Abstract 12860: Effects of Marine Omega-3 and Vitamin D Supplementation on Circulating Biomarkers of Glucose-Insulin Homeostasis and Incident Cardiovascular Disease in the Vitamin D and Omega-3 Trial (VITAL)

Introduction: Dysglycemia and insulin resistance increase cardiovascular disease (CVD) risk. Associations between specific glucose-insulin biomarkers and CVD have been inconsistent. Hypothesis: We hypothesized that higher insulin, C-peptide, insulin resistance score (IRS), and HbA1c are associated with incident CVD and coronary heart disease (CHD) events and that both vitamin D and omega-3 fatty acids (n-3 FA) would improve these biomarkers and attenuate their risks with CVD. Methods: VITAL (NCT01169259) was a 2x2 factorial design RCT testing vitamin D (cholecalciferol, 2000 IU/d) and n-3 FA (EPA+DHA, 1 g/d) for the primary prevention of CVD. Incident CVD cases [non-fatal myocardial infarction (MI), non-fatal stroke, or CV death] were matched 1:1 on age and sex to healthy controls (n=715 CVD pairs including 423 CHD [MI, revascularization, CHD death] pairs). Conditional logistic regression adjusting for demographics, CV risk factors, and randomized treatment was used to assess the adjusted odds ratio (aOR) and 95% CI between baseline levels of insulin, C-peptide, IRS (Insulinх0.0265+C-peptideх0.00511+Creatinineх-3.2641), and HbA1c with risk of CVD and CHD events. In control participants, we examined the randomized effects of vitamin D or n-3 FA on changes in these biomarkers at 1- or 2-years follow-up. Results: Mean age of participants was 71 years, approximately 42% were female, and 12% were African American. Baseline insulin, C-peptide, and IRS were not associated with CVD ( Figure 1 ). HbA1c was associated with CVD risk, aOR (95% CI) per SD increment, 1.17 (1.01, 1.38). Of the 4 biomarkers, only IRS was associated with CHD risk, aOR (95% CI): 1.22 (1.01, 1.46). Randomization to vitamin D or n-3 FA did not modify levels of these biomarkers or their associations. Conclusions: HbA1c was significantly associated with CVD risk, whereas IRS was associated with CHD risk. Neither vitamin D nor n-3 FA appreciably modified these biomarker levels or their risk associations.