Antepartum and early postpartum predictors of type 2 diabetes development in women with gestational diabetes mellitus

OBJECTIVES: This study aimed at identifying ante-partum and early post-partum (one year) clinical and metabolic characteristics capable of predicting the future development of type 2 diabetes in pregnant women of Mediterranea area affected by gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Seventy GDM patients were evaluated: mean age during pregnancy, plasma glucose levels under OGTT (100 gr. glucose), fasting, 1-h post-prandial plasma glucose levels, HbA(1c) at the third trimester, gestational week of GDM diagnosis, insulin therapy, and weight gain were all taken into consideration. Some maternal risk factors such as pre-pregnancy BMI, and maternal and fetal outcome of index pregnancy were also assessed. One year after delivery in the same patients, BMI, fasting and 1-h post-prandial plasma glucose, plasma glucose and insulinemia under OGTT (75 gr. glucose) were measured. We focused our attention on women who presented type 2 diabetes 5 years after pregnancy or IGT and those who, one year after pregnancy, were normal. RESULTS: Five years after pregnancy 49 women were normal, 5 had developed type 1 diabetes and were not considered, 6 had developed IGT, and 10 type 2 diabetes. Analysis of variables during pregnancy showed that those variables predicting type 2 diabetes were pre-pregnancy BMI, gestational week of diagnosis, need for insulin therapy, obesity, and plasma glucose at 60' OGTT. Analysis of variables evaluated one year after pregnancy showed that BMI, fasting and post-prandial plasma glucose, plasma glucose at each point of the OGTT, and plasma insulin at 30' OGTT were predictive of the development of type 2 diabetes. Furthermore, age, post-partum fasting plasma glucose, and plasma glucose under OGTT post-partum were predictive of the development of IGT. Our data show for the first time that, also in a Caucasian Mediterranean population, markers of the future development of diabetes do exist, as reported in literature. They also stress the importance of correct identification of GDM patients, in order to screen those at greater risk of developing diabetes, for whom it is imperative to set up prevention programs.     

Maternal triglyceride levels and newborn weight in pregnant women with normal glucose tolerance.

OBJECTIVE: To determine the predictive value of serum triglyceride levels (TG) for neonatal weight in pregnant women with positive diabetic screening but normal glucose tolerance. RESEARCH DESIGN AND METHODS: We enrolled 180 pregnant Caucasian women with positive diabetic screening. All women underwent a 3-h 100-g oral glucose tolerance test (OGTT) at 27th +/- 4 week of gestation. At the time of OGTT, we measured: fasting plasma glucose, fasting lipids profile and determined ApoE polymorphisms to evaluate the effects on lipid levels. In 83 women with normal glucose tolerance and at term delivery we evaluated the association between maternal serum TG, specific maternal parameters known to affect fetal growth and newborn weight. RESULTS: Based on OGTT, gestational diabetes mellitus (GDM) was diagnosed in 36 women (20%), impaired glucose tolerance (IGT) in 23 (13%), and normal glucose tolerance (NGT) in 121 (67%). Serum TG concentration was significantly higher in women with GDM (2.47 +/- 0.77 mmol/l) as compared with NGT (1.99 +/- 0.64 mmol/l) or IGT (1.98 +/- 0.81 mmol/l) (P < 0.01). ApoE3 allelic frequency was 86%, ApoE2 and ApoE4 were 5 and 9%, respectively. We found no clear-cut association between apoE genotype and serum TG concentration. Macrosomia and LGA newborns were more frequent in IGT than in GDM or NGT (P < 0.01). In the 83 women with positive diabetic screening but normal glucose tolerance who delivered at term, the incidence of LGA infants was significantly higher in those with TG levels higher than the 75th percentile (> 2.30 mmol/l) (21%) than in mothers who had normal TG levels (4.5%) (P < 0.05). Pre-pregnancy BMI (r(2) = 0.067), weight gain during pregnancy (r(2) = 0.062), fasting serum TG (r(2) = 0.09), and 2-h post-OGTT glucose levels (r(2) = 0.044) were all associated with neonatal body weight (all P < 0.05 or less). However, on a multiple regression analysis, only pre-pregnancy BMI (F-test = 7.26, P < 0.01), and fasting serum TG (F-test = 4.07, P < 0.01) were independently associated with birth weight. CONCLUSIONS: Pre-pregnancy BMI and fasting maternal serum TG determined in the last trimester of gestation were independently associated with neonatal birth weight in women with normal glucose tolerance, but positive screening test. TG levels measured in the third trimester of pregnancy are independent of the genetic polymorphism of ApoE.     

