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Metabolite Alterations and Cardiometabolic Disease: A Nutritional Perspective

Smith, Einar LU (2024) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • professor Landberg, Rikard, Chalmers University of Technology
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Metabolomics, Nutrition, Nutritional metabolomics, Biomarkers, Cardiometabolic disease, Cardiovascular disease, Type 2 diabetes, Prospective cohort studies, Dietary intervention
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2024:57
pages
72 pages
publisher
Lund University, Faculty of Medicine
defense location
Aulan, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö
defense date
2024-05-08 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-550-3
language
English
LU publication?
yes
id
ff512729-522f-4fcd-95f0-9db56a69c3fa
date added to LUP
2024-03-22 15:15:35
date last changed
2024-04-11 12:19:17
@phdthesis{ff512729-522f-4fcd-95f0-9db56a69c3fa,
  abstract     = {{<p class="tabeltext">Background</p><br>
<br>
<p class="tabeltext">Cardiovascular<br>
disease (CVD), type 2 diabetes (T2DM), and atrial fibrillation (AF)<br>
collectively impact millions globally, necessitating a comprehensive<br>
understanding of preceding metabolic alterations for early intervention. This<br>
thesis aims to explore metabolic shifts across populations-based cohorts and<br>
evaluate the metabolic impact of a dietary intervention.</p><br>
<br>
<p class="tabeltext">Method</p><br>
<br>
<p class="tabeltext">Utilizing<br>
liquid-chromatography mass spectrometry, we quantified approximately 110<br>
metabolites in over 6000 subjects from the Malmö Preventive Project (MPP),<br>
Malmö Diet and Cancer (MDC), Malmö Offspring Study (MOS), and the Cilento<br>
dietary intervention study (CDI). Paper I investigates associations between<br>
metabolites and future atrial fibrillation in MDC. Paper II examines<br>
associations between metabolites and a healthy dietary pattern in MDC, and<br>
their associations with future CVD, T2DM, and mortality. Paper III presents a<br>
metabolite-based model for healthy dietary intake assessed in MOS, testing its<br>
association with future T2DM and CVD in MDC and MPP. Paper IV assesses the<br>
metabolic effects of a 6-day Mediterranean diet intervention among Swedish<br>
participants in the CDI.</p><br>
<br>
<p class="tabeltext">Results</p><br>
<br>
<p class="tabeltext">Paper I<br>
identifies 15 metabolites with significant associations with AF, particularly<br>
acylcarnitines (1). Paper II associates six<br>
metabolites with healthy dietary intake, with ergothioneine especially<br>
inversely related to CVD and overall mortality (2). Paper III's metabolic signature<br>
for healthy dietary intake associates with lower T2DM and CVD incidence in both<br>
MPP and MDC (3). Paper IV reports significant<br>
post-intervention metabolite changes, especially in the dietary related<br>
metabolome.</p><br>
<br>
<p class="tabeltext">Discussion</p><br>
<br>
<p class="tabeltext">This<br>
thesis provides a comprehensive analysis of metabolite alterations associated<br>
with CVD, T2DM, and AF, elucidating the relationships between metabolic and<br>
dietary pattern biomarkers and disease risk. The findings emphasize the utility<br>
of plasma metabolites as potential predictors and intermediaries in the pathways<br>
leading to these major diseases. Paper 3 and 4 combined acts as a proof of<br>
concept that plasma metabolites can be used to identify subgroups with higher<br>
risk for CVD and T2DM that might be caused by poor dietary intake Similar<br>
methods could be used to develop validated metabolic analyses as biomarkers for<br>
healthy dietary intake, with potential application in personalized preventive<br>
medicine.<i/></p>}},
  author       = {{Smith, Einar}},
  isbn         = {{978-91-8021-550-3}},
  issn         = {{1652-8220}},
  keywords     = {{Metabolomics; Nutrition; Nutritional metabolomics; Biomarkers; Cardiometabolic disease; Cardiovascular disease; Type 2 diabetes; Prospective cohort studies; Dietary intervention}},
  language     = {{eng}},
  number       = {{2024:57}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Metabolite Alterations and Cardiometabolic Disease: A Nutritional Perspective}},
  url          = {{https://lup.lub.lu.se/search/files/177856135/Kappa_Einar_Smith_.pdf}},
  year         = {{2024}},
}