Associations of mid-pregnancy HbA1c with gestational diabetes and risk of adverse pregnancy outcomes in high-risk Taiwanese women.
ABSTRACT: The objective of this study was to investigate the associations among the mid-pregnancy glycated hemoglobin A1c (HbA1c) level, gestational diabetes (GDM), and risk of adverse pregnancy outcomes in women without overt diabetes and with positive 50-g, 1-h glucose challenge test (GCT) results (140 mg/dL or greater).This prospective study enrolled 1,989 pregnant Taiwanese women. A two-step approach, including a 50-g, 1-h GCT and 100-g, 3-h oral glucose tolerance test (OGTT), was employed for the diagnosis of GDM at weeks 23-32. The mid-pregnancy HbA1c level was measured at the time the OGTT was performed. A receiver operating characteristic (ROC) curve was used to determine the relationship between the mid-pregnancy HbA1c level and GDM. Multiple logistic regression models were implemented to assess the relationships between the mid-pregnancy HbA1c level and adverse pregnancy outcomes.An ROC curve demonstrated that the optimal mid-pregnancy HbA1c cut-off point to predict GDM, as diagnosed by the Carpenter-Coustan criteria using a two-step approach, was 5.7%. The area under the ROC curve of the mid-pregnancy HbA1c level for GDM was 0.70. Compared with the levels of 4.5-4.9%, higher mid-pregnancy HbA1c levels (5.0-5.4, 5.5-5.9, 6.0-6.4, 6.5-6.9, and >7.0%) were significantly associated with increased risks of gestational hypertension or preeclampsia, preterm delivery, admission to the neonatal intensive care unit, low birth weight, and macrosomia (the odds ratio [OR] ranges were 1.20-9.98, 1.31-5.16, 0.88-3.15, 0.89-4.10, and 2.22-27.86, respectively).The mid-pregnancy HbA1c level was associated with various adverse pregnancy outcomes in high-risk Taiwanese women. However, it lacked adequate sensitivity and specificity to replace the two-step approach in the diagnosis of GDM. The current study comprised a single-center prospective study; thus, additional, randomized control design studies are required.
Project description:Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes such as preeclampsia and macrosomia. Women with polycystic ovary syndrome (PCOS) are at increased risk of developing GDM. Today, GDM is diagnosed by oral glucose tolerance test (OGTT), a rather cumbersome test for the women and health care system. The objectives of this study were to investigate whether HbA1c in first trimester of pregnancy could be used as a screening test for GDM in first trimester and throughout pregnancy in order to reduce the number of OGTTs, and whether it could predict preeclampsia and macrosomia in women with PCOS.Post hoc analyses of data from 228 women from a prospective, randomised, multicenter study comparing metformin to placebo from first trimester to delivery. Fasting and 2-h plasma glucose were measured during a 75 g OGTT in first trimester, gestational week 19 and 32 as well as fasting plasma glucose in gestational week 36. GDM was diagnosed by WHO criteria from 1999 in first trimester and throughout pregnancy and by modified IADPSG criteria (i.e. lacking the 1-h plasma glucose value) in first trimester. The diagnostic accuracy was assessed by logistic regression and ROC curve analysis.The area under the ROC curve for first trimester HbA1c for screening of GDM diagnosed by WHO criteria in first trimester was 0.60 (95 % CI 0.44-0.75) and 0.56 (95 % CI 0.47-0.65) for GDM diagnosed throughout pregnancy. Only 2.2 % (95 % CI 0.7-5.1 %) of the participants could have avoided OGTT. HbA1c was not statistically significantly associated with GDM diagnosed by modified IADPSG criteria in first trimester. However, first trimester HbA1c was statistically significantly associated with preeclampsia. Both HbA1c and GDM by WHO criteria in first trimester, but not by IADPSG, were negatively associated with birth weight.First trimester HbA1c can not be used to exclude or predict GDM in women with PCOS, but it might be better to predict preeclampsia than the GDM diagnosis.
