Abstract 11848: Biomarkers of Glucose-Insulin Homeostasis, Randomized Treatment With Omega-3 and Vitamin D Supplementation, and Incident Type 2 Diabetes: Prospective Analysis From the Vitamin D and Omega-3 Trial (VITAL)

Introduction: Insulin resistance is central to the development of type 2 diabetes (T2D). Association between specific biomarkers of glucose-insulin homeostasis and T2D have been inconsistent. Whether vitamin D or omega-3 fatty acids (n-3 FA) can modify these associations is also unclear. Hypothesis: We hypothesized that higher insulin, C-peptide, insulin resistance score (IRS), and HbA1c are each associated with higher T2D risk, and that these associations would be attenuated among participants who received vitamin D or n-3 FA. Methods: VITAL Diabetes (NCT01633177) was a pre-specified ancillary 2x2 factorial study in the VITAL RCT to assess whether vitamin D (cholecalciferol, 2000 IU/d) or n-3 FA (EPA + DHA, 1 g/d) could prevent T2D. Subjects without baseline reported T2D and with HbA1c <6.5% were included. Incident cases were matched 1:1 on age and sex to healthy controls (N=359 pairs). Conditional logistic regression models with adjustment for demographics, risk factors including BMI, and randomized treatment were used to estimate the adjusted odds ratio (aOR) and 95% CI between baseline measurements of insulin, C-peptide, IRS (Insulinх0.0265+C-peptideх0.00511+Creatinineх-3.2641), HbA1c, and T2D. Interaction was tested between each biomarker and treatment groups (placebo vs vitamin D or n-3 FA). Results: Mean age of participants was 66 years, approximately 45% were female, and 16% were African American. Each of the glucose-insulin homeostasis biomarkers was associated with T2D risk ( Table 1 ), aOR (95% CI) per SD increment, insulin: 1.46 (1.10, 1.94), C-peptide: 1.72 (1.28, 2.31), IRS: 1.59 (1.26, 2.01), and HbA1c: 80.43 (25.90, 249.77). Biomarker associations did not differ by randomized treatment ( P interaction >0.05). Conclusions: In VITAL Diabetes, insulin, C-peptide, IRS, and HbA1c were each associated with an increased risk of T2D, independent of other risk factors. Randomization to either vitamin D or n-3 FA did not modify these associations.