Title: Inflammatory markers from the Kynurenine Pathway: Runway for
Cardiovascular disease in Diabetes?
Collaborators: Dr. Simone JPM Eussen (contact: [email protected]),
Prof. Pieter C Dagnelie, Prof. Coen DA Stehouwer
Proposal:
Introduction: Inflammatory markers from the kynurenine pathway (kynurenines) have been associated with
phenotypes for diabetes and cardiovascular disease (CVD).
Hypothesis and Objectives:
Hypotheses:
1. Aberrant concentrations of metabolites from the kynurenine pathway are involved in the development and
progression of diabetes and CVD
2. Kynurenines modify the association between diabetes and CVD.
Specific research questions:
1. Are plasma concentrations of kynurenines at baseline associated with changes in insulin sensitivity and βcell function over time?
2. Are plasma concentrations of kynurenines associated with indicators of atherosclerosis, arterial stiffness,
blood pressure, heart function and structure, and cardiac arrhythmia?
3. Do plasma kynurenines affect the association between diabetes and CVD?
Setting and Methods:
This is the first research that combines a large panel of kynurenine metabolites with detailed and extensive
metabolic and vascular phenotypes for diabetes and CVD, and will be conducted within the framework of
CODAM and Maastricht Study (www.demaastrichtstudie.nl).
Impact: Given the strong positive preliminary associations of kynurenines with diabetes and CVD, it is likely
that findings will contribute to knowledge on biological markers for diabetes and CVD, and thereby also
improve diagnosis of these etiologies. Moreover, results will give insight into common pathways for diabetes
and CVD. Further, since diet and lifestyle can have major effects on kynurenine metabolism, the current
research may also provide dietary guidelines to prevent or delay the onset of type 2 diabetes and its
complications. It is anticipated that insight in this pathway may contribute to formulate specific dietary and
lifestyle recommendations to reduce the burden of diabetes.
Requirements candidate: Background in Medicine, Biology, or Immunology/Inflammation
Basic knowledge on epidemiology and/or statistical analyses
Keywords:
Inflammation, diet, diabetes, cardiovascular disease (CVD), epidemiology, statistics
Selected publications:
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Zuo H, Ueland PM, Ulvik A, Eussen SJ, Vollset SE, Nygård O, Midttun Ø, Theofylaktopoulou D, Meyer K, Tell
GS. Plasma Biomarkers of Inflammation, the Kynurenine Pathway, and Risks of All-Cause, Cancer, and
Cardiovascular Disease Mortality: The Hordaland Health Study. Am J Epidemiol. 2016;183(4):249-58.
Eussen SJPM, Ueland PM, Vollset SE, Nygård O, Midttun Ø, Sulo G, Ulvik A, Meyer K, Pedersen ER, Tell GS.
Kynurenines as predictors of acute coronary events in the Hordaland Health Study. Int J Cardiol.
2015;189:18-24
Pedersen ER, Tuseth N, Eussen SJPM, Ueland PM, Strand E, Svingen GF, Midttun Ø, Meyer K, Mellgren G,
Ulvik A, Nordrehaug JE, Nilsen DW, Nygård O.. Associations of plasma kynurenines with risk of acute
myocardial infarction in patients with stable angina pectoris. Arterioscler Thromb Vasc Biol.
2015;35(2):455-62
Theofylaktopoulou D, Midttun Ø, Hustad S, Ulvik A, Nygård, OK, Tell GS, Ueland PM, Ulvik A, Vollset SE,
Eussen SJPM. Vitamins B2 and B6 as determinants of catabolites of the kynurenine pathway and related
markers of cellular immune activation in the community based Hordaland Health Study. Br J Nutr.
2014;112(7):1065-72
Theofylaktopoulou D, Midttun Ø, Ulvik A, Nygård, OK, Tell GS, Ueland PM, Ulvik A, Vollset SE, Eussen SJPM.
Determinants of plasma neopterin, kynurenine:tryptophan ratio and kynurenines in the Hordaland
Homocysteine Study. Clin Exp Immunol. 2013;173(1):121-30.