Subsequent Risk Of Gestational Diabetes Mellitus Research Articles

The associations of maternal liver biomarkers in early pregnancy with the risk of gestational diabetes mellitus: a prospective cohort study and Mendelian randomization analysis.

Associations of liver function with the risk of gestational diabetes mellitus (GDM) remain unclear. This study aimed to examine the relationship and the potential causality between maternal liver biomarkers and the risk of subsequent GDM, as well as to evaluate the interaction between liver biomarkers and lipids on GDM risk. In an ongoing Zhoushan Pregnant Women Cohort, pregnant women who finished the first prenatal follow-up record, underwent liver function tests in early pregnancy, and completed the GDM screening were included in this study. Logistic regression models were used to investigate the association, and the inverse-variance weighted method supplemented with other methods of two-sample Mendelian randomization (MR) analysis was applied to deduce the causality. Among 9,148 pregnant women, 1,668 (18.2%) developed GDM. In general, the highest quartile of liver function index (LFI), including ALT, AST, GGT, ALP, and hepatic steatosis index, was significantly associated with an increased risk of GDM (OR ranging from 1.29 to 3.15), especially an elevated risk of abnormal postprandial blood glucose level. Moreover, the causal link between ALT and GDM was confirmed by the MR analysis (OR=1.28, 95%CI:1.05-1.54). A significant interaction between AST/ALT and TG on GDM risk was observed (P interaction = 0.026). Elevated levels of LFI in early pregnancy were remarkably associated with an increased risk of GDM in our prospective cohort. Besides, a positive causal link between ALT and GDM was suggested.

Ultrasonographic abdominal adipose tissue thickness for the prediction of gestational diabetes mellitus: A meta-analysis.

Obesity has been linked to the risk of gestational diabetes mellitus (GDM). The meta-analysis aimed to assess the predictive role of ultrasonographic measurements of the abdominal adipose tissue thickness for GDM in pregnant women. Cohort studies evaluating the association between abdominal subcutaneous and/or visceral adipose thickness (SAT and/or VAT) and subsequent risk of GDM were retrieved from PubMed, Embase, and Web of Science databases. Only studies with SAT/VAT measured before the diagnosis of GDM were included. Random-effects models incorporating the influence of potential heterogeneity were used to pool the results. A total of 13 studies involving 5616 pregnant women were included. Pooled results showed that both a high abdominal SAT (odds ratio [OR] for per 1-cm increment: 1.23, 95% confidence interval [CI]: 1.07 to 1.41, P = 0.003, I2 = 13%; OR for high versus low category: 3.42, 95% CI: 2.31 to 5.07, P < 0.001, I2 = 0%) and VAT (OR for per 1-cm increment: 1.54, 95% CI: 1.16 to 2.06, P = 0.003, I2 = 63%; OR for high versus low category: 5.73, 95% CI: 3.39 to 9.77, P < 0.001, I2 = 31%) at early stages of pregnancy were associated with a higher subsequent risk of GDM. Subgroup analysis based on study design, timing of ultrasound examination, GDM diagnostic criteria, and study quality score showed consistent results. In conclusion, ultrasound-measured abdominal adipose tissue thickness may be useful for predicting the subsequent risk of GDM in pregnant women.

Association between eating habits during adolescence and gestational diabetes: data from the Japan environment and children's study.

It is difficult to change pre-pregnancy eating habits, yet establishing healthy eating habits before pregnancy is important for preventing gestational diabetes mellitus (GDM). This study aimed to examine whether the weight-loss behavior of avoiding between-meal and midnight snacking in teenagers is associated with a reduction in the risk of subsequent GDM. We used a dataset (jecs-an-20,180,131) from a nationwide, prospective birth cohort study, the Japan Environment and Children's Study (JECS). We included 89,227 (85.7% of the total) mother-infant pairs with live births. Participants in their second or third trimester were asked to report their weight-loss behavior during their teenage years. The prevalence of GDM was investigated. Differences in maternal characteristics were examined using chi-square tests. Crude and adjusted logistic regression models were constructed to assess the associations of various maternal characteristics with the weight-loss behavior of avoiding between-meal and midnight snacking during teenage years. A total of 2,066 (2.3%) participants had GDM. Weight-loss behavior in teenagers was associated with a decreased risk of GDM. Among participants with normal weight or overweight prior to pregnancy, the adjusted odds ratios were 0.79 (95% confidence interval, 0.70-0.89) and 0.82 (95% confidence interval, 0.69-0.98), respectively. The results suggest that teenage weight-loss behaviors, such as avoiding between-meal and midnight snacking, are associated with a decreased risk of developing GDM. The online version contains supplementary material available at 10.1007/s40200-023-01294-2.

