Relationships between gut microbiota,plasma glucose and gestational diabetes mellitus

Aims/IntroductionTo investigate the changes in the gut microbiome in the second trimester of pregnancy associated with later‐diagnosed gestational diabetes mellitus (GDM) and their relationship with fasting serum levels of metabolites, especially glucose.Materials and MethodsWe carried out a case–control study with 110 GDM patients and 220 healthy pregnant women who provided fecal samples for 16S ribosomal ribonucleic acid sequencing in the second trimester of pregnancy.ResultsOur results showed that GDM patients had lower α‐diversity that was significantly associated with glycemic traits. Principal coordinates analysis showed significantly different microbial communities, as within GDM patients, seven genera within the phylum Firmicutes and two within the phylum Actinobacteria were significantly decreased, and four genera within phylum Bacteroidetes were increased. In addition, microbiota co‐occurrence network analysis was carried out, and decreased genera within the phylum Firmicutes in GDM patients showed a significant negative correlation with oral glucose tolerance test values. Finally, microbial gene functions related to glycan biosynthesis and metabolism were found to be enriched in GDM patients.ConclusionsOur results show the relationship between changed gut microbiota composition in the second trimester of pregnancy before the diagnosis of GDM and fasting serum levels of metabolites, which might inform the diagnosis, prevention and treatment of GDM.     

Serum uric acid in early pregnancy and risk of gestational diabetes mellitus: A cohort study of 85,609 pregnant women

AimsHigher serum uric acid (UA) has been associated with increased risk of Type 2 diabetes mellitus. This cohort study examined whether there are any associations between serum UA in early pregnancy and the subsequent risk of gestational diabetes mellitus (GDM).MethodsThis cohort study was conducted in Shanghai, China, and included 85,609 pregnant women. Generalised additive models were used to estimate the associations of serum UA with risk of GDM.ResultsThe prevalence of GDM was 14.0% (11,960/85,609). Non-linear associations between serum UA and GDM risk were observed and these associations varied by gestational ages. Only elevated serum UA levels at 13–18 weeks gestation was associated with substantially increased risk of GDM. Analysis by UA quintiles at 13–18 weeks gestation showed the odds ratios for GDM were 1.11 (95%CI, 1.03–1.20) for the second, 1.27 (95%CI, 1.17–1.37) for the third, 1.37 (95%CI, 1.27–1.48) for the fourth and 1.70 (95%CI, 1.58–1.84) for the fifth quintile of serum UA in comparison with the first quintile. Stratified analysis showed the associations of serum UA with GDM were stronger among pregnant women aged 35 years or older.ConclusionWe found higher serum UA at 13–18 gestational weeks was a risk factor for GDM. Our findings provide new evidence for the role of serum UA in the prevention and early intervention of GDM, and highlighted the need for monitoring serum UA at 13–18 gestational weeks.     

Metabolomic profiling of women with gestational diabetes mellitus and their offspring: Review of metabolomics studies

BackgroundGestational diabetes mellitus (GDM) reflects an increased risk of developing type 2 diabetes (T2D) after pregnancy in women. Offspring born to mothers with GDM are at an elevated risk of obesity and T2D at a young age. Currently, there are lack of ways for identifying women in early pregnancy who are at risk of developing GDM. As a result, both mothers and fetus are not treated until late in the second trimester when GDM is diagnosed. The recent advance in metabolomics, a new approach of systematic investigation of the metabolites, provides an opportunity for early detection of GDM, and classifying the risk of subsequent chronic diseases among women and their offspring.MethodsWe reviewed the literatures published in the past 20 years on studies using high-throughput metabolomics technologies to investigate women with GDM and their offspring.ConclusionsDespite the inconsistent results, previous studies have identified biomarkers that involved in specific metabolite groups and several pathways, including amino acid metabolism, steroid hormone biosynthesis, glycerophospholipid metabolism, and fatty acid metabolism. However, most studies have small sample sizes. Further research is warranted to determine if metabolomics will result in new indicators for the diagnosis, management, and prognosis of GDM and related complications.     

