Plasma metabolite predictors of metabolic syndrome incidence and reversion
Background:
Metabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known on metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion.
Methods:
The study included 1,468 participants without cardiovascular disease but at high cardiovascular risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) trial with baseline metabolomics data. MetS was defined in accordance with the updated harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria. MetS incidence was defined by not having MetS at baseline but meeting the MetS criteria at a follow-up visit. MetS reversion was defined by MetS at baseline but not meeting MetS criteria at a follow-up visit. Plasma metabolome was profiled by LC-MS. Multivariable-adjusted Cox regression models and elastic net regularized regressions were used to assess the association between 385 known metabolites and MetS incidence or reversion after adjusting for potential risk factors.
Results:
Of the 603 participants without baseline MetS, 298 developed MetS over the median 4.4-year follow-up. Of the 865 participants with baseline MetS, 285 experienced MetS reversion. A total of 103 and 88 individual metabolites were associated with MetS incidence and MetS reversion, respectively, after adjusting for confounders and false discovery rate correction. A metabolomic signature comprised of 77 metabolites was robustly associated with MetS incidence (HR per +1 SD: 1.56 (95%CI: 1.33-1.83)), and a metabolomic signature of 83 metabolites associated with MetS reversion (HR per +1 SD: 1.44 (95%CI: 1.25-1.67)), both p<0.001. C34:2 phosphatidylethanolamine plasmalogen, isoleucine, and C2 carnitine were the top positive metabolites (based on the beta-coefficients) from the MetS incidence signature, while C38:2 phosphatidylcholine, phenylacetylglutamine and ribothymidine the top negative metabolites. From the MetS reversion signature, C18:2 lipophosphatidylcholine, histidine, and C34:3 phosphatidylcholine plasmalogen were the top positive metabolites, and alanine, fructose-glucose-galactose, and C36:4 phosphatidylethanolamine plasmalogen the top negative metabolites.
Conclusion:
We identified unique metabolomic signatures, which included several plasma lipids and amino acids, associated with MetS incidence and reversion.
Keywords:
Metabolomics, Metabolic Syndrome
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