Does depression increase the risk of gestational diabetes mellitus? A systematic review and meta-analysis.

Data on the relationship between depression and gestational diabetes mellitus (GDM) is scarce and conflicting. We, hereby, aimed to review evidence if prior depression increases the risk of GDM. PubMed, Embase, CENTRAL, and Google Scholar databases were searched from inception to 11th September 2021 for English language studies reporting the relationship between depression and subsequent risk of GDM. Ten studies were included. Meta-analysis of data from nine studies including 127,195 patients indicated that prior depression was associated with a significantly increased risk of GDM (OR: 1.29 95% CI: 1.10, 1.52). There was no change in the significance of the results on sensitivity analysis. On subgroup analysis based on study location, we noted that the association between depression and GDM was seen only in USA-based studies with the pooled analysis of non-USA studies indicating no such relationship. Similar conflicting results were noted on subgroup analysis based on diagnostic criteria for GDM and depression. Our study indicates that prior depression can lead to a 29% increased risk of GDM in pregnant females. Current evidence is derived from a limited number of studies with significant heterogeneity in the timing and diagnostic criteria for depression.

Association of Early Pregnancy Free and Total Triiodothyronine With the Subsequent Risk of Gestational Diabetes Mellitus

ObjectiveTo estimate the association of free triiodothyronine (FT3) and total triiodothyronine (TT3) in early pregnancy and subsequent gestational diabetes mellitus (GDM) risk and define appropriate TT3 thresholds for GDM screening. MethodsThis investigation is a hospital-based cohort study of pregnant women submitted to a universal thyroid function test before 24 weeks of gestation. GDM was diagnosed according to a 75-g oral glucose tolerance test. The association of maternal high FT3 and TT3 levels in early pregnancy with the risk of GDM was estimated using logistic regression. The potential nonlinear association was probed by the restricted cubic spline curve method. ResultsA total of 27 184 pregnant women and 3073 GDM cases were included in the analysis. FT3 and TT3 were associated with an increased subsequent risk of GDM in a nonlinear fashion. The adjusted odds ratios were 1.59 (95% confidence interval, 1.50-1.68) and 2.80 (95% confidence interval, 2.46-3.18) for FT3 and TT3 continuous levels, respectively. Associations were strong in euthyroid women, showed heterogeneity in women with mild thyroid dysfunction, and lacked in patients with overt hypothyroidism and hyperthyroidism. The TT3 thresholds of 1.5 and 2.0 ng/mL between 7 and 12 weeks of gestation and 1.6 and 2.1 ng/mL for 13 to 23 weeks of gestation effectively distinguished the subsequent risk of GDM. ConclusionThe increased FT3 and TT3 levels in early pregnancy were associated with a subsequent higher risk of GDM. These findings provide measures for early detection and potential prevention of GDM.

