Evidence for threshold effects of 25-hydroxyvitamin D on glucose tolerance and insulin resistance in black and white obese postmenopausal women.

We identified normal vs. abnormal 25-hydroxyvitamin D [25(OH)D] concentrations by examining the relation of 25(OH)D to non-bone-related measures (plasma glucose, insulin resistance, lipids, blood pressure, fitness, obesity, and regional adiposity) and asking whether there is a 25(OH)D concentration above and below which the relation between 25(OH)D and outcome changes. We examined the relation between 25(OH)D and outcome by race to see whether race-specific normal ranges are needed, and we examined the role of insulin-like growth factor-1 (IGF-1) in modulating the relation between 25(OH)D and outcome. In a cross-sectional study of 239 overweight and obese, sedentary postmenopausal women without diabetes (83 black, 156 white), outcome measures included plasma lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), IGF-1, parathyroid hormone (PTH), aerobic fitness, body composition, subcutaneous abdominal and visceral fat, and blood pressure. We identified threshold effects in the association between 25(OH)D and these variables using piecewise linear regressions. We found that 25(OH)D was inversely related to fasting glucose, fasting and 2-h insulin, HOMA-IR, visceral abdominal fat, percentage fat, PTH, and triglycerides. Evidence for a threshold effect of 25(OH)D was found for 2-h glucose, 2-h insulin, fasting insulin, and HOMA-IR. There was no evidence suggesting the need for race-specific normal 25(OH)D concentrations. IGF-1 modulated the relation between 25(OH)D and outcome but only below, and not above, a threshold 25(OH)D concentration. Our findings suggest a threshold effect of 25(OH)D on glucose-insulin metabolism such that 25(OH)D ≥ ∼26 μg/L (65.0 pmol/L) supports normal glucose homeostasis and that the same cut point defining normal 25(OH)D concentration can be used in black and white women. This study was registered at clinicaltrials.gov as NCT01798030.