Effect of Vitamin D3 Supplementation on Insulin Sensitivity in Prediabetes With Hypovitaminosis D: A Randomized Placebo-Controlled Trial

Introduction The interplay of vitamin D and glucose metabolism is an area of ongoing research. The need for vitamin D supplementation trials in individuals with prediabetes and hypovitaminosis D has been stressed by earlier research studies. The objective of this study was to assess the effect of vitamin D3 supplementation on oral glucose insulin sensitivity (OGIS) index in patients with prediabetes and hypovitaminosis D. Methods  We enrolled 120 individuals with prediabetes (ADA definition) and hypovitaminosis D (vitamin D < 30 ng/mL) and randomized them into the vitamin D supplementation (60,000 IU weekly) group and the placebo group. Primary outcome measure (i.e., 2-hour OGIS index) and secondary outcome measures (i.e., fasting and postprandial blood glucose, glycosylated hemoglobin, body mass index, and insulin sensitivity indices, i.e., quantitative insulin sensitivity check index [QUICKI] and homeostatic model assessment for insulin resistance [HOMA-IR]) were analyzed for change with the 12 weeks of intervention. Results  A total of 52 subjects in the vitamin D group and 49 in the placebo group completed the study. Serum vitamin D levels (10.11 ± 2.73 to 52.2 ± 13.14 ng/mL; p < 0.0001) and OGIS index (376.4 ± 39.7 to 391.7 ± 40.7 mL/min/m²; p = 0.011) increased significantly on per-protocol analysis in the vitamin D group. There was no significant change observed in vitamin D levels and OGIS index in the placebo group. Between-group comparison showed a rise in OGIS index (15.3 ± 47.1 mL/min/m²) in the vitamin D group and decrease in OGIS index (-10.4 ± 44.7 mL/min/m²) in the placebo group, and the difference was statistically significant (p = 0.0029). The inter-group comparison showed relative fall in fasting glucose levels in the vitamin D group, with no significant change observed in the other secondary outcome measures. Conclusions The correction of hypovitaminosis D in subjects with prediabetes led to improved insulin sensitivity as assessed by OGIS index at 120 minutes, signifying the role of vitamin D in glucose homeostasis.