Insulin resistance limits corneal nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic
Georgios Ponirakis1,2, Muhammad A Abdul-Ghani3,4, Amin Jayyousi3
1Weill Cornell Medicine in Qatar, Qatar Foundation, Education City, Doha, Qatar.
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.
Insights
Insulin resistance in type 2 diabetes limits nerve regeneration during intensive glycemic control. Even with treatment, individuals with higher insulin resistance showed no improvement in neuropathy.
Area of Science:
- Endocrinology
- Neurology
- Metabolic Disorders
Background:
- Type 2 diabetes is often associated with insulin resistance (IR).
- Diabetic neuropathy is a common complication, impacting nerve health.
- Intensive glycemic control aims to mitigate diabetes complications.
Purpose of the Study:
- To determine if insulin resistance influences neuropathy improvement in type 2 diabetes patients undergoing intensive glycemic control.
- To explore the relationship between baseline insulin resistance and nerve regeneration markers.
Main Methods:
- An exploratory substudy of a randomized controlled trial involving patients with type 2 diabetes.
- Baseline insulin resistance was assessed using homeostasis model assessment of IR (HOMA-IR).
- Neuropathy changes were evaluated using corneal confocal microscopy.
Main Results:
- A total of 38 