Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome

Abstract

The aim of this study is to determine the relationships of vitamin D with diabetes, insulin resistance obesity, and metabolic syndrome. Intra cellular vitamin D receptors and the 1-α hydroxylase enzyme are distributed ubiquitously in all tissues suggesting a multitude of functions of vitamin D. It plays an indirect but an important role in carbohydrate and lipid metabolism as reflected by its association with type 2 diabetes (T2D), metabolic syndrome, insulin secretion, insulin resistance, polycystic ovarian syndrome, and obesity. Peer-reviewed papers, related to the topic were extracted using key words, from PubMed, Medline, and other research databases. Correlations of vitamin D with diabetes, insulin resistance and metabolic syndrome were examined for this evidence-based review. In addition to the well-studied musculoskeletal effects, vitamin D decreases the insulin resistance, severity of T2D, prediabetes, metabolic syndrome, inflammation, and autoimmunity. Vitamin D exerts autocrine and paracrine effects such as direct intra-cellular effects via its receptors and the local production of 1,25(OH)₂D₃, especially in muscle and pancreatic β-cells. It also regulates calcium homeostasis and calcium flux through cell membranes, and activation of a cascade of key enzymes and cofactors associated with metabolic pathways. Cross-sectional, observational, and ecological studies reported inverse correlations between vitamin D status with hyperglycemia and glycemic control in patients with T2D, decrease the rate of conversion of prediabetes to diabetes, and obesity. However, no firm conclusions can be drawn from current studies, because (A) studies were underpowered; (B) few were designed for glycemic outcomes, (C) the minimum (or median) serum 25(OH) D levels achieved are not measured or reported; (D) most did not report the use of diabetes medications; (E) some trials used too little (F) others used too large, unphysiological and infrequent doses of vitamin D; and (G) relative paucity of rigorous clinical data on the effects of vitamin D sufficiency on non-calcium endpoints. Although a large number of observational studies support improving T2D, insulin resistance, obesity, and metabolic syndrome with vitamin D adequacy, there is a lack of conclusive evidence from randomized control clinical trials that, these disorders are prevented following optimization of serum levels of 25(OH)D. However, none of the currently conducted clinical studies would resolve these issues. Thus, specifically designed, new clinical studies are needed to be conducted in well-defined populations, following normalizing the serum vitamin D levels in vitamin D deficient prediabetes subjects, to test the hypothesis that hypovitaminosis D worsens these disorders and correction would alleviate it.

Keywords: 1,25(OH)(2)D; 25(OH) D; Bariatric surgery; Cardiovascular; Complications; Hypertension; Insulin; Morbidity and mortality; Premature death.