The metabolic syndrome in early pregnancy and risk of gestational diabetes mellitus

AimThe objective of the present study was to determine whether or not maternal metabolic syndrome in early pregnancy in women without previous diabetes is associated with the development of gestational diabetes mellitus (GDM).MethodsA total of 508 women from the Rhea study—involving a pregnant cohort in Crete, Greece (2007–2009)—with singleton pregnancies were included in the present analysis. Maternal fasting serum samples were collected and blood pressure measured before gestational week 15. The metabolic syndrome in early pregnancy was defined according to NHLBI/AHA criteria. Pregnant women were screened for GDM between weeks 24 and 28 of gestation, as defined by Carpenter and Coustan criteria. Multivariable log-binomial regression models were used to estimate the effect of the metabolic syndrome in early pregnancy on the risk of GDM, after adjusting for confounding factors.ResultsWomen with the metabolic syndrome were at high risk of GDM (RR = 3.17; 95% CI: 1.06–9.50). Among the components of the metabolic syndrome, the most significant risk factors were impaired fasting glucose (RR = 4.92; 95% CI: 1.41–17.23) and pre-pregnancy obesity (RR = 2.65; 95% CI: 1.23–5.70). A 10-mmHg rise in systolic and diastolic blood pressure increased the relative risk of GDM by 49% (RR = 1.49; 95% CI: 1.10–2.02) and 34% (RR = 1.34; 95% CI: 1.04–1.73), respectively, whereas a 1-unit increase in pre-pregnancy BMI increased the relative risk of GDM by 6% (RR = 1.06; 95% CI: 1.01–1.12).ConclusionThese findings suggest that women with the metabolic syndrome in early pregnancy have a greater risk of developing GDM.     

Serum growth differentiation factor 15 is closely associated with metabolic abnormalities in Chinese pregnant women

AimsTo explore the relationship between serum growth differentiation factor 15 (GDF15) and metabolic abnormalities in Chinese pregnant women.Materials and MethodsWe recruited 200 patients with gestational diabetes mellitus (GDM) and 211 matched normal control within 24–28 weeks of pregnancy. Enzyme‐linked immunosorbent assay (ELISA) was used to determine the serum GDF15 levels of all participants. Then we grouped participants according to the number of metabolic abnormalities (including blood glucose, blood lipids and blood pressure), divided them into a normal metabolic group, one metabolic abnormality group, two or more metabolic abnormalities group. Finally, multinomial logistic regression analysis was used to estimate the odds radio (OR) and 95% CIs expressing the association between GDF15 and metabolic abnormalities in pregnant women.ResultsThrough bivariate correlation analysis, we found that serum GDF15 is linearly correlated with glucose metabolism indices, such as 1h‐PG, 2h‐PG, HbA1c (all P < 0.05). In addition, serum GDF15 and triglycerides were linearly correlated (P < 0.05). Grouping by the number of metabolic abnormalities, we found that as GDF15 levels increased, the risk of metabolic abnormalities also increased (OR > 1), and the risk of multiple metabolic abnormalities was higher. As the number of metabolic abnormalities increased, serum GDF15 levels also were elevated (P < 0.001).ConclusionsThe results suggest that serum GDF15 levels are closely associated with metabolic abnormalities in pregnant women and may be used as a predictor of metabolic abnormalities during pregnancy.     

Predictors of postpartum glucose metabolism disorders in women with gestational diabetes mellitus

