Vitamin D and tissue-specific insulin sensitivity in humans with overweight/obesity

Abstract

Context: Vitamin D deficiency in obesity has been linked to insulin resistance. However, studies that examined the association between plasma 25-hydroxyvitamin D3 [25(OH)D3] as well as plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and tissue-specific insulin sensitivity are scarce. Furthermore, vitamin D receptor (VDR) and vitamin D-metabolizing enzymes [cytochrome 450 (CYP)] expression in adipose tissue (AT) might affect AT insulin sensitivity. Objective: To investigate the association between body mass index (BMI) and plasma 25(OH)D3 and 1,25(OH)2D3, AT VDR; between plasma 25(OH)D3, 1,25(OH)2D3, AT VDR, and tissue-specific insulin sensitivity in individuals with overweight/obesity. Design and Patients: This analysis included 92 adult individuals (BMI,>.25 kg/m2). A two-step hyperinsulinemic-euglycemic clamp with a [6,6-2H2]-glucose tracer was performed to assess tissuespecific insulin sensitivity. Abdominal subcutaneous AT (SAT) mRNA expression of VDR and CYP was determined by using quantitative RT-PCR. Setting: University medical center. Main Outcome Measures: Plasma 25(OH)D3, 1,25(OH)223, 1,25(OH)2D3/25(OH)D3 ratio, SAT VDR and CYPs mRNA, and tissue-specific insulin sensitivity. Results: BMI was inversely associated with plasma 25(OH)D3 (β = -0.274; P = 0.011) but not with plasma 1,25(OH)2D3. Plasma 25(OH)D3 was not related to CYPs or VDR expression in SAT. Plasma 1,25(OH)2D3 and 25(OH)D3 were not related to tissue-specific insulin sensitivity. Interestingly, SAT VDR mRNA was negatively associated with AT insulin sensitivity (β = -0.207; P = 0.025). Conclusions: BMI was inversely associated with 25(OH)D3 concentrations, which could not be explained by alterations in SAT VDR and CYP enzymes. Plasma vitamin D metabolites were not related to tissue-specific insulin sensitivity. However, VDR expression in SAT was negatively associated with AT insulin sensitivity.