25-hydroxyvitamin D is associated with adiposity and cardiometabolic risk factors in a predominantly vitamin D-deficient and overweight/obese but otherwise healthy cohort

•25-hydroxyvitamin D levels were associated with cardiometabolic risk factors including adiposity, glucose intolerance, insulin resistance, and inflammation in predominantly overweight/obese but otherwise healthy adults.•Most associations between 25-hydroxyvitamin D levels and cardiometabolic risk factors were mediated by adiposity.•The mediating effect of adiposity on the relationship between 25-hydroxyvitamin D and cardiometabolic risk was only observed when using direct adiposity measures such as percent body fat, but not when using indirect measures such as body mass index. Vitamin D deficiency has reached epidemic proportions worldwide and has recently been linked to cardiometabolic risk factors including obesity, insulin resistance, hypertension, dyslipidemia, as well as type 2 diabetes and cardiovascular disease. The objective of this study was to examine the associations between circulating 25-hydrovitamin D (25(OH)D) levels and cardiometabolic risk factors using direct measures of adiposity, glucose intolerance, and insulin resistance, as well as lipids, blood pressure, and plasma markers of inflammation. We measured circulating 25(OH)D, physical activity (International Physical Activity Questionnaire- IPAQ), anthropometry (body mass index (BMI), waist-to-hip ratio (WHR), % body fat (dual energy X-ray absorptiometry)), metabolic parameters (fasting and 2-h plasma glucose levels during oral glucose tolerance test; insulin sensitivity (M, hyperinsulinaemic-euglycaemic clamp), and cardiovascular and inflammatory profiles (blood pressure (BP), pulse pressure (PP), mean arterial pressure (MAP), plasma lipid levels, white blood cell count (WBC), and plasma high-sensitivity C-reactive protein levels (hsCRP)) in 111 healthy, non-diabetic adults (66 males/45 females; age 31.1±9.2years; % body fat 36.0±10.2%). Mean 25(OH)D was 39.8±19.8 nmol/L with no difference between genders (p=0.4). On univariate analysis, 25(OH)D was associated with% body fat (r=−0.27; p=0.005), 2-h glucose (r=−0.21; p=0.03), PP (r=0.26; p=0.006), and insulin sensitivity (r=0.20, p=0.04), but not with age, BMI, WHR, fasting glucose, BP, MAP, lipids, or inflammatory markers (all p>0.05). After adjusting for age and sex, 25(OH)D remained associated with% body fat (β=−0.12%; p=0.003), 2-h glucose (β=−0.13mmol/L; p=0.02), PP (β=0.12mmHg; p=0.009), and insulin sensitivity (β=0.22mg/kg/min; p=0.03), and became associated with fasting glucose (β=−0.04mmol/L; p=0.04) and hsCRP (β=−0.51mg/L; p=