Sex differences in urine metabolites related with risk of diabetes using NMR spectroscopy: results of the study of health in pomerania

Recently research provides evidence that blood metabolite profiles predicted type 2 diabetes. We aimed to assess the relation of urine metabolites measured via nuclear magnetic resonance spectroscopy with incident type 2 diabetes in a sample of 1353 men and 1356 women. Within 5 years, 87 men and 50 women developed diabetes. Five and 16 urine metabolites were associated with incident diabetes in men and women, respectively. Only three of these metabolites (glucose, lactate and glycine) were found in both sexes. In women, e.g. acetate, carnitine, N,N-dimethylglycine, trigonelline, 3-hydroxyisovalerate, alanine, formate, glycolate, trimethylamine N-oxide and tau-methylhistidine were positively related with diabetes. Receiver operating characteristic (ROC) analysis revealed that compared with a standard model, a model additionally adjusted for urine glucose, trigonelline and trimethylamine N-oxide levels showed a better discrimination between incident diabetes cases and non-cases in women (AUC = 0.874 and 0.903, p = 0.019). In men, valine and 4-hydroxyphenylacetate were found as markers of diabetes. However, ROC analysis did not reveal any improvement in discrimination based on urine metabolites. In conclusion, we confirmed the potential of metabolomics to assess the risk of type 2 diabetes and detected pronounced sex differences. Moreover, we demonstrated the practicability of spot urine samples as potential non-invasive diabetes screening approach.