Abstract
The association between low vitamin D status and the development of type 2 diabetes mellitus is well established; however, intervention trials that increased serum vitamin D (through ultraviolet B exposure or dietary supplementation) provide mixed outcomes. Recent evidence suggests that metabolites directly related to vitamin D receptor activation—1α,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3—may be better markers of vitamin D repletion status. We tested the hypothesis that a vitamin D metabolite (VDM) index, calculated as the sum of normalized fasting serum concentrations of 1α,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3, is associated with metabolic function. We measured subcutaneous and visceral adipose tissue volume, intrahepatic triglyceride content, maximum oxygen uptake, insulin sensitivity (4 h hyperinsulinemic-euglycemic clamp), and insulin secretion (3 h meal tolerance test with mathematical modeling) and calculated the VDM index in 65 healthy Asian adults. Subjects with a low VDM index had lower peripheral insulin sensitivity and beta-cell function compared to subjects with a high VDM index (both p < 0.05), matched for age, sex, BMI, and serum 25-hydroxyvitamin D3. Serum 25-hydroxyvitamin D3 was not associated with peripheral insulin sensitivity or beta-cell function. Our results suggest that, rather than enhancing vitamin D substrate availability, upregulation of vitamin D action is more likely to lead to improvements in glucose homeostasis.
Highlights
Hypovitaminosis D, or vitamin D deficiency, is traditionally associated with the development of rickets and musculoskeletal disorders
Out of the 65 subjects analyzed and starting from the subject with the lowest vitamin D metabolite (VDM) index, we identified 17 subjects (9 males and 8 females) with a low VDM index and matched them for age, sex, BMI, and serum 25(OH)D3 to 17 subjects with a ≥10% higher VDM index; the difference in the VDM index among matched pairs of subjects ranged from 12% to 27%
Our data suggest that vitamin D status, determined from serum concentrations of 1,25(OH)2 D3 and 24,25(OH)2 D3, is associated with insulin sensitivity and beta-cell function independent of body composition, fat distribution, and vitamin D exposure
Summary
Hypovitaminosis D, or vitamin D deficiency, is traditionally associated with the development of rickets and musculoskeletal disorders. It is estimated that one billion people worldwide are at risk of vitamin D deficiency, with 30–60% of both children and adults in the United States, Europe, South. The Middle East, and the Far East reported to be vitamin D deficient or insufficient. The major causes of vitamin D deficiency are the lack of exposure to sunlight and reduced intake from dietary sources [1]. Significant links between vitamin D deficiency and metabolic diseases, such as diabetes, obesity, and metabolic syndrome, have been established [2,3]. Only a small proportion of these studies have reported significant positive outcomes [4,5]
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