98108, USA.
Diabetes Care. 2006 Feb;29(2):356-62. doi: 10.2337/diacare.29.02.06.dc05-1963.
To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AIRg) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance.
We studied 219 healthy subjects (88 male and 131 female subjects, aged 26-75 years) with fasting plasma glucose (FPG) <6.11 mmol/l. Subjects underwent an intravenous glucose tolerance test to determine the insulin sensitivity index (Si), AIRg, and the glucose disappearance constant (Kg), the latter a measure of intravenous glucose tolerance.
Si and AIRg were inversely related for the entire cohort, and this relationship was not significantly different from hyperbolic. The inverse relationship between Si and AIRg was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG <5.56 mmol/l vs. IFG, FPG 5.56-6.11 mmol/l) or by the Kg quartile. However, the curve relating Si and AIRg was left shifted in the IFG compared with NFG group (P < 0.001) and was progressively more left shifted with decreasing Kg (P < 0.001), consistent with decreasing beta-cell function. These changes were not observed for the curves relating Si and fasting insulin, suggesting that in the fasting state beta-cell function is maintained even in patients with mild IFG. Finally, the disposition index (DI) (Si x AIRg) was calculated as a measure of beta-cell function. The DI progressively decreased with increasing FPG, even in the group of subjects classified as NFG.
The inverse relationship between insulin sensitivity and AIRg is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased Kg. Based on a hyperbolic relationship, a decrease in beta-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.
确定空腹血糖受损（IFG）或糖耐量降低的受试者中是否存在胰岛素敏感性与葡萄糖急性胰岛素反应（AIRg）之间的双曲线关系。
我们研究了219名空腹血糖（FPG）<6.11 mmol/l的健康受试者（88名男性和131名女性，年龄26 - 75岁）。受试者接受静脉葡萄糖耐量试验以确定胰岛素敏感性指数（Si）、AIRg和葡萄糖消失常数（Kg），后者是静脉葡萄糖耐量的一种测量指标。
整个队列中Si和AIRg呈负相关，且这种关系与双曲线关系无显著差异。基于空腹血糖分组（正常空腹血糖[NFG]，FPG <5.56 mmol/l与IFG，FPG 5.56 - 6.11 mmol/l）或按Kg四分位数比较时，Si和AIRg之间的负相关无显著差异。然而，与NFG组相比，IFG组中Si和AIRg的曲线左移（P < 0.001），并且随着Kg降低曲线逐渐更向左移（P < 0.001），这与β细胞功能降低一致。在Si和空腹胰岛素相关曲线中未观察到这些变化，这表明在空腹状态下，即使是轻度IFG患者，β细胞功能也得以维持。最后，计算处置指数（DI）（Si×AIRg）作为β细胞功能的一种测量指标。即使在分类为NFG的受试者组中，DI也随着FPG升高而逐渐降低。
胰岛素敏感性与AIRg之间的负相关不仅在糖耐量正常的受试者中，而且在轻度IFG或Kg降低的受试者中均与双曲线一致。基于双曲线关系，即使在糖耐量正常的患者中，随着FPG升高也可检测到β细胞功能降低。
