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Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes
Karolinska Institute, Sweden; Uppsala University, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.ORCID iD: 0000-0002-1680-1000
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).ORCID iD: 0000-0002-9095-403X
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2016 (English)In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, no 1, 40- p.Article in journal (Refereed) Published
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Abstract [en]

Aims/hypothesis: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease. Methods: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used. Results: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality. Conclusions/Interpretations: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD , 2016. Vol. 15, no 1, 40- p.
Keyword [en]
Type 2 diabetes; TNF; Laplace regression; Incident cardiovascular disease; Mortality; Inflammation
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Cardiac and Cardiovascular Systems Family Medicine
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URN: urn:nbn:se:liu:diva-126836DOI: 10.1186/s12933-016-0359-8ISI: 000371581000001PubMedID: 26928194OAI: oai:DiVA.org:liu-126836DiVA: diva2:917197
Note

Funding Agencies|Swedish Research Council; Swedish Heart-Lung foundation; Thureus foundation; Marianne and Marcus Wallenberg Foundation; Dalarna University; Uppsala University

Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2017-11-30

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Östgren, Carl JohanNyström, Fredrik HLänne, TosteJennersjö, Pär

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Östgren, Carl JohanNyström, Fredrik HLänne, TosteJennersjö, Pär
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Division of Community MedicineFaculty of Medicine and Health Sciences"Primary Health Care in Motala"Division of Cardiovascular MedicineDepartment of EndocrinologyDepartment of Thoracic and Vascular SurgeryCenter for Medical Image Science and Visualization (CMIV)
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Cardiovascular Diabetology
Cardiac and Cardiovascular SystemsFamily Medicine

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