Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control

Georgios Ponirakis, Muhammad A. Abdul-Ghani, Amin Jayyousi, Mahmoud A. Zirie, Murtaza Qazi, Hamad Almuhannadi, Ioannis N. Petropoulos, Adnan Khan, Hoda Gad, Osama Migahid, Ayman Megahed, Salma Al-Mohannadi, Fatema AlMarri, Fatima Al-Khayat, Ziyad Mahfoud, Hanadi Al Hamad, Marwan Ramadan, Ralph DeFronzo, Rayaz A. Malik

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/Introduction: Painful diabetic peripheral neuropathy (pDPN) is associated with small nerve fiber degeneration and regeneration. This study investigated whether the presence of pDPN might influence nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control. Materials and Methods: This exploratory substudy of an open-label randomized controlled trial undertook the Douleur Neuropathique en 4 questionnaire and assessment of electrochemical skin conductance, vibration perception threshold and corneal nerve morphology using corneal confocal microscopy in participants with and without pDPN treated with exenatide and pioglitazone or basal–bolus insulin at baseline and 1-year follow up, and 18 controls at baseline only. Results: Participants with type 2 diabetes, with (n = 13) and without (n = 28) pDPN had comparable corneal nerve fiber measures, electrochemical skin conductance and vibration perception threshold at baseline, and pDPN was not associated with the severity of DPN. There was a significant glycated hemoglobin reduction (P < 0.0001) and weight gain (P < 0.005), irrespective of therapy. Participants with pDPN showed a significant increase in corneal nerve fiber density (P < 0.05), length (P < 0.0001) and branch density (P < 0.005), and a decrease in the Douleur Neuropathique en 4 score (P < 0.01), but no change in electrochemical skin conductance or vibration perception threshold. Participants without pDPN showed a significant increase in corneal nerve branch density (P < 0.01) and no change in any other neuropathy measures. A change in the severity of painful symptoms was not associated with corneal nerve regeneration and medication for pain. Conclusions: This study showed that intensive glycemic control is associated with greater corneal nerve regeneration and an improvement in the severity of pain in patients with painful diabetic neuropathy.

Original languageEnglish (US)
Pages (from-to)1642-1650
Number of pages9
JournalJournal of Diabetes Investigation
Volume12
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • Corneal confocal microscopy
  • Exenatide
  • Painful diabetic neuropathy

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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