Supplementary Material for: Vitamin D Status, Gender Differences, and Cardiometabolic Health Disparities

Background: Vitamin D deficiency is an unrecognized epidemic found in India and also worldwide. Despite the high prevalence of diabetes among Indians, there is a paucity of data showing the relationship between vitamin D status and cardiometabolic disparities. In this study, we have examined the relationship between vitamin D and cardiometabolic traits in a population from India. Methods: Circulating 25(OH)D levels were measured in 3,879 participants from the Asian Indian Diabetic Heart Study using ELISA kits. Results: Vitamin D levels were significantly reduced (p < 0.0001) in both men and women with obesity. However, compared to women, serum vitamin D was consistently lower in men (p < 0.02), irrespective of the presence of obesity and type 2 diabetes. Multivariate regression revealed strong interaction of vitamin D with body mass index that resulted in increased fasting glucose (p = 0.001) and reduced homeostasis model assessment of β-cell function (HOMA-B; p = 0.01) in normoglycemic individuals. However, in gender-stratified analysis, this association was restricted to men for both fasting glucose (p = 2.4 × 10^-4) and HOMA-B (p = 0.001). Conclusions: Our findings suggest that vitamin D deficiency may significantly enhance the risk of cardiometabolic disease among Asian Indians. Future randomized trials and genetic studies are expected to clarify the underlying mechanisms for gender differences in vitamin D deficiency, and whether vitamin D-driven improvement in testosterone may contribute to beneficial cardiometabolic outcomes in men.