Soluble RAGE in type 2 diabetes: Association with oxidative stress

Eleonora Devangelio, Francesca Santilli, Gloria Formoso, Patrizia Ferroni, Loredana Bucciarelli, Noemi Michetti, Cristina Clissa, Giovanni Ciabattoni, Agostino Consoli, Giovanni Davì

Research output: Contribution to journalArticlepeer-review

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 (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 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.

Original languageEnglish
Pages (from-to)511-518
Number of pages8
JournalFree Radical Biology and Medicine
Volume43
Issue number4
DOIs
Publication statusPublished - Aug 15 2007

Keywords

  • ADMA
  • Oxidative stress
  • RAGE
  • Type 2 diabetes

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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