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Baseline Plasma Metabolites Associated with Subsequent Response to Lifestyle Intervention in People with Prediabetes
Peace Asuzu1, Frankie Stentz1, Chi-Yang Chiu2
1Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
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.