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01.10.2011 | Article

Soluble receptor for AGE (RAGE) is a novel independent predictor of all-cause and cardiovascular mortality in type 1 diabetes

verfasst von: M. C. Thomas, J. Söderlund, M. Lehto, V.-P. Mäkinen, J. L. Moran, M. E. Cooper, C. Forsblom, P.-H. Groop, on behalf of the FinnDiane Study Group

Erschienen in: Diabetologia | Ausgabe 10/2011

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Abstract

Aims/hypothesis

Activation of the receptor for AGE (RAGE) is implicated in the development and progression of vascular complications of diabetes. In this study, we explore factors and mortality outcomes associated with soluble RAGE (sRAGE) in a multicentre nationwide cohort of Finnish adults with type 1 diabetes.

Methods

Baseline sRAGE concentrations were estimated in 3,100 adults with type 1 diabetes. Clinical and biological variables independently associated with sRAGE were identified using multivariate regression analysis. Independent predictors of mortality were determined using Cox and Fine–Gray proportional-hazards models.

Results

The main independent determinants of sRAGE concentrations were estimated glomerular filtration rate, albuminuria, body mass index, age, duration of diabetes, HbA_1c and insulin dose (all p < 0.05). During a median of 9.1 years of follow-up there were 202 deaths (7.4 per 1,000 patient years). sRAGE was independently associated with all-cause (Cox model: HR 1.03) and cardiovascular mortality (Fine–Gray competing risks model: HR 1.06) such that patients with the highest sRAGE concentrations had the greatest risk of mortality, after adjusting for age, sex, macrovascular disease, HDL-cholesterol, HbA_1c, triacylglycerol, high-sensitivity C-reactive protein (hsCRP) and the presence and severity of chronic kidney disease. Although polymorphisms in the gene coding for RAGE were significantly associated with sRAGE concentrations, none were associated with mortality outcomes.

Conclusions/interpretation

Increased concentrations of sRAGE are associated with increased all-cause and cardiovascular mortality in type 1 diabetes, potentially reflecting the activation and production of RAGE in the context of accelerated vascular disease. These novel findings highlight the importance of the RAGE activation in the prevention and management of diabetic complications.

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Titel: Soluble receptor for AGE (RAGE) is a novel independent predictor of all-cause and cardiovascular mortality in type 1 diabetes
verfasst von: M. C. Thomas
J. Söderlund
M. Lehto
V.-P. Mäkinen
J. L. Moran
M. E. Cooper
C. Forsblom
P.-H. Groop
on behalf of the FinnDiane Study Group
Publikationsdatum: 01.10.2011
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 10/2011
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2186-5

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Soluble receptor for AGE (RAGE) is a novel independent predictor of all-cause and cardiovascular mortality in type 1 diabetes