Plasma Amino Acids in Early and Mid-Pregnancy With Subsequent Risk of Gestational Diabetes and Cardiometabolic Markers – Both Type of Amino Acids and Gestational Timing Matter

ObjectivesTo prospectively evaluate associations of plasma amino acids (AAs) in early and mid-pregnancy with gestational diabetes mellitus (GDM) risk and cardiometabolic biomarkers in a longitudinal U.S. multiracial pregnancy cohort.MethodsWe conducted a nested case-control study within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort. Individual AAs at gestational weeks (GW) of 10–14, 15–26, 23–31, and 33–39 were assessed among 107 GDM cases (mean GW for GDM ascertainment: 27.4) and 214 controls matched on age, race/ethnicity, and gestational age at sample collection. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations of plasma AAs at 10–14 GW and 15–26 GW with subsequent risk of GDM, adjusting for major covariates. We estimated Spearman's partial correlation coefficients between AAs at 10–14 GW and fasting cardiometabolic markers at 15–26 GW.ResultsAt 10–14 GW, each SD increment in glycine levels was related to a 45% lower risk of GDM (adjusted OR, 95% CI: 0.55, 0.39–0.79), whereas each SD increase in alanine, aspartic acid, and glutamic acid was associated with a 43% (aOR, 95% CI: 1.43, 1.08–1.88), 41% (aOR, 95% CI: 1.41, 1.11–1.80), and 39% (aOR, 95% CI: 1.39, 0.98–1.98) greater risk of GDM, respectively. At 15–26 GW, similar findings to those at GW 10–14 were observed for glycine, alanine, and aspartic acid. In addition, each SD increment in glutamine-to-glutamic acid-ratio was related to a 50% lower risk of GDM (OR, 95% CI: 0.50, 0.26–0.94). By contrast, higher levels of branched-chain AA (BCAA) isoleucine and aromatic AAs tyrosine and phenylalanine were associated with a higher risk of GDM (OR, 95% CI: 1.64, 1.19–2.27 for isoleucine; 1.56, 1.16–2.09 for tyrosine; and 1.15, 0.87–1.53 for phenylalanine). Higher levels of glycine and lower levels of alanine, BCAA, and aromatic AAs were associated with a more favorable cardiometabolic biomarker profile.ConclusionsAssociations of AAs with GDM differed by both types of AAs and timing over pregnancy. These findings suggest potentially important roles of glycine in both early- and mid-pregnancy, and BCAA and aromatic AAs in mid-pregnancy in the development of GDM and maternal cardiometabolic profiles.Funding SourcesThe Eunice Kennedy Shriver NICHD, American Recovery and Reinvestment Act.

Serum Fetuin-A and Risk of Gestational Diabetes Mellitus: An Observational Study and Mendelian Randomization Analysis.

Fetuin-A was reported to be associated with risk of type 2 diabetes, but its association with incident gestational diabetes mellitus (GDM) was less studied. We aimed to examine the association between fetuin-A levels in early pregnancy and risk of incident GDM and to evaluate whether this association was causal. A total of 332 pregnant women with GDM and 664 matched controls were included in this nested case-control study. Multivariable conditional logistic regression was applied to investigate the prospective association between serum fetuin-A in early pregnancy and subsequent risk of GDM. Two-sample Mendelian randomization (MR) analysis was used to examine the causal association, using summary statistics from the CHARGE Consortium and the FinnGen consortium. The mean age of the participants was 28.0 years, and the mean gestational age was 11.0 weeks (range 6-15) at enrollment. In the final model, the odds ratio (OR) for GDM comparing the extreme quartiles of fetuin-A levels was 1.78 (95% CI 1.06, 2.98; P for trend = 0.009), and the restricted cubic spline analysis indicated a linear association (P for nonlinearity = 0.83). This positive association was found in women with waist circumference <80 cm but not in those with waist circumference ≥80 cm (P for interaction = 0.04). However, MR analyses showed no evidence of a causal association with an OR of 0.91 (95% CI 0.67, 1.23) per unit increment of fetuin-A. Serum fetuin-A levels in early pregnancy were positively associated with risk of GDM, particularly in those with normal waist circumference. However, we found no genetic evidence for a causal association.

