Vitamin D supplementation in patients with type 2 diabetes

Abstract

Vitamin D, the so called sun-shine vitamin, is a hot topic currently, with number of studies proclaiming its benefits for several non-skeletal illnesses including cancer, cardiovascular diseases, autoimmune and inflammatory diseases, dementia, and diabetes. Conversely, recent studies have been more cautious and questioning its perceived benefits (1) .Along with numerous non-skeletal effects, vitamin D has received its attention on potential pancreatic beta cell function and insulin sensitivity. Historically the role of vitamin D in diabetes was recognized by a seasonal variation in glycemic control reported in patients with diabetes being worse in the winter. This may be due to insufficient vitamin D as a result of reduced sunlight in winter. Additional evidence supported the role of vitamin D in diabetes; presence of vitamin D receptors on pancreatic β cells, expression of 1α hydroxylase activity at pancreatic β cells causing activation of vitamin D, and increased transcription of insulin receptor genes by 1,25(OH)D (2). As β-cells in the pancreas are affected via cytokine-induced apoptosis, systemic inflammation has an important role in insulin resistance and cardiovascular events in patients with diabetes. Vitamin D could decrease the effects of systemic inflammation and protect β-cells. Other proposed mechanism where vitamin D affects insulin resistance is through the renin angiotensin aldosterone system (RAAS). Low levels of 1,25(OH)2D is shown to increase angiotensin II which inhibit the action of insulin in vascular and skeletal muscle tissues, leading to impaired glucose uptake (3) . Large number of cross-sectional studies have generally reported an inverse association between vitamin D status and prevalent hyperglycemia, favouring the biological perspective, where vitamin D have both direct and indirect effects on various mechanisms related to the pathophysiology of type 2 diabetes.The study by Forouhi et al. reported that the baseline serum vitamin D levels are inversely associated with glucose and insulin levels collected 10 years later(4). Finnish cohort study also showed an inverse association between baseline serum 25(OH) D and 17-year risk of type 2 diabetes, after adjustment for confounders like obesity and low physical activity (5) . A post hoc analysis of a trial designed for bone-related outcomes, found that 700 IU/day of Vitamin D3 (combined with calcium) decreased homeostasis model assessment of insulin resistance in participants with impaired glucose tolerance but not in those with normal fasting glucose. Numerous other prospective cohort studies have also demonstrated that higher vitamin D status was associated with reduced risk of type 2 diabetes. The important role of vitamin D in the development of diabetes evidenced by these epidemiological studies prompts clinicians to prescribe more and more vitamin D supplements. Subsequently several researches on the positive preventive effect of vitamin D supplementation were widely carried out. Number of randomized controlled trials study showed t...