Journal Article

Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes

Länne, Toste, Carlsson, Axel C., Östgren, Carl Johan, Nystrom, Fredrik H., Jennersjö, Pär, Larsson, Anders, Ärnlöv, Johan

2016

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Albuminuria - blood / Albuminuria - diagnosis / Albuminuria - epidemiology / Angiology / Biomarkers - blood / Cardiology / Cardiovascular Diseases - blood / Cardiovascular Diseases - diagnosis / Cardiovascular Diseases - epidemiology / Cardiovascular Diseases - mortality / Cross-Sectional Studies / Diabetes / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - diagnosis / Diabetes Mellitus, Type 2 - epidemiology / Diabetes Mellitus, Type 2 - mortality / Diabetic Nephropathies - blood / Diabetic Nephropathies - diagnosis / Diabetic Nephropathies - epidemiology / Diabetic Nephropathies - mortality / Female / Glycated Hemoglobin A - metabolism / Health and Welfare / Humans / Hälsa och välfärd / Incidence / Incident cardiovascular disease / Inflammation / Inflammation Mediators - blood / Laplace regression / Logistic Models / Longitudinal Studies / Male / Medicine / Medicine & Public Health / Middle Aged / Mortality / Multivariate Analysis / Odds Ratio / Original Investigation / Predictive Value of Tests / Prevalence / Prognosis / Proportional Hazards Models / Prospective Studies / Receptors, Tumor Necrosis Factor, Type I - blood / Receptors, Tumor Necrosis Factor, Type II - blood / Risk Assessment / Risk Factors / Time Factors / TNF / Type 2 diabetes / Up-Regulation