Postprandial metabolite profiles associated with type 2 diabetes clearly stratify individuals with impaired fasting glucose.

Introduction: Fasting metabolite profiles have been shown to distinguish type 2 diabetes (T2D) patients from normal glucose tolerance (NGT) individuals.

Objectives: We investigated whether, besides fasting metabolite profiles, postprandial metabolite profiles associated with T2D can stratify individuals with impaired fasting glucose (IFG) by their similarities to T2D.

Methods: Three groups of individuals (age 45-65 years) without any history of IFG or T2D were selected from the Netherlands Epidemiology of Obesity study and stratified by baseline fasting glucose concentrations (NGT (n = 176), IFG (n = 186), T2D (n = 171)). 163 metabolites were measured under fasting and postprandial states (150 min after a meal challenge). Metabolite profiles specific for a high risk of T2D were identified by LASSO regression for fasting and postprandial states. The selected profiles were utilised to stratify IFG group into high (T2D probability ≥ 0.7) and low (T2D probability ≤ 0.5) risk subgroups. The stratification performances were compared with clinically relevant metabolic traits.

Results: Two metabolite profiles specific for T2D (nfasting  = 12 metabolites, npostprandial  = 4 metabolites) were identified, with all four postprandial metabolites also being identified in the fasting state. Stratified by the postprandial profile, the high-risk subgroup of IFG individuals (n = 72) showed similar glucose concentrations to the low-risk subgroup (n = 57), yet a higher BMI (difference: 3.3 kg/m2 (95% CI 1.7-5.0)) and postprandial insulin concentrations (21.5 mU/L (95% CI 1.8-41.2)).

Conclusion: Postprandial metabolites identified T2D patients as good as fasting metabolites and exhibited enhanced signals for IFG stratification, which offers a proof of concept that metabolomics research should not focus on the fasting state alone.