Diabetologia

, Volume 60, Issue 9, pp 1782–1790 | Cite as

Urinary liver-type fatty acid binding protein is an independent predictor of stroke and mortality in individuals with type 1 diabetes

  • Nicolae M. Panduru
  • Carol Forsblom
  • Markku Saraheimo
  • Lena M. Thorn
  • Daniel Gordin
  • Nina Elonen
  • Valma Harjusalo
  • Angelika Bierhaus
  • Per M. Humpert
  • Per-Henrik Groop
  • on behalf of the FinnDiane Study Group
Article

Abstract

Aims/hypothesis

In type 1 diabetes, cardiovascular disease (CVD) and diabetic nephropathy progress in parallel, thereby potentiating the risk of premature death during their development. Since urinary liver-type fatty acid binding protein (L-FABP) predicts the progression of diabetic nephropathy, the aim of this study was to investigate whether urinary L-FABP also predicts cardiovascular outcomes and mortality.

Methods

We tested our hypothesis in a Finnish cohort of 2329 individuals with type 1 diabetes and a median follow-up of 14.1 years. The L-FABP to creatinine ratio was determined from baseline urine samples. The predictive value of urinary L-FABP was evaluated using Cox regression models, while its added predictive benefit for cardiovascular outcomes and mortality was evaluated using a panel of statistical indexes.

Results

Urinary L-FABP predicted incident stroke independently of traditional risk factors (HR 1.33 [95% CI 1.20, 1.49]) and after further adjustment for eGFR (HR 1.28 [95% CI 1.14, 1.44]) or AER (HR 1.24 [95% CI 1.06, 1.44]). In addition, it predicted mortality independently of traditional risk factors (HR 1.34 [95% CI 1.24, 1.45]), and after adjustment for eGFR (HR 1.29 [95% CI 1.18, 1.39]) or AER (HR 1.22 [95% CI 1.09, 1.36]). Urinary L-FABP was as good a predictor as eGFR or AER, and improved the AUC for both outcomes on top of traditional risk factors, with no reclassification benefit (integrated discrimination improvement/net reclassification improvement) for stroke or mortality when AER or eGFR were added to traditional risk factors. However, urinary L-FABP was not a predictor of other cardiovascular endpoints (coronary artery disease, peripheral vascular disease and overall CVD events) when adjusted for the AER.

Conclusions/interpretation

Urinary L-FABP is an independent predictor of stroke and mortality in individuals with type 1 diabetes.

Keywords

Cardiovascular disease Diabetic complications Liver-type fatty acid binding protein Mortality Stroke Type 1 diabetes Urinary biomarkers Urinary L-FABP 

Abbreviations

CAD

Coronary artery disease

CVD

Cardiovascular disease

ESRD

End-stage renal disease

IDI

Integrated discrimination improvement

L-FABP

Liver-type fatty acid binding protein

NRI

Net reclassification improvement

PVD

Peripheral vascular disease

ROC

Receiver operating characteristic

Supplementary material

125_2017_4328_MOESM1_ESM.pdf (341 kb)
ESM(PDF 340 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Nicolae M. Panduru
    • 1
    • 2
    • 3
    • 4
  • Carol Forsblom
    • 2
    • 3
    • 4
  • Markku Saraheimo
    • 2
    • 3
    • 4
  • Lena M. Thorn
    • 2
    • 3
    • 4
  • Daniel Gordin
    • 2
    • 3
    • 4
  • Nina Elonen
    • 2
    • 3
    • 4
  • Valma Harjusalo
    • 2
    • 3
    • 4
    • 5
  • Angelika Bierhaus
    • 6
  • Per M. Humpert
    • 6
    • 7
  • Per-Henrik Groop
    • 2
    • 3
    • 4
    • 8
  • on behalf of the FinnDiane Study Group
  1. 1.Second Clinical Department – Diabetes, Nutrition and Metabolic Disorders Unit‘Carol Davila’ University of Medicine and PharmacyBucharestRomania
  2. 2.Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum 1 Helsinki, Haartmaninkatu 8, P.O. Box 63University of HelsinkiHelsinkiFinland
  3. 3.Research Programmes Unit, Diabetes and ObesityUniversity of HelsinkiHelsinkiFinland
  4. 4.Abdominal Center NephrologyUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  5. 5.Chronic Disease Prevention UnitNational Institute for Health and WelfareHelsinkiFinland
  6. 6.Department of Medicine I and Clinical ChemistryUniversity of HeidelbergHeidelbergGermany
  7. 7.Stoffwechselzentrum Rhein PfalzMannheimGermany
  8. 8.Baker IDI Heart and Diabetes InstituteMelbourneAustralia

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