Animal studies suggested that vitamin D might decrease insulin resistance. Estrogen increased insulin sensitivity and glucose tolerance in rodents. However, sex-specific association of vitamin D with insulin resistance in humans remains unclear.To investigate the sex-dependency of the association of insulin resistance and 25(OH)D in a large Caucasian population.Cross-sectional study from out-patients' blood samples with measurements of 25(OH)D and HOMA-IR drawn at exactly the same day (N=1887). This cohort was divided into three groups: i) group with vitamin D deficiency (n=1190), ii) group with vitamin D sufficiency (N=686)), iii) vitamin D excess groups (n=11), the vitamin D excess group was excluded from further analysis due to the small size.Analysis of the entire study population showed that serum 25-hydroxyvitamin D was inversely associated with HOMA-IR (rs=-0.19, P<0.0001). When considering the vitamin D status, this association was only seen in the vitamin D deficiency group, but not in the vitamin D sufficient group. The correlation was sex-dependent: HOMA-IR was inversely correlated with vitamin D in women with vitamin D deficiency (rs=-0.26, P<0.0001) but not in men with vitamin D deficiency (rs=0.01, P=0.714). After multivariate linear regression analysis considering confounding factors, this relationship was again only seen in women.Vitamin D was inversely and independently associated with insulin resistance only in women with vitamin D deficiency. Based on our data, we suggest that in particular vitamin D deficient women might benefit from vitamin D substitution by improving insulin resistance. This, however, needs to be proven in adequately designed double-blind placebo-controlled clinical studies.
Xin Chen, Chang Chu, Cornelia Doebis, Volker von Baehr, Berthold Hocher