187-OR: Circulating MicroRNAs Predict Weight Loss in Participants from the Diabetes Prevention Program

Abstract

Introduction: Weight loss is an important strategy for prevention of type 2 diabetes (T2D). Circulating microRNAs (miRs) are emerging as promising biomarkers of risk for T2D and responses to risk reduction interventions. The purpose of this study was to determine whether baseline microRNAs predict weight loss in a subset of participants in the Diabetes Prevention Program (DPP). Methods: This study was a secondary analysis of a subset of participants from DPP (n=150, equally stratified by trial arm (intensive lifestyle, metformin, and placebo)). MiRs (58 total) were measured in banked plasma from the baseline timepoint using a custom Fireplex assay. Lasso was used to apply shrinkage for feature selection to identify a composite score of optimal miR predictors and logistic regression was used to model >7% weight loss after 2 years. Results: Five miRs (miR-122, miR-151a, miR-192, miR-197, miR-23b) were identified as the optimal predictors of weight loss using Lasso. After adjustment for significant covariates (age, gender, race or ethnicity, and trial arm), the odds ratio of composite score for >7% weight loss was 3.16 (95% confidence interval (CI) 1.62, 6.18; p<0.001). There was no significant interaction between the composite score and the trial arms (p=0.239), where odds ratio of composite score in the metformin arm, the intensive lifestyle arm and placebo are 1.16, 4.67, 2.42, respectively. Five-fold cross validation showed an accuracy score of 80%. The area under the receiver operating characteristic curve for >7% weight loss after 2-years was 0.85. Conclusions: MiRs are significant predictors of weight loss for prevention of T2D. Future directions include external validation in order to determine whether this risk score may have clinical utility, and functional analysis of the potential genes and pathways targeted by the miRs that were included in the risk score. Disclosure X.Gong: None. K.A.Lewis: None. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc. B.Aouizerat: None. A.M.Kanaya: None. L.Zhang: None. E.Flowers: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124228, X01DK115999)