The Apparent Relation between Plasma 25-Hydroxyvitamin D and Insulin Resistance Is Largely Attributable to Central Adiposity in Overweight and Obese Adults

Background: Research indicates that plasma 25-hydroxyvitamin D [25(OH)D] is associated with insulin resistance, but whether regional adiposity confounds this association is unclear. Objective: This study assessed the potential influence of adiposity and its anatomical distribution on the relation between plasma 25(OH)D and insulin resistance. Methods: A secondary analysis of data from middle-aged overweight and obese healthy adults [n = 336: 213 women and 123 men; mean +/- SD (range); age: 48 +/- 8 y (35-65 y); body mass index (BMI; in kg/m(2)): 30.3 +/- 2.7 (26-35)] from West Lafayette, Indiana (40.4 degrees N), were used for this cross-sectional analysis. Multiple linear regression analyses that controlled for multiple covariates were used as the primary statistical model. Results: Of all participants, 8.6% and 20.5% displayed moderate [20.1-37.5 nmol/L plasma 25(OH)D] to mild (37.6-49.9 nmol/L) vitamin D insufficiency, respectively. A regression analysis controlling for age, sex, race, plasma parathyroid hormone concentration, season of year, and supplement use showed that 25(OH) D was negatively associated with fasting insulin (P = 0.021). Additional regression analyses showed that total and central adiposity but not peripheral adiposity predicted low plasma 25(OH) D [total fat mass index (FMI): P = 0.018; android FMI: P = 0.052; gynoid FMI: P = 0.15; appendicular FMI: P = 0.07) and insulin resistance (homeostasis model assessment of insulin resistance: total and android FMI, P < 0.0001; gynoidFMI, P = 0.94; appendicular FMI, P = 0.86). The associations of total and central adiposity with insulin resistance remained significant after adjusting for plasma 25(OH)D. However, adjusting for central adiposity but not other anatomical measures of fat distribution eliminated the association between plasma 25(OH)D and insulin resistance. Conclusion: Central adiposity drives the association between plasma 25(OH)D and insulin resistance in overweight and obese adults. The trial was registered at clinicaltrials.gov as NCT00812409.