Urinary liver-type fatty acid binding protein (L-FABP) is an independent predictor of stroke

in patients with Type 1 diabetes

Nicolae M. PANDURU, Carol FORSBLOM, Markku SARAHEIMO, Lena M. THORN, Daniel GORDIN, Nina TOLONEN, Valma HARJUTSALO,

Angelika BIERHAUS†, Per M. HUMPERT, Per-Henrik GROOP, on behalf of the FinnDiane Study Group

„Carol Davila” University of Medicine and Pharmacy from Bucharest 2nd Clinical Department, Diabetes Chair

Folkhälsan Research Center – Folkhälsan Institute of Genetics

FinnDiane

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modified after Yamamoto T et al. JASN 2007;18:2894-2902

Anemia

Hypoxia

RAAS

Hyperglycemia

L-FABP is produced by tubular cells through multiple mechanisms

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the FinnDiane Study

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Panduru NM, et all. Diabetes Care. 2013;36(7):2077-83.

L-FABP predicted progression of diabetic nephropathy

the FinnDiane Study

1) to investigate the prognostic value of urinary L-FABP for the prediction of the most important cardiovascular outcomes and mortality

2) to investigate the added clinical benefit of urinary L-FABP for the prediction of the most important cardiovascular outcomes and mortality

in patients with type 1 diabetes

Study objectives

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the FinnDiane Study

• This study is part of the ongoing FinnDiane Study

• The study included 1952 subjects with type 1 diabetes

• The patients have been followed for a median of 10.6 years (IQR 8.9 – 11.8) until 18 september 2011

• Data on medication and clinical history were registered at baseline with the use of a standardized questionnaire

• L-FABP was measured in a single 24-h urine collection with an Cobas Elecsys 411 Immunoanalyzer (Roche Diagnostics, Basel, Switzerland). L-FABP values were then normalized with u-creatinine.

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Material and methods

the FinnDiane Study

• Statistical methods:

- Prediction - Cox regression analysis

- Added benefit: - ROC curve analysis

- net reclassification improvement (NRI)

- integrated discrimination improvement (IDI)

- explained variability (R2)

- Traditional adjustment model - Age, sex, diabetes duration, LDL cholesterol, glycated

hemoglobin A1c, systolic blood pressure.

• Outcomes were documented

- FinnDiane data

- Finish Hospital Discharge Registry (HDR)

- Finnish Cause of Death Registry (CDR)

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Material and methods

the FinnDiane Study

Outcomes

• Stroke (ischemic or haemorrhagic) - history of ischemic a history of ischemic, haemorrhagic or not specified stroke.

• CAD - history of acute myocardial infarction or a coronary artery procedure (bypass grafting surgery or angioplasty)

• PVD - limb amputation or peripheral artery procedure (bypass grafting surgery or angioplasty)

• CVD - composite outcome (stroke, CAD and PVD)

• Mortality – death of any cause

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Material and methods

the FinnDiane Study

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Baseline clinical and biological data the FinnDiane Study

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Results – prediction of outcomes

the FinnDiane Study Urinary L-FABP predicted stroke and mortality

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Results – comparison with other markers

the FinnDiane Study

L-FABP was as good as AER or eGFR for stroke and mortality prediction

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Results – comparison with other markers

the FinnDiane Study

L-FABP was better than HbA1c or LDL and as good as SBP for stroke and mortality prediction

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Results – added clinical benefit on top of actual markers

the FinnDiane Study

Urinary L-FABP added benefit for prediction of stroke but not mortality

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Conclusions

• Urinary L-FABP is an independent predictor for stroke and mortality in type 1 diabetes.

• Urinary L-FABP was as good as eGFR, AER or SBP and better than HbA1c or LDL for the prediction of stroke and mortality

• Urinary L-FABP added clinical benefit when used alone or together with AER or eGFR, only for the prediction of stroke

the FinnDiane Study

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The FinnDiane Study Group Per-Henrik Groop

Aila Ahola Maija Feodoroff Carol Forsblom Daniel Gordin Valma Harjutsalo Kustaa Hietala Nicu Panduru Heidi Tikkanen

Janne Kytö Raija Lithovius Kim Pettersson-Fernholm Milla Rosengård-Bärlund Anna-Reetta Salonen Johan Wadèn Stefanie Hägg Freja Sandström

Markku Saraheimo Aino Soro-Paavonen Lena Thorn Nina Tolonen Anna Sandelin Jaana Tuomikangas

Ville-Petteri Mäkinen Tomi Peltola Niina Sandholm

Lina Peräneva Mariann Lassenius Chris Fogarty Rasmus Simonsen Tuula Soppela Markku Lehto

Emma Fagerholm Maikki Parkkonen Jenny Söderlund Nadja Vuori Anna Syreeni

Physicians and nurses collecting the patients

FINNDIANE CENTERS

PHENOTYPING TEAM

CELL BIOLOGY GENOTYPING TEAM BIOINFORMATICS COLLABORATORS

Angelika BIERHAUS, PhD† Heidelberg, Germany

Per M. HUMPERT, PhD Mannheim, Germany

Friedeman Krause, PhD Roche, Germany

FinnDiane