Diabetes mellitus has been recognized as a main independent risk factor for cardiovascular diseases.14
Clinical studies indicate that most diabetic patients die due to cardiovascular diseases, with atherosclerosis accounting for about 8% to 10% of all diabetic deaths.15
Diabetes mellitus is a complex, progressive disease, accompanied by multiple complications. Hyperglycemia has been accepted as being essential for the development of diabetic complications. The Diabetes Control and Complication Trial (DCCT) established that prolonged exposure to hyperglycemia is considered the primary factor associated with the development of diabetic macrovascular complications in type 1 diabetic patients.16
The DCCT showed that improvement of glycemic control, as measured by reduction in glycosylated hemoglobin levels, significantly reduced the risk of development and/or progression of all diabetic complications and also reduced the mortality and morbidity due to cardiovascular diseases in type 1 diabetes mellitus patients.
Insulin resistance plays a larger role in the type 1 diabetes disease process than is commonly recognized. Subsets of people with mild manifestations of the type 1 autoimmune disease process could benefit from treatments aimed at improving the insulin-resistant state.17
There is evidence that vitamin D is important in the prevention of islet cell death.18
Reports have shown the association of hypovitaminosis D with insulin resistance and beta-cell dysfunction,3,19,20
and vitamin D is required to improve the production of insulin.3,4
There are few studies that have examined the effect of supplementation with a variety of formulations of vitamin D on type 2 diabetes mellitus parameters. Among 18 young healthy men, supplementation with 1,25-(OH)2D3 for 7 days did not change fasting glycemia or insulin sensitivity.21
In another small study of 14 patients with type 2 diabetes mellitus, 1-OHD3 administration daily for 3 weeks enhanced insulin secretion, but had no effect on post-load glucose tolerance.22
Ljunghall et al randomized 65 middle-aged men with impaired glucose tolerance or mild diabetes and sufficient vitamin D levels at baseline to 0.75 g/d of 1-OHD3 or placebo for 3 months and found no effect on fasting or stimulated glucose tolerance.23
In a crossover trial, 20 patients with type 2 diabetes mellitus and vitamin D deficiency were treated for 4 days with 1,25-OHD, and no change was seen in fasting or stimulated glucose, insulin or C-peptide concentrations.24
Pittas et al have shown that insulin sensitivity is improved by as much as 60% when levels of vitamin D are increased from 25 to 75 nmol/L.25
In a post hoc analysis of a 2-year trial, supplementation with vitamin D3 or 1-OHD3 had no effect on fasting glycemia in postmenopausal nondiabetic women.26
One study reported that glycemic control became worse in three Asian patients following vitamin D supplementation;27
however, these patients received vitamin D2 and not vitamin D3. Vitamin D2 has several unknown metabolites with unknown effects, and certain vitamin D receptor genotypes are big determinants of insulin secretory capacity in various ethnic groups.28,29
Luo et al showed that among 109 patients aged over 50 years with type 2 diabetes who received cholecalciferol 2000 IU daily for 3 months, glycosylated hemoglobin concentrations and insulin use did not change significantly.30
The patients in our study were repleted with vitamin D3, and using up to 4000 IU of vitamin D3 to reverse states of deficiency was found to be safe.31
There are no studies that have examined the effect of supplementation with a variety of formulations of vitamin D on glycemic control in type 1 diabetes mellitus. We are the first to have undertaken a study that has shown that the addition of vitamin D3 to insulin therapy produces a significant improvement in glycemic control. This effect on glycemic control was sustained over a period of 12 weeks; we do not know if this effect would be sustained further.
The study had some limitations. Increased hypoglycemia is a well-known complication of improved glucose control, and an important goal of therapy is to minimize this risk. Hypoglycemic episodes were not obtained by our patients. The study was neither blinded nor randomized, and the incremental doses of insulin were not analyzed.
In conclusion, diabetes is one of the fastest-growing chronic diseases worldwide. Vitamin D deficiency is common, and repletion might improve glycemic control in type 1 diabetes. Vitamin D3 is inexpensive and readily available. Well-designed clinical studies are required to ascertain if improving 25-OHD levels from deficiency to sufficiency improves glycemic control in patients with type 1 diabetes.