title: Soluble RAGE in type 2 diabetes: association with oxidative stress.
abstract: Advanced glycation end products (AGEs) contribute to diabetic vascular complications by engaging the AGE receptor (RAGE). A soluble RAGE form (sRAGE) acts as a decoy domain receptor, thus decreasing AGE cellular binding. A cross-sectional comparison of sRAGE, asymmetric dimethylarginine (ADMA) plasma levels (index of endothelial dysfunction), and urinary 8-iso-prostaglandin (PG)F(2alpha) (marker of oxidative stress) was performed between 86 diabetic patients and 43 controls. Plasma sRAGE levels were significantly lower and ADMA levels were significantly higher in diabetic patients as compared to controls (P<0.0001). HbA1c and urinary 8-iso-PGF(2alpha) were correlated inversely with sRAGE and directly with ADMA. On multivariate analysis HbA1c was independently related to sRAGE levels in diabetic patients. Twenty-four of 86 patients with newly diagnosed diabetes and 12 patients in poor metabolic control were reevaluated after treatment with a hypoglycemic agent or insulin, respectively. Improvement in metabolic control by oral agents or insulin resulted in a significant increase in sRAGE and decrease in ADMA levels (P<0.0001). Thus, poor glycemic control reduces sRAGE levels, in association with enhanced oxidative stress and endothelial dysfunction in diabetes. These abnormalities are susceptible to modulation by improvement in metabolic control.
authors.affiliation: Center of Excellence on Aging and Departments of Medicine and Drug Sciences, University of Chieti "G. D'Annunzio" Schools of Medicine and Pharmacy, 66013 Chieti, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Devangelio
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.forename: Gloria
authors.initials: G
authors.lastname: Formoso
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.forename: Loredana
authors.initials: L
authors.lastname: Bucciarelli
authors.forename: Noemi
authors.initials: N
authors.lastname: Michetti
authors.forename: Cristina
authors.initials: C
authors.lastname: Clissa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: Agostino
authors.initials: A
authors.lastname: Consoli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000187:drug effects; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000097:blood / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000187:drug effects
chemical_list: D001120:Arginine; D015237:Dinoprost; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C517652:hemoglobin A1c protein, human; C075750:8-epi-prostaglandin F2alpha; C018524:N,N-dimethylarginine