妊娠糖尿病患者胰岛素抵抗及胰岛β细胞功能的初步研究

Preliminary study on insulin resistance and pancreatic beta cell function in pregnant women with gestationaldiabetes mellitus

目的研究孕中期不同血糖水平孕妇胰岛素抵抗及胰岛B细胞功能的特点，探讨妊娠糖尿病（GDM）可能的发病机制。方法选取2008年4月至2011年3月在苏州市立医院本部常规产检的孕妇，在孕中期50g糖筛查阳性者共2489例患者，行75g口服葡萄糖耐量试验（OGTF）和胰岛素释放试验，分别测定空腹、1h、2h、3h的各点血糖和胰岛素。根据血糖结果分为正常糖耐量（NGT）组及GDM组，GDM组进一步分为：GDM1组：1h血糖异常（≥10．0mmol/L）；GDM2组：2h血糖异常（≥8．5mmol／L）；GDM3组：空腹血糖异常（I〉5．1mmol／L）；GDM4组：多点血糖异常（2点或2点以上血糖异常）。比较不同血糖特点患者的血糖曲线下面积（AUCG）、胰岛素曲线下面积（AUCI）、稳态模型评估的胰岛B细胞功能指数（HOMA．B）、混合胰岛素敏感度（ISI）、稳态模型评估的胰岛素抵抗指数（HOMA—IR）、胰岛素分泌指数（△I60／△G60）。结果（1）GDM组AUCG、AUCI、HOMA—IR高于NGT组，HOMA—β、ISI低于NGT组（P〈0．05）。（2）GDMl、3、4组HOMA—IR较NGT组相比明显升高（P〈0．01），GDM3、4组HOMA—β明显低于NGT组（P〈0.01）。GDMl-4组IsI降低（P〈0．01）。结论GDM患者胰岛素抵抗较孕期正常妇女增高，且同时伴有胰岛分泌功能受损。不同血糖水平孕妇其胰岛素分泌功能障碍各具特点：空腹血糖升高者以基础状态胰岛素分泌下降为主，餐后血糖升高者以糖负荷后胰岛素分泌功能下降为主，而多点血糖升高者基础状态及糖负荷后胰岛素分泌功能均明显受损。

Objective To study the distinguishing features of insulin resistance and pancreatic β-cell secretion in mid-term pregnant patients with different blood glucose levels, and to investigate the possible pathogenesis of gestational diabetes （GDM）. Methods A total of 2 489 pregnant women during the second trimester （ gestational age 24-28 weeks） with positive 50 g GCT test were included in the study. Based on the results of oral 75 g glucose tolerance test, the patients were divided into GDM group and normal glucose tolerance （NGT） group, the GDM group were further divided into four groups according to levels of blood glucose ： 1 h postprandial blood glucose abnormality only （ GDM-1,〉 10.0 retool/L）, 2h postprandial blood glucose abnormality only （ GDM-2, ≥8.5 mmol/L） , fasting glucose abnormality only （ GDM-3,≥5.1 retool/L） and two or more glucose abnormality （GDM-4）. In homeostasis model assessment, insulin resistance index（HOMA-IR） ,β-cell function （HOMA-β） , area under curve of glucose （AUCG） , area under curve of insulin （ AUCI）, ratio of 60-minute insulin increase to 60-minute glucose increase （ △I60/△G60 ） , and insulin sensitivity index composite （ISI） were assessed and compared between NGT and GDM1-4 groups. Results （ 1 ） AUCG, AUCI, and HOMA-IR in the GDM group were statistically higher than those in NGT group （ P〈0.05 ）, while HOMA-β and ISI in the GDM group were lower than those in NGT group （ P〈0.05 ）. （ 2 ） HOMA-IR was higher in GDM1 , 3 and 4 groups compared with NGT group （ P〈0.01 ）. The level of HOMA- β in GDM1,2 groups was similar with NGT group, but was significantly decreased in GDM3,4 groups（ P〈0.01 ）. ISI was significantly decreased in GDM1,2, 3, and 4 groups compared with NGT group（P〈0.01 ）. Conclusions Patients with gestational diabetes manifest stronger insulin resistance and significant impaired insulin secretion compared with normal pregnancies. Abnormal fasting blood glucose levels are usually accompanied with insufficient fasting insulinlevels. Patients with higher postprandial glucose secrete less insulin after glucose loading, and those with multiple time points of glucose abnormality show impaired insulin secretion, in both basal and after glucose challenge.