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目的研究胰岛素抵抗(IR)和β细胞功能在2型糖尿病(T2DM)发生、发展过程中的作用。方法在2013年浙江省玉环县健康队列基线调查基础上,选取269名初诊T2DM患者,按照性别相同、年龄差小于3岁且无血缘关系的条件选取糖调节受损(IGR)和正常糖耐量(NGT)各269例。将初诊T2DM亚分类为单纯空腹血糖升高(IFH)、单纯负荷后血糖升高(IPH)和空腹合并负荷后血糖升高(CH),IGR分为单纯空腹血糖受损(IFG)、单纯负荷后血糖受损(IGT)和空腹合并负荷后血糖受损(CGI)。采用稳态模型胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)和葡萄糖处置指数(DI)对IR、胰岛β细胞功能和代偿IR的β细胞功能进行评价。结果从NGT到IGR到T2DM,HOMA-IR逐渐增高,而HOMA-β和DI逐渐降低(P<0.05)。调整年龄、性别、肥胖及高血压后,与NGT比较,IFG和CGI的HOMA-IR增高、HOMA-β和DI降低,而IGT仅HOMA-β和DI降低(P<0.05);IFG、CGI较IGT的HOMA-IR升高、HOMA-β和DI降低(P<0.05);IFH、CH较IPH的HOMA-IR升高、HOMA-β和DI降低(P<0.05),CH仅DI低于IFH(P<0.05),且IFH与IFG比较及CH与CGI比较,均为HOMA-IR增高、HOMA-β和DI降低,而IPH仅HOMA-β和DI低于IGT(P<0.05)。多因素线性回归分析显示,HOMA-IR在NGT组对空腹血糖有显著影响(P<0.05),DI在各组对空腹血糖和负荷后血糖均有显著影响(P<0.05)。结论 IFG和CGI主要表现为IR和β细胞功能受损,而IGT则主要表现为β细胞功能受损。空腹血糖升高以基础状态下胰岛β细胞功能受损和IR为主要特征,同时基础状态下胰岛β细胞功能对负荷后血糖有所影响。
Objective To study the role of insulin resistance (IR) and β-cell function in the development and progression of type 2 diabetes mellitus (T2DM). Methods Based on the baseline survey of healthy cohorts of Yuhuan County in Zhejiang Province in 2013, 269 newly diagnosed T2DM patients were selected according to the conditions of the same sex, the age difference of less than 3 years and no blood relationship between the conditions of impaired glucose regulation (IGR) and normal glucose tolerance NGT) 269 cases each. The newly diagnosed T2DM was subdivided into simple hyperglycemia (IFH), simple hyperglycemia (IPH), and elevated fasting glucose (CH) after fasting combined load. IGR was divided into simple impaired fasting glucose (IFG) Post-impaired glucose (IGT) and impaired glucose tolerance (CGI) after an empty stomach consolidation load. The function of IR, islet β-cell function and IR-compensated β-cell function were evaluated by homeostasis model assessment of insulin resistance index (HOMA-IR), islet β cell function index (HOMA-β) and glucose disposal index (DI) Results From NGT to IGR to T2DM, HOMA-IR increased gradually, while HOMA-β and DI gradually decreased (P <0.05). Compared with NGT, HOMA-IR, HOMA-βand DI were decreased in IFG and CGI, but only HOMA-βand DI in IGT were decreased (P <0.05) compared with NGT after adjusting for age, sex, obesity and hypertension; HOMA-IR, HOMA-β and DI in IGT increased (P <0.05); HOMA-IR increased, HOMA-β and DI decreased (P <0.05) (P <0.05). Compared with IFG, CH and CGI, HOMA-IR and HOMA-β and DI were decreased, while HOMA-β and DI were lower in IPH than in IGT (P <0.05). Multivariate linear regression analysis showed that HOMA-IR had significant effects on fasting blood glucose in NGT group (P <0.05), and DI had a significant effect on fasting blood glucose and post-loading blood glucose in each group (P <0.05). Conclusions IFG and CGI are mainly manifested as impaired IR and β-cell functions, while IGT is mainly impaired in β-cell function. Fasting plasma glucose increased basal state islet β-cell dysfunction and IR as the main feature, while basal state islet β-cell function has an impact on post-load blood glucose.