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The kynurenine:tryptophan ratio as a predictor of incident type 2 diabetes mellitus in individuals with coronary artery disease

Authors
  • Rebnord, Eirik W.1, 2, 3
  • Strand, Elin1
  • Midttun, Øivind4
  • Svingen, Gard F.T.3
  • Christensen, Monika H.E.1, 5
  • Ueland, Per M.1, 6
  • Mellgren, Gunnar1, 2, 7
  • Njølstad, Pål R.1, 2, 8
  • Tell, Grethe S.9
  • Nygård, Ottar K.1, 2, 3
  • Pedersen, Eva R.2, 3
  • 1 University of Bergen, Department of Clinical Science, Bergen, Norway , Bergen (Norway)
  • 2 University of Bergen, KG Jebsen Centre for Diabetes Research, Bergen, Norway , Bergen (Norway)
  • 3 Haukeland University Hospital, Department of Heart Disease, Jonas Lies vei 65, Bergen, 5021, Norway , Bergen (Norway)
  • 4 Bevital, Bergen, Norway , Bergen (Norway)
  • 5 Haukeland University Hospital, Department of Medicine, Bergen, Norway , Bergen (Norway)
  • 6 Haukeland University Hospital, Laboratory of Clinical Biochemistry, Bergen, Norway , Bergen (Norway)
  • 7 Haukeland University Hospital, Hormone Laboratory, Bergen, Norway , Bergen (Norway)
  • 8 Haukeland University Hospital, Department of Pediatrics, Bergen, Norway , Bergen (Norway)
  • 9 University of Bergen, Department of Global Public Health and Primary Care, Bergen, Norway , Bergen (Norway)
Type
Published Article
Journal
Diabetologia
Publisher
Springer-Verlag
Publication Date
Jun 13, 2017
Volume
60
Issue
9
Pages
1712–1721
Identifiers
DOI: 10.1007/s00125-017-4329-9
Source
Springer Nature
Keywords
License
Green

Abstract

Aims/hypothesisThe tryptophan metabolite kynurenine has potent immune modulatory and vasoactive properties. Experimental data implicate kynurenine in obesity-related morbidities. Epidemiological studies are, however, sparse. We evaluated associations of the plasma and urine kynurenine:tryptophan ratio (KTR) to incident type 2 diabetes.MethodsWe followed 2519 individuals with coronary artery disease (CAD; 73.1% men) without diabetes at baseline for a median of 7.6 years, during which 173 (6.9%) new incidences of type 2 diabetes were identified. Multivariate Cox regression analyses were applied to investigate the prospective relationships of plasma and urine KTR with new onset type 2 diabetes.ResultsAt inclusion, mean (SD) age was 61.3 (10.4) years, BMI was 25.9 (3.71) kg/m2 and median (interquartile range) HbA1c was 5.6% (5.0%–6.0%) (38 [31–42] mmol/mol). Plasma KTR was not significantly related to type 2 diabetes risk. By contrast, urine KTR showed a strong positive association. Comparing quartile 4 with quartile 1, the HRs (95% CIs) were 2.59 (1.56, 4.30) and 2.35 (1.39, 3.96) in the age- and sex-adjusted and multivariate models, respectively.Conclusions/interpretationUrine KTR is a strong predictor of incident type 2 diabetes in individuals with CAD. Potential clinical implications and possible pathogenic roles of renal kynurenine excretion in type 2 diabetes development should be further elucidated.

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