Project description:The purpose of this study was to test the hypothesis that any degree of abnormal glucose homeostasis detected on antepartum screening for gestational diabetes mellitus (GDM) should be associated with an increased risk of postpartum pre-diabetes or diabetes.In this prospective cohort study, 487 women underwent 1) antepartum GDM screening by a glucose challenge test (GCT) and a diagnostic oral glucose tolerance test (OGTT) and 2) postpartum metabolic characterization by OGTT at 3 months after delivery. Four baseline glucose tolerance groups were defined on the basis of the antepartum GCT/OGTT: 1) GDM (n = 137); 2) gestational impaired glucose tolerance (GIGT) (n = 91); 3) abnormal GCT with normal glucose tolerance on an OGTT (abnormal GCT NGT) (n = 166); and 4) normal GCT with NGT on an OGTT (normal GCT NGT) (n = 93).The prevalence of postpartum glucose intolerance (pre-diabetes or diabetes) increased across the groups from normal GCT NGT (3.2%) to abnormal GCT NGT (10.2%) to GIGT (16.5%) to GDM (32.8%) (P(trend) < 0.0001). On logistic regression analysis, all three categories of abnormal glucose homeostasis in pregnancy independently predicted postpartum glucose intolerance: abnormal GCT NGT odds ratio (OR) 3.6 (95% CI 1.01-12.9); GIGT OR 5.7 (1.6-21.1); and GDM OR 14.3 (4.2-49.1). Furthermore, both in pregnancy and at 3 months postpartum, insulin sensitivity (IS(OGTT)) and pancreatic beta-cell function (insulinogenic index/homeostasis model assessment of insulin resistance) progressively decreased across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all P(trend) < 0.0001).Any degree of abnormal glucose homeostasis in pregnancy independently predicts an increased risk of glucose intolerance postpartum.
Project description:Screening for gestational diabetes mellitus (GDM) during pregnancy is cumbersome. Measurement of plasma fructosamine may help simplify the first step of detecting GDM. We aimed to assess the predictive value of mid-pregnancy fructosamine for GDM, and its association with postpartum glycemic indices. Among 1488 women from Project Viva (mean ± SD: 32.1 ± 5.0 years old; pre-pregnancy body mass index 24.7 ± 5.3 kg/m²), we measured second trimester fructosamine and assessed gestational glucose tolerance with a 50 g glucose challenge test (GCT) followed, if abnormal, by a 100 g oral glucose tolerance test (OGTT). Approximately 3 years postpartum (median 3.2 years; SD 0.4 years), we measured maternal glycated hemoglobin (n = 450) and estimated insulin resistance (HOMA-IR; n = 132) from fasting blood samples. Higher glucose levels 1 h post 50 g GCT were associated with higher fructosamine levels (Pearson's r = 0.06; p = 0.02). However, fructosamine ≥222 µmol/L (median) had a sensitivity of 54.8% and specificity of 48.6% to detect GDM (area under the receiver operating characteristic curve = 0.52); other fructosamine thresholds did not show better predictive characteristics. Fructosamine was also weakly associated with 3-year postpartum glycated hemoglobin (per 1 SD increment: adjusted β = 0.03 95% CI [0.00, 0.05] %) and HOMA-IR (per 1 SD increment: adjusted % difference 15.7, 95% CI [3.7, 29.0] %). Second trimester fructosamine is a poor predictor of gestational glucose tolerance and postpartum glycemic indices.