Background and aimsPostpartum glucose metabolism disorders are a common problem in women with gestational diabetes mellitus (GDM). They are often underdiagnosed since many patients do not attend the postpartum screening. This study aims to assess predictors of postpartum glucose metabolism disorders and type 2 diabetes mellitus (T2DM) after GDM.Material and methodsRetrospective study in women with GMD who underwent postpartum screening for glucose metabolism disorders (n = 2688). Logistic regression was used in the statistical analysis.Results24.6% of women had postpartum glucose metabolism disorder. In multivariate analysis, pre-pregnancy body mass index (BMI) 25–30 kg/m² (OR 1.46, 95%CI 1.05 to 2.02) or BMI ≥30 kg/m² (OR 2.62, 95%CI 1.72 to 3.96), diagnosis of GDM before 20 weeks of pregnancy (OR 2.33, 95%CI 1.57 to 3.46), fasting plasma glucose after diagnosis of GDM ≥90 mg/dl (OR 2.12, 95%CI 1.50 to 2.98), postprandial glucose ≥100 mg/dl (OR 1.47, 95%CI 1.09 to 2.99), and HbA1c in the third trimester of pregnancy ≥5.3% (2.04, 95%CI, 1.52 to 2.75) were independent predictors for any postpartum glucose metabolism disorder.Conclusionpostpartum screening for T2DM should be performed in all women with GDM, and it is especially important not to lose follow-up in those with one or more predictive factors.     

Prediction of pre-diabetes and type 2 diabetes nine years postpartum using serum metabolome in pregnant women with gestational diabetes requiring pharmacological treatment

AimsWe examined the association between serum metabolome in women with pharmacologically treated gestational diabetes (GDM) and measures of glucose metabolism 9 years postpartum.MethodsSerum targeted metabolome, adiponectin, inflammatory markers, and insulin-like growth factor-binding protein-1 phosphoisoforms were analyzed at the time of diagnosing GDM. Glucose metabolism and insulin resistance were assessed at 9 years postpartum. Data from 119 subjects were available for analyses. Associations between baseline measures and future measures of glycemia were examined with univariate regressions and multivariate prediction models. This is a secondary analysis of a previous prospective trial (NCT02417090).ResultsBaseline serum markers were most strongly related to measures of insulin resistance at 9-years follow-up. In multivariate analyses combination of IDL cholesterol, early gestational weight gain and in oral glucose tolerance test fasting and 2-h glucose predicted development of disorders of glucose metabolism (pre-diabetes and/or type 2 diabetes) better than clinical predictors alone (ROC-AUC 0.75 vs. 0.65, p = 0.020).ConclusionsSerum metabolome in pregnancy in women with GDM is related to future glucose metabolism and insulin resistance. Compared to clinical variables alone metabolome might result in better prediction of future disorders of glucose metabolism and could facilitate personalized risk stratification for postpartum interventions and follow-up.     

Serum CathepsinD in pregnancy: Relation with metabolic and inflammatory markers and effects of fish oils and probiotics

Background and aimsElevated circulating levels of CathepsinD (CatD) have been linked to metabolic deviations including liver inflammation. We investigated 1) whether supplementation with probiotics and/or fish oil affects CatD and 2) whether the CatD concentration would associate with gestational diabetes (GDM), low-grade inflammation, lipid metabolism, body fat % and dietary composition.Methods and resultsOverweight/obese pregnant women (n = 438) were randomized into fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo groups. Fish oil contained 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid and probiotics were Lacticaseibacillus rhamnosus HN001 (formerly Lactobacillus rhamnosus HN001) and Bifidobacterium animalis ssp. lactis 420, 10¹⁰ colony-forming units each). Serum CatD levels were analysed by ELISA, GlycA and lipid metabolites by NMR, high sensitive C-reactive protein (hsCRP) by immunoassay, and intakes of energy yielding nutrients and n-3 and n-6 fatty acids from food diaries at both early and late pregnancy. GDM was diagnosed by OGTT. CatD concentrations did not differ between the intervention groups or by GDM status. Multivariable linear models revealed that body fat % and GlycA affected CatD differently in healthy women and those with GDM.ConclusionThe serum CatD concentration of pregnant women was not modified by this dietary intervention. Serum CatD was influenced by two parameters, body fat and low grade inflammation, which were dependent on the woman's GDM status.Clinical trial reg. noNCT01922791, clinicaltrials.gov (secondary analysis).     

