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

Autor: Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Johan Sundström, Carl Johan Östgren, Fredrik H. Nystrom, Juan Jesus Carrero, Lars Lind, Tove Fall, Erik Ingelsson, Axel C. Carlsson
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Oncology
Male
Proteomics
medicine.medical_specialty
Growth Differentiation Factor 15
Albumin-creatinine ratio
type 2 diabetes mellitus
Renal function
lcsh:Medicine
030209 endocrinology & metabolism
Type 2 diabetes
Disease
Endocrinology and Diabetes
Cohort Studies
03 medical and health sciences
0302 clinical medicine
proteomics
Risk Factors
Diabetes mellitus
Internal medicine
Medicine
Humans
Diabetic Nephropathies
Risk factor
Aged
Sweden
glomerular filtration rate
030219 obstetrics & reproductive medicine
business.industry
lcsh:R
Klinisk medicin
Type 2 Diabetes Mellitus
General Medicine
Articles
Middle Aged
medicine.disease
diabetic kidney disease
3. Good health
risk factor
Diabetes Mellitus
Type 2
Cardiovascular Diseases
Endokrinologi och diabetes
Biomarker (medicine)
biomarker
Female
GDF15
Clinical Medicine
business
Biomarkers
Zdroj: Upsala Journal of Medical Sciences
Upsala Journal of Medical Sciences, Vol 125, Iss 1, Pp 37-43 (2020)
ISSN: 2000-1967
0300-9734
Popis: 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 = 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.
Databáze: OpenAIRE
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