Reduced endogenous secretory receptor for advanced glycation end products (esRAGE) in young people with Type 1 diabetes developing microalbuminuria.
OBJECTIVE
The endogenous secretory receptor for advanced glycation end products (esRAGE) appears to work as a scavenger for AGEs and it has been implicated in the pathogenesis of diabetic complications. The aim of the present study was to perform a longitudinal evaluation of esRAGE in young people with Type 1 diabetes (T1D) in relation to the development of microalbuminuria (MA).


METHODS
Serum esRAGE levels were measured in longitudinally collected blood samples from 49 T1D patients with MA (MA+) and 49 matched normoalbuminuric patients (MA-), followed in the Oxford Regional Prospective Study. esRAGE levels were compared between MA+ and MA- subjects in relation to the time of MA onset.


RESULTS
Overall, esRAGE levels were significantly lower in MA+ than in MA- subjects (0.727 +/- 0.396 vs. 0.936 +/- 0.433 ng/ml; P = 0.015). These differences between the two groups were present both before (0.725 +/- 0.410 vs. 0.956 +/- 0.505 ng/ml, P = 0.038) and after the onset of MA (0.750 +/- 0.433 vs. 0.948 +/- 0.418 ng/ml, P = 0.04). In a longitudinal analysis there was no effect of age, duration, glycated haemoglobin (HbA(1c)) or body mass index standard deviation scores on esRAGE levels (all P > 0.05). In a Cox model, esRAGE levels significantly contributed to the probability of developing MA [Exp(B)(95% confidence interval): 0.34(0.12-0.98); P = 0.04), independently of HbA(1c).


CONCLUSIONS
In this longitudinal study of young people with T1D, esRAGE levels were reduced in MA+ subjects, even before the onset of MA, and appeared to be related to its development, thus suggesting a potential role of esRAGE in the pathogenesis of this complication. Diabet. Med. 26, 815-819 (2009).
Marcovecchio
M L
ML
Department of Paediatrics and Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Giannini
C
C
Dalton
R N
RN
Widmer
B
B
Chiarelli
F
F
Dunger
D B
DB
D000293:Adolescent; D000419:Albuminuria / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D005260:Female; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012307:Risk Factors; D013223:Statistics as Topic
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic