Baseline Plasma Metabolites Associated with Subsequent Response to Lifestyle Intervention in People with Prediabetes

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ID: 330790
2026
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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-hr plasma glucose (FPG, 2hrPG), insulin sensitivity and secretion, and plasma metabolites (18 amino acids, 45 acylcarnitines, 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 versus 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% confidence intervals] for persistent prediabetes were 2.405 [1.341-4.312], P = 0.0032 for 2hrPG and 1.850 [1.047- 3.271], P = 0.034 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. CONCLUSIONS: 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 versus reversion to normoglycemia in response to lifestyle intervention.
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Authors Peace Asuzu, Frankie B. Stentz, Chi‐Yang Chiu, Jim Y. Wan, Nawajes A. Mandal, Samuel E. Dagogo-Jack
Journal the journal of clinical endocrinology & metabolism
Year 2026
DOI
10.1210/clinem/dgag403
URL
https://doi.org/10.1210/clinem/dgag403
Keywords Keywords not found

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