Metabolite traits and genetic risk provide complementary information for the prediction of future type 2 diabetes

Diabetes Care. 2014 Sep;37(9):2508-14. doi: 10.2337/dc14-0560. Epub 2014 Jun 19.


Objective: A genetic risk score (GRS) comprised of single nucleotide polymorphisms (SNPs) and metabolite biomarkers have each been shown, separately, to predict incident type 2 diabetes. We tested whether genetic and metabolite markers provide complementary information for type 2 diabetes prediction and, together, improve the accuracy of prediction models containing clinical traits.

Research design and methods: Diabetes risk was modeled with a 62-SNP GRS, nine metabolites, and clinical traits. We fit age- and sex-adjusted logistic regression models to test the association of these sources of information, separately and jointly, with incident type 2 diabetes among 1,622 initially nondiabetic participants from the Framingham Offspring Study. The predictive capacity of each model was assessed by area under the curve (AUC).

Results: Two hundred and six new diabetes cases were observed during 13.5 years of follow-up. The AUC was greater for the model containing the GRS and metabolite measurements together versus GRS or metabolites alone (0.820 vs. 0.641, P < 0.0001, or 0.820 vs. 0.803, P = 0.01, respectively). Odds ratios for association of GRS or metabolites with type 2 diabetes were not attenuated in the combined model. The AUC was greater for the model containing the GRS, metabolites, and clinical traits versus clinical traits only (0.880 vs. 0.856, P = 0.002).

Conclusions: Metabolite and genetic traits provide complementary information to each other for the prediction of future type 2 diabetes. These novel markers of diabetes risk modestly improve the predictive accuracy of incident type 2 diabetes based only on traditional clinical risk factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Logistic Models
  • Male
  • Metabolome / genetics*
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors