A Randomized Double-Blind Placebo-Controlled Trial Evaluating the Efficacy of Oral Vitamin D3 in Improving Renal and Vascular Functions in Vitamin D Deficient Patients with Type 2 Diabetes Mellitus

The prevalence of chronic kidney disease (CKD) estimated to be 8–16% globally and is showing a progressively increasing trend. This is substantially contributed by growing global population of patients with diabetes. Diabetic patients develop diabetic nephropathy (DN), which along with co-existing hypertension leads to progressive impairment in renal function. Albuminuria in diabetes is associated with linear decline in glomerular filtration rate, progression to end stage renal disease and cardiovascular mortality. Drugs reducing the extent of proteinuria are considered to be a promising approach for preventing the progression of DN. Diabetic patients with early CKD tend to have multiple cardiovascular comorbidities mainly due to inflammation and endothelial dysfunction. Microalbuminuria, manifested in DN is considered to be an atherosclerotic risk factor and has been implicated as an independent risk factor for cardiovascular and cerebrovascular disease and premature cardiovascular mortality for patients with diabetes.

Patients with CKD are profoundly deficient in both serum 25(OH)D3 and 1,25(OH)2D3, with 50-80% of patients at the initiation of chronic hemodialysis showing serum 25-hydroxy vitamin D levels below the lower limits of normal. They often have co-existing hypertension, which leads to increased mortality, cardiovascular complications and renal disease progression. Observational studies have demonstrated that CKD patients treated with vitamin D analogues have a significant better renal outcome as compared to untreated patients. It has been demonstrated that vitamin D deficiency has a negative effect on albuminuria in DN while vitamin D supplementation has a beneficial effect on the risk factors of diabetes, such as, hyperlipidemia, hypertension and hyperglycemia.

A recent Indian study has shown that diabetics with vitamin D deficiency may be also at higher risk of vascular complications including coronary artery disease. A recent study from our centre has exhibited that oral vitamin D3 supplementation of 60,000 IU per week for 8 weeks significantly improves vascular functions and reduces oxidative stress in type 2 diabetic patients with vitamin D deficiency. Available evidence from low-to-moderate quality observational studies and fewer randomized control trials (RCTs) suggests that vitamin D supplementation improves biochemical endpoints, renal and vascular functions in diabetic kidney disease. However, whether such improvements in the early or intermediate stage of CKD in diabetes can translate into clinically significant outcomes, such as, slowing the progression of CKD or improving vascular functions on a long term basis is yet to be determined. If this study comes with a positive outcome, vitamin D supplementation might be warranted to prevent progression of renal dysfunction and also to improve vascular functions in patients with type 2 diabetes mellitus.