妊娠期糖尿病患者胰岛自身抗体随访的研究

摘要

目的 探讨谷氨酸脱羧酶抗体( GAD-Ab)和蛋白酪氨酸磷酸酶抗体(IA-2A)对妊娠期糖尿病(GDM)患者随访的意义.方法 选取GDM患者84例(GDM组)和口服葡萄糖耐量试验正常孕妇82例(对照组),GDM组又分为抗体阳性(GAD-Ab、IA-2A任何一项阳性)组18例和抗体阴性(GAD-Ab、IA-2A均阴性)组66例,分别于孕24～28周、产后6～12周和产后2年进行随访,测定GAD-Ab、IA-2A、胰岛素水平及糖代谢指标.结果 GDM组稳态模型胰岛素抵抗指数(HOMA-IR)高于对照组(3.87±2.17比2.31±0.52,P＜0.05),稳态模型胰岛β细胞功能指数(HBCI)和30 min净增胰岛素/30 min净增血糖(△I30/△G30)低于对照组[206.38±138.06比422.43±228.93和(20.16±11.38) mU/mmol比(26.54±24.30) mU/mmol,P＜ 0.05].抗体阳性组糖尿病家族史、在孕期需胰岛素治疗率均高于抗体阴性组[83.3％(15/18)比28.8％ (19/66)和77.8％(14/18)比30.3％(20/66),P＜0.05],HOMA-IR、△I30/△G30和HBCI均低于抗体阴性组[3.20±0.84比4.02±0.36,(16.81±2.91)mU/mmol比(21.55±11.11) mU/mmol和124.95±5.03比217.43±115.64,P＜0.01)；抗体阻性组产后6～ 12周和2年空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)均高于抗体阴性组[产后6～ 12周:(8.20±3.11) mmol/L比(5.39±0.76) mmol/L,( 15.22±7.29) mmol/L比(8.15±1.93)mmol/L,(7.26±1.04)％比(5.88±0.41)％；产后2年:(8.91±2.80) mmol/L比(4.93±0.66)mmol/L,( 15.75±7.87) mmol/L比(7.85±1.79) mmol/L,(7.18±1.22)％比(5.64±0.32)％,P＜0.01],而产后2年抗体阳性组△I30/△G30、HBCI明显下降,抗体阴性组无显著变化.抗体阳性组产后6～ 12周和2年分别有16.7％(3/18)、33.3％(6/18)的患者发展为1型糖尿病(T1DM),而抗体阴性组无转为T1DM病例.结论 GDM患者中混有一些亚临床状态的T1 DM患者；孕期需要胰岛素治疗,GAD-Ab和IA-2A阳性者,产后发展为T1DM的几率增加；GAD-Ab和IA-2A阳性是GDM患者产后发展为T1DM的一个重要预测因素.%Objective To investigate the role ofglutamic acid decarboxylase autoantibody(GAD-Ab)and protein tyrosine phosphatase autoantibody (IA-2A) in postpartum follow-up of gestational diabetes mellitus (GDM).Methods GAD-Ab,IA-2A,insulin and glucose metabolism index were measured in 82subjects with normal glucose tolerance (control group) and 84 patients with GDM(GDM group) during 24 to 28 weeks in pregnancy,postpartum 6 to 12 weeks and 2 years.GDM group was divided into antibodies positive group (GAD-Ah or IA-2A were positive) with 18 cases and antibodies negative group (GAD-Ab and IA-2A was negative) with 66 cases.Results Homeostasis model insulin resistance index (HOMA-IR) in GDM group was higher than that in control group (3.87 ± 2.17 vs.2.31 ± 0.52,P ＜ 0.05 ).Homeostasis β -cell function index (HBCI) and 30 min net increment of insulin/30 min net increment of glucose ( △ I30/△ G30) in GDM group were lower than those in control group [206.38 ± 138.06 vs.422.43 ± 228.93 and (20.16 ±11.38) mU/mmol vs.(26.54 ±24.30) mU/mmol,P ＜0.05].The numbers who had the family history of diabetes mellitus and the used of insulin for treatment in antibodies positive group were higher than those in antibodies negative group [ 83.3％ (15/18) vs.28.8％ (19/66) and 77.8％ ( 14/18 ) vs.30.3％ (20/66) ],HOMA-IR,△ I30/ △ G30 and HBCI in antibodies positive group were lower than those in antibodies negative group [3.20±0.84 vs.4.02±0.36,(16.81 ±2.91) mU/mmol vs.(21.55± 11.11) mU/mmol and 124.95 ± 5.03 vs.217.43 ± 115.64,P＜ 0.01 ].Fasting plasma glucose (FPG),2 hours postprandial glucose (2hPG)and glycosylated hemoglobin (HbA1c) in antibodies positive group were higher than those in antibodies negative group during postpartum 6 to 12 weeks and 2 years [postpartum 6 to 12 weeks: (8.20 ±3.11)mmol/L vs.(5.39 ±0.76) mmol/L,(15.22 ±7.29) mmol/L vs.(8.15 ± 1.93) mmol/L,(7.26 ± 1.04)％ vs.(5.88 ±0.41)％ ;postpartum 2 years: (8.91 ±2.80) mmol/L vs.(4.93 ±0.66) mmol/L,(15.75 ±7.87)mmol/L vs.(7.85 ± 1.79) mtmol/L,(7.18 ± 1.22)％ vs.(5.64 ± 0.32 )％,P ＜ 0.01].△ I30/ △ G30 and HBCI were significantly decreased in antibodies positive group postpartum 2 years.No change of the above parameters in antibodies negative group was found.The occurrence rate of type 1 diabetes mellitus (T1DM) was 16.7％(3/18) and 33.3％(6/18) postpartum 6 to 12 weeks and 2 years in antibodies positive group,there was no T1DM in antibodies negative group.Conclusions Women with GDM are partly associated with T1DM.Requiring insulin therapy during pregnancy and GAD-Ab or IA-2A positive have considerable risk for developing T1DM.It is also an important predictor to GDM after parturition.