Free-Triiodothyronine to Free-Thyroxine Ratio Mediated the Effect of Prepregnancy Body Mass Index or Maternal Weight Gain During Early Pregnancy on Gestational Diabetes Mellitus

ObjectiveMaternal overweight or obesity during early pregnancy can increase the subsequent risk of gestational diabetes mellitus (GDM). However, whether these associations are mediated by thyroid hormones and their effect sizes is still unknown. This study aimed to identify the mediating effects of thyroid parameters between prepregnancy body mass index (BMI) or maternal weight gain during early pregnancy on the subsequent risk of GDM. MethodsThis prospective mother-infant cohort study was conducted from 2018 to 2019. A total of 2772 singleton pregnant women were included in the analysis. A questionnaire survey, anthropometric measures, and thyroid function testing were conducted during early pregnancy. Deiodinase activity was evaluated using the free-triiodothyronine-to-free-thyroxine ratio (FT3:FT4). The standard 75-g oral glucose tolerance test was performed during 24 to 28 weeks of gestation to diagnose GDM. A mediation analysis was performed using PROCESS 3.5 to examine the mediating effects of thyroid parameters between prepregnancy BMI or maternal weight gain during early pregnancy on the subsequent risk of GDM. ResultsThe FT3:FT4 ratio was a significant mediator between prepregnancy BMI or maternal weight gain and GDM, accounting for 16.5% and 18.6% of total effects, respectively. FT3 also mediated the association of prepregnancy BMI with GDM, accounting for 3.3% of the total effects. Thyroid-stimulating hormone suppressed the effects of prepregnancy BMI and maternal weight gain on GDM risk, and the proportion of their total effects was 2.4% and 6.4%, respectively. ConclusionDeiodinase activity, as indicated by the FT3:FT4 ratio, was the strongest mediator among thyroid parameters between prepregnancy BMI or maternal early weight gain and GDM.

The Predictive Ability of Hepatic Steatosis Index for Gestational Diabetes Mellitus and Large for Gestational Age Infant Compared with Other Noninvasive Indices Among Chinese Pregnancies: A Preliminary Double-center Cohort Study

ObjectiveTo evaluate the association of hepatic steatosis index (HSI) in the first trimester and the risk of gestational diabetes mellitus (GDM) as well as large for gestational age (LGA) infant in Chinese women.MethodsA total of 1082 pregnant women were included in this study. Maternal basic laboratory data, including ALT, AST, FBG, insulin, TG, and HDL-C, were tested during 6–12 weeks of gestation and anthropometric characteristics were monitored during gestation. A 75-g oral glucose tolerance test (OGTT) was conducted at 24–28 weeks of gestation. HSI, nonalcoholic fatty liver disease (NAFLD) liver fat score, triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) and triglyceride-glucose (TyG) index were calculated. Odds ratio with 95% confidence interval for subsequent risk of GDM and LGA by HSI quartiles were assessed by binary logistic regression model. The predictive ability of HSI for GDM and LGA was evaluated by the receiver operating characteristic (ROC) curve analysis and was compared with other indices.ResultsThe incidence of GDM and LGA were 22.09% (239/1082) and 10.53% (87/826). HSI was higher in GDM group than in NGT group (median, interquartile range: 30.67, 27.20–35.10 vs 27.98, 25.70–30.82, P<0.001). Incidence of GDM was gradually increased with increasing HSI values. Women in the highest HSI quartile had significantly higher risk of LGA delivery than those in the lowest HSI quartile (P<0.05). The area under the ROC curves of HSI for GDM and LGA were higher than other indices, reaching 0.646 (95%CI: 0.605–0.686) and 0.600 (95%CI: 0.541–0.660), respectively.ConclusionHigher HSI was independently associated with higher risk of GDM and LGA in Chinese women. HSI in the first trimester can predict the risk of GDM and LGA.

