Insulin resistance limits corneal nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control

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

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/Introduction: This study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy. Materials and Methods: This was an exploratory substudy of an open-label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin <7.0% (<53 mmol/mol). Baseline IR was defined using homeostasis model assessment of IR, and change in neuropathy was assessed using corneal confocal microscopy. Results: A total of 38 individuals with type 2 diabetes aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR were studied. There was a significant decrease in glycated hemoglobin (P < 0.0001), diastolic blood pressure (P < 0.0001), total cholesterol (P < 0.01) and low-density lipoprotein (P = 0.05), and an increase in bodyweight (P < 0.0001) with treatment. Individuals with homeostasis model assessment of IR <1.9 showed a significant increase in corneal nerve fiber density (P ≤ 0.01), length (P ≤ 0.01) and branch density (P ≤ 0.01), whereas individuals with homeostasis model assessment of IR ≥1.9 showed no change. IR was negatively associated with change in corneal nerve fiber density after adjusting for change in bodyweight (P < 0.05). Conclusions: Nerve regeneration might be limited in individuals with type 2 diabetes and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control.

Original languageEnglish (US)
JournalJournal of Diabetes Investigation
DOIs
StateAccepted/In press - 2021

Keywords

  • Corneal confocal microscopy
  • Diabetic peripheral neuropathy
  • Insulin resistance

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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