Results

The age of the participants ranged between 43.42 ±7.877 years with the 25(OH)D insufficiency (18.49 ±3.497 ng/ml) and the assessed glycaemic control with FBS(146.22 ± 45.007 mg/dl), PPBS(275.28 ±66.400mg/dl) and HBA1C (8.326 ±1.15843) is shown in (Table/Fig 1).

The low serum vitamin D levels were negatively correlated with the fasting as well as the postprandial blood sugar levels. There was a trend towards an inverse 25(OH) D - HbA1C association, which did not show statistical significance, most probably due to the relatively small sample size.

Discussion

The present study observed that the type 2 diabetic individuals with a vitamin D insufficiency showed a poor glycaemic control. According to various studies (6), vitamin D has a potential influence on the glucose homeostasis, as was suggested by the following factors.

Effect of Vitamin D on Insulin Secretion
Specific vitamin D cell receptors are present on the pancreatic β cells (7). The pancreatic β cells express 1 alpha hydroxylase which is responsible for an active vitamin D3 synthesis (8) and also by increasing the insulin response to the glucose stimulation, but not affecting the basal insulin secretion (9). In some populations, type I diabetes is associated with certain polymorphisms within the VDR gene (10) which is present in the human insulin gene promoter and also in the skeletal muscle and in adipose tissues (11) Pancreatic islets have both VDR and vitamin D-dependent calcium-binding proteins (CaBP) (12),(13), thus suggesting a role of vitamin D in insulin secretion. The insulin secretion and sensitivity is influenced by Vitamin D mediated intracellular calcium secretion. Raised intracellular calcium levels enhance the binding of the calcium binding protein to the IRS – 1 (Insulin receptor substrate 1), stimulating tyrosine phosphorylation and PI3 kinase activation and thus promoting insulin secretion (11).

Vitamin D deficiency may also impair the insulin secretion through its associated increase in the PTH levels. It was proposed that vitamin D deficiency-associated hyperparathyroidism may actually cause a paradoxical increase in the intracellular calcium levels (12),(13). This PTH-induced increase in calcium may in turn impair the calcium signal which is needed for glucose-induced insulin secretion (14). Of significance is the finding, that the vitamin D potentiation of glucose-induced insulin secretion is seen in normal individuals but not in patients with established type-2 DM (15). This could be because type-2 diabetes by itself may be a condition of impaired intracellular calcium homeostasis (16).

Whether the insulin secretion is influenced by the direct action of Vitamin D or through its receptor or through changes in calcium, or PTH, is a matter of ongoing studies. It is also possible that the insulin secretion may be influenced by a combination of different mechanisms.

Effect of vitamin D on the insulin sensitivity
Type-2 DM is a state of chronic systemic inflammation and it has been found to increase the insulin resistance (17). Type-2 DM was found to be associated with an increase in the levels of the tumour necrosis factor-a and b, the C reactive protein, the plasminogen activator inhibitor-1 (PAI-1), and interleukin-6 (IL-6) (18),(19),(20). The increase in these inflammatory mediators may precede and even predict the development of type-2 DM. In support of this concept, is the finding that VDR has been found on almost all the cells of the immune system (21) and that vitamin D can repress the type 1 cytokines, inhibit dendritic cell maturation, and upregulate the regulatory T cells. Furthermore, immune cells such as macrophages contain 1ά-hydroxylase that can be upregulated by the inflammatory mediators and not by PTH (22). Vitamin D also suppresses the antigen-presenting capacity of the macrophages, it modulates the development of the CD4 lymphocytes and it inhibits the production of IFNc (interferon c) and IL-2 (interleukin 2) (23), among other cytokines. These cytokines are known to activate the macrophages and the cytotoxic T cells, which in turn can lead to the destruction of the pancreatic islets. By the modulation of the immune and the inflammatory processes, vitamin D may also decrease insulin resistance and increase the insulin secretion in type-2 DM (24), which are the two characteristic defects in this condition.

From the above discussion, it is clear that vitamin D has a significant role to play in the molecular mechanisms of the synthesis, secretion and the peripheral sensitivity of insulin. Hence, hypovitaminosis D may be associated with insulin resistance and beta cell dysfunction.

A variety of limitations of this study need however to be addressed. The small sample size did not allow a multivariate approach for incorporating additional, potentially meaningful factors for modifying the levels of serum 25(OH) D, but it should be declared that from the evidence which was provided, that improving the vitamin D status will help in establishing a better glycaemic control in people with DM type 2. Nevertheless, it seems that the routine screening for vitamin D insufficiency may provide meaningful information and that it could be considered for diabetic care. Interventional studies are needed to evaluate whether the long-term supplementation of vitamin D could reduce the morbidity in a diabetic population, with an awareness of the side effects.

Conflict of Interest: The authors declare no conflict of interest.