High level of complement factor Ba within first prenatal test of gestation increases the risk of subsequent gestational diabetes: a propensity score-matched study

Objective This study was to assess the alteration of circulating complement factor Ba (CFBa) within 11 to 17 weeks of gestation and its association with subsequent gestational diabetes mellitus (GDM) and its delivery outcome. Methods Biochemical parameters and blood samples were collected from 399 pregnant women within 11 to 17 weeks of gestation. At 24 to 28 weeks of gestation, all participants underwent 75-g oral glucose tolerance test and were assigned to GDM group (n = 80) and normal control group (n = 319). Perinatal data were collected after delivery. A propensity score-matched (PSM) analysis was performed to reduce the impact of confounding factors on glucose metabolism during pregnancy between the two groups. Results Two groups of 74 well-matched patients who maintained balance in terms of baseline characteristics. The levels of CFBa in pregnant women who later developed GDM were significantly higher than those in healthy pregnant women [0.4(0.1–0.8) vs. 0.2(0.2–0.3), p = 0.024]. Logistic regression analysis results confirmed that the level of CFBa was an independent impact factor for the occurrence of GDM (OR = 1.57, 95% CI: 1.118–2.210, p = 0.009). Further grouping according to the median level of CFBa, it was found that the incidence of GDM in category two (>0.23 ng/ml, n = 74) was markedly higher than that in the first category (≤0.23 ng/ml, n = 74) (p = 0.021). Conclusions High level of the CFBa within 11 to 17 weeks of gestation increases the risk of subsequent GDM, and maybe a biomarker for predicting GDM.

Pre-pregnancy menstrual cycle regularity and length and the risk of gestational diabetes mellitus: prospective cohort study.

Menstrual cycle dysfunction has been associated with many endocrine-related diseases, but evidence linking menstrual cycle dysfunction with gestational diabetes mellitus (GDM) is scant. The current study investigated the association of pre-pregnancy menstrual cycle regularity and length during adolescence, early adulthood and mid-adulthood with the subsequent risk of GDM. Between 1993 and 2009, we followed 10,906 premenopausal women participating in the Nurses' Health Study II who reported menstrual cycle characteristics during adolescence (age 14-17years), early adulthood (age 18-22years) and mid-adulthood (age 29-46years). Incident GDM was ascertained from a self-reported questionnaire regarding physician diagnosis. Log-binomial models with generalised estimating equations were used to estimate the RRs and 95% CI for the associations between menstrual cycle characteristics and GDM. We documented 578 incident cases of GDM among 14,418 pregnancies over a 16year follow-up. After adjusting for potential confounders, women reporting always having irregular menstrual cycles during mid-adulthood had a 65% (95% CI 21, 125%) higher risk of GDM than women reporting very regular cycles. GDM risk was also greater among women reporting that their cycles were usually ≥32days during mid-adulthood, compared with women reporting cycles between 26 and 31days (RR 1.42 [95% CI 1.15, 1.75]). The risk of GDM was greater for women whose cycles changed from regular early in their reproductive years to irregular or from <32days to ≥32days during mid-adulthood, compared with women whose cycles remained <32days or regular, respectively. Women whose cycles were long or irregular during mid-adulthood, but not in adolescence or young adulthood, were at higher risk of GDM.

Triglyceride–glucose index predicts the risk of gestational diabetes mellitus: a systematic review and meta-analysis

Aims We aimed to investigate the potential predictive efficacy of triglyceride–glucose (T/Gly) index for gestational diabetes mellitus (GDM) in a systematic review and meta-analysis. Materials and methods Cohort studies demonstrating the association between T/Gly index measured at the first trimester or before pregnancy and the subsequent incidence of GDM were identified by search of PubMed, Embase, China National Knowledge Infrastructure, and WanFang databases. A random-effect model incorporating the heterogeneity was applied to pool the results. Five cohort studies including 382,213 women were included in this meta-analysis. Results Compared to those with the lowest category of T/Gly index, women with the highest category of T/Gly index were independently associated with higher risk of subsequent GDM (odds ratio [OR]: 2.52, 95% confidence interval [CI]: 1.33 ∼ 4.67, I 2=65%, p=.004) after adjustment of potential confounding factors including age, body mass index, and family history of diabetes. The association was stronger in prospective cohort studies than retrospective cohort studies (p for subgroup difference=.007), and a significant association was detected in Asian women (OR: 3.30, 95% CI: 1.50–7.28, p =.003), but not in non-Asian women (OR: 0.96, 95% CI: 0.35–2.63, p=.94). Conclusions Higher T/Gly index may independently predict the risk of GDM in Asian women.

