Insulin resistance, i.e., reduction in insulin responsiveness with a decrease in glucose uptake in insulin target tissues (muscle and adipose tissue) is common in end-stage renal disease (ESRD), but is also present at earlier stages of renal disease with mild-moderate renal function impairment as well as in microalbuminuria and nephrotic syndrome.~Population-based cross-sectional studies have shown that low levels of vitamin D (25(OH) vitamin D) is associated with impaired glucose tolerance in subjects with normal renal function and that reduced renal function and 25(OH) vitamin D deficiency are independently associated with insulin resistance.~Vitamin D has well-known effects on calcium metabolism and skeletal mineralisation but recent experimental studies suggest that vitamin D in addition reduces several inflammatory mediators that are of importance in the development and progression of renal disease which also associated with insulin resistance such as TNF-α and IL-6.~This is a prospective, single-blind, explorative, randomized, placebo-controlled, single-centre, two-way cross-over study with two treatment periods of 10 weeks separated by a washout period of 6 weeks. Non-diabetic patients with chronic kidney disease (CKD) stage 3 and 4 (GFR 15-60 ml/min/1.73m2) who have low serum 25-OH-vitamin D levels (< 30 ng/mL) and elevated fasting serum insulin levels (>10 IU/L) will be randomized to receive either vitamin D3 (cholecalciferol) 3200U orally (tablets) daily or placebo.~Approximately 24 patients are going to complete the study. A pre-entry wash-out period of 6 weeks is needed for patents already on vitamin D treatment. An in vivo assessment of insulin secretion and insulin sensitivity will be made by insulin-glucose clamp at the end of each treatment period.
The purpose of this study is to evaluate the impact of vitamin D3 supplementation on the insulin resistance in non-diabetic patients with chronic kidney disease (CKD) stages 3-4, vitamin D deficiency/insufficiency and elevated fasting serum insulin levels.