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Diabetologia

, Volume 62, Issue 1, pp 169–177 | Cite as

Prospective associations of circulating adipocyte fatty acid-binding protein levels with risks of renal outcomes and mortality in type 2 diabetes

  • Chi Ho Lee
  • Chloe Y. Y. Cheung
  • Yu Cho Woo
  • David T. W. Lui
  • Michele M. A. Yuen
  • Carol H. Y. Fong
  • Wing Sun Chow
  • Amin Xu
  • Karen S. L. Lam
Article
  • 145 Downloads

Abstract

Aims/hypothesis

Elevated circulating adipocyte fatty acid-binding protein (AFABP) levels have been found to correlate with diabetic nephropathy staging in cross-sectional studies. However, it remains unclear whether these higher serum levels reflect a role of AFABP in the development of diabetic kidney disease (DKD), or simply result from its impaired renal clearance in DKD. Here we investigated prospectively the prognostic importance of serum AFABP level in the development of adverse renal outcomes in a large clinic-based cohort of participants with type 2 diabetes.

Methods

Baseline serum AFABP levels were measured in 5454 Chinese participants from the Hong Kong West Diabetes Registry. The association between circulating AFABP levels and incident adverse renal outcomes—defined as a composite endpoint of a sustained 40% decline in eGFR, end-stage renal disease requiring renal replacement therapy or kidney transplantation, or renal deaths—was evaluated using multivariable Cox regression analysis.

Results

Over a median follow-up of 5 years, 754 of the 5454 participants developed incident adverse renal outcomes. Elevated circulating AFABP levels were independently associated with incident adverse renal outcomes (HR 1.43, 95% CI 1.31, 1.57, p < 0.001) after adjustments for conventional risk factors for DKD progression. Importantly, the prognostic role of serum AFABP was independent of the baseline albuminuria status or eGFR levels of the study participants.

Conclusions/interpretation

Circulating AFABP levels were predictive of incident adverse renal outcomes, even in participants with relatively well-preserved kidney function at baseline, suggesting its potential to be a useful marker for early risk stratification in DKD.

Keywords

Adipocyte fatty acid-binding protein Microvascular complications Nephropathy Prediction model Type 2 diabetes mellitus 

Abbreviations

ACEI

ACE inhibitor

AFABP

Adipocyte fatty acid-binding protein

ARB

Angiotensin II receptor blocker

DKD

Diabetic kidney disease

ER

Endoplasmic reticulum

ESRD

End-stage renal disease

HDL-C

HDL-cholesterol

hsCRP

High-sensitivity C-reactive protein

IDI

Integrated discrimination improvement

JNK

c-Jun NH2-terminal kinase

KIM-1

Kidney injury molecule-1

LDL-C

LDL-cholesterol

NRI

Net reclassification index

TNFR

Tumour necrosis factor receptor

WC

Waist circumference

Notes

Acknowledgements

We thank RLC Wong (Department of Medicine, University of Hong Kong, Hong Kong) for her technical assistance in the measurements of serum AFABP and hsCRP levels. Some of the data were presented as an abstract at the International Diabetes Federation Western Pacific Region Congress (IDF-WPR) in 2014.

Contribution statement

CHL contributed to analysis of the data and writing of the manuscript. CYYC, YCW, DTWL, MMAY, WSC and AX contributed to the interpretation of data and revising the manuscript. CHYF contributed to analysis of the data and writing of the manuscript. KSLL initiated and supervised the study, critically revised for important intellectual content and is the guarantor of this work, and as such has had full access to all study data and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors have approved the final version.

Funding

This work was supported by the Health and Medical Research Fund (reference 14150781).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2018_4742_MOESM1_ESM.pdf (184 kb)
ESM (PDF 184 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Chi Ho Lee
    • 1
    • 2
  • Chloe Y. Y. Cheung
    • 1
  • Yu Cho Woo
    • 1
  • David T. W. Lui
    • 1
  • Michele M. A. Yuen
    • 1
  • Carol H. Y. Fong
    • 1
  • Wing Sun Chow
    • 1
  • Amin Xu
    • 1
    • 2
    • 3
  • Karen S. L. Lam
    • 1
    • 2
    • 3
  1. 1.Department of MedicineThe University of Hong Kong, Queen Mary HospitalHong KongPeople’s Republic of China
  2. 2.Research Center of Heart, Brain, Hormone and Healthy AgingThe University of Hong KongHong KongPeople’s Republic of China
  3. 3.State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong KongPeople’s Republic of China

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