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Metabolite Alterations and Cardiometabolic Disease: A Nutritional Perspective

In English

Författare

Summary, in English

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.

Publiceringsår

2024

Språk

Engelska

Publikation/Tidskrift/Serie

Lund University, Faculty of Medicine Doctoral Dissertation Series

Issue

2024:57

Dokumenttyp

Doktorsavhandling

Förlag

Lund University, Faculty of Medicine

Ämne

  • Endocrinology and Diabetes

Nyckelord

  • Metabolomics
  • Nutrition
  • Nutritional metabolomics
  • Biomarkers
  • Cardiometabolic disease
  • Cardiovascular disease
  • Type 2 diabetes
  • Prospective cohort studies
  • Dietary intervention

Status

Published

Forskningsgrupp

  • Cardiovascular Research - Hypertension

ISBN/ISSN/Övrigt

  • ISSN: 1652-8220
  • ISBN: 978-91-8021-550-3

Försvarsdatum

8 maj 2024

Försvarstid

09:00

Försvarsplats

Aulan, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö

Opponent

  • Rikard Landberg (professor)