Association between sleep duration in early pregnancy and risk of gestational diabetes mellitus: a prospective cohort study

AimsAs cohort studies of the impact of sleep duration during early pregnancy on gestational diabetes mellitus (GDM) are lacking, our study aimed to explore the association between sleep duration in the first trimester and GDM in one region of mainland China.MethodsFor this prospective cohort study, sleep duration data were collected from 3692 pregnant women at the first prenatal care appointment before 14 weeks of gestation. Multivariable log-binomial regression models were used to analyze the association of sleep duration with GDM after adjusting for demographic characteristics, health status (such as family history of diabetes, history of GDM, prepregnancy body mass index, gestational weight gain) and lifestyle habits (such as physical activity, dietary intakes).ResultsOur cohort included 166 (4.5%) short sleepers and 505 (14%) long sleepers. Shorter sleep duration was more likely to be observed in women aged ≥35 years who were multiparous, and had previous pregnancy, insufficient gestational weight gain, engaged in more vigorous physical activity, drank alcohol, were vegan and/or never took folic-acid supplements. Compared with normal sleepers (29%), the prevalence of GDM was significantly higher in short sleepers (38%; P = 0.01), but not in long sleepers (31%; P = 0.224). In the multivariable model, women with short sleep durations during early pregnancy had a 32% greater risk of GDM [adjusted risk ratio (aRR): 1.32, 95% CI: 1.06–1.63], whereas long sleepers did not (aRR: 1.09, 95% CI: 0.94–1.26).ConclusionShort sleep duration during early pregnancy is associated with an increased risk of GDM. This suggests that more attention should be paid to controlling the development of GDM in pregnant women with insufficient sleep.     

Effect of maternal lifestyle intervention on metabolic health and adiposity of offspring: Findings from the Finnish Gestational Diabetes Prevention Study (RADIEL)

AimTo assess in women at high risk of gestational diabetes mellitus (GDM) the effect of a lifestyle intervention on the metabolic health of their offspring around 5 years after delivery.MethodsFor the original Finnish gestational diabetes prevention study (RADIEL), 720 women with a prepregnancy body mass index (BMI) ≥ 30 kg/m² and/or previous GDM were enrolled before or during early pregnancy and allocated to either an interventional (n = 126) or conventional (n = 133) care group. The present 5-year follow-up substudy assessed the metabolic health outcomes of their offspring. Age- and gender-standardized residuals of metabolic health components (waist circumference, mean arterial pressure, high-density lipoprotein and triglyceride levels, and fasting insulin/glucose ratio) were also combined to determine the accumulation of metabolic effects. Body composition was assessed by electrical bioimpedance.ResultsOffspring of women in the intervention group had a less optimal metabolic profile after the 5-year follow-up compared with offspring in the usual care group (P = 0.014). This difference in metabolic health was primarily related to lipid metabolism, and was more prominent among boys (P = 0.001) than girls (P = 0.74). Neither GDM, gestational weight gain, prepregnancy BMI, offspring age nor timing of randomization (before or during pregnancy) could explain the detected difference, which was also more pronounced among the offspring of GDM pregnancies (P = 0.010). Offspring body composition was similar in both groups (P > 0.05).ConclusionThe lifestyle intervention aimed at GDM prevention was associated with unfavourable metabolic outcomes among offspring at around 5 years of age.     

Study of the metabolomics characteristics of patients with metabolic syndrome based on liquid chromatography quadrupole time-of-flight mass spectrometry

BackgroundMetabolic syndrome (MS) is a disease with complex pathophysiology and pathogenesis involving multiple systems of the human body. This study aimed to identify serum metabolites that are relevant to MS.Material and methodsThis study involved 40 patients with MS and 28 healthy adults, and the following data were statistically analyzed: basic clinical data, blood lipids, fasting blood glucose, blood pressure, waist circumference, and visceral fat coefficient. Serum samples from both groups were collected and analyzed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS); multivariate and univariate statistical methods were used to identify potential MS biomarkers and MS-related metabolic pathways. In addition, leucine and valine levels in serum from MS patients and normal subjects were measured using enzyme-linked immunosorbent assays (ELISAs).ResultsIn this study, 23 potential biomarkers were identified in the plasma of MS patients. These biomarkers were mainly related to metabolism; the tricarboxylic acid cycle; galactose metabolism; arachidonic acid metabolism; valine, leucine, and isoleucine degradation; and valine, leucine, and isoleucine biosynthesis. ELISAs were utilized to verify serum leucine and valine levels, and the results supported the experimental metabolomics results.ConclusionsIn total, 23 MS-related metabolites were identified in the serum; these differential metabolites were mainly associated with lipid metabolism, amino acid metabolism, glucose metabolism, purine metabolism, and other related metabolic pathways. This study shows that LC/MS-based metabolomics methods can be used to investigate the pathological changes in MS patients and identify biomarkers for the early diagnosis of MS.     

