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
Creators: name: Beyene, Habtamu
name: Huynh, Kevin
name: Wang, Tingting
name: Paul, Sudip
name: Cinel, M
name: Mellett, NA
name: Olshansky, G
name: Meikle, Thomas
name: Watts, GF
name: Hung, J
name: Hui, J
name: Beilby, J
name: Blangero, J
name: Moses, EK
name: Shaw, Jonathan
name: Magliano, Dianna
name: Giles, Corey
name: Meikle, Peter
Publisher: name: La Trobe
Year: 2024
Subjects: classificationCode: 320202
subject: Clinical chemistry (incl. diagnostics)
classificationCode: 32
subject: Biomedical and clinical sciences
classificationCode: 4206
subject: Public health
classificationCode: 320507
subject: Metabolic medicine
classificationCode: 42
subject: Health sciences
subject: FOS: Health sciences
classificationCode: 3202
subject: Clinical sciences
classificationCode: 4202
subject: Epidemiology

description: 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).