The vitamin D metabolites 25(OH)D and 1,25(OH)₂D are not related to either glucose metabolism or insulin action in obese women

Aim: Vitamin D deficiency has been proposed to be involved in obesity-induced metabolic disease. However, data on the relationship between 25-hydroxycholecalciferol (25(OH)D) and insulin resistance have been inconsistent, and few studies have investigated the active vitamin D metabolite, 1,25-dihydroxycholecalciferol (1,25(OH)₂D). This study aimed to determine the relationship between circulating levels of both 25(OH)D and 1,25(OH)₂D and direct measures of glucose metabolism and insulin action in obese women. Methods: Serum levels of 25(OH)D and 1,25(OH)₂D, and glucose metabolism and tissue-specific insulin action, as assessed in the basal state and during a two-step euglycaemic-hyperinsulinaemic clamp study with [6,6-²H₂]glucose infusion, were measured in 37 morbidly obese women (age: 43±10 years; body mass index: 44±6kg/m²). Results: Sixteen subjects had circulating 25(OH)D levels<50nmol/L, consistent with vitamin D deficiency, and 21 had normal 25(OH)D levels. There were no differences in either baseline characteristics or parameters of glucose metabolism and insulin action between the groups. Serum 25(OH)D, but not 1,25(OH)₂D, was negatively correlated with both body mass index (r =-0.42, P =0.01) and total body fat (r =-0.46, P <0.01). Neither 25(OH)D nor 1,25(OH)₂D levels were related to any measured metabolic parameters, including fasting glucose, fasting insulin, basal endogenous glucose production, and hepatic, adipose-tissue and skeletal muscle insulin sensitivity. Conclusion: Obesity was associated with lower levels of circulating 25(OH)D, but not with the hormonally active metabolite 1,25(OH)₂D. Neither 25(OH)D nor 1,25(OH)₂D were related to glucose metabolism and tissue-specific insulin sensitivity in obese women, suggesting that vitamin D does not play a major role in obesity-related insulin resistance.