Abstract
Type 2 diabetes prevalence is increasing, reaching ‘pandemic’ proportions globally, and associated with increasing obesity rates. Concomitantly, vitamin D deficiency persists world-wide and is worsened by obesity because it reduces hepatic 25-hydroxylation of vitamin D, which reduces circulating 25(OH)D availability to target tissues; these include islet beta cells, since vitamin D is essential for adequate insulin responses to hyperglycemia. Increased insulin resistance increases type-2 diabetes risks and precedes its development by decades, reflecting changes in hepatic and muscle function that are corrected experimentally by activated hormonal vitamin D [calcitriol]; similarly, abnormal insulin resistance can be corrected in humans by correcting vitamin D deficiency using oral supplementation. Since vitamin D deficiency and inadequacy persist world-wide despite various guidelines on vitamin D intake, the possibility that correcting deficiency would contribute to reducing T2DM risks through beneficial effects on pancreatic islet beta cells and on the metabolic disorders contributing to insulin resistance through vitamin D inadequacy warrants consideration. If this is the case, then ensuring vitamin D adequacy in populations at high risk of Type-2 diabetes would be a valuable adjunct to other measures being taken to reduce that risk such as increased exercise and weight reduction. It would also reduce cardiovascular disease risks, well known to increase with insulin resistance, with or without concomitant Type-2 diabetes. Cardiovascular disease risks themselves can be reduced by adequately correcting deficiency and are lower with higher lifetime circulating 25-hydroxyvitamin D in deficient subjects from Mendelian randomization analysis. This report, therefore, reviews the evidence for increased insulin resistance as a risk factor for Type-2 diabetes, the beneficial effects of correcting vitamin deficiency on insulin resistance, Type-2 diabetes and cardiovascular risks, some basic mechanisms accounting for those benefits, the reasons for the persistence of vitamin D inadequacy globally and how best that problem could be corrected.