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

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.