title: Endogenous secretory RAGE but not soluble RAGE is associated with carotid atherosclerosis in type 1 diabetes patients.
abstract: Advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) system play an important role in the development of diabetic complications. The soluble form of RAGE (sRAGE) that potentially counteracts AGEs consists of several forms, including endogenous secretory RAGE (esRAGE; a splice variant of RAGE) and cleaved-type soluble RAGE derived from cell-surface RAGE. The aim of this study was to compare sRAGE and esRAGE directly in patients with type 1 diabetes. The associations of both total sRAGE and esRAGE with markers of glycaemic control and with carotid intima-media thickness (IMT) as a marker of atherosclerosis were examined in 130 type 1 diabetes patients (aged 23.6+/-4.9 years) and 22 age-matched non-diabetic subjects. IMT was inversely correlated with esRAGE (r=-0.254, p=0.0015) but neither with sRAGE nor subtracted soluble RAGE values (that is, circulating total sRAGE values - circulating esRAGE values). Furthermore, a stepwise multivariate regression analysis revealed that esRAGE (F=7.3), but not sRAGE, was a variable that interacted independently of IMT. It is likely that circulating sRAGE and esRAGE are distinct markers and that circulating esRAGE levels, but not sRAGE levels, are associated with the status of early-stage atherosclerosis.
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: Tetsuyuki
authors.initials: T
authors.lastname: Yasuda
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007564:Japan; D008297:Male; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C517652:hemoglobin A1c protein, human