Metabolite Alterations and Cardiometabolic Disease: A Nutritional Perspective

Background

Cardiovascular disease (CVD), type 2 diabetes (T2DM), and atrial fibrillation (AF) collectively impact millions globally, necessitating a comprehensive understanding of preceding metabolic alterations for early intervention. This thesis aims to explore metabolic shifts across populations-based cohorts and evaluate the metabolic impact of a dietary intervention.

Method

Utilizing liquid-chromatography mass spectrometry, we quantified approximately 110 metabolites in over 6000 subjects from the Malmö Preventive Project (MPP), Malmö Diet and Cancer (MDC), Malmö Offspring Study (MOS), and the Cilento dietary intervention study (CDI). Paper I investigates associations between metabolites and future atrial fibrillation in MDC. Paper II examines associations between metabolites and a healthy dietary pattern in MDC, and their associations with future CVD, T2DM, and mortality. Paper III presents a metabolite-based model for healthy dietary intake assessed in MOS, testing its association with future T2DM and CVD in MDC and MPP. Paper IV assesses the metabolic effects of a 6-day Mediterranean diet intervention among Swedish participants in the CDI.

Results

Paper I identifies 15 metabolites with significant associations with AF, particularly acylcarnitines (1). Paper II associates six metabolites with healthy dietary intake, with ergothioneine especially inversely related to CVD and overall mortality (2). Paper III's metabolic signature for healthy dietary intake associates with lower T2DM and CVD incidence in both MPP and MDC (3). Paper IV reports significant post-intervention metabolite changes, especially in the dietary related metabolome.

Discussion

This thesis provides a comprehensive analysis of metabolite alterations associated with CVD, T2DM, and AF, elucidating the relationships between metabolic and dietary pattern biomarkers and disease risk. The findings emphasize the utility of plasma metabolites as potential predictors and intermediaries in the pathways leading to these major diseases. Paper 3 and 4 combined acts as a proof of concept that plasma metabolites can be used to identify subgroups with higher risk for CVD and T2DM that might be caused by poor dietary intake Similar methods could be used to develop validated metabolic analyses as biomarkers for healthy dietary intake, with potential application in personalized preventive medicine.