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

J Diabetes Investig. 2021 Nov;12(11):2002-2009. doi: 10.1111/jdi.13582. Epub 2021 Jun 19.

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.

Keywords: Corneal confocal microscopy; Diabetic peripheral neuropathy; Insulin resistance.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Cornea / innervation*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / physiopathology*
  • Exenatide / administration & dosage
  • Female
  • Glycated Hemoglobin / drug effects
  • Glycemic Control / methods
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Insulin / administration & dosage
  • Insulin Resistance / physiology*
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Nerve Fibers / pathology
  • Nerve Regeneration*
  • Pioglitazone / administration & dosage
  • Treatment Outcome

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Exenatide
  • Pioglitazone