Vitamin D status during pregnancy and the risk of gestational diabetes mellitus: A longitudinal study in a multiracial cohort

Jin, Xin; Song, Yiqing; Rawal, Shristi; Wu, Jing; Hinkle, Stefanie N.; Tsai, Michael Y.; Zhang, Cuilin

doi:10.1111/dom.13748

Cited by 43 publications

(35 citation statements)

References 50 publications

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“…In the present study, glucose concentrations post-OGTT and GDM were shown to be inversely associated with not just total 25(OH)D concentration, which has been widely reported [25,[27][28][29] though inconsistently [30][31][32], but also with VDBP. This novel relationship between VDBP and GDM has not previously been reported with the single earlier study examining VDBP in women with and without GDM, finding no association [33], contrary to our findings. The lack of association reported by Xia et al [33] may be attributed to their use of monoclonal assays to measure VDBP since, as acknowledged by the authors, these assays have been criticised for their lack of sensitivity to several genetically determined isoforms found in individuals who carry the GC-1F allele (predominantly in certain ethnicities) [17].…”

Section: Comparison With Previous Literature and Potential Mechanismscontrasting

confidence: 99%

“…This novel relationship between VDBP and GDM has not previously been reported with the single earlier study examining VDBP in women with and without GDM, finding no association [33], contrary to our findings. The lack of association reported by Xia et al [33] may be attributed to their use of monoclonal assays to measure VDBP since, as acknowledged by the authors, these assays have been criticised for their lack of sensitivity to several genetically determined isoforms found in individuals who carry the GC-1F allele (predominantly in certain ethnicities) [17]. Conversely, our study utilised polyclonal assay technology, which is less affected by genetic and/or ethnic variations and this may explain the discrepant findings between the two studies.…”

Section: Comparison With Previous Literature and Potential Mechanismscontrasting

confidence: 99%

“…This would mean that both higher VDBP and proportionally lower free and bioavailable 25(OH)D concentrations would be associated with GDM risk. As mentioned above, this was not demonstrated in our study or in other earlier studies [33,40]. We speculate that the influence of VDBP on GDM may be direct and independent of its role as a vitamin D carrier protein.…”

Section: Comparison With Previous Literature and Potential Mechanismscontrasting

confidence: 62%

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Early Pregnancy Vitamin D Binding Protein Is Independently Associated with the Development of Gestational Diabetes: A Retrospective Cohort Study

Fernando

Ellery

Guingand

et al. 2020

JCM

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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 (β = −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 (β = 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.

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Section: Comparison With Previous Literature and Potential Mechanismscontrasting

confidence: 99%

Section: Comparison With Previous Literature and Potential Mechanismscontrasting

confidence: 99%

Section: Comparison With Previous Literature and Potential Mechanismscontrasting

confidence: 62%

See 1 more Smart Citation

Early Pregnancy Vitamin D Binding Protein Is Independently Associated with the Development of Gestational Diabetes: A Retrospective Cohort Study

Fernando

Ellery

Guingand

et al. 2020

JCM

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“…This is due to an increased understanding of the potential role of VDBP in the physiology underlying vitamin D deficiency and the metabolic changes in pregnancy [16]. VDBP concentrations have been shown to increase dramatically in pregnancy and thus influence the biologically and functionally active portion of vitamin D, free vitamin D, which is postulated to be more representative of vitamin D status in the pregnancy state than total 25(OH)D. VDBP itself has been implicated as a potential biomarker of pregnancy outcomes as it has been linked to several adverse outcomes including gestational diabetes, pre-eclampsia and preterm labour, although the present literature exploring this protein remains very limited [17][18][19]. Importantly, VDBP has been linked to various biological processes that are often exacerbated or heightened in the pregnant state, including immunoregulation, glucose metabolism, and regulation of blood pressure [20].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D-Binding Protein in Pregnancy and Reproductive Health