Association of Gut Microbiota during Early Pregnancy with Risk of Incident Gestational Diabetes Mellitus.

We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24 to 28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced. In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp., and Veillonellaceae were overrepresented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia, and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-hour and 2-hour postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P < 0.001) from 0.69 to 0.75. Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.

Healthcare Professionals' Perspectives on the Cross-Sectoral Treatment Pathway for Women with Gestational Diabetes during and after Pregnancy-A Qualitative Study.

Gestational diabetes mellitus (GDM) increases the risk of adverse outcomes during and after pregnancy, including a long-term risk of type 2 diabetes. Women with GDM are treated by numerous healthcare professionals during pregnancy and describe a lack of preventive care after pregnancy. We aim to investigate healthcare professionals’ perspectives on the cross-sectoral treatment pathway for women with GDM—during and after pregnancy. A qualitative study was conducted using systematic text condensation. Nine healthcare professionals (two general practitioners, four midwives, two obstetricians and one diabetes nurse) were interviewed and eight health visitors participated in two focus group discussions., Three major themes emerged: (1) “professional identities”, which were identified across healthcare professionals and shaped care practices; (2) ”unclear guidelines on type 2 diabetes prevention after GDM”, which contributed to uncertainty about tasks and responsibilities during and after pregnancy; and (3) “cross-sectoral collaboration”, which relied heavily on knowledge transfers between hospitals, general practice and the local municipality. The findings implicate that clear, transparent guidelines for all sectors should be prioritized to strengthen cross-sectoral care to women with GDM during and after pregnancy. As a result, strong cross-sectoral care throughout the GDM care pathway may improve maternal health by supporting healthy behaviors, facilitate weight loss and reduce the risk of subsequent GDM and early onset diabetes.

Gestational Diabetes Mellitus: Predictive Value of Fetal Growth Measurements by Ultrasonography at 22-24 Weeks: A Retrospective Cohort Study of Medical Records.

Early intervention of gestational diabetes mellitus (GDM) is effective in reducing pregnancy disorders. Fetal growth, measured by routine ultrasound scan a few weeks earlier before GDM diagnosis, might be useful to identify women at high risk of GDM. In the study, generalized estimating equations were applied to examine the associations between ultrasonic indicators of abnormal fetal growth at 22–24 weeks and the risk of subsequent GDM diagnosis. Of 44,179 deliveries, 8324 (18.8%) were diagnosed with GDM between 24 and 28 weeks. At 22–24 weeks, fetal head circumference (HC) < 10th, fetal femur length (FL) < 10th, and estimated fetal weight (EFW) < 10th percentile were associated with 13% to 17% increased risks of maternal GDM diagnosis. Small fetal size appeared to be especially predictive of GDM among women who were parous. Fetal growth in the highest decile of abdominal circumference (AC), HC, FL and EFW was not associated with risk of subsequent GDM. The observed mean difference in fetal size across gestation by GDM was small; there was less than 1 mm difference for AC, HC, and FL, and less than 5 g for EFW before 24 weeks. Despite similar mean fetal growth among women who were and were not later diagnosed with GDM, mothers with fetuses in the lowest decile of HC, FL and EFW at 22–24 weeks tended to have higher risk of GDM.

The effect of sleep impairment on gestational diabetes mellitus: a systematic review and meta-analysis of cohort studies

This systematic review and meta-analysis evaluated the influence of sleep duration or impairment (poor sleep quality, snoring, and obstructive sleep apnea [OSA]) on gestational diabetes mellitus (GDM) risk. PubMed, Embase, EBSCO, and WOS databases were searched up to March 4th, 2019. Cohort studies were included and relative risk (RR) with 95% confidence interval (CI) were used as the measure of effects. Heterogeneity was assessed by the Chi-squared and I2 tests. Subgroup analyses, sensitivity analysis, and dose-response analysis were performed. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 16 studies with 2,551,017 pregnant women and 142,103 GDM cases were included in this study. Both short and long sleep duration were associated with increased risk of GDM. There was a U-shaped relationship between sleep duration and GDM risk (P-nonlinearity < 0.001), and pregnant women with 8 h of sleep presented lower GDM risk. Poor sleep quality, snoring and OSA also increased the subsequent risk of GDM. Pregnant women should be made aware of the benefits of proper sleep, and those with poor sleep quality, snoring, and OSA should be screened for GDM.

