Abstract 18688: Plasma Lipid Profiling to Predict Cardiovascular Events in Type 2 Diabetes
Introduction: Type 2 diabetes (T2D) is a major risk factor for cardiovascular disease (CVD). Within this group there is an imperative to identify those at highest risk to focus intensive intervention strategies. Dyslipidaemia is a risk factor for cardiovascular events (CVE), including myocardial infarction (MI), stroke and CVD death. However, traditional lipid measurements do not show the full complexity of the dyslipidemia associated with T2D or CVD. In this study we have applied a lipidomic strategy to identify novel plasma lipids that are associated with CVE outcomes in patients with T2D. We propose that use of these lipid biomarkers will assist the development of risk stratification models that improve CVD risk prediction in patients with T2D.
Methods: Plasma lipid profiles containing 310 lipids were measured using electrospray-ionisation tandem mass spectrometry on 3779 individuals selected from the (ADVANCE) study in a case/cohort design. The cohort consisted of T2D patients who had a CVE during the 5-year follow up (n=612) and T2D patients who did not have CVE (n=3167). Weighted cox regression was used to identify those lipid species associated with future CVE.
Results: We observed significant associations between 47 lipid species and CVE (p<0.05, corrected for multiple comparison using Benjamini-Hochberg approach). Species of ceramide, glycosphingolipids, sphingomyelin, phosphatidylcholine, alkylphosphatidylcholine, alkenylphosphatidylcholine, lysophosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylethanolamine, cholesteryl ester, diacylglycerol and triacylglycerol were significantly associated with future CVE. Glycosphingolipids showed the strongest positive associations with future CVE. Interestingly, ether linked phospholipids were also positively associated with CVE while phospholipid and glycerolipid species containing omega-3 and -6 polyunsaturated fatty acids (n-3 and n-6 PUFA) showed negative associations with CVE.
Summary: This is the single largest lipidomic profiling study to date. The strong associations observed suggest that plasma lipids may represent new therapeutic targets and biomarkers for risk stratification for CVE in T2D.
Author Disclosures: Z.H. Alshehry: None. G. Wong: None. P.A. Mundra: None. C.K. Barlow: None. N.A. Mellett: None. S. Zoungas: None. G.S. Hillis: None. J. Chalmers: None. M. Woodward: None. P.J. Meikle: None.
- © 2014 by American Heart Association, Inc.