et al. 2020

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Vitamin D-binding protein (VDBP), the main carrier of vitamin D, has recently been implicated in reproductive health and pregnancy outcomes including endometriosis, polycystic ovary syndrome (PCOS), pre-eclampsia, and gestational diabetes mellitus (GDM). Improved methods for measuring VDBP and an increased understanding of its role in biological processes have led to a number of newly published studies exploring VDBP in the context of pregnancy. Here, we synthesize the available evidence regarding the role of VDBP in reproductive health and pregnancy, and we highlight areas requiring further study. Overall, low levels of maternal serum VDBP concentrations have been associated with infertility, endometriosis, PCOS and spontaneous miscarriage, as well as adverse pregnancy outcomes including GDM, pre-eclampsia, preterm birth and fetal growth restriction. However, increased VDBP concentration in cervicovaginal fluid has been linked to unexplained recurrent pregnancy loss and premature rupture of membranes. Some genetic variants of VDBP have also been associated with these adverse outcomes. Further studies using more accurate VDBP assays and accounting for ethnic variation and potential confounders are needed to clarify whether VDBP is associated with reproductive health and pregnancy outcomes, and the mechanisms underlying these relationships.

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“…Increased 25-OH-VitD levels after VitD supplementation correlate with significant reduction in rate of preterm labour, pre-eclampsia, and GDM in pregnant Indian women 43 . Women with persistent 25-OH-VitD deficiency up to 26 th weeks of gestation had a 4.46-fold elevated risk for GDM 55 . Significant reduction in GDM risk was observed with increasing 25-OH-VitD levels 56 .…”

Section: Discussionmentioning

confidence: 97%

Vitamin D Status and Pregnancy Complications: Serum 1,25-di-hydroxyl-Vitamin D and its Ratio to 25-hydroxy-Vitamin D are Superior Biomarkers than 25-hydroxy-Vitamin D

Albahlol¹,

Almaeen²,

Alduraywish³

et al. 2020

Int. J. Med. Sci.

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Vitamin D (VitD) deficiency during pregnancy has been associated with adverse neonatal outcomes and increased risk of late pregnancy complications. We planned to correlate serum VitD biomarkers; 25-hydroxyvitamin D (25-OH-VitD) and 1,25-dihydroxyvitamin D (1,25-diOH-VitD) levels; and their ratio with the frequency of feto-maternal pregnancy complications. A prospective cross-sectional case-control study was conducted at Aljouf Maternity and Children Hospital, Sakaka, Saudi Arabia, during the period of September 1, 2017 to September 30, 2019. 322 pregnant women were stratified into 2 groups: controls (110 cases) and complicated group (212 cases). The later comprised severe preeclamptic toxemia associated with intrauterine growth restriction (58 cases), gestational diabetes mellitus (GDM; 82 cases), abortion (26 cases), undisturbed ectopic pregnancy (16 cases), premature rupture of membranes (PROM; 14 cases), and, inevitable preterm labour (16 cases). After clinical assessment, peripheral blood samples were collected. Serum biomarkers were measured using specific immunoassays. The direct 1,25-diOH-VitD/25-OH-VitD ratio was calculated. Serum 25-OH-VitD indicated widely spreading VitD deficiency among participants with significantly higher levels in controls vs. GDM subgroup only. 1,25-diOH-VitD levels and the ratio were markedly reduced in the six complicated subgroups vs. controls, with non-significant differences amongst the complicated subgroups. ROC analysis showed very high sensitivity and specificity, to differentiate patients from controls, only for 1,25-diOH-VitD (AUC = 0.965; 0.947 - 0.983, p <0.001) followed by the ratio but not 25-OH-VitD. In conclusions, 25-OH-VitD did not show significant changes except for GDM. 1,25-diOH-VitD levels and the ratio showed strong associations with pregnancy complications. Serum 1,25-di-OH-VitD and its ratio to 25-OH-VitD are more reliable and physiologically relevant biomarkers for VitD status in pregnancy.

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Vitamin D status during pregnancy and the risk of gestational diabetes mellitus: A longitudinal study in a multiracial cohort

Cited by 43 publications

References 50 publications

Early Pregnancy Vitamin D Binding Protein Is Independently Associated with the Development of Gestational Diabetes: A Retrospective Cohort Study

Early Pregnancy Vitamin D Binding Protein Is Independently Associated with the Development of Gestational Diabetes: A Retrospective Cohort Study

Vitamin D-Binding Protein in Pregnancy and Reproductive Health

Vitamin D Status and Pregnancy Complications: Serum 1,25-di-hydroxyl-Vitamin D and its Ratio to 25-hydroxy-Vitamin D are Superior Biomarkers than 25-hydroxy-Vitamin D

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