妊娠期糖尿病患者产后5~6年糖代谢转归及胰岛β细胞功能变化的研究

Follow-up study of glucose metabolism outcome and islet β cell function in patients with previous gestational diabetes mellitus in postpartum 5-6 years

目的了解妊娠期糖尿病(GDM)患者产后5~6年糖代谢转归,并探讨从产后短期(6~12周)到长期(5~6年)胰岛素抵抗及胰岛β细胞功能变化及与糖代谢状态的关系。方法纳入2007年2月至2008年12月在北京大学第一医院生产且进行了产后短期及长期随访、资料完整的GDM患者72例,根据产后5~6年的糖代谢状况,分为糖代谢正常(NGT)组及糖代谢异常(AGT)组。收集两组患者孕前、孕期、围产期、产后短期及长期相关临床资料,包括人口测量学指标、糖脂代谢指标[口服葡萄糖耐量试验(OGTT)空腹血糖(FPG)、1 h血糖(1hPG)、2 h血糖(2hPG)、3 h血糖(3hPG)、总胆固醇、甘油三酯(TG)、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇]、使用胰岛素比例、空腹胰岛素(FINS)、OGTT 2 h胰岛素(2hINS),并计算胰岛素敏感性指数(ISI)、稳态模型评估胰岛素抵抗指数(HOMA-IR)及稳态模型评估胰岛β细胞功能指数(HOMA-β)。两组间比较采用独立样本t检验、秩和检验、χ^(2)检验或Fisher精确概率检验。采用多因素logistic回归分析法分析糖代谢异常的影响因素。结果72例GDM患者中,NGT组38例(52.78%),AGT组34例(47.22%)。从孕期到产后长期,与NGT组比较,AGT组相关代谢指标差异均具有统计学意义。孕期:AGT组75 g OGTT 3hPG更高,使用胰岛素比例更高(均P<0.05);产后6~12周:AGT组OGTT 2hPG即显著升高,血糖异常的发生率、高TG血症的比例也更高(均P<0.05),但两组间HOMA-IR及HOMA-β的差异未见有统计学意义(P>0.05);产后5~6年:AGT组的FPG、OGTT 2hPG及FINS均更高,胰岛素抵抗程度更重,ISI更低(均P<0.05)。与产后短期(6~12周)比较,无论产后5~6年血糖是否正常,FPG、FINS、HOMA-IR、HOMA-β均显著升高,AGT组OGTT 2hPG和2hINS升高更显著(P<0.05)。多因素logistic回归分析结果显示,孕期OGTT 2hPG、使用胰岛素降糖为产后5~6年发生糖代谢异常的危险因素,OR值(95%CI)分别为1.646(1.015~2.671)和3.570(1.009~12.624)。结论GDM患者产后5~6年糖代谢异常发生率高;随着时间的延长,无论血糖是否正常,胰岛素抵抗均逐渐加重,糖代谢异常者尤甚;孕期OGTT 2hPG及孕期应用胰岛素对产后5~6年糖代谢转归有预测作用,提示GDM与T2DM存在发病时间上的延续性及发病机制上的相似性。

Objective To investigate the glucose metabolic status in patients with previous gestational diabetes mellitus(GDM)in the 5-6 years after delivery,and to explore the changes in insulin resistance and isletβcell function from postpartum short-term(6-12 weeks)to the long-term(5-6 years)after delivery,as well as the relationship with glucose metabolic status.MethodsA total of 72 patients with a history of GDM who delivered in Peking University First Hospital and had complete short-and long-term postpartum follow-up data were included.They were divided into normal glucose metabolism(NGT)and abnormal glucose metabolism(AGT)groups according to their glucose metabolism status in 5-6 years after delivery.Pre-pregnancy,pregnancy,perinatal,short-and long-term postpartum clinical data were collected and compared between the two groups,including demographic indicators,glucose and lipid metabolism indicators[oral glucose tolerance test(OGTT)fasting blood glucose(FPG),1-hour blood glucose(1hPG),2-hour blood glucose(2hPG),3-hour blood glucose(3hPG),total cholesterol,triglycerides(TG),high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,insulin use ratio,fasting insulin(FINS),OGTT 2-hour insulin(2hINS),insulin sensitivity index(ISI),homeostasis model assessment of insulin resistance index(HoMA-IR)and homeostasis model assessment ofβcell function index(HOMA-β)were calculated.The comparison between the two groups was conducted using independent sample t-test,rank sum test χ^(2) test or Fisher's exact probability test.Multivariate logistic regression analysis was used to analyze the influence factors of abnormal glucose metabolism.Results There were 38(52.78%)cases in NGT group and 34(47.22%)cases in AGT group.Compared with the NGT group,there are differences in related metabolic indicators in AGT group from pregnancy to long-term postpartum period:During pregnancy,3hPG in 75 g OGTT and the proportion of insulin users were higher in AGT group.As for 6-12 weeks postpartum,OGTT 2hPG and the incidence of blood glucose abnormalities and the proportion of hypertriglyceridemia were higher(all P<0.05).However,there was no statistically significant difference in HOMA-IR and HOMA-βbetween the two groups(P>0.05).At 5-6 years postpartum,FPG,OGTT 2hPG,and FINS were all higher,with a higher degree of insulin resistance and lower insulin sensitivity(ISI)in AGT group(all P<0.05).Compared with short-term postpartum period(6-12 weeks),FPG,FINS,HOMA-IR,HOMA-βwere all significantly increased regardless of glucose metabolic status at 5-6 years postpartum,while OGTT 2hPG and 2hINS increased further in the AGT group(all P<0.05).OGTT 2hPG and insulin use during pregnancy were risk factors for abnormal glucose metabolism 5-6 years postpartum according to multivariate logistic regression analysis,with OR values(95%CI)of 1.646(1.015-2.671)and 3.570(1.009-12.624),respectively.Conclusions The incidence of AGT was still high in patients with previous GDM 5-6 years after delivery.Insulin resistance progressed gradually after delivery regardless of glucose metabolism,especially in patients with abnormal glucose metabolism.OGTT 2hPG and insulin use in pregnancy were risk factors for abnormal glucose metabolism in postpartum 5-6 years,suggesting that there is continuity in time and similarity in pathogenesis between GDM and T2DM.