RGD Reference Report - Soluble receptor for AGE (RAGE) is a novel independent predictor of all-cause and cardiovascular mortality in type 1 diabetes. - Rat Genome Database

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

Authors: Thomas, MC  Soderlund, J  Lehto, M  Makinen, VP  Moran, JL  Cooper, ME  Forsblom, C  Groop, PH  Groop, PH 
Citation: Thomas MC, etal., Diabetologia. 2011 Oct;54(10):2669-77. doi: 10.1007/s00125-011-2186-5. Epub 2011 May 24.
RGD ID: 7243944
Pubmed: PMID:21607631   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-011-2186-5   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Albuminuria  IEP 7243944associated with Diabetes Mellitus more ...RGD 
Albuminuria  ISOAGER (Homo sapiens)7243944; 7243944associated with Diabetes Mellitus more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Mus musculus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Homo sapiens)
AGER  (advanced glycosylation end-product specific receptor)


Additional Information