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title:Skin Advanced Glycation End Products (Ages), (RAGE) and Glyoxalase-I (GLO-I) is Associated With Diabetic Neuropathy in Patients With Type 1 Diabetes

Author:Ahmed Alahmar, Ioannis 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 A. Malik

Keywords:Diabetic neuropathy, Advanced glycationendproducts (AGEs), RAGE, Glyoxalase-I

Type:Original Article

Abstract:Introduction: Advanced Glycation End Products (AGEs), their receptor (RAGE) and their detoxifying enzyme Glyoxalase-I (GLO-I) have been implicated in the development of experimental diabetic peripheral neuropathy (DPN). However, few studies have assessed their role in the tissues of diabetic patients. Aim: We have assessed the relationship between skin expression of AGEs, RAGE, GLO-I and diabetic neuropathy in patients with type 1 diabetes. Materials and Methods: Sixty-two patients with type 1 diabetes mellitus (16 with and 46 without DPN) and 30 age-matched control subjects underwent detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, corneal confocal microscopy (CCM) , intraepidermal nerve fibre density (IENFD) and AGEs, RAGE and GLO1-I expression in foot skin biopsies. Results: Skin AGEs and RAGE expression was significantly higher and GLO-I was significantly lower in the epidermis, microvessels and reticular extracellular matrix of patients with diabetic neuropathy as compared to diabetic patients without neuropathy and control subjects. Skin AGEs and RAGE expression was also moderately but significantly increased and GLO-I expression was decreased in some skin structures in patients without diabetic neuropathy as compared to control subjects. Skin AGEs and RAGE expression correlated negatively and GLO-I expression correlated positively with sural nerve amplitude and velocity, IENFD and corneal nerve pathology. Conclusion: These findings suggest that AGEs, RAGE and GLO-I may play an important role in the etiology of human diabetic neuropathy.

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