Vitamin D Deficiency, Insulin Resistance, and Inflammation

Overview

Prior to the widespread vitamin and mineral supplementation of modern food supplies, rickets — and the skeletal weakness for which that disease is responsible — was a formidable medical condition. Once rickets was substantially eradicated by vitamin supplementation in modern food processing, many medical authorities considered that solution to have eliminated all of the consequences of vitamin D deficiency. More recently, medical researchers have identified so many other significant medical consequences attributable to hypovitaminosis D that contemporary clinicians now regard rickets as only the tip of the proverbial iceberg of vitamin D-related ailments (Holick 2007).

Specifically, hypovitaminosis D has been implicated in the development of type 2 diabetes mellitus as well as in systemic inflammation. This observation becomes tremendously significant by virtue of the fact that type 2 diabetes is directly associated with considerable mortality and morbidity, and that the incidence of the disease is increasing both nationally and globally (Pittas, Harris, Stark, et al. 2007). Initially, it was assumed that immunomodulatory action was the mechanism by which vitamin D treatment seemed to improve and prevent type 1 diabetes mellitus in both humans and animals.

However, recent studies strongly suggest that hypovitaminosis D is also a causal factor in type 2 diabetes by virtue of reducing insulin secretion and aspects of glucose tolerance in both rats and humans (Palomer, Gonzalez-Clemente, Blanco-Vaca, et al. 2008). With as many as 1 billion cases of vitamin D insufficiency or deficiency (21–29 ng/ml and <20 ng/ml, respectively), the implications of hypovitaminosis D in relation to chronic deadly disease take on increasing importance (Holick 2007). Given the epidemic proportion of hypovitaminosis D and its apparent connection to the development of type 2 diabetes, the proposed research is crucial in terms of addressing the global incidence of that disease — particularly to the extent that vitamin D and calcium supplementation present a simple and cost-effective preventative method, especially in global communities where modern disease management is comparatively unavailable.

Furthermore, the available evidence also implicating hypovitaminosis D in systemic inflammation — including inflammation contributing to congestive heart failure (Zittermann, Schleithoff, Tenderich, et al. 2003) and rheumatoid arthritis (Merlino, Curtis, Mikuls, et al. 2004) — only increases the importance of the proposed study. Ultimately, the effective prevention of type 2 diabetes mellitus may require nothing more technologically sophisticated than recommendations to increase sunlight exposure. Solar radiation, rather than diet, is actually the most effective and reliable method of preventing vitamin D insufficiency and deficiency (Holick 2007). In that regard, Holick (2007) reports that vitamin D insufficiency and deficiency is even prevalent in communities inhabiting extremely sunny desert climates, because traditional cultural dress in garments that efficiently shield the body from sunlight undermines natural vitamin D synthesis.

Specific Aims of the Proposed Research

The specific aims of the proposed research concern the establishment of a causal relationship between hypovitaminosis D and insulin resistance, diabetes, and systemic inflammation. The primary purpose of the proposed research study is to augment the research data — and the substantial anecdotal evidence — currently available implicating hypovitaminosis D in these conditions.

Background and Significance

The secondary purpose of the proposed research study is to devise a research method capable of distinguishing the respective beneficial roles of vitamin D and calcium, in light of current evidence suggesting that dual supplementation is associated with greater preventative effects than supplementation of either alone (Pittas, Harris, Stark, et al. 2007).

Generally, vitamin D has long been known to be essential to the biological process of bone remodeling because it facilitates the gut uptake and renal reabsorption of dietary calcium (Palomer, Gonzalez-Clemente, Blanco-Vaca, et al. 2008). More recently, numerous research efforts have established that vitamin D also provides a preventative effect on the pathogenesis of type 2 diabetes by contributing directly to glucose intolerance, insulin resistance, and beta cell dysfunction (Chiu, Chu, Go, et al. 2004; Dakovska & Kovacheva 2003; Zella, McCary, and DeLuca 2003).

In addition to its skeletal functions, substantial volumes of research indicate that hypovitaminosis D also contributes to systemic inflammation by virtue of more than 200 distinct gene control functions of 1,25-dihydroxyvitamin D (Holick 2007). While the etiology of rheumatoid arthritis relates to skeletal issues, the available evidence of the role of hypovitaminosis D in systemic inflammation strongly suggests that even aspects of skeletal health are directly attributable to inflammatory responses moderated by adequate absorption of vitamin D (Barger-Lux, Heaney, Dowell, et al. 1998).