Identification of putative biomarkers for type 2 diabetes using metabolomics in the Korea Association REsource (KARE) cohort

Heun Sik Lee, Tao Xu, Young Lee, Nam Hee Kim, Yeon Jung Kim, Jeong Min Kim, Sang Yun Cho, Kwang Youl Kim, Moonsuk Nam, Jerzy Adamski, Karsten Suhre, Wolfgang Rathmann, Annette Peters, Rui Wang-Sattler, Bok Ghee Han, Bong Jo Kim

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6 Citations (Scopus)


Introduction: Type 2 diabetes (T2D) is a multifactorial disease resulting from a complex interaction between environmental and genetic risk factors. Metabolomics provide a logical framework that reflects the functional endpoints of biological processes being triggered by genetic information and various external influences. Objectives: Identification of metabolite biomarkers can shed insight into etiological pathways and improve the prediction of disease risk. Here, we aimed to identify serum metabolites as putative biomarkers for T2D and their association with genetic variants in the Korean population. Methods: A targeted metabolomics approach was employed to quantify serum metabolites for 2240 participants in the Korea Association REsource (KARE) cohort. T2D-related metabolites were identified by statistical methods including multivariable linear and logistic regression, and were independently replicated in the Cooperative Health Research in the Region of Augsburg (KORA) cohort. Additionally, by combining a genome wide association study (GWAS) with metabolomics, genetic variants associated with the identified T2D-related metabolites were uncovered. Results: 123 metabolites were quantified from fasting serum samples and four metabolites, hexadecanoylcarnitine (C16), glycine, lysophosphatidylcholine acyl C18:2 (lysoPC a C18:2), and phosphatidylcholine acyl-alkyl C36:0 (PC ae C36:0), were significantly altered in T2D compared to non-T2D subjects (after the Bonferroni correction for multiple testing with P < 4.07E − 04, α = 0.05). Among them, C16, glycine, and lysoPC a C18:2 were independently replicated in the KORA cohort. Alterations of these metabolites were associated with ten genetic loci including six that were previously implicated in T2D or obesity. Conclusion: Using a targeted-metabolomics and in combination with GWAS approach, we identified three serum metabolites associated with risk of T2D in both the KARE and KORA cohort and discovered ten genetic variants in relation to the identified metabolites. These findings provide a better understanding to develop novel preventive strategies for T2D in the Korean population.

Original languageEnglish
Article number178
Issue number12
Publication statusPublished - 1 Dec 2016



  • Cohort study
  • Genetic variants
  • Korean population
  • Serum metabolites
  • Targeted metabolomics
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

Lee, H. S., Xu, T., Lee, Y., Kim, N. H., Kim, Y. J., Kim, J. M., Cho, S. Y., Kim, K. Y., Nam, M., Adamski, J., Suhre, K., Rathmann, W., Peters, A., Wang-Sattler, R., Han, B. G., & Kim, B. J. (2016). Identification of putative biomarkers for type 2 diabetes using metabolomics in the Korea Association REsource (KARE) cohort. Metabolomics, 12(12), [178].