Midtveisevaluering - Eirik W. Rebnord

Abstract: “Biomarkers of metabolism and inflammation in a prospective cohort of patients with stable coronary artery disease”

Patients with stable coronary artery disease (CAD) are susceptible to acute myocardial infarction and mortality. Diabetes mellitus type 2 (T2D) increases the risk of the same events and people with both stable CAD and T2D are at particularly high risk. 

The present project evaluates biomarkers of energy metabolism and inflammation in a prospective cohort of 2519 patients with stable angina pectoris, but without diabetes mellitus at study enrolment. All participants were recruited from Haukeland or Stavanger University Hospital and were followed for up to 10 years, with regard to mortality, acute coronary events and incident T2D.

The first paper concerns glycated hemoglobin (HbA1c). This biomarker is currently in clinical use for the diagnostics and monitoring of diabetes mellitus. However, the associations of HbA1c levels within the pre-diabetic range to long-term risk of acute atherosclerotic complications in patients with stable CAD are not fully elucidated.

Secondly, we focus on acylcarnitines, which are intermediate products from the oxidation of fatty acids in the mitochondria. Circulating levels may be elevated in patients with obesity and insulin resistance. These metabolites have been linked to lipotoxicity, and may play a role in the pathogenesis of T2D.

The urine kynurenine:tryptophan ratio (KTR) is a biomarker of interferon γ mediated immune activation, which also has been implicated in diabetes development. Prospective data on acylcarnitines and urine KTR are sparse. A more thorough understanding of established and novel biomarkers may guide the identification of subjects at risk and thus improve the targeting of lifestyle- and medical interventions.   

So far, we have found that HbA1c values within the pre-diabetes category are not associated with an increased risk of mortality or acute coronary events. We have revealed associations of acylcarnitines and carnitine precursors to incident T2D. Our preliminary results further show strong associations between baseline urine KTR levels and the risk of subsequent TD2, possibly reflecting the inflammatory component of this disease.