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VDR Variants rather than Early Pregnancy Vitamin D Concentrations Are Associated with the Risk of Gestational Diabetes: The Ma'anshan Birth Cohort (MABC) Study.

ABSTRACT: Aim:This study investigated the associations among early pregnancy vitamin D concentrations, seasonality, and vitamin D metabolic gene variants and how these variables related alone and in interaction with the risk of gestational diabetes mellitus (GDM). Methods:Research participants were women from the Ma'anshan birth cohort study in China. The overall study included 3110 women to explore the association between early pregnancy vitamin D concentrations and the risk of GDM. In the current analysis, a nested case-control study of 274 GDM cases and 380 controls was conducted to investigate seven vitamin D metabolic gene variants and the risk of GDM. Vitamin D concentrations were measured by radioimmunoassay. Genotypes were determined by improved multiple ligase detection reaction. Interactions between genetic variants and vitamin D as predictors of the risk of GDM were evaluated by a pair-wise analysis under a multiplicative interaction model. Results:Vitamin D concentrations were not significantly associated with the risk of GDM (OR = 0.79, 95% CI = 0.55-1.13) after adjusting for seasonality. Fall-winter conceptions had a 37% decreased risk of GDM compared with spring-summer conceptions (OR = 0.63, 95% CI = 0.49-0.81), independent of vitamin D concentrations. Two VDR gene variants rs1544410 (OR = 2.03, 95% CI = 1.17-3.51 for CT versus CC) and rs731236 (OR = 2.42, 95% CI = 1.29-4.55 for GA versus AA) were significantly associated with the risk of GDM. No interactions among genetic variants and vitamin D concentrations were detected. Conclusion:Early pregnancy vitamin D insufficiency or deficiency was not significantly associated with the risk of GDM. The results of this study emphasize the importance of genetic variants in VDR and conception season as factors that affect the risk of GDM.

SUBMITTER: Zhu B

PROVIDER: S-EPMC6613005 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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VDR Variants rather than Early Pregnancy Vitamin D Concentrations Are Associated with the Risk of Gestational Diabetes: The Ma'anshan Birth Cohort (MABC) Study.

Zhu Beibei B Huang Kun K Yan Shuangqin S Hao Jiahu J Zhu Peng P Chen Yao Y Ye Aoxing A Tao Fangbiao F

Journal of diabetes research 20190624

<h4>Aim</h4>This study investigated the associations among early pregnancy vitamin D concentrations, seasonality, and vitamin D metabolic gene variants and how these variables related alone and in interaction with the risk of gestational diabetes mellitus (GDM).<h4>Methods</h4>Research participants were women from the Ma'anshan birth cohort study in China. The overall study included 3110 women to explore the association between early pregnancy vitamin D concentrations and the risk of GDM. In the ...[more]

PMID: 31341914

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Project description:BACKGROUND:Vitamin D-binding protein (VDBP) has been implicated in several adverse pregnancy outcomes either directly or indirectly via influencing the concentrations of biologically active vitamin D metabolites. However, human studies exploring these metabolites in pregnancy remain sparse. Here, we examine whether VDBP and total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D) metabolites in early pregnancy are associated with subsequent adverse pregnancy outcomes. METHODS:We conducted a retrospective analysis of 304 pregnant women in early pregnancy (<20 weeks gestation). The demographic characteristics, anthropometric data, and total 25(OH)D were measured and plasma or serum samples were collected and bio-banked. Using these samples, we measured VDBP (polyclonal ELISA) and albumin (automated colorimetry), and calculated free and bioavailable 25(OH)D using validated formulae. Pregnancy outcomes were derived from scanned medical records. Regression models were used to analyse the relationships between vitamin D metabolites in early pregnancy and subsequent pregnancy outcomes (gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth), with adjustment for predetermined clinically relevant maternal factors including age, body mass index (BMI), and ethnicity. RESULTS:Lower VDBP concentrations were associated with higher glucose levels and a greater likelihood of developing GDM at 26-28 weeks gestation (odds ratio [OR] (95% CI) = 0.98 (0.97,0.99), p = 0.015). This finding remained significant after adjustment for maternal covariates including age, BMI, and ethnicity (? = -0.003, p = 0.03). Lower total, free and bioavailable 25(OH)D, but not VDBP, were associated with a shorter length of gestation, but only the relationship with total 25(OH)D remained significant after adjustment for the above maternal covariates (? = 0.02, p = 0.006). CONCLUSIONS:This is the first study to examine VDBP, and total, free and bioavailable 25(OH)D in relation to pregnancy outcomes in a well characterised multi-ethnic cohort of pregnant women. Our findings show that VDBP and total 25(OH)D are associated with GDM and length of gestation, respectively; however, further investigations using large-scale prospective studies are needed to confirm our findings.