Fibrinolytic dysfunction after gestation is associated to components of insulin resistance and early type 2 diabetes in latino women with previous gestational diabetes

Among patients with metabolic syndrome (MS), atherosclerosis and abnormal fibrinolytic function are frequently present, mostly owing to an increase in plasminogen activator inhibitor-1(PAI-1). We analyze PAI-1 in pregnant women, both normal and with gestational diabetes (GDM) and postpartum regarding its correlation to MS surrogates. Clinical characteristics, glucose tolerance (100g-OGTT), lipids, PAI-1 antigen, insulin sensitivity (HOMA-S), and pancreatic beta-cell function (HOMA-B) were investigated in 34 women. Eleven had normal glucose tolerance (NGT) during pregnancy and 23 had GDM (all GAD antibodies-negative). All patients were studied at 28-34 weeks of gestation and 16-24 weeks after delivery (75 g-OGTT). Parameters of interest were determined using commercial test systems. During pregnancy, PAI-1 was not statistically different between NGT and GDM (47+/-25 ng/ml versus 47+/-28 ng/ml, p=0.9). After gestation, 19 (56%) women had NGT (11 of them from previous NGT group) and 15 (44%) had impaired glucose tolerance (IGT) or DM. The IGT (IGT+DM) group had higher PAI-1 (p=0.01), which did not decreased after delivery NGT-NGT before and after delivery (47+/-25 ng/ml versus 6+/-5 ng/ml; p<0.001), GDM-NGT (62+/-36 ng/ml versus 14+/-15 ng/ml; p=0.001) and GDM-IGT (39+/-20 ng/ml versus 27+/-23 ng/ml; p=0.15). PAI-1 levels were positively correlated (p<0.05) to total cholesterol (r(s)=0.37), triglycerides (r(s)=0.48), fasting plasma glucose (r(s)=0.52), 2-h plasma glucose in the OGTT (r(s)=0.58) and were negatively correlated (p<0.05) with HOMA-S (r(s)=-0.42) and HOMA-B (r(s)=-0.38). Fibrinolytic dysfunction is still present in GDM women and is associated with early development of IGT or T2DM. PAI correlated with surrogate markers of MS levels and may identify a group of women at risk for macroangiopathy.     

Insulin resistance has no impact on ghrelin suppression in pregnancy

Ghrelin is reduced in various states of insulin resistance. The aim of this study was to examine the relationship between ghrelin and glucose metabolism during pregnancy - a natural insulin-resistant state - in women with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or gestational diabetes mellitus (GDM) and potential changes 3 months after delivery. A total of 54 women, 37 pregnant and with various degrees of insulin resistance and 24 postpartum (PP, seven of them also studied during pregnancy) were studied. Ghrelin plasma concentrations at fasting and 60' following glucose loading (75 g-2 h-oral glucose tolerance test), area under the curve of plasma glucose (G-AUC(OGTT)) and insulin sensitivity [homeostatic model assessment (HOMA) and oral glucose sensitivity index (OGIS) indices, respectively] were determined. Both baseline and 60' ghrelin concentrations were to a comparable degree ( approximately by 65%) suppressed in NGT, IGT and GDM as compared to the PP group (the latter being indistinguishable from NGT regarding glucose tolerance and insulin sensitivity). In all women studied both during and after pregnancy, ghrelin levels rose from pregnancy to PP (mean increase 313.8%; P < 0.03). There was no correlation between baseline ghrelin and insulin sensitivity as estimated from both baseline (HOMA) and dynamic (OGTT:OGIS) glucose and insulin data. Ghrelin is substantially decreased during pregnancy, but glucose-induced ghrelin suppression is preserved at a lower level. There is apparently no relation to the degree of insulin resistance.     

