早期胰岛素分泌降低是正常血糖人群糖代谢异常的主要危险因素

目的 评价早期胰岛素分泌降低及胰岛素抵抗在糖代谢异常发病中的作用,探讨正常血糖人群发生糖代谢异常的主要危险因素.方法 对来自78个2型糖尿病家系的成员进行口服葡萄糖耐量试验(OGTT),选择其中年龄在30岁以上的糖耐量正常(NGT)人群空腹血糖(FPG)<6.1mmol/L,糖负荷后2h血糖(2hPG)<7.8 mmol/L]共118人进行随访,在4-7年后复查OGTT,确定其糖代谢状态,分别以糖负荷30min净增胰岛素与净增葡萄糖的比值(AINS30/APG30)评估早期胰岛素分泌能力,以稳态模型法胰岛素抵抗指数(HOMA-IR)估测胰岛素抵抗状况,以稳态模型法β细胞功能指数(HOMA-B)估测B细胞功能,分析其对糖代谢状态转归的影响.结果 来自78个2型糖尿病家系的118人NGT人群随访4～7年后,66人仍为NGT,52人出现糖耐量恶化,其中糖尿病11人,糖尿病前期41人.分别以HOMA-IR及AINS30/APG30的中位数为切点将这118人人群分4组,4组中糖代谢异常的发生率分别为23.1%、36.4%、45.5%、73.1%,早期胰岛素分泌降低且胰岛素抵抗较重者糖代谢异常发生率较高(P<0.05);Logistic回归分析显示基线时早期胰岛素分泌能力与糖耐量恶化的发生呈明显负相关,而年龄、性别、胰岛素抵抗状况、β细胞功能均与糖调节受损的发生无显著相关性.结论 早期胰岛素分泌降低是正常血糖人群发生糖代谢异常的主要危险因素.

Impaired early-phase insulin secretion is the major risk factor for glucose metabolism deterioration in the population with normal glucose tolerance

Objective To evaluate the effect of early-phase insulin secretion and insulin resistance in the pathogenesis of type 2 diabetes, and to analysis the risk factors of glucose tolerance deterioration. Methods Oral glucose tolerance test (OGTT) was performed in subjects over 30 years old coming from 78 families with type 2 diabetes. A total of 118 subjects with normal glucose tolerance (NGT) fasting plasma glucose (FPG)<6.1 mmol/L and 2h postprandial glucose (2hPG)<7.8 mmol/L] were enrolled. Another OGTT was performed in them to define the glucose tolerance status at the end of the 4-7 years follow-up. AINS30/APG30, the ratio of the increment of insulin to that of plasma glucose at 30 min after the glucose load, was used to assess the early phase insulin secretion. HOMA-IR and HOMA-β were calculated to assess the insulin resistance and β-cell function respectively. Results After 4-7 years follow-up, 66 of 118 subjects still remained NGT, while 52 became either diabetic (n=11)or pre-diabetic (n=41). Using the median of HOMA-IR and AINS30/APG30 as the cutoff points, all subjects were divided into four groups: subjects with good early phase insulin secretion and no insulin resistance, subjects with good early insulin secretion but relative insulin resistance, subjects with impaired early phase insulin secretion but no insulin resistance, subjects with impaired early phase insulin secretion and also relative insulin resistance. The incidences of abnormal glucose tolerance among these four groups were 23.1%, 36.4%, 45.5% and 73.1% respectively. There was a statistical difference between the former three groups and the last one (P<0.05). Log/st/c regression analysis showed that only the early phase insulin secretion was the risk factor of glucose tolerance deterioration, while age, gender, insulin resistance or β-cell function were not. Conclusion Impaired early phase insulin secretion is a major risk factor for the disturbance of glucose metabolism in the population with NGT.