Exposure to multiple metals in early pregnancy and gestational diabetes mellitus: A prospective cohort study

BackgroundA growing number of epidemiologic studies have estimated associations between type 2 diabetes mellitus and exposure to metals. However, studies on the associations of internal assessments of metal exposure and gestational diabetes mellitus (GDM) are limited in scope and have inconsistent outcomes. ObjectivesThis investigation aimed to explore the associations between urinary nickel (Ni), arsenic (As), cadmium (Cd), antimony (Sb), cobalt (Co), or vanadium (V) in early pregnancy and the subsequent risk of GDM in Chinese pregnant women. MethodsThe study population included 2090 women with singleton pregnancy from the Tongji Maternal and Child Health Cohort (TMCHC). Urine samples were collected before 20 gestational weeks, and an oral glucose tolerance test (OGTT) was conducted at 24–28 gestational weeks to diagnose GDM. The concentrations of urinary metals were measured using inductively coupled plasma mass spectrometry (ICP-MS) and were corrected for urinary creatinine. The associations between the risk of GDM and urinary metals were assessed using Poisson regression with a robust error variance with generalized estimating equations (GEE) models and Bayesian kernel machine regression (BKMR). ResultsA total of 241 participants (11.53%) were diagnosed with GDM. Five metals (Ni, As, Sb, Co, and V) were found significantly and positively associated with GDM based on single-metal models. In multiple-metal models, for each unit increase of ln-transformed urinary Ni or Sb, the risk of GDM increased 18% [relative risk (RR):1.18, 95%confidence interval (CI): 1.00, 1.38 or RR: 1.18, 95%CI: 1.00, 1.39, respectively]. The BKMR analysis revealed a statistically significant and positive joint effect of the six metals on the risk of GDM, when the urinary levels of the six metals were all above the 55th percentile, compared to the median levels. The effect of metal Ni was significant when the concentrations of the other metals were all fixed at their 25th percentile, and metal Sb displayed a significant and positive effect when all the other metals were fixed at 25th, 50th, and 75th percentiles. ConclusionsTo the best of our knowledge, this study is the first to demonstrate that increased concentrations of urinary Ni in early pregnancy are associated with an elevated risk of GDM, either evaluated individually or as a metal mixture. All six metals mixed exposure was positively associated with the risk of GDM, while Sb and Ni were demonstrated more important effects than the other four metals in the mixture.

A Prospective Study of Leukocyte Telomere Length and Risk of Gestational Diabetes in a Multiracial Cohort.

Short telomere length (TL), an indicator of cellular aging and oxidative stress, has been implicated in glucose homeostasis. Additionally, studies have illustrated that the association of TL with health outcomes may vary by age. Yet, data on the association between TL and gestational diabetes mellitus (GDM) are sparse and the potential effect modification by age remains unknown. We prospectively investigated TL in early pregnancy in relation to the subsequent GDM risk in a case-control study of 93 women with GDM and 186 randomly selected controls matched on age, race/ethnicity, and gestational weeks at blood collection. TL was measured using blood samples collected at 10-14 gestational weeks and reported as the T/S ratio, a ratio of telomere repeat length T to copy number of a single copy gene S. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusted for major risk factors. Overall, TL was not significantly associated with GDM risk. The TL-GDM association was significantly modified by age (Pinteraction = 0.02). Shorter TL in early pregnancy was associated with an increased GDM risk among women <30 years old (adjusted OR comparing the shortest vs. longest tertile: 3.1, 95% CI = 1.2, 8.1), but not associated with GDM risk among women ≥30 years. Our findings suggest that TL in early pregnancy may be implicated in GDM development, particularly among younger women.