Project description:Predictors for glucose intolerance postpartum were evaluated in women with gestational diabetes mellitus (GDM) based on the 2013 World Health Organization (WHO) criteria. 1841 women were tested for GDM in a prospective cohort study. A postpartum 75g oral glucose tolerance test (OGTT) was performed in women with GDM at 14 ± 4.1 weeks. Of all 231 mothers with GDM, 83.1% (192) had a postpartum OGTT of which 18.2% (35) had glucose intolerance. Women with glucose intolerance were more often of Asian origin [15.1% vs. 3.7%, OR 4.64 (1.26?17.12)], had more often a recurrent history of GDM [41.7% vs. 26.7%, OR 3.68 (1.37?9.87)], higher fasting glycaemia (FPG) [5.1 (4.5?5.3) vs. 4.6 (4.3?5.1) mmol/L, OR 1.05 (1.01?1.09)], higher HbA1c [33 (31?36) vs. 32 (30?33) mmol/mol, OR 4.89 (1.61?14.82)], and higher triglycerides [2.2 (1.9?2.8) vs. 2.0 (1.6?2.5) mmol/L, OR 1.00 (1.00?1.01)]. Sensitivity of glucose challenge test (GCT) ?7.2 mmol/l for glucose intolerance postpartum was 80% (63.1%?91.6%). The area under the curve to predict glucose intolerance was 0.76 (0.65?0.87) for FPG, 0.54 (0.43?0.65) for HbA1c and 0.75 (0.64?0.86) for both combined. In conclusion, nearly one-fifth of women with GDM have glucose intolerance postpartum. A GCT ?7.2 mmol/L identifies a high risk population for glucose intolerance postpartum.
Project description:Gestational impaired glucose tolerance (GIGT), defined by a single abnormal value on antepartum 3-h oral glucose tolerance test (OGTT), is a metabolically heterogeneous disorder. Indeed, the antepartum metabolic phenotype of women with a single abnormal value at 1 h during the OGTT (1-h GIGT) resembles that of women with gestational diabetes mellitus (GDM), whereas GIGT at 2 or 3 h (2/3-h GIGT) is similar to normal glucose tolerance (NGT). Thus, we hypothesized that 1-h GIGT would be associated with the same adverse outcomes as GDM, i.e., increased infant birth weight and postpartum metabolic dysfunction.A total of 361 women underwent an antepartum glucose challenge test (GCT) and a 3-h OGTT, assessment of obstetrical outcome at delivery, and metabolic characterization by OGTT at 3 months postpartum. The antepartum GCT/OGTT identified five study groups: GDM (n = 97), 1-h GIGT (n = 28), 2/3-h GIGT (n = 34), abnormal GCT NGT (abnormal GCT with NGT on OGTT) (n = 128), and normal GCT NGT (normal GCT with NGT on OGTT) (n = 74).Caesarian section rate was higher in women with 1-h GIGT, but birth weight did not differ significantly between the non-GDM groups (P = 0.1978). At 3 months postpartum, glycemia (area under the glucose curve) progressively increased across the groups from normal GCT NGT to abnormal GCT NGT to 2/3-h GIGT to 1-h GIGT to GDM (P < 0.0001), while both insulin sensitivity (IS(OGTT)) and beta-cell function (insulinogenic index/homeostasis model assessment of insulin resistance [HOMA-IR]) progressively decreased (P = 0.002 and P < 0.0001, respectively). The strongest independent negative predictors of insulinogenic index/HOMA-IR were GDM (t = -4.1, P < 0.0001) and 1-h GIGT (t = -3.8, P = 0.0002).Like GDM, 1-h GIGT is associated with postpartum glycemia, insulin resistance, and beta-cell dysfunction.
