胰岛素抵抗和β细胞功能在新诊断2型糖尿病发生中的作用

Chen Xiaoying, Su Meifang, Wang Congyun, Wu Zhaofan, Li Songtao, Ying Xuhua, Wei Guorong, Fu Chaowei, Jiang Qingwu

Wei Sheng Yan Jiu. 2015 Nov;44(6):881-6.

OBJECTIVE

To assess the possible role of insulin resistance (IR) and β cell function in the pathophysiology of newly diagnosed type 2 diabetics (T2DM).

METHODS

An oral glucose tolerance test was obtained at the health cohort baseline. Subjects with normal glucose tolerance (NGT, n = 269), impaired glucose regulation (IGR, n = 269) and newly diagnosed type 2 diabetics (T2DM, n = 269) were defined by ADA criteria. Subjects with NGT and IGR were selected from residents living in the same community of diabetic patients with the same gender and age (± 3 years old). The T2DM group was sub-classified as isolated fasting hyperglycemia (IFH), isolated post-challenge hyperglycemia (IPH) and combined hyperglycemia (CH). The IGR group was sub-classified as impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and combined glucose intolerance (CGI). Homeostasis model assessment of insulin resistance (HOMA-IR), β cell function (HOMA-β) and deposition index (DI) were to evaluate the insulin resistance or sensitivity, islet β cell function and that when insulin compensated respectively.

RESULTS

From NGT to T2DM, HOMA-IR increased while HOMA-β and DI decreased significantly (P < 0.05). After the adjustment of age, gender, obesity and hypertension, IFG and CGI subgroup had statistically higher HOMA-IR and lower HOMA-β and DI, and IGT subgroup only had lower HOMA-β and DI than NGT subgroup (P < 0.05). Compared to IGT subgroup, IFG and CGI subgroup had significantly higher HOMA-IR and lower HOMA-β and DI (P < 0.05). IFH and CH subgroup had statistically higher HOMA-IR and lower HOMA-β and DI than IFH subgroup (P < 0.05), DI of CH subgroup significantly decreased than that of IPH subgroup (P < 0.05). IFH and CH subgroup had statistically higher HOMA-IR and lower HOMA-β and DI than IFG and CGI subgroup respectively. HOMA-β and DI decreased of IPH subgroup compared to IGT subgroup, and multiple linear regression analysis showed that HOMA-IR had significant influence on fasting plasma glucose (FPG) in NGT (P < 0.05), whereas two-hour plasma glucose and FPG were influenced by DI (P < 0.05) in the progression.

CONCLUSIONS

Both basic β cell dysfunction and IR exist in IFG and CGI, while only basic β cell dysfunction exist in IGT. The basic β cell dysfunction and IR are the primary features of fasting hyperglycemia, and basic β cell dysfunction also contribute to post- challenge hyperglycemia.

目的

评估胰岛素抵抗（IR）和β细胞功能在新诊断2型糖尿病（T2DM）病理生理过程中的可能作用。

方法

在健康队列基线时进行口服葡萄糖耐量试验。根据美国糖尿病协会（ADA）标准定义葡萄糖耐量正常（NGT，n = 269）、糖调节受损（IGR，n = 269）和新诊断2型糖尿病（T2DM，n = 269）的受试者。NGT和IGR受试者从与糖尿病患者居住在同一社区、性别和年龄相同（±3岁）的居民中选取。T2DM组进一步分为单纯空腹血糖升高（IFH）、单纯餐后血糖升高（IPH）和混合性血糖升高（CH）。IGR组进一步分为空腹血糖受损（IFG）、糖耐量受损（IGT）和混合性糖耐量受损（CGI）。采用稳态模型评估胰岛素抵抗（HOMA-IR）、β细胞功能（HOMA-β）和沉积指数（DI），分别评估胰岛素抵抗或敏感性、胰岛β细胞功能以及胰岛素代偿情况。

结果

从NGT到T2DM，HOMA-IR升高，而HOMA-β和DI显著降低（P < 0.05）。在调整年龄、性别、肥胖和高血压后，IFG和CGI亚组的HOMA-IR在统计学上更高，HOMA-β和DI更低，且IGT亚组的HOMA-β和DI仅比NGT亚组低（P < 0.05）。与IGT亚组相比，IFG和CGI亚组的HOMA-IR显著更高，HOMA-β和DI更低（P < 0.05）。IFH和CH亚组的HOMA-IR在统计学上高于IFG亚组，HOMA-β和DI低于IFG亚组（P < 0.05），CH亚组的DI显著低于IPH亚组（P < 0.05）。IFH和CH亚组的HOMA-IR分别高于IFG和CGI亚组，HOMA-β和DI低于IFG和CGI亚组。与IGT亚组相比，IPH亚组的HOMA-β和DI降低，多元线性回归分析显示，在NGT中HOMA-IR对空腹血糖（FPG）有显著影响（P < 0.05），而在疾病进展过程中，两小时血糖和FPG受DI影响（P < 0.05）。