Vitamin D deficiency is associated with indicators of pre-diabetes including, insulin resistance, β-cell dysfunction and elevated plasma glucose with controversial findings from current trials. This study aims to investigate the long-term effect of vitamin D on glucose metabolism and insulin sensitivity in pre-diabetic and highly vitamin-deficient subjects. Methods: 132 participants were randomized to 30,000 IU vitamin D weekly for 6 months. Participants underwent oral glucose tolerance test

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... TT) at 3-month intervals to determine the change in plasma glucose concentration at 2h after 75g OGTT (2hPCG). Secondary measurements included glycated hemoglobin, fasting plasma glucose and insulin, post-prandial insulin, indices of insulin sensitivity (HOMA-IR, Matsuda Index), β-cell function (HOMA-β, glucose and insulin area under the curve (AUC), disposition and insulinogenic indices), and lipid profile. Results: A total of 57 (vitamin D) and 75 (placebo) subjects completed the study. Mean baseline serum 25(OH) D levels were 17.0 ng/ml and 14.9 ng/ml for placebo and vitamin D group, respectively. No significant differences were observed for 2hPC glucose or insulin sensitivity indices between groups. HOMA-β significantly decreased in the vitamin D group, while area under curve for glucose and insulin showed a significant reduction in β-cell function in both groups. Additionally, HOMA-β was found to be significantly different between control and treatment group and significance persisted after adjusting for confounding factors. Conclusion: Vitamin D supplementation in a pre-diabetic and severely vitamin-deficient population had no effect on glucose tolerance or insulin sensitivity. The observed reduction in β-cell function in both placebo and vitamin D groups could be attributed to factors other than supplementation. Trial registration: The trial was registered at www.clinicaltrials.gov with number: NCT02098980. Background Low levels of vitamin D has been identified as a major health issue globally. Current literature provides evidence for the association of hypovitaminosis D with various health conditions including bone health [1], cardiovascular disease [2], hypertension [3], cancer risk [4] and diabetes mellitus [5]. In particular, higher prevalence of low serum vitamin D [25-(OH)D] levels has been observed among Conclusions According to our findings, supplementation with vitamin D did not improve insulin sensitivity, insulin secretion, or glucose tolerance in our pre-diabetic and highly vitamin D deficient population. Larger 13 and multicenter intervention studies, in such populations, with longer duration are required to examine the role of vitamin D, combined with other lifestyle interventions targeting risk factors and surrogate markers of T2DM. Abbreviations [25-(OH)D]