1269-P: Trajectories of MicroRNAs Are Associated with Trajectories of Weight but Not Fasting Blood Glucose in the Diabetes Prevention Program Trial

Abstract

Introduction: Circulating microRNAs (miRs) are emerging as promising biomarkers of risk for type 2 diabetes (T2D) and responses to risk-reduction interventions, but no prior study has examined longitudinal associations between miRs and fasting blood glucose (FBG) or weight in adults at high risk for T2D. Prior studies have been cross-sectional or only measured longitudinal outcomes. We determined the association between longitudinal trajectories of miRs, FBG, and weight in a subset of participants from the Diabetes Prevention Program (DPP). Methods: This study was a secondary analysis of a subset of participants (N=150) from DPP. A custom Fireplex assay was used to quantify 58 miRs from banked plasma samples collected at baseline, 1-year, and 2-years. Generalized linear mixed models were used to analyze associations between the miRs, FBG (mg/dL), and weight (kg) over time, adjusting for covariates (i.e., age, body mass index, race or ethnicity, gender, trial arm, and high density lipoprotein cholesterol). The Benjamini-Hochberg false discovery rate method was used to adjust for multiple comparisons. Results: The sample was 73% female, 19% Black, 14% Hispanic, and mean age was 51 ± 11 years. At baseline, the participants were normotensive, obese, and had dyslipidemia and prediabetes. After adjusting for multiple comparisons, 39 miRs were significantly associated with weight, of which 12 miRs (let-7c-5p, miR-1066-5p, miR-1287-5p, miR-133b, miR-15a-5p, miR-15b-5p, miR-181c-3p, miR-197-5p, miR-23b-5p, miR-296-5p, miR-877-5p, miR-98-5p) remained significant after adjusting for covariates. In the FBG model, none of the miRs were significant. Conclusions: Twelve miRs were associated with longitudinal weight but no miRs were associated with FBG trajectories in a subset of participants from the DPP trial. These miRs may provide mechanistic, diagnostic, or therapeutic insights about T2D prevention. Disclosure K.A.Lewis: None. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc. B.Aouizerat: None. A.M.Kanaya: None. E.Flowers: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124228, X01DK115999)