A Longitudinal Study of Thyroid Markers Across Pregnancy and the Risk of Gestational Diabetes.

T3 is the biologically active thyroid hormone involved in glucose metabolism. The free T3 (fT3)/free T4 (fT4) ratio, a marker indicating conversion of fT4 to fT3, is also implicated in glucose homeostasis. To examine associations of fT3 and the fT3/fT4 ratio with gestational diabetes mellitus (GDM). In a case-control study, thyroid markers (fT3, fT4, TSH) were measured and the fT3/fT4 ratio was derived across four visits in pregnancy, including first (gestational weeks 10 to 14) and second (weeks 15 to 26) trimester. Conditional logistic regression adjusting for thyroid autoimmunity status and major GDM risk factors estimated trimester-specific associations of thyroid markers with subsequent GDM risk. Twelve US clinical centers. One hundred seven GDM cases and 214 non-GDM controls from a multiracial pregnancy cohort of 2802 women. GDM diagnosis ascertained from medical records. Both fT3 and the fT3/fT4 ratio were positively associated with GDM: adjusted OR (95% CI) comparing the highest vs lowest fT3 quartile was 4.25 (1.67, 10.80) at the first trimester and 3.89 (1.50, 10.10) at the second trimester. Similarly, the corresponding risk estimates for the fT3/fT4 ratio were 8.63 (2.87, 26.00) and 13.60 (3.97, 46.30) at the first and second trimester, respectively. Neither TSH nor fT4 was significantly associated with GDM. Higher fT3 levels, potentially resulting from de novo synthesis or increased fT4 to fT3 conversion, may be an indicator of GDM risk starting early in pregnancy.

A prospective and longitudinal study of plasma phospholipid saturated fatty acid profile in relation to cardiometabolic biomarkers and the risk of gestational diabetes

Data on saturated fatty acids (SFAs) in relation to metabolic function and glucose homeostasis remain controversial. Such data are lacking among pregnant women. We prospectively investigated objectively measured individual and subclasses of plasma phospholipid SFAs throughout pregnancy in relation to cardiometabolic markers and gestational diabetes mellitus (GDM) risk. Within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort of 2802 singleton pregnancies, 107 GDM cases were ascertained via medical record review and matched to 214 non-GDM controls on age, race/ethnicity, and gestational week (GW) at blood collection. Individual plasma phospholipid SFA concentrations were repeatedly measured throughout pregnancy at GWs 10-14, 15-26, 23-31, and 33-39 and also grouped into subclasses of even- or odd-chain SFAs. From GW 10, even-chain SFA concentrations were significantly higher among women who later developed GDM, whereas odd-chain SFAs were significantly lower among GDM cases compared with controls. At GWs 10-14, the SFA palmitic acid (16:0) was positively associated with impaired insulin resistance and cardiometabolic markers and the risk of GDM [adjusted OR comparing the highest with the lowest quartile (aORQ4-Q1): 4.76; 95% CI: 1.72, 13.10; P-trend=0.001]. In contrast, odd-chain SFAs were inversely related to the previously mentioned markers and GDM risk [aORQ4-Q1 for pentadecanoic acid (15:0): 0.32; 95% CI: 0.11, 0.92; P-trend=0.025; for heptadecanoic acid (17:0): 0.20; 95% CI: 0.07, 0.58; P-trend=0.003]. Women with high (median or greater) even-chain SFA concentrations and low (less than median) odd-chain SFAs had a 9.43-fold (95%: CI 3.26-, 27.30-fold) increased risk compared with women with low even-chain and high odd-chain SFA concentrations. Similar results were observed at GWs 15-26. The study provided one of the first lines of evidence suggesting that circulating concentrations of SFAs varying by SFA chain length, as early as GWs 10-14, were significantly and differentially associated with subsequent risk of GDM. Our findings highlight the importance of assessing objectively measured, individual, and subclasses of SFAs to investigate their distinct biological and pathophysiologic roles in glucose homeostasis and cardiometabolic outcomes. This study was registered at www.clinicaltrials.gov as NCT00912132.