Baseline plasma metabolites associated with subsequent response to lifestyle intervention in people with prediabetes

Abstract Context Plasma metabolites have been associated with the development of type 2 diabetes (T2D) and prediabetes. Objective To test the hypothesis that baseline metabolites predict response to lifestyle intervention (LI) in people with prediabetes. Design Longitudinal cohort study. Setting Academic health center. Participants Adults with prediabetes enrolled in the 5-year Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study. Interventions PROP-ABC participants received LI for 5 years. Assessments included anthropometry, fasting and 2-hour plasma glucose (2hrPG), insulin sensitivity and secretion, and plasma metabolites (18 amino acids, 45 acylcarnitines, and 54 sphingolipids) measured with liquid chromatography tandem mass spectrometry. Main Outcome Measure The primary outcome was glycemic response during 5 years of LI. The present report assessed baseline metabolites as predictors of persistent prediabetes vs reversion to normal glucose regulation (NGR) (10 subjects with T2D were excluded). Results Participants with persistent prediabetes or NGR post-LI showed significant baseline differences in specific metabolites. In logistic regression models, the odds ratio per 1-SD [95% CI] for persistent prediabetes were 2.405 [1.341-4.312], P = .0032 for 2hrPG and 1.850 [1.047-3.271], P = .034 for ceramide C18:0/C18:1 ratio, adjusted for age, sex, race, adiposity, insulin sensitivity and secretion, and percentage changes in weight and waist circumference. Conclusion Out of 117 metabolites examined in adults with prediabetes, higher baseline levels of 2hrPG and the saturated/monounsaturated ratio of stearic acid ceramide (C18:0/C18:1) emerged as potential candidate biomarkers for the outcome of persistent prediabetes vs reversion to normoglycemia in response to LI.