Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach

  • Axel C. Carlsson Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden
  • Christoph Nowak Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden
  • Lars Lind Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  • Carl Johan Östgren Department of Medical and Health Sciences, Link€oping University, Link€oping, Sweden
  • Fredrik H. Nyström Department of Medical and Health Sciences, Link€oping University, Link€oping, Sweden
  • Johan Sundström Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  • Juan Jesus Carrero Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • Ulf Riserus Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden http://orcid.org/0000-0002-8620-4586
  • Erik Ingelsson Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA; Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
  • Tove Fall Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
  • Johan Ärnlöv Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden
Keywords: Albumin-creatinine ratio, biomarker, diabetic kidney disease, glomerular filtration rate, proteomics, risk factor, type 2 diabetes mellitus

Abstract

Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful.

Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes.

Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate <60 mg/mL/1.73 m2 and/or urinary albumin-creatinine ratio ≥3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline.

Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27–2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16–1.69); myoglobin (OR 1.57, 95% CI 1.30–1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17–1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03–1.98]) but not after further adjustments for cardiovascular risk factors.

Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.

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Published
2019-12-05
How to Cite
Carlsson, A. C., Nowak, C., Lind, L., Östgren, C. J., Nyström, F. H., Sundström, J., Carrero, J. J., Riserus, U., Ingelsson, E., Fall, T., & Ärnlöv, J. (2019). Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach. Upsala Journal of Medical Sciences, 125(1), 37-43. https://doi.org/10.1080/03009734.2019.1696430
Section
Original Articles

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