Project description:Maternal vitamin D status has been associated with both gestational diabetes mellitus (GDM) and fetal growth restriction, however, the evidence is inconsistent. In Finland, maternal vitamin D status has improved considerably due to national health policies. Our objective was to compare maternal 25-hydroxy vitamin D concentrations [25(OH)D] between mothers with and without GDM, and to investigate if an association existed between maternal vitamin D concentration and infant birth size.This cross-sectional study included 723 mother-child pairs. Mothers were of Caucasian origin, and infants were born at term with normal birth weight. GDM diagnosis and birth size were obtained from medical records. Maternal 25(OH)D was determined on average at 11 weeks of gestation in pregnancy and in umbilical cord blood (UCB) at birth.GDM was observed in 81 of the 723 women (11%). Of the study population, 97% were vitamin D sufficient [25(OH)D???50 nmol/L]. There was no difference in pregnancy 25(OH)D concentration between GDM and non-GDM mothers (82 vs 82 nmol/L, P?=?0.99). Regression analysis confirmed no association between oral glucose tolerance test results and maternal 25(OH)D (P?>?0.53). Regarding the birth size, mothers with optimal pregnancy 25(OH)D (? 80 nmol/L) had heavier newborns than those with suboptimal pregnancy 25(OH)D (P?=?0.010). However, mothers with optimal UCB 25(OH)D had newborns with smaller head circumference than those with suboptimal 25(OH)D (P?=?0.003), which was further confirmed as a linear association (P?=?0.024).Maternal vitamin D concentration was similar in mothers with and without GDM in a mostly vitamin D sufficient population. Associations between maternal vitamin D status and birth size were inconsistent. A sufficient maternal vitamin D status, specified as 25(OH)D above 50 nmol/L, may be a threshold above which the physiological requirements of pregnancy are achieved.The project protocol is registered in ClinicalTrials.gov in November 8, 2012 ( NCT01723852 ).

Project description:Aims/hypothesisThe prevalence of gestational diabetes mellitus (GDM) is increasing worldwide in all ethnic groups. Low vitamin B12 and low/high folate levels may contribute to GDM risk, but there is conflicting evidence. Our aim is to assess the relationships of early pregnancy vitamin B12 and folate levels with the risk of GDM status at 26-28 weeks of gestation.MethodsThis was a prospective, multi-centre, multi-ethnic cohort study (n = 4746) in the UK. Participants who were eligible to be selectively screened as per the National Institute for Health and Care Excellence (NICE) criteria were included in the study.ResultsGDM prevalence was 12.5% by NICE and 14.7% by International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Folate deficiency (1.3%) was rare but B12 insufficiency (42.3% at <220 pmol/l) and folate excess (36.5%) were common in early pregnancy. Early pregnancy median B12 levels were lower, and folate levels higher, in women who were diagnosed with GDM at 26-28 weeks. B12 was negatively associated with fasting plasma glucose (1 SD: -0.06 mmol/l; 95% CI -0.04, -0.08; p < 0.0001) and 2 h plasma glucose levels (-0.07 mmol/l; 95% CI -0.02, -0.12; p = 0.004). Higher B12 was associated with 14.4% lower RR of IADPSG-GDM (0.856; 95% CI 0.786, 0.933; p = 0.0004) after adjusting for key confounders (age, parity, smoking status, ethnicity, family history, household income and folate status). Approximately half of this association was mediated through BMI. Folate was positively associated with 2 h plasma glucose levels (0.08 mmol/l; 95% CI 0.04, 0.13; p = 0.0005) but its relationship with fasting plasma glucose was U-shaped (quadratic β: 0.011; p = 0.05). Higher folate was associated with 11% higher RR of IADPSG-GDM (adjusted RR 1.11; 95% CI 1.036, 1.182; p = 0.002) (age, parity, smoking status, ethnicity, family history, household income and B12 status). Although no interactions were observed for B12 and folate (as continuous variables) with glucose levels and GDM risk, a low B12-high folate combination was associated with higher blood glucose level and risk of IADPSG-GDM (adjusted RR 1.742; 95% CI 1.226, 2.437; p = 0.003).Conclusions/interpretationB12 insufficiency and folate excess were common in early pregnancy. Low B12 and high folate levels in early pregnancy were associated with small but statistically significant changes in maternal blood glucose level and higher RR of GDM. Our findings warrant additional studies on the role of unmetabolised folic acid in glucose metabolism and investigating the effect of optimising early pregnancy or pre-conception B12 and folate levels on subsequent hyperglycaemia.Trial registrationClinicalTrials.gov NCT03008824.

Dataset Information

VDR Variants rather than Early Pregnancy Vitamin D Concentrations Are Associated with the Risk of Gestational Diabetes: The Ma'anshan Birth Cohort (MABC) Study.

Publications

VDR Variants rather than Early Pregnancy Vitamin D Concentrations Are Associated with the Risk of Gestational Diabetes: The Ma'anshan Birth Cohort (MABC) Study.

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