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Observational studies suggest a link between vitamin D and diabetes.
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The potential effect of vitamin D appears to be more prominent among persons at risk for diabetes.
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The optimal blood 25-hydroxyvitamin D concentration associated with reduced risk of type 2 diabetes is not clear.
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The evidence from randomized controlled trials to support the hypothesis that vitamin D supplementation prevents type 2 diabetes is lacking.
Vitamin D and Diabetes
Section snippets
Key points
Review of vitamin D physiology
Vitamin D exists in 2 forms: cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). Vitamin D3 is synthesized in the skin on exposure to solar ultraviolet B (UVB) radiation. During exposure to solar UVB radiation, 7-dehydrocholesterol in the skin is converted to previtamin D3, which is immediately converted to vitamin D3 in a heat-dependent nonenzymatic process. Excessive exposure to sunlight degrades previtamin D3 and vitamin D3 into inactive phyto-products (photo-degradation), avoiding
Classification of vitamin D status
Clinicians and researchers use blood concentration of 25OHD as a biomarker to determine vitamin D status. However, there is no consensus on the 25OHD thresholds for vitamin D deficiency or insufficiency. The main guidelines by the Institute of Medicine (IOM) and the Endocrine Society differ on classification of vitamin D status, as shown in Table 1.1, 2 The differences are explained by what populations were targeted by the guidelines and how the evidence was synthesized. The IOM guidelines
Vitamin D intake requirements
The IOM report on dietary reference intakes for calcium and vitamin D recommends 600 international units (IU) per day of vitamin D for individuals 9 to 70 years and 800 international units for those older than 70 years as the recommended dietary allowance (RDA) (Table 2),2 which is defined as the intake that meets the needs of 97.5% of the healthy population. The IOM report also concluded that the tolerable upper intake level (UL), above which the potential for adverse effects may increase with
Biologic plausibility of an association between vitamin D and type 2 diabetes
Type 2 diabetes results from impaired beta cell function, increased insulin resistance, and systemic inflammation, and there is evidence that vitamin D affects these pathways, as described next.
Cross-Sectional Studies
There are many cross-sectional observational studies that have examined the association between vitamin D and type 2 diabetes and most have reported an inverse association between vitamin D status (25OHD concentration) and prevalent diabetes. One of the largest such cohorts is the National Health and Nutrition Examination Survey in United States, which reported an inverse association between 25OHD concentration and prevalence of diabetes in non-Hispanic white and Mexican-American individuals,
The influence of vitamin D supplementation on type 2 diabetes
The effect of vitamin D supplementation on glycemia or incident type 2 diabetes has been reported in several trials with mixed results (Table 4).
In trials that included participants with normal glucose tolerance at baseline, vitamin D supplementation had a neutral effect on measures of glycemia, including fasting plasma glucose or hemoglobin A1c and insulin resistance measured by homeostasis model assessment (HOMA).69, 70, 71, 72, 73, 74, 75, 76, 77 Similarly, vitamin D supplementation had no
Vitamin D and type 1 diabetes
Type 1 diabetes is characterized by autoimmune destruction of pancreatic islet beta cells, leading to absolute insulin deficiency. Many effects of vitamin D on the pathophysiology of type 1 diabetes have been described, including changes in the immune-mediated destruction,89 but also the beta cell itself. The latter effect may, at least in part, be mediated indirectly by the effect of vitamin D on calcium homeostasis. It also has been reported that specific vitamin D receptor polymorphisms
Summary
Findings from basic science suggest that vitamin D may play a significant role in both types of diabetes. In human studies, the evidence for a potential association is stronger for vitamin D and type 2 diabetes with much fewer data on type 1 diabetes. However, the evidence about type 2 diabetes in humans is derived almost exclusively from observational studies, which may be confounded by a variety of factors and, therefore, these studies preclude an assessment of cause and effect. There are no
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Source of Funding: By research grants R01DK76092, U34DK091958 and U01DK098245 (to A.G. Pittas) from the National Institute of Diabetes and Digestive and Kidney Disease, the Office of the Director, National Institutes of Health, and the National Institutes of Health Office of Dietary Supplements.