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.     

Heterogeneity of pregnancy outcomes and risk of LGA neonates in Caucasian females according to IADPSG criteria for gestational diabetes mellitus

ObjectiveThe International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines for gestational diabetes mellitus (GDM) diagnosis determines that fasting, 1-h and 2-h glucose values may contribute independently to adverse outcomes. However, given the different physiological bases of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), differences in pregnancy outcomes are to be expected. This study aimed to determine whether classification of GDM women according to glucose homoeostasis results in heterogeneity in maternal and/or fetal outcomes.Material and methodsOf the 75 pregnant women included after a 75-g 2-h OGTT performed between weeks 24–32 of gestation as per WHO criteria, 55 were classified as GDM (16 with IFG and 39 with IGT) according to IADSPG criteria. Their anthropometric and metabolic characteristics were compared with those of non-GDM women with IFG or IGT. Maternal and neonatal outcomes were prospectively recorded for each group.ResultsGDM women with IFG, including isolated IFG and combined IFG + IGT, were significantly heavier, had higher leptin values and were more frequently multiparous than GDM women with isolated IGT. HOMA-IR was significantly higher when fasting glucose was impaired. There were no significant differences in maternal outcomes according to metabolic status. In addition, large for gestational age (LGA) neonates were significantly seen more often in the IFG group. Fasting glucose was significantly associated with LGA independently of BMI and 2-h OGTT glucose. The > 5.1 mmol/L cut-off value for fasting glucose was highly predictive of delivery of LGA infants.ConclusionIFG in GDM women was associated with increases in BMI, fat mass and hepatic insulin resistance. Delivery of LGA neonates was more frequent when fasting glycaemia was increased during the third trimester of pregnancy, and was independent of BMI and 2-h OGTT glucose values.     

Risk factors associated with postpartum impaired glucose regulation in women with previous gestational diabetes

AimsFor women with previous gestational diabetes (GDM), international guidelines recommend 75 g oral glucose tolerance test (OGTT) at 4–12 weeks after delivery to assess glucose tolerance, considering their increased risk of type 2 diabetes. We evaluated prevalence of postpartum impaired glucose regulation (IGR) and identified associated risk factors.MethodsWe retrospectively collected data from 749 women with previous GDM (IADPSG criteria) who underwent postpartum OGTT for type 2 diabetes screening between 2011 and 2019. IGR was identified according to ADA criteria.ResultsPrevalence of IGR was 12.7%, lower in women with pre-pregnancy normal weight, higher in women with family history of type 2 diabetes and in those treated with insulin during pregnancy. Prevalence of IGR raised with increasing number of altered glucose values at OGTT performed during pregnancy for GDM screening. HbA1c and triglycerides measured during the third trimester of pregnancy were higher in women with postpartum IGR. At postpartum screening, women with IGR had higher BMI, waist, blood pressure. At multivariate logistic regression analysis, family history of diabetes (OR 2.21; 95% CI: 1.33–3.69; p < 0.01) and presence of all three glucose values exceeding threshold at OGTT during pregnancy (OR 2.89; 95% CI: 1.42–5.86; p < 0.01) were independently associated with IGR.ConclusionsIn women with GDM, persistence of IGR in the immediate postpartum period is associated with family history of diabetes and the presence of all three glucose values exceeding diagnostic threshold for GDM at OGTT in pregnancy, suggesting that these women should undergo specific diabetes monitoring and prevention programs.     

