Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: a randomised, placebo-controlled trial

OBJECTIVE: To determine whether vitamin D3 supplementation improves insulin sensitivity, using the hyperinsulinemic-euglycemic clamp. DESIGN: This single-center, double-blind, placebo-controlled trial randomized 96 participants at high risk of diabetes or with newly diagnosed type 2 diabetes to vitamin D3 5,000 IU daily or placebo for 6 months. METHODS: We assessed at baseline and 6 months: 1) primary aim: peripheral insulin sensitivity (M-value using a 2-h hyperinsulinemic-euglycemic clamp); 2) secondary aims: other insulin sensitivity (HOMA2%S, Matsuda) and insulin secretion (insulinogenic index, C-peptide area under the curve, HOMA2-B) indices using a 2h-oral glucose tolerance test (OGTT); s-cell function (disposition index: M-value x insulinogenic index); fasting and 2-h glucose post-OGTT; HbA1c; anthropometry. RESULTS: Baseline characteristics were similar between groups (% or mean±SD): women 38.5%; age 58.7±9.4 years; BMI 32.2±4.1 kg/m2; prediabetes 35.8%; diabetes 20.0%; 25-hydroxyvitamin D (25(OH)D) 51.1±14.2 nmol/L. At 6 months, mean 25(OH)D reached 127.6±26.3 nmol/L and 51.8±16.5 nmol/L in the treatment and placebo groups, respectively (p<0.001). A significant beneficial effect of vitamin D3 compared with placebo was observed on M-value (mean change (95% CI): 0.92 (0.24 to 1.59) versus -0.03 (-0.73 to 0.67); p=0.009) and disposition index (mean change (95% CI): 267.0 (-343.4 to 877.4) versus -55.5 (-696.3 to 585.3); p=0.039) after 6 months. No effect was seen on other outcomes. CONCLUSIONS: In individuals at high risk of diabetes or with newly diagnosed type 2 diabetes, vitamin D supplementation for 6 months significantly increased peripheral insulin sensitivity and β-cell function, suggesting that it may slow metabolic deterioration in this population.