Early detection of insulin sensitivity and beta-cell function with simple tests indicates future derangements in late pregnancy

OBJECTIVE: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The oral glucose tolerance test (OGTT) was performed in 903 women at 16-20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26-30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and beta-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests. RESULTS: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower beta-cell function than ND. During the late visit, GDM2 also showed impaired beta-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2. CONCLUSIONS: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. beta-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.     

妊娠期糖尿病对双胎妊娠母婴围产结局的影响

目的:探讨妊娠期糖尿病（GDM）对双胎妊娠母婴围产结局的影响。方法:对2013年1月至2019年10月在北京市海淀区妇幼保健院住院分娩的772例双绒毛膜性双胎妊娠孕妇进行回顾性研究,收集孕妇基本信息和母婴围产结局数据（包括年龄、孕产次、孕周、受孕方式、分娩方式）及孕产妇及新生儿并发症等。所有研究对象于孕24~28周行口...     

Gestational diabetes: A link between OGTT,maternal-fetal outcomes and maternal glucose tolerance after childbirth

Background and aimThe relationship among distribution of pathological values at the Oral Glucose Tolerance Test (OGTT), metabolic risk factors and pregnancy outcomes in women with Gestational Diabetes (GDM), has not been clearly identified. We retrospectively compared metabolic and therapeutic parameters, maternal–fetal outcomes and post-partum OGTTs, with respect to the number and distribution of altered values of diagnostic OGTT in pregnancy. Secondly, we assessed whether insulin therapy predictive factors were identifiable.Methods and resultsThis analysis included 602 pregnant women with GDM, followed in Diabetes and Pregnancy Unit of Perugia Hospital from diagnosis to childbirth. All women were diagnosed diabetic upon 75g OGTT, according IADPSG criteria. Women were divided into 3 groups, respect to distribution of diagnostic blood glucose (BG) values at OGTT: Group 1: only fasting BG (OGTT0h); Group 2: 1 and/or 2h (OGTT1-2h); Group 3: both fasting and 1 h and/or 2h (OGTT0+1–2h) BG.Pregnant women with fasting hyperglycemia at OGTT (Groups 1 and 3) had similar metabolic characteristics (weight, prevalence of obesity, gestational weight gain, HbA1c), a greater need for insulin therapy, and a higher risk of impaired glucose tolerance persistence after childbirth, as compared to Group 2. No significant differences were observed in terms of maternal and neonatal outcomes (p > 0.05), except for a greater prevalence of caesarean sections in Group 3.ConclusionThe metabolic characteristics of GDM women are mirrored by OGTT values at diagnosis, but are not associated with adverse pregnancy outcomes. Intensive management and a tailored treatment of GDM improve maternal-neonatal outcomes, regardless of diagnostic values distribution and pre-gestational metabolic characteristics.     

Detection and care of women with gestational diabetes mellitus from early weeks of pregnancy results in birth weight of newborn babies appropriate for gestational age

The policy of screening for gestational diabetes mellitus (GDM) between 24 and 28 weeks of gestation and care has resulted in a few women delivering big babies despite good glycemic control. Hence we undertook a study to assess the merits of care given to women in whom GDM was diagnosed in different weeks of gestation and to find out the ideal period of screening in women with history of high-risk pregnancies. A total of 207 consecutive pregnant women irrespective of trimester referred to our referral clinic for diabetes in pregnancy, underwent a 75g oral glucose tolerance test (OGTT) and GDM was diagnosed if 2h plasma glucose (PG) >/=140mg/dl. A1c was estimated in all of them. Women who failed to respond to medical nutrition therapy were advised insulin and the dose titrated to maintain fasting PG (FPG) <90mg/dl and 2h PG <120mg/dl. The mean age of the population screened was 28.38+/-4.31 years and the mean gestational age of screening was 20.05+/-10.71 weeks. Among them, 87 were diagnosed as GDM. The gestational week at diagnosis was 相似文献   