Pregnancy to postpartum transition of serum metabolites in women with gestational diabetes

ContextGestational diabetes is commonly linked to development of type 2 diabetes mellitus (T2DM). There is a need to characterize metabolic changes associated with gestational diabetes in order to find novel biomarkers for T2DM.ObjectiveTo find potential pathophysiological mechanisms and markers for progression from gestational diabetes mellitus to T2DM by studying the metabolic transition from pregnancy to postpartum.DesignThe metabolic transition profile from pregnancy to postpartum was characterized in 56 women by mass spectrometry-based metabolomics; 11 women had gestational diabetes mellitus, 24 had normal glucose tolerance, and 21 were normoglycaemic but at increased risk for gestational diabetes mellitus. Fasting serum samples collected during trimester 3 (gestational week 32 ± 0.6) and postpartum (10.5 ± 0.4 months) were compared in diagnosis-specific multivariate models (orthogonal partial least squares analysis). Clinical measurements (e.g., insulin, glucose, lipid levels) were compared and models of insulin sensitivity and resistance were calculated for the same time period.ResultsWomen with gestational diabetes had significantly increased postpartum levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, and their circulating lipids did not return to normal levels after pregnancy. The increase in BCAAs occurred postpartum since the BCAAs did not differ during pregnancy, as compared to normoglycemic women.ConclusionsPostpartum levels of specific BCAAs, notably valine, are related to gestational diabetes during pregnancy.     

Association between pre‐pregnancy body mass index and gestational weight gain and perinatal outcomes in pregnant women diagnosed with gestational diabetes mellitus: The Japan Environment and Children's Study

Aims/IntroductionWe investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre‐pregnancy body mass index (BMI) and/or gestational weight gain (GWG).Materials and MethodsData from the national birth cohort in the Japan Environment and Children''s Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM.ResultsThe OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre‐pregnancy BMI of ≥25.0 kg/m² and insufficient GWG (<2.75 kg) was 1.78 (1.02–3.12). The OR of having a large for gestational age infant of the same BMI group with excessive GWG (>7.25 kg) was 2.04 (1.56–2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m² in the GDM group than in the non‐GDM group.ConclusionsLarge for gestational age and hypertensive disorders of pregnancy were associated with pre‐pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m² are at risk of having small for gestational age and large for gestational age infants depending on GWG.     

Association of glycated hemoglobin at an early stage of pregnancy with the risk of gestational diabetes mellitus among non‐diabetic women in Japan: The Japan Environment and Children’s Study

Aims/IntroductionGestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is associated with adverse pregnancy outcomes. This study aimed to explore the associations between glycated hemoglobin (HbA1c) levels at the early stage of pregnancy and the GDM risk among non‐diabetic women in a nationwide study in Japan. In addition, the relationship between GDM and adverse pregnancy outcomes was also analyzed.Materials and MethodsThis cohort study (n = 89,799) used data from the Japan Environment and Children’s Study. We stratified the participants into four groups according to HbA1c levels at an early stage of pregnancy. We investigated the association of HbA1c at an early stage of pregnancy with the risk of GDM, and of GDM with the risk of some representative adverse pregnancy outcomes, using the multiple logistic regression model with adjustment for potential confounders.ResultsThe adjusted odds ratio for GDM per 0.1 percentage point increase in HbA1c (%) was 1.20. The adjusted odds ratio for developing GDM was significantly increased in women from the HbA1c 5.0–5.4% category. GDM significantly increased the adjusted odds ratio for adverse pregnancy outcomes, such as hypertensive disorders of pregnancy, polyhydramnios and premature birth.ConclusionsHigh‐normal HbA1c levels at the early stage of pregnancy are significantly associated with GDM risk in women in Japan. GDM was significantly associated with adverse pregnancy outcomes.     