Project description:Both gestational diabetes mellitus (GDM) and mild glucose intolerance in pregnancy identify women at increased risk of future type 2 diabetes. In this context, we queried whether metabolic changes that occur in the 1st year postpartum vary in relation to gestational glucose tolerance status.Three-hundred-and-ninety-two women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy followed by repeat OGTT at both 3 months' postpartum and 12 months' postpartum. The antepartum testing defined four gestational glucose tolerance groups: GDM (n = 107); gestational impaired glucose tolerance (GIGT) (n = 75); abnormal GCT with normal glucose tolerance (NGT) on OGTT (abnormal GCT NGT) (n = 137); and normal GCT with NGT on OGTT (normal GCT NGT) (n = 73).The prevalence of dysglycemia progressively increased across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM at both 3 months' postpartum (2.7% to 10.2% to 18.7% to 34.6%, P < 0.0001) and 12 months' postpartum (2.7% to 11.7% to 17.3% to 32.7%, P < 0.0001). Between 3 and 12 months' postpartum, the groups did not differ with respect to changes in waist circumference, weight, or insulin sensitivity. Importantly, however, they exhibited markedly different changes in beta-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]) (P = 0.0036), with ISSI-2 declining in both the GDM and GIGT groups. Furthermore, on multiple linear regression analysis, both GDM (t = -3.06, P = 0.0024) and GIGT (t = -2.18, P = 0.03) emerged as independent negative predictors of the change in ISSI-2 between 3 and 12 months' postpartum.Women with GDM and GIGT exhibit declining beta-cell function in the 1st year postpartum that likely contributes to their future diabetic risk.
Project description:BACKGROUND:This study aimed to analyze the incidence of early postpartum dyslipidemia and its potential predictors in women with a history of gestational diabetes mellitus (GDM). METHODS:This was a retrospective study. Five hundred eighty-nine women diagnosed with GDM were enrolled and followed up at 6-12?weeks after delivery. A 75?g oral glucose tolerance test (OGTT) and lipid levels were performed during mid-trimester and the early postpartum period. Participants were divided into the normal lipid group and dyslipidemia group according to postpartum lipid levels. Demographic and metabolic parameters were analyzed. Multiple logistic regression was performed to analyze the potential predictors for early postpartum dyslipidemia. A receiver operating characteristic curve (ROC) was calculated to determine the cut-off values. RESULTS:A total of 38.5% of the 589 women developed dyslipidemia in early postpartum and 60% of them had normal glucose metabolism. Delivery age, systolic blood pressure (SBP), glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) were independent predictors of early postpartum dyslipidemia in women with a history of GDM. The cut-offs of maternal age, SBP, HbA1c values, and LDL-C levels were 35?years, 123?mmHg, 5.1%, and 3.56?mmol/L, respectively. LDL-C achieved a balanced mix of high sensitivity (63.9%) and specificity (69.2%), with the highest area under the receiver operating characteristic curve (AUC) (0.696). When LDL-C was combined with age, SBP, and HbA1c, the AUC reached to 0.733. CONCLUSIONS:A lipid metabolism evaluation should be recommended in women with a history of GDM after delivery, particularly those with a maternal age?>?35?years, SBP?>?123?mmHg before labor, HbA1c value >?5.1%, or LDL-C levels >?3.56?mmol/L in the second trimester of pregnancy.
Project description:This study determines if a modified two-step screening strategy with a glucose challenge test (GCT) ? 7.2 mmol/L and clinical risk factors improves the diagnostic accuracy for gestational diabetes mellitus (GDM), based on 2013 WHO criteria, while limiting the number of oral glucose tolerance tests (OGTT). This was a prospective multicentric cohort study with 1811 participants receiving both GCT and 75 g OGTT in pregnancy. Participants and health care providers were blinded for GCT. Characteristics were analyzed across four glucose tolerance groups: abnormal (?7.2 mmol/L), GCT GDM (n = 165), normal GCT GDM (n = 63), abnormal GCT normal glucose tolerant (NGT) (n = 472); normal GCT NGT (n = 1113). Compared to normal GCT NGT women, normal GCT GDM women had increased rates of obesity (23.8% vs. 10.5%, p < 0.001), ethnic minority background (19.3% vs. 8.2%, p < 0.001) and a history of GDM (13.8% vs. 4.6%, p = 0.03). By combined screening of GCT ? 7.2 mmol/L with these risk factors, sensitivity increased to respectively, 74.1?78.1% using one risk factor, and to 82.9% using any of these risk factors with a specificity of 57.5%. By using a modified two-step screening strategy, the number of women needing both a GCT and OGTT would be reduced to 25.5%, and 52.6% of all OGTTs could be avoided, compared to a universal one-step approach.