2069例不同糖耐量状态孕妇的血脂谱及围生结局分析

目的在大样本群体中探讨不同糖耐量状态孕妇血脂谱及其围生结局,并寻找巨大儿发生的独立危险因素。方法50g口服葡萄糖筛查试验（GCT）1hPG≥7．8mmol／L的孕妇共2069例,按100gOGTT结果分为NGT（n=911）、IGT（n=422）和GDM（n=736）3组,并测定3组HbA1c、TG、TC、LDL-C、HDL-C水平,以上指标均在24～28孕周获得。结果（1）不同糖耐量状态的孕妇TG、TC、LDL-C、HDL-C均较非孕参考范围明显升高。从NGT—IGT—GDM组,TG逐步上升（P〈O．01）,HDL-C逐步下降（P〈0．01）,TC和LDL-C无统计学差异。（2）经过对血糖的严格干预后,3组的孕期体重增加,新生儿体重无差异,然而巨大儿的发生率在GDM和IGT组仍明显高于NGT组（14．1％,13．1％7J$6．6％,P〈0．01）。（3）二项分类Logistic回归分析发现OGTT中的FPG（OR=2．98,95％CI1．63～5．48,P〈0．01）、孕期体重增加（OR=1．12,95％CI1．06～1．19,P〈0．01）为巨大儿发生的独立危险因素,而HDL-C为独立保护因素（OR—0．41,95％C10．20～0．86,P〈0．05）。结论妊娠时,血脂各组分较非孕状态明显升高,从NGT→IGT→GDM,TG逐步上升而HDL-C逐步下降。即使经过血糖的严格干预,巨大儿的发生率并不能降低到NGT组水平。FPG水平和孕重增加是巨大儿发生的独立危险因素,而HDL-C是保护因素。     

Does parity increase insulin resistance during pregnancy?

AIMS: To study the effect of parity on impairment of insulin sensitivity during pregnancy and on the risk of gestational diabetes (GDM). METHODS: We studied the relationship between parity and peripheral insulin sensitivity index (ISI(OGTT)) or GDM in 1880 caucasian women, who underwent a 100-g, 3-h oral glucose tolerance test (OGTT) between the 24th and 28th gestational week and in 75 women who underwent an OGTT in two consecutive pregnancies. A proxy for beta-cell function (basal plasma C peptide/fasting plasma glucose; CP/FPG) was also measured. RESULTS: By univariate analysis parity was related to decreased ISI(OGTT) and to increased CP/FPG in those with parity > 3 and likewise GDM, diagnosed in 124 women (6.58%), was linearly related to parity (P = 0.0034) and strongly age dependent. The relationships between parity and ISI(OGTT), CP/FPG and GDM were no longer significant after adjustment for age, pregestational body mass index (BMI), and weight gain. GDM was significantly related to age and pregestational weight, while ISI(OGTT) and CP/FPG were inversely related to prepregnancy BMI or weight gain. In comparison with the index pregnancy, the subsequent pregnancy was characterized by an increase in actual and prepregnancy BMI, in 2 h area under curve (AUC) glucose and by a decrease in ISI(OGTT) (P = 0.0001). The longer the time interval between pregnancies and the higher the increment in pregestational BMI or in weight gain during the pregnancy, the greater were the ISI(OGTT) decrease and 2-h AUC glucose increase. CONCLUSIONS: Parity is not directly linked to insulin sensitivity deterioration, to CP/FPG increase during pregnancy, or to GDM appearance, although it is linked through the mediation of progressive ageing and weight gain either before or during pregnancy, when there is a sufficiently long time interval between pregnancies.