Clinical Characteristics In Women With Gestational Hyperglycaemia With Antibodies To Beta-cell Antigens

Objective:To evaluate the prevalence of anti-islet cell antibodies in women with gestational hyperglycaemia and the impact of different periods of pregnancy on anti-islet cell antibodies and the function of islet cells, and identify clinical characteristics differentiating hyperglycaemic patients with and without anti-islet cell antibodies.Methods:After informed consent, One hundred and forty seven-women with GDM and one hundred and sixty-four women with GIGT were selected as study group, sixty women with normal pregnancy were selected as normal control group, from March 2010 to March 2011 in the first affiliated hospital of JINAN university.1. In the study group, the fasting blood was drew off the next morning of oral glucose tolerance test (OGTT) held during 24th to 28th gestational weeks, glutamic acid decarboxylase autoantibody (GADA), islet cell autoantibody (ICA), insulin autoantibody (IAA), blood glucose, insulin, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG) were tested. Prioring to delivery or the next day after delivery, the blood was drew off and the targets above were tested again. The cord blood was collected and the GADA, IAA, ICA, blood glucose, insulin were also tested. The OGTT and anti-islet cell antibodies were deteced at about 42 (range:39-345)days after delivery.2. In the normal control group, the fasting blood was drew off prior to delivery, the targets were test including GADA, IAA, ICA, blood glucose, insulin, TC, HDL-C,LDL-C and TG 3. The detail informations of participants were recorded, including:age, BMI, waistline, weight gain during pregnancy, family history of diabetes, blood glucose monitored during pregnancy, the use of insulin, the resistance of uterine artery and umbilical artery, puerperal weeks, amniotic fluid index, the character of amniotic fluid. The perinatal outcomes were also recorded such as spontaneous abortion, preterm delivery, fetal anomaly, fetal death, hypertensive disorder complicating pregnancy, fetal growth restriction, premature rupture of membrane, obstetric lacerations, C-sect, postpartum hemorrhage, etc.Results:1. During the third trimester, autoantibody positivity of GAD A, ICA, IAA in the 248 pregnant women with gestational hyperglycaemia was 5.2%,3.6%,29.0%,respectively. The positivity of IAA was higher than of GADA or ICA (P<0.01).33.9% women with gestational hyperglycaemia had at least one kind of anti-islet cell antibodies. The positivity of any of kind of the anti-islet cell antibodies was not significantly different between GDM and GIGT women. The proportion of GADA and/or ICA positive women with gestational hyperglycaemia was higher than that of normal control group, also the total antibody positivity (P<0.05).2. Compared with midtrimester pregnancy, the concentration of IAA and ICA was lower in late pregnancy (P<0.05), the concentration of IAA and ICA was higher in postpartum (P<0.05). The concentration of GADA in postpartum was the highest among midtrimester pregnancy,late pregnancy and postpartum (P>0.05), and the concentration of GADA was not significantly different between midtrimester pregnancy and late pregnancy (P>0.05). Autoantibody positivity of IAA-ICA and the total antibody positivity was higher in postpartum, comparing with late pregnancy (P <0.05), and autoantibody positivity ICA was higher in postpartum, comparing with midtrimester pregnancy (P<0.05). The concentration of GADA,IAA and ICA during the second trimester were highly related to those in the late pregnancy (P<0.01), also highly related to those in postpartum (P<0.01). 3. The OGTT2hPG of the GADA-positive women in midtrimester was lower than that of antibody-negative women (P<0.01), the rate of polyhydramnios in midtrimester was higher than those of antibody-negative women (P<0.05). The OGTTlhPG of the IAA-positive women in midtrimester was lower than that of antibody-negative women (P<0.05). The OGTT2hPG of the GADA and/or ICA-positive women in midtrimester was lower than that of antibody-negative women(P<0.05). The patients with GADA-positive had a higher percentage of polyhydramnios in midtrimester and a higher percentage of the resistance of uterine artery and umbilical artery increased during the second and the third trimester than those without