Gestational diabetes mellitus in Korea: prevalence and prediction of glucose intolerance at early postpartum

To determine the prevalence of glucose intolerance in Korean women with gestational diabetes mellitus (GDM) between 6 and 8 weeks postpartum and identify which antepartum variables were predictive of postpartum diabetes and impaired glucose tolerance (IGT), we prospectively performed 75 g oral glucose tolerance test (OGTT) between 6 and 8 weeks postpartum in women with GDM. WHO criteria were used for classification of glucose tolerance postpartum. Of 392 women with GDM were detected during the study period, 311 women participated in this study. Of the 311 participants, 119 (38.3%) women were found to have persistent glucose intolerance; 47 (15.1%) had diabetes and 72 (23.2%) had IGT. The prevalence of postpartum IGT and diabetes increased in parallel with the metabolic severity during pregnancy. Multiple logistic regression analysis revealed that pre-pregnancy weight, gestational age at diagnosis of GDM, 2-h glucose and 3-h insulin concentrations of diagnostic OGTT were independently associated with postpartum diabetes. Pre-pregnancy weight, 2-h glucose and 1-h insulin concentrations were independently associated with postpartum IGT. Our results support the importance of postpartum testing in Korean women with GDM, and demonstrated that impaired beta-cell function and pre-pregnancy obesity were associated with glucose intolerance at early postpartum.     

Second-trimester maternal lipid profiles rather than glucose levels predict the occurrence of neonatal macrosomia regardless of glucose tolerance status: A matched cohort study in Beijing

AimsThe mechanism underlying fetal overgrowth during pregnancy remains elusive. We aimed to establish a predictive model to identify the high-risk individuals with macrosomia in the second trimester of pregnancy.DesignA total of 2577 pregnant women with a routine 75-g oral glucose tolerance test during 24–28 gestational weeks were screened in a prospective cohort. Gestational diabetes mellitus (GDM) cases were 1:1 matching with age (±2 years) in normal glucose tolerance (NGT) ones from the same region. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve were performed to determine the index and its inflection point for predicting macrosomia occurrence.ResultsThe data of perinatal outcomes of 565 GDM and 549 NGT who had given birth to single live babies at term were analyzed. Notably, we found serum apolipoprotein B (ApoB) level higher than 4.04 g/L combined with triglycerides (TG)/high-density lipoprotein cholesterol (HDLC) ratio above 1.36 formed the predictive model in both groups. The area under the ROC curve of this predictive model included ApoB and TG/HDL-C reached 0.807 (95% CI: 0.771–0.873) with a sensitivity of 71.9% and a specificity of 78.6%. Mediation analysis revealed that ApoB and TG/HDL-C ratio mediated the harmful effect of FBG on the risk of macrosomia.ConclusionMaternal ApoB levels and TG/HDL-C ratio could predict macrosomia occurrence in pregnancy, which might be a new target for early intervention to prevent excess fetal growth.     

Early vs. standard screening and treatment of gestational diabetes in high-risk women – An attempt to determine relative advantages and disadvantages

Background and aimsScreening for Gestational Diabetes (GDM) is usually recommended between 24 and 28 weeks of pregnancy; however available evidence suggests that GDM may be already present before recommended time for screening, in particular among high-risk women as those with prior GDM or obesity. The purpose of this retrospective study was to evaluate whether early screening (16–18 weeks) and treatment of GDM may improve maternal and fetal outcomes.Methods and resultsIn 290 women at high-risk for GDM, we analyzed maternal and fetal outcomes, according to early or standard screening and GDM diagnosis time. Early screening was performed by 50% of high-risk women. The prevalence of GDM was 62%. Among those who underwent early screened, GDM was diagnosed at the first evaluation in 42.7%. Women with early diagnosis were more frequently treated with insulin and had a slightly lower HbA1c than women with who were diagnosed late. No differences were observed in the prevalence of Cesarean section, operative delivery, gestational age at the delivery, macrosomia, neonatal weight, Ponderal Index and Large-for-Gestational-Age among women with early or late GDM diagnosis or NGT. However, compared to NGT women, GDM women, irrespective of the time of diagnosis, had a lower gestational weight gain, lower prevalence of macrosomia (3.9% vs. 11.4%), small (1.7% vs. 8.3%) as well as large for gestational age (3.3% vs. 16.7%), but higher prevalence of pre-term delivery (8.9% vs. 2.7%).ConclusionEarly vs. standard screening and treatment of GDM in high-risk women is associated with similar short-term maternal-fetal outcomes, although women with an early diagnosis were treated to a greater extent with insulin therapy.