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

Abstract

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=0.04). After adjusting for age, sex, and % body fat, 25(OH)D was no longer associated with insulin sensitivity, 2-h glucose, or hsCRP, but remained associated with fasting glucose (β=-0.05mmol/L; p=0.03) and PP (β=0.10mmHg; p=0.03). 25(OH)D remained associated with fasting glucose (β=-0.06mmol/L; p=0.02) after hsCRP and physical activity were added to the model with % body fat, age, and sex. ​These cross-sectional data suggest that associations between vitamin D and cardiometabolic risk among healthy, non-diabetic adults are largely mediated by adiposity. Large-scale intervention and mechanistic studies are needed to further investigate whether vitamin D has an independent role in the prevention and/or management of cardiometabolic risk and disease.

Keywords: 25-Hydroxyvitamin D; Cardiometabolic risk; Cardiovascular disease; Diabetes; Obesity; Vitamin D.