autoantibodies. Moreover, the percentage of polyhydramnios in midtrimester and the percentage of the resistance of uterine artery and umbilical artery increased during the second and the third trimester were not significantly different between the patients without autoantibodies and the normal control group (P>0.05). The patients with ICA-positive had lower TC in the second and the third trimester and lower HbAlc in the second trimester than those without autoantibodies (P<0.05). The patients with IAA-positive had a higher percentage of fetal growth restriction(FGR) and lower HbAlc in the second trimester than those without autoantibodies (P<0.05). The patients with GADA and/or ICA-positive had higher fasting insulin (FINS), HOMA-IR, TC and LDL-C in the third trimester, lower TC and HbAlc in the second trimester than those without autoantibodies (P<0.05). The patients with autoantibodies had higher FINS in the third trimester and lower TC in the second trimester than those without autoantibodies (P<0.05). In addition, the patients with autoantibodies had a higher percentage of fetal anomaly and low birth weight newborns than those without autoantibodies, though the difference was not signifficant (0.05≤P≤0.15)4. The concentration of GADA and IAA, and the positive rate of anti-body in the cord blood were higher than those of maternal blood in the late pregnancy (P<0.05). The concentration of GADA,IAA and ICA in the cord blood were highly related to those in maternal blood in the late pregnancy (P<0.01). The outcomes of mothers and fetus were not significantly different between the women with gestational hyperglycaemia with and withour autoantibodies in cord blood. (P>0.05). The insulin of cord blood was not related to the weigh of newborn (P>0.05)5. Compared with the group of the lower concentrations of HbA1c, the rate of newborn going to NICU and obstetric lacerations, OGTTFPG, OGTT2hPG, FPG and TG in the second trimester and third trimeste, HOMA-IR and HbAlc in the second trimester, weight gain in the late pregnancy of the women with higher concentrations of HbAlc were higher(P<0.05), HDL in the late pregnancy of the women with higher concentrations of HbAlc was lower(P<0.05).6. The rate of newborns going to NICU was significantly associated with preterm delivery(odds ratio [OR]=11.08; 95% confidence interval [95%CI],2.28-53.73), the character of amniotic fluid (OR=3.23; 95%CI,1.82-5.73),OGTT1hPG value (OR =1.28; 95%CI,1.04-1.59), ICA positive in the third trimester (OR=6.36; 95%CI,1.22-33.26) and the resistance of uterine artery and umbilical artery increased during the third trimester(OR=2.19; 95%CI,0.94-5.09).7. The rate of newborns asphyxia was significantly associated with low birth weight (odds ratio [OR]=19.25; 95% confidence interval [95%CI],3.74-99.08), GADA positive in the secong trimester (OR=10.44; 95%CI,1.46-74.92) and GADA positive in the third trimester (OR=8.33; 95%CI,1.45-47.82).Conclusion:1. About 1/3 women with gestational hyperglycaemia had anti-islet cell antibodies in the late pregnancy, and the positivity of IAA was the highest. GDM and GIGT women shared similar islet autoimmune characteristics.2. The concentration of anti-islet cell antibodies in the women with gestational hyperglycaemia was highest at 6 weeks after delivery, followed by midtrimester of pregnancy, it was lowest in the late pregnancy. The concentration of anti-islet cell antibodies in cord blood was higher than that in the maternal blood in the late pregnancy.3. Compared with the women with gestational hyperglycaemia without autoantibodies, those with autoantibodies had higher FINS and HOMA-IR in the late pregnancy lower HbAlc in the second trimester and lower TC, LDC-C. The BMI, age, family history of diabetes, waistline, HOMA-β,usage of insulin during pregnancy and HbAlc in the late pregnancy were similar between the women with gestational hyperglycaemia with and without antoantibodies.4. Among the women with gestational hyperglycaemia with IAA-positive, the rate of FGR was higher than those without antoantibodies. ICA-positive in the third trimester was a risk factor for newborns going to NICU. GADA-positive was a risk factor for neonatal asphyxia. The outcomes of mother and fetus were not significantly different between the women with gestational hyperglycaemia with and withour autoantibodies in cord blood.