Project description:The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommends universal screening with a 75 g oral glucose tolerance test (OGTT) using stricter criteria for gestational diabetes (GDM). This may lead to important increases in the prevalence of GDM and associated costs, whereas the gain in health is unclear. The goal of 'The Belgian Diabetes in Pregnancy Study' (BEDIP-N) is to evaluate the best screening strategy for pregestational diabetes in early pregnancy and GDM in an ethnically diverse western European population. The IADPSG screening strategy will be followed, but in addition risk questionnaires and a 50 g glucose challenge test (GCT) will be performed, in order to define the most practical and most cost effective screening strategy in this population.BEDIP-N is a prospective observational cohort study in 6 centers in Belgium. The aim is to enroll 2563 pregnant women in the first trimester with a singleton pregnancy, aged 18-45 years, without known diabetes and without history of bariatric surgery. Women are universally screened for overt diabetes and GDM in the first trimester with a fasting plasma glucose and for GDM between 24-28 weeks using the 50 g GCT and independently of the result of the GCT, all women will receive a 75 g OGTT using the IADPSG criteria. Diabetes and GDM will be treated according to a standardized routine care protocol. Women with GDM, will be reevaluated three months postpartum with a 75 g OGTT. At each visit blood samples are collected, anthropometric measurements are obtained and self-administered questionnaires are completed. Recruitment began in April 2014.This is the first large, prospective cohort study rigorously assessing the prevalence of diabetes in early pregnancy and comparing the impact of different screening strategies with the IADPSG criteria on the detection of GDM later in pregnancy.ClinicalTrials.gov: NCT02036619. Registered 14-1-2014.
Project description:BACKGROUND:Early diagnosis of gestational diabetes mellitus (GDM) is crucial to prevent short term delivery risks and long term effects such as cardiovascular and metabolic diseases in the mother and infant. Diagnosing GDM in Sub-Saharan Africa (SSA) however, remains sub-optimal due to associated logistical and cost barriers for resource-constrained populations. A cost-effective strategy to screen for GDM in such settings are therefore urgently required. We conducted this study to determine the prevalence of gestational diabetes mellitus (GDM) and assess utility of various GDM point of care (POC) screening strategies in a resource-constrained setting. METHODS:Eligible women aged ?18 years, and between 24 and 32 weeks of a singleton pregnancy, prospectively underwent testing over two days. On day 1, a POC 1-h 50 g glucose challenge test (GCT) and a POC glycated hemoglobin (HbA1c) was assessed. On day 2, fasting blood glucose, 1-h and 2-h 75 g oral glucose tolerance test (OGTT) were determined using both venous and POC tests, along with a venous HbA1c. The International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria was used to diagnose GDM. GDM prevalence was reported with 95% confidence interval (CI). Specificity, sensitivity, positive predictive value, and negative predictive value of the various POC testing strategies were determined using IADPSG testing as the standard reference. RESULTS:Six hundred-sixteen eligible women completed testing procedures. GDM was diagnosed in 18 women, a prevalence of 2.9% (95% CI, 1.57% - 4.23%). Compared to IADPSG testing, POC IADPSG had a sensitivity and specificity of 55.6% and 90.6% respectively while that of POC 1-h 50 g GCT (using a diagnostic cut-off of ?7.2 mmol/L [129.6 mg/dL]) was 55.6% and 63.9%. All other POC tests assessed showed poor sensitivity. CONCLUSIONS:POC screening strategies though feasible, showed poor sensitivity for GDM detection in our resource-constrained population of low GDM prevalence. Studies to identify sensitive and specific POC GDM screening strategies using adverse pregnancy outcomes as end points are required. TRIALS REGISTRATION:Clinical trials.gov : NCT02978807 , Registered 29 November 2016.