Vitamin D and Tissue-Specific Insulin Sensitivity in Humans With Overweight/Obesity

Context: Vitamin D deficiency in obesity has been linked to insulin resistance. However, studies that examined the association between plasma 25-hydroxyvitamin D-3 [25(OH)D-3] as well as plasma 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] 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)D-3 and 1,25(OH)(2)D-3, AT VDR; between plasma 25(OH)D-3, 1,25(OH)(2)D-3, AT VDR, and tissue-specific insulin sensitivity in individuals with overweight/obesity.

Design and Patients: This analysis included 92 adult individuals (BMI, >25 kg/m(2)). A two-step hyperinsulinemic-euglycemic clamp with a [6,6-2H(2)]-glucose tracer was performed to assess tissue-specific 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)D-3, 1,25(OH)(2)D-3, 1,25(OH)(2)D-3/25(OH)D-3 ratio, SAT VDR and CYPs mRNA, and tissue-specific insulin sensitivity.

Results: BMI was inversely associated with plasma 25(OH)D-3 (beta = 20.274; P = 0.011) but not with plasma 1,25(OH)(2)D-3. Plasma 25(OH)D-3 was not related to CYPs or VDR expression in SAT. Plasma 1,25(OH)(2)D-3 and 25(OH)D-3 were not related to tissue-specific insulin sensitivity. Interestingly, SAT VDR mRNA was negatively associated with AT insulin sensitivity (b = 20.207; P = 0.025).

Conclusions: BMI was inversely associated with 25(OH)D-3 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.