2型糖尿病家系中初诊糖尿病患者的胰岛β细胞功能

Dysfunction of islet β-cell in newly diagnosed diabetic patients in type 2 diabetes families

目的研究2型糖尿病(T2D)家系中初诊T2D患者的胰岛β细胞功能和胰岛素抵抗(IR)状况;探讨新诊断T2D人群胰岛β细胞功能与糖代谢的关系。方法来自T2D家系的初诊T2D患者158例、无糖尿病家族史的正常糖耐量配偶(NC)62例进行75 g口服葡萄糖耐量试验(OGTT)和胰岛素释放试验。据空腹血糖(FPG)的水平,将T2D分为DM1(FPG<6.1 mmol/L)、DM2(6.1 mmol/L≤FPG<7.8 mmol/L)和DM3(FPG≥7.8 mmol/L)3组。用胰岛素抵抗指数(Ho-ma-IR)和胰岛素作用指数(IAI)评估胰岛素敏感性;用3种胰岛素分泌指数及3种相应的葡萄糖处置指数(DI)分别评估基础、早期和糖负荷后的胰岛β细胞功能。结果①家系的初诊T2D,随着空腹血糖的升高,Homa-IR逐渐增加,IAI、胰岛素分泌指数和DI进行性下降,两组之间差异均具有统计学意义(P<0.01或0.05);与胰岛素敏感性降低相比,胰岛β细胞功能下降更为明显。②在NC组FPG的变化主要由Homa-IR解释(近60%);而初诊T2D各亚组则主要由Homa-β解释,在DM3组Homa-β可解释的比例高达89.6%。结论T2D家系的初诊T2D患者存在胰岛素敏感性和胰岛β细胞功能下降,但胰岛β细胞功能降低更加突出,对空腹血糖的影响更大,提示胰岛β细胞功能缺陷可能在T2D的发生发展过程中起的作用更大。

Objective To investigate the dysfunction of islet β-cell and insalin-resistence in newly diagnosed type 2 diabetic patients （T2D） with family history, and explore the role of β-cell dysfunction in the worsening of glucose tolerance. Methods An oral glucose tolerance test（OGTF） and insulin release test were given to 158 newly diagnosed patients （T2D） with family history and their 62 spouses with normal glucose tolerance （ NC group） who had no diabetic family history. The subjects were divided into 3 groups based on the level of fasting plsama glucose（ FPG）. DM1 （ FPG 〈6.1 mmol/L） ,DM2（6.1 mmol/L≤ FPG 〈7.8 mmol/L） ,DM3 （ FPG ≥7.8 mmol/L）. Insulin sensitivity was estimated by Homeostasis model assessment for insulin resistence （Homa-IR） and insulin action index （IAI）. The islet β-cell function was evaluated by 3 insulin release indices [ Homa-β, △I30/△G30 ： the ratio of incremental glucose and insulin 30 min after glucose intake, modified betacell function index（MBCI） and their corresponding disposition indices （ DI1 = Homa-β/Homa-IR, DI2 = △I30/ △G30/Homa-IR, DI3=MBCI×IAI）]. Results （1） Progressive increase was observed in the Homa-IR from DMI through DM2 to DM3 as FPG augmented while progressive decrease in IAI （all P 〈 0.01 or 0. 05 ） in newly diagnosed T2D. Compared with insulin sensitivity, islet β-cell function declined more obviously. （2）In NC group, the level of FPG was mainly determined by Homa-IR, however, Homa-β which could explain the FPG growing up to 90% in DM3 group was a more important contributor than Homa-IR for FPG in subgroups of newly diagnosed diabetes. Conclusion Both decreased insulin sensitivity and impaired β-cell function are associated with increased glucose level in newly diagnosed diabetes. Future more, β-cell function declines more obvious than insulin sensitivity. It indicates that β-cell function defect may play more important role in the development and progression of T2D.