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      Association of Maternal Vitamin D Status with Glucose Tolerance and Caesarean Section in a Multi-Ethnic Asian Cohort: The Growing Up in Singapore Towards Healthy Outcomes Study

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          Abstract

          Objective

          Epidemiological studies relating maternal 25-hydroxyvitamin D (25OHD) with gestational diabetes mellitus (GDM) and mode of delivery have shown controversial results. We examined if maternal 25OHD status was associated with plasma glucose concentrations, risks of GDM and caesarean section in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study.

          Methods

          Plasma 25OHD concentrations, fasting glucose (FG) and 2-hour postprandial glucose (2HPPG) concentrations were measured in 940 women from a Singapore mother-offspring cohort study at 26–28 weeks’ gestation. 25OHD inadequacy and adequacy were defined based on concentrations of 25OHD ≤75nmol/l and >75nmol/l respectively. Mode of delivery was obtained from hospital records. Multiple linear regression was performed to examine the association between 25OHD status and glucose concentrations, while multiple logistic regression was performed to examine the association of 25OHD status with risks of GDM and caesarean section.

          Results

          In total, 388 (41.3%) women had 25OHD inadequacy. Of these, 131 (33.8%), 155 (39.9%) and 102 (26.3%) were Chinese, Malay and Indian respectively. After adjustment for confounders, maternal 25OHD inadequacy was associated with higher FG concentrations (β = 0.08mmol/l, 95% Confidence Interval (CI) = 0.01, 0.14), but not 2HPPG concentrations and risk of GDM. A trend between 25OHD inadequacy and higher likelihood of emergency caesarean section (Odds Ratio (OR) = 1.39, 95% CI = 0.95, 2.05) was observed. On stratification by ethnicity, the association with higher FG concentrations was significant in Malay women (β = 0.19mmol/l, 95% CI = 0.04, 0.33), while risk of emergency caesarean section was greater in Chinese (OR = 1.90, 95% CI = 1.06, 3.43) and Indian women (OR = 2.41, 95% CI = 1.01, 5.73).

          Conclusions

          25OHD inadequacy is prevalent in pregnant Singaporean women, particularly among the Malay and Indian women. This is associated with higher FG concentrations in Malay women, and increased risk of emergency caesarean section in Chinese and Indian women.

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          Most cited references37

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          The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis.

          Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM). EVIDENCE ACQUISITION AND ANALYSES: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented. Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16-0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57-0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72-0.93) for highest vs. lowest combined vitamin D and calcium intake; 0.86 (0.79-0.93) for highest vs. lowest dairy intake]. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and did not adjust for important confounders, whereas intervention studies were short in duration, included few subjects, used a variety of formulations of vitamin D and calcium, or did post hoc analyses. Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.
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            Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey.

            To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity. We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged > or =20 years with fasting and/or 2-h plasma glucose and serum insulin measurements. Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicity-specific odds ratios (ORs) for diabetes (fasting glucose > or =7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11-0.60] for non-Hispanic whites and 0.17 [0.08-0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD > or =81.0 nmol/l) compared with the lowest 25OHD (< or =43.9 nmol/l). This inverse association was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (log e) was inversely associated with serum 25OHD in Mexican Americans (P=0.0024) and non-Hispanic whites (P=0.058) but not non-Hispanic blacks (P=0.93), adjusting for confounders. These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.
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              Worldwide vitamin D status.

              The aim of the present study is to summarize existing literature on vitamin D levels in adults in different continents and different countries worldwide. The best determinant of vitamin D status is the serum concentration of 25-hydroxyvitamin D (25(OH)D). Most investigators agree that serum 25(OH)D should be higher than 50 nmol/l, but some recommend higher serum levels. Traditional risk groups for vitamin D deficiency include pregnant women, children, older persons, the institutionalized, and non-western immigrants. This chapter shows that serum 25(OH)D levels are not only suboptimal in specific risk groups, but also in adults in many countries. Especially, in the Middle-East and Asia, vitamin D deficiency in adults is highly prevalent. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 November 2015
                2015
                : 10
                : 11
                : e0142239
                Affiliations
                [1 ]KK Research Centre, KK Women’s and Children’s Hospital, Singapore
                [2 ]Duke-NUS Graduate Medical School, Singapore
                [3 ]Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore
                [4 ]Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, (A*STAR), Singapore
                [5 ]Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health Systems, Singapore
                [6 ]Division of Obstetrics and Gynaecology, KK Women’s and Children’s Hospital, Singapore
                [7 ]Department of Maternal Fetal Medicine, KK Women’s and Children’s Hospital, Singapore
                [8 ]Liggins Institute, University of Auckland, Auckland, New Zealand
                [9 ]MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom
                [10 ]NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
                [11 ]Saw Swee Hock School of Public Health, National University of Singapore, Singapore
                [12 ]Institute for Social Medicine, Epidemiology and Health Economics, Charite University Medical Centre, Berlin, Germany
                [13 ]Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
                [14 ]Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore
                [15 ]Department of Reproductive Medicine, KK Women’s and Children’s Hospital, Singapore
                University of Alabama at Birmingham, UNITED STATES
                Author notes

                Competing Interests: PDG, KMG and YSC report receiving reimbursement for speaking at conferences sponsored by companies selling nutritional products. PDG, KMG and YSC report being part of an academic consortium that has received research funding from Abbott Nutrition, Nestle and Danone. No other disclosures were reported. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: KK PDG KMG SMS YSC. Performed the experiments: NP. Analyzed the data: SLL SES NL FY KHT AB GSHY FMR MFFC. Wrote the paper: SLL MFFC JKYC.

                ‡ JKYC and MFFC are Joint Senior Authors.

                ¶ Membership of the GUSTO study group is provided in the Acknowledgments.

                Article
                PONE-D-15-34256
                10.1371/journal.pone.0142239
                4646602
                26571128
                a36d2204-0d47-48c7-95b6-69c8470c6c63
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 4 August 2015
                : 18 October 2015
                Page count
                Figures: 1, Tables: 4, Pages: 16
                Funding
                This study was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore—NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. KMG is supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre and by the European Union's Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant agreement number 289346. JKYC received salary support from the Ministry of Health’s National Medical Research Council, Singapore (NMRC/CSA/043/2012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                Due to an ethical restriction (patient confidentiality), data are available upon request to the GUSTO team. Please contact the GUSTO data team at Chang_Mei_Ling@ 123456sics.a-star.edu.sg to request access to the data.

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