Development and validation of a plasmalogen score as an independent modifiable marker of metabolic health: population based observational studies and a placebo-controlled cross-over study.

Tingting Wang, Gavriel Olshansky, Michelle Cinel, Habtamu B Beyene, Thomas G Meikle, Jonathan E Shaw, Dianna J Magliano, Gerald F Watts, John Blangero, Sudip Paul, Peter J Meikle, Kevin Huynh, Natalie A Mellett, Corey Giles, Jennie Hui, John Beilby, Joseph Hung, Eric K Moses

Journal: EBioMedicine 2024;105():105187

PMID: 38861870

Free Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Decreased levels of circulating ethanolamine plasmalogens [PE(P)], and a concurrent increase in phosphatidylethanolamine (PE) are consistently reported in various cardiometabolic conditions. Here we devised, a plasmalogen score (Pls Score) that mirrors a metabolic signal that encompasses the levels of PE(P) and PE and captures the natural variation in circulating plasmalogens and perturbations in their metabolism associated with disease, diet, and lifestyle.

METHODS

We utilised, plasma lipidomes from the Australian Obesity, Diabetes and Lifestyle study (AusDiab; n = 10,339, 55% women) a nationwide cohort, to devise the Pls Score and validated this in the Busselton Health Study (BHS; n = 4,492, 56% women, serum lipidome) and in a placebo-controlled crossover trial involving Shark Liver Oil (SLO) supplementation (n = 10, 100% men). We examined the association of the Pls Score with cardiometabolic risk factors, type 2 diabetes mellitus (T2DM), cardiovascular disease and all-cause mortality (over 17 years).

FINDINGS

In a model, adjusted for age, sex and BMI, individuals in the top quintile of the Pls Score (Q5) relative to Q1 had an OR of 0.31 (95% CI 0.21-0.43), 0.39 (95% CI 0.25-0.61) and 0.42 (95% CI 0.30-0.57) for prevalent T2DM, incident T2DM and prevalent cardiovascular disease respectively, and a 34% lower mortality risk (HR = 0.66; 95% CI 0.56-0.78). Significant associations between diet and lifestyle habits and Pls Score exist and these were validated through dietary supplementation of SLO that resulted in a marked change in the Pls Score.

INTERPRETATION

The Pls Score as a measure that captures the natural variation in circulating plasmalogens, was not only inversely related to cardiometabolic risk and all-cause mortality but also associate with diet and lifestyle. Our results support the potential utility of the Pls Score as a biomarker for metabolic health and its responsiveness to dietary interventions. Further research is warranted to explore the underlying mechanisms and optimise the practical implementation of the Pls Score in clinical and population settings.

FUNDING

National Health and Medical Research Council (NHMRC grant 233200), National Health and Medical Research Council of Australia (Project grant APP1101320), Health Promotion Foundation of Western Australia, and National Health and Medical Research Council of Australia Senior Research Fellowship (#1042095).

Address: Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia; Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia.; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia; Baker Department of Cardiometabolic Health, Melbourne University, Melbourne, VIC, Australia.; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia.; Medical School, University of Western Australia, Perth, WA, Australia; Cardiometabolic Service, Department of Cardiology and Internal Medicine, Royal Perth Hospital, Perth, WA, Australia.; Medical School, University of Western Australia, Perth, WA, Australia.; PathWest Laboratory Medicine of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, WA, Australia; School of Population and Global Health, University of Western Australia, Crawley, WA, Australia.; School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia.; South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, USA.; School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia; Baker Department of Cardiometabolic Health, Melbourne University, Melbourne, VIC, Australia. Electronic address: [email protected].; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia; Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Melbourne, VIC, Australia; Baker Department of Cardiometabolic Health, Melbourne University, Melbourne, VIC, Australia. Electronic address: [email protected].

DOI: 10.1016/j.ebiom.2024.105187

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MeSH Terms: Humans, Plasmalogens, Biomarkers, Female, Male, Middle Aged, Diabetes Mellitus, Type 2, Australia, Cross-Over Studies, Adult, Cardiovascular Diseases, Aged, Phosphatidylethanolamines, Life Style, Cardiometabolic Risk Factors