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 |
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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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