Expression of skin Glyoxalase-I, advanced glycation end products (AGEs) and receptor (RAGE) in patients with long term type 1 diabetes and diabetic neuropathy

Ahmed T. Alahmar, Ioannis N. Petropoulos, Maryam Ferdousi, Wendy Jones, Hassan Fadavi, Shazli Azmi, Uazman Alam, Omar Asghar, Aisha Meskiri, Ahmad Kheyami, Georgios Ponirakis, Andrew Marshall, Andrew J.M. Boulton, Mitra Tavakoli, Maria Jeziorska, Rayaz Malik

Research output: Contribution to journalArticle

Abstract

Background: Certain group of diabetic patients have been shown to remain free of diabetic complications despite having had diabetes for longer periods. Advanced glycation end products (AGEs), their receptor (RAGE) and Glyoxalase-I (GLO-I) have been implicated in the development of diabetic neuropathy. Objective: To assess the effect of long term type 1 diabetes mellitus on skin distribution and expression of AGEs, RAGE and GLO-I and to correlate these expressions with measures of small and large nerve fibre damage. Methods: Sixty-seven patients with type 1 diabetes mellitus of shorter ( < 15 years, n=20), intermediate (15-40 years, n=25) and longer ( > 40 years, n=22) duration and 34 non-diabetic controls underwent diabetic neuropathy assessment: Neuropathy disability score (NDS), quantitative sensory testing (QST) including vibration pressure and thermal thresholds, nerve conduction studies (NCS), deep breathing heart rate variability (DB-HRV), corneal confocal microscopy (CCM) and intraepidermal nerve fibre density (IENFD) and AGEs, RAGE and GLO-I expression in foot skin biopsies. Results: Compared to controls, type 1 diabetes mellitus patients showed progressively increased skin expression of AGEs, RAGE but progressively lower GLO-I expression with increasing duration of diabetes. Thus patients with longerduration diabetes demonstrated significantly higher skin AGEs and RAGE but lower GLO-I expression than both shorter and intermediate duration diabetic groups. In patients with longer duration diabetes who developed diabetic neuropathy, the skin expression of AGEs and RAGE were significantly higher but GLO-I were significantly lower than those who did not develop diabetic neuropathy. These expressions also correlated with IENFD, CCM and NCS measures. Conclusion: Patients with type 1 diabetes mellitus showed progressively increased skin expression of AGEs, RAGE but progressively lower GLO-I expression with increasing duration of diabetes. Patients with longer duration diabetes who developed diabetic neuropathy have significantly higher skin AGEs and RAGE and decreased GLO-I expression suggesting a potential role for these macromolecules as aetiological, marker of the disease as well as therapeutic target for diabetic neuropathy.

Original languageEnglish
Pages (from-to)180-193
Number of pages14
JournalBrunei International Medical Journal
Volume13
Issue number6
Publication statusPublished - 1 Dec 2017

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Keywords

  • Advanced glycation end products
  • Diabetes mellitus
  • Diabetic neuropathy
  • GLO-I protein
  • Human
  • Receptor for advanced glycation end products
  • Type 1

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Alahmar, A. T., Petropoulos, I. N., Ferdousi, M., Jones, W., Fadavi, H., Azmi, S., Alam, U., Asghar, O., Meskiri, A., Kheyami, A., Ponirakis, G., Marshall, A., Boulton, A. J. M., Tavakoli, M., Jeziorska, M., & Malik, R. (2017). Expression of skin Glyoxalase-I, advanced glycation end products (AGEs) and receptor (RAGE) in patients with long term type 1 diabetes and diabetic neuropathy. Brunei International Medical Journal, 13(6), 180-193.