title: Decreased endogenous secretory advanced glycation end product receptor in type 1 diabetic patients: its possible association with diabetic vascular complications.
abstract: OBJECTIVE
  The binding of advanced glycation end products (AGEs) to their receptor (RAGE) plays an important role in the development of diabetic vascular complications. In the present study, we examined circulating endogenous secretory RAGE (esRAGE) levels in subjects with type 1 diabetes and explored the possible association between esRAGE levels and the severity of diabetic vascular complications.
  
  
  METHODS
  Circulating esRAGE levels in serum were examined in 67 Japanese type 1 diabetic patients (22 men and 45 women, age 24.0 +/- 4.4 years [means +/- SD]) and 23 age-matched healthy nondiabetic subjects (10 men and 13 women aged 24.9 +/- 1.4 years). Daily urinary albumin excretion, the presence of retinopathy, and intima-media thickness (IMT) of the carotid artery were also evaluated. We further explored the association between esRAGE levels and severity of diabetic vascular complications.
  
  
  RESULTS
  Circulating esRAGE levels were significantly lower in subjects with type 1 diabetes than in nondiabetic subjects (0.266 +/- 0.089 vs. 0.436 +/- 0.121 ng/ml, respectively, P < 0.0001) and was inversely correlated with HbA(1c) (A1C) levels (r = -0.614, P < 0.0001). In addition, multivariate regression analysis demonstrated that A1C was an independent risk factor for a low esRAGE value. Furthermore, circulating esRAGE levels were inversely correlated with carotid IMT (r = -0.325, P = 0.0017) and was one of the independent risk factors for IMT thickening. Furthermore, there was a significant difference (P = 0.0124) in esRAGE levels between patients without retinopathy (0.286 +/- 0.092 ng/ml) and those with retinopathy (0.230 +/- 0.074 ng/ml).
  
  
  CONCLUSIONS
  Circulating esRAGE levels were significantly lower in type 1 diabetic patients than in nondiabetic subjects and were inversely associated with the severity of some diabetic vascular complications.
authors.affiliation: Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. katakami@medone.med.osaka-u.ac.jp
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Matsuoka
authors.forename: Ken'ya
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ohtoshi
authors.forename: Rieko
authors.initials: R
authors.lastname: Hayaishi-Okano
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kosugi
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000503:physiopathology / Q000517:prevention & control; D002340:Carotid Artery Diseases / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000032:analysis; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood / Q000378:metabolism*; D012044:Regression Analysis; D012307:Risk Factors; D012720:Severity of Illness Index; D017539:Tunica Intima / Q000473:pathology; D014463:Ultrasonography
chemical_list: D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic