Non-targeted metabolomic biomarkers and metabotypes of type 2 diabetes: A cross-sectional study of PREDIMED trial participants

Diabetes Metab. 2019 Apr;45(2):167-174. doi: 10.1016/j.diabet.2018.02.006. Epub 2018 Feb 20.

Abstract

Aim: To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D.

Methods: A metabolomics analysis using the 1H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively. Metabotypes associated with T2D were identified using the k-means algorithm.

Results: A total of 33 metabolites were significantly different (P<0.05) between T2D and non-T2D participants. The multi-metabolite signature of T2D comprised high levels of methylsuccinate, alanine, dimethylglycine and guanidoacetate, and reduced levels of glutamine, methylguanidine, 3-hydroxymandelate and hippurate, and had a 96.4% AUC, which was higher than the metabolites on their own and glucose. Amino-acid and carbohydrate metabolism were the main metabolic alterations in T2D, and various metabotypes were identified in the studied population. Among T2D participants, those with a metabotype of higher levels of phenylalanine, phenylacetylglutamine, p-cresol and acetoacetate had significantly higher levels of plasma glucose.

Conclusion: The multi-metabolite signature of T2D highlights the altered metabolic fingerprint associated mainly with amino-acid, carbohydrate and microbiota metabolism. Metabotypes identified in this patient population could be related to higher risk of long-term cardiovascular events and therefore require further studies. Metabolomics is a useful tool for elucidating the metabolic complexity and interindividual variation in T2D towards the development of stratified precision nutrition and medicine. Trial registration at www.controlled-trials.com: ISRCTN35739639.

Keywords: Metabolomics; Metabotypes; Multi-metabolite signature; NMR; PREDIMED; Type 2 diabetes.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers* / analysis
  • Biomarkers* / metabolism
  • Cardiovascular Diseases / prevention & control
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / classification*
  • Diabetes Mellitus, Type 2 / diet therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetic Angiopathies / prevention & control
  • Diet, Mediterranean
  • Female
  • Humans
  • Male
  • Metabolome / physiology*
  • Metabolomics / methods*
  • Middle Aged
  • Risk Factors
  • Urinalysis / methods

Substances

  • Biomarkers