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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
Karolinska Inst, Sweden.
Karolinska Inst, Sweden.
Uppsala Univ, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
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2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967Article in journal (Refereed) Epub ahead of print
Abstract [en]

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 amp;lt;60 mg/mL/1.73 m(2) and/or urinary albumin-creatinine ratio amp;gt;= 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.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD , 2019.
Keywords [en]
Albumin-creatinine ratio; biomarker; diabetic kidney disease; glomerular filtration rate; proteomics; risk factor; type 2 diabetes mellitus
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:liu:diva-162870DOI: 10.1080/03009734.2019.1696430ISI: 000501063900001PubMedID: 31805809OAI: oai:DiVA.org:liu-162870DiVA, id: diva2:1382268
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02

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Östgren, Carl JohanNyström, Fredrik H
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Division of Community MedicineFaculty of Medicine and Health SciencesPrimary Health Care Center ÖdeshögDivision of Cardiovascular MedicinePrimary Health Care Center Cityhälsan Centrum, Norrköping
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Upsala Journal of Medical Sciences
Endocrinology and Diabetes

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