Lipidomic risk score independently and cost-effectively predicts risk of future type 2 diabetes: Results from diverse cohorts

Manju Mamtani, Hemant Kulkarni, Gerard Wong, Jacquelyn M. Weir, Christopher K Barlow, Thomas D. Dyer, Laura Almasy, Michael C. Mahaney, Anthony G. Comuzzie, David C. Glahn, Dianna J. Magliano, Paul Zimmet, Jonathan Shaw, Sarah Williams-Blangero, Ravindranath Duggirala, John Blangero, Peter J. Meikle, Joanne E. Curran

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

Background: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening. Methods: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The LRS derived from SAFHS as well as its recalibrated version were validated in an independent cohort from Australia -The AusDiab cohort. The participants were T2D-free at baseline and followed for 9197 person-years in the SAFHS cohort (n = 771) and 5930 person-years in the AusDiab cohort (n = 644). Statistically and clinically improved T2D prediction was evaluated with established statistical parameters in both cohorts. Modeling studies were conducted to determine whether the use of LRS would be cost-effective for T2D screening. The main outcome measures included accuracy and incremental value of the LRS over routinely used clinical predictors of T2D risk; validation of these results in an independent cohort and cost-effectiveness of including LRS in screening/intervention programs for T2D. Results: The LRS was based on plasma concentration of dihydroceramide 18:0, lysoalkylphosphatidylcholine 22:1 and triacyglycerol 16:0/18:0/18:1. The score predicted future T2D independently of prediabetes with an accuracy of 76 %. Even in the subset of initially euglycemic individuals, the LRS improved T2D prediction. In the AusDiab cohort, the LRS continued to predict T2D significantly and independently. When combined with risk-stratification methods currently used in clinical practice, the LRS significantly improved the model fit (p < 0.001), information content (p < 0.001), discrimination (p < 0.001) and reclassification (p < 0.001) in both cohorts. Modeling studies demonstrated that LRS-based risk-stratification combined with metformin supplementation for high-risk individuals was the most cost-effective strategy for T2D prevention. Conclusions: Considering the novelty, incremental value and cost-effectiveness of LRS it should be used for risk-stratification of future T2D.

Original languageEnglish
Article number67
Number of pages12
JournalLipids in Health and Disease
Volume15
DOIs
Publication statusPublished - 4 Apr 2016
Externally publishedYes

Keywords

  • Diabetes
  • Diagnostic tools
  • Endocrine disorders
  • Genetics
  • Lipidomics

Cite this