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      Effects of Vitamin D Supplementation on Glucose and Insulin Homeostasis and Incident Diabetes among Nondiabetic Adults: A Meta-Analysis of Randomized Controlled Trials

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          Abstract

          Aims

          Emerging evidence has suggested a mechanistic link from vitamin D metabolism to glucose and insulin homeostasis. This study is aimed at specifically quantifying the direct effects of vitamin D supplementation on indexes of glucose and insulin homeostasis as well as incidence of type 2 diabetes (T2D) among nondiabetic adults.

          Methods

          We systematically searched randomized controlled trials (RCTs) of vitamin D supplementation in nondiabetic adults in PubMed, EMBASE, and CENTRAL. Random-effects meta-analysis was conducted to pool the estimates.

          Results

          Our meta-analysis included 47 RCTs involving 44,161 nondiabetic individuals with a median trial duration of 4 months and a median dose of 4000 IU/d. Vitamin D supplementation significantly reduced fasting glucose by 0.11 mmol/L, fasting insulin by 1.47 mIU/L, and HOMA-IR by 0.32 while increasing total 25 (OH) D levels by 40.14 nmol/L. We found no significant effects of vitamin D supplementation on insulin secretion or beta cell function indexes. Based on the data from six trials involving 39,633 participants and 2533 incident T2D cases, vitamin D supplementation was not associated with the risk of incident diabetes compared to placebo (pooled relative risk: 1.01, 95% confidence interval: 0.93 to 1.08).

          Conclusions

          Our meta-analysis found that vitamin D supplementation might improve glucose and insulin metabolism without affecting the risk of T2D among nondiabetic adults.

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          Most cited references30

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          From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health.

          Anthony W Norman (2008)
          New knowledge of the biological and clinical importance of the steroid hormone 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] and its receptor, the vitamin D receptor (VDR), has resulted in significant contributions to good bone health. However, worldwide reports have highlighted a variety of vitamin D insufficiency and deficiency diseases. Despite many publications and scientific meetings reporting advances in vitamin D science, a disturbing realization is growing that the newer scientific and clinical knowledge is not being translated into better human health. Over the past several decades, the biological sphere of influence of vitamin D(3), as defined by the tissue distribution of the VDR, has broadened at least 9-fold from the target organs required for calcium homeostasis (intestine, bone, kidney, and parathyroid). Now, research has shown that the pluripotent steroid hormone 1alpha,25(OH)(2)D(3) initiates the physiologic responses of >/=36 cell types that possess the VDR. In addition to the kidney's endocrine production of circulating 1alpha,25(OH)(2)D(3,) researchers have found a paracrine production of this steroid hormone in >/=10 extrarenal organs. This article identifies the fundamentals of the vitamin D endocrine system, including its potential for contributions to good health in 5 physiologic arenas in which investigators have clearly documented new biological actions of 1alpha,25(OH)(2)D(3) through the VDR. As a consequence, the nutritional guidelines for vitamin D(3) intake (defined by serum hydroxyvitamin D(3) concentrations) should be reevaluated, taking into account the contributions to good health that all 36 VDR target organs can provide.
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            The nonskeletal effects of vitamin D: an Endocrine Society scientific statement.

            Clifford Rosen, John Adams, Daniel Bikle … (2012)
            Significant controversy has emerged over the last decade concerning the effects of vitamin D on skeletal and nonskeletal tissues. The demonstration that the vitamin D receptor is expressed in virtually all cells of the body and the growing body of observational data supporting a relationship of serum 25-hydroxyvitamin D to chronic metabolic, cardiovascular, and neoplastic diseases have led to widespread utilization of vitamin D supplementation for the prevention and treatment of numerous disorders. In this paper, we review both the basic and clinical aspects of vitamin D in relation to nonskeletal organ systems. We begin by focusing on the molecular aspects of vitamin D, primarily by examining the structure and function of the vitamin D receptor. This is followed by a systematic review according to tissue type of the inherent biological plausibility, the strength of the observational data, and the levels of evidence that support or refute an association between vitamin D levels or supplementation and maternal/child health as well as various disease states. Although observational studies support a strong case for an association between vitamin D and musculoskeletal, cardiovascular, neoplastic, and metabolic disorders, there remains a paucity of large-scale and long-term randomized clinical trials. Thus, at this time, more studies are needed to definitively conclude that vitamin D can offer preventive and therapeutic benefits across a wide range of physiological states and chronic nonskeletal disorders.
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              Blood 25-Hydroxy Vitamin D Levels and Incident Type 2 Diabetes

              Yiqing Song, Lu Wang, Anastassios G Pittas … (2013)
              OBJECTIVE To quantitatively assess the strength and shape of the association between blood 25-hydroxy vitamin D [25(OH)D] levels and incident risk of type 2 diabetes. RESEARCH DESIGN AND METHODS A systematic search of the MEDLINE and Embase databases and a hand search of references from original reports were conducted up to 31 October 2012. Prospective observational studies that assessed the association between blood levels of 25(OH)D and risk of incident type 2 diabetes were included for meta-analysis. DerSimonian and Laird’s random-effects model was used. A quadratic spline regression analysis was used to examine the shape of the association with a generalized least-squares trend test performed for the dose-response relation. RESULTS A total of 21 prospective studies involving 76,220 participants and 4,996 incident type 2 diabetes cases were included for meta-analysis. Comparing the highest to the lowest category of 25(OH)D levels, the summary relative risk for type 2 diabetes was 0.62 (95% CI 0.54–0.70). A spline regression model showed that higher 25(OH)D levels were monotonically associated with a lower diabetes risk. This inverse association did not differ by sex, duration of follow-up, study sample size, diabetes diagnostic criteria, or 25(OH)D assay method. A linear trend analysis showed that each 10 nmol/L increment in 25(OH)D levels was associated with a 4% lower risk of type 2 diabetes (95% CI 3–6; P for linear trend < 0.0001). CONCLUSIONS Our meta-analysis showed an inverse and significant association between circulating 25(OH)D levels and risk of type 2 diabetes across a broad range of blood 25(OH)D levels in diverse populations.
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                Author and article information

                Contributors
                Yiqing Song:
                ORCID: http://orcid.org/0000-0002-2097-7332
                Xinli Li:
                ORCID: http://orcid.org/0000-0002-3535-4787
                Journal
                Journal ID (nlm-ta): Int J Endocrinol
                Journal ID (iso-abbrev): Int J Endocrinol
                Journal ID (publisher-id): IJE
                Title: International Journal of Endocrinology
                Publisher: Hindawi
                ISSN (Print): 1687-8337
                ISSN (Electronic): 1687-8345
                Publication date Collection: 2018
                Publication date (Electronic): 3 December 2018
                Volume: 2018
                Electronic Location Identifier: 7908764
                Affiliations
                1Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA
                2Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA
                3School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, China
                4Department of Endocrinology, Beijing Pinggu Hospital, Beijing, China
                5Clinical Research Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
                6Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu, China
                Author notes

                Academic Editor: Vito Giagulli

                Author information
                http://orcid.org/0000-0002-5814-6657
                http://orcid.org/0000-0002-2097-7332
                http://orcid.org/0000-0002-3535-4787
                Article
                DOI: 10.1155/2018/7908764
                PMC ID: 6304827
                PubMed ID: 30627160
                SO-VID: 79e3c829-d0a7-4ecd-8545-4bdcaf81b283
                Copyright © Copyright © 2018 Huilin Tang et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 July 2018
                Date revision received : 25 October 2018
                Date accepted : 12 November 2018
                Funding
                Funded by: School of Medicine
                Funded by: Indiana University
                Funded by: Indiana University Health
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

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