de Courten Barbora
Published: 2017
Total Pages:
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Background:Vitamin D supplementation has been proposed as a potential strategy for preventing type 2 diabetes and cardiovascular disease (CVD). Existing clinical trials are limited by short durations, low doses of vitamin D, variability in participantsu2019 vitamin D deficiency status, and use of surrogate measures of body composition, insulin sensitivity, and insulin secretion. Aims:To address existing knowledge gaps, we conducted a double-blind randomized placebo-controlled trial to investigate whether vitamin D supplementation, provided in a sufficient dose and duration to vitamin D-deficient individuals, would improve cardiometabolic risk factors including body fat, insulin sensitivity and secretion as measured by gold-standard methods, as well as blood pressure, serum lipids and high-sensitivity C-reactive protein (hsCRP) concentrations. We hypothesized that vitamin D supplementation would improve cardiometabolic risk factors, compared to placebo. Methods:Sixty-five overweight or obese (body mass index (BMI)u2265 25 kg/m2), vitamin D-deficient (25-hydroxyvitamin D (25OH)D)u2264 50 nmol/L) adults were randomized to either a bolus oral dose of 100,000 IU followed by 4,000 IU daily of cholecalciferol, or matching placebo for 16 weeks. Before and after intervention, participants had gold-standard assessment of body composition (% body fat by dual energy X-ray absorptiometry), insulin sensitivity (hyperinsulinemic-euglycemic clamps) and total, first phase, and second phase insulin secretion (intravenous glucose tolerance tests), as well as measurement of BMI, waist-to-hip ratio (WHR), blood pressure, pulse pressure (PP), mean arterial pressure (MAP), serum lipids (ELISA), and hsCRP (immunoturbidimetric assay). Multivariable regression was performed to assess differences between groups after adjustment for clinically relevant factors, and all analyses were adjusted for multiple testing using Bonferroni correction.Results:Fifty-four participants completed the study (35M/19F; age= 31.9 u00b1 8.5 years; BMI= 30.9 u00b1 4.4 kg/m2 (mean u00b1 SD)). Serum 25(OH)D increased with vitamin D supplementation compared to placebo (57.0 u00b1 21.3 versus 1.9 u00b1 15.1nmol/L, p=0.02). Vitamin D and placebo groups did not differ in change in anthropometric measures including BMI (0.003 u00b1 0.9 versus -0.1 u00b1 1.2, p= 0.9), WHR (-0.01 u00b1 0.04 versus 0.001 u00b1 0.01) or % body fat (-0.4 u00b1 1.6 versus -0.3 u00b1 1.7, p=0.9). There were no differences between vitamin D and placebo groups in markers of glucose metabolism, including fasting glucose (0.04 u00b1 0.5 versus 0.2 u00b1 0.4 mmol/l, p=0.9), fasting insulin (0.1 u00b1 5.9 versus 2.1 u00b1 6.3 mlU/L) insulin sensitivity (0.02 u00b1 2.0 versus -0.03 u00b1 2.8mg/kg/min, p=0.9) or total insulin secretory response (insulin area under the curve (AUC)) (-6.9 u00b1 843 versus 130 u00b1 1092 mlU/L, p=0.9), respectively. First phase insulin AUC (-21 u00b1 212 versus 24 u00b1 184 mlU/L, p=0.9) and second phase insulin AUC (13 u00b1 598 versus 124 u00b1 818 mlU/L, p=0.9) also did not differ between vitamin D and placebo groups, respectively. Cardiovascular parameters including systolic and diastolic blood pressure, PP, MAP, serum lipids (total, high-, and low- density lipoprotein cholesterol, or triglycerides) and hsCRP concentrations did not differ between groups (all p>0.1). Results remained non-significant in multivariable logistic regression models after adjustment for age, sex, and % body fat (all p>0.1), and after further adjustment for ethnicity, sun exposure, physical activity, and dietary vitamin D intake (all p>0.1).Discussion:Vitamin D supplementation does not improve cardiometabolic risk factors in vitamin D-deficient, overweight or obese adults, despite using high dose vitamin D supplementation and robust endpoint measures. It is therefore unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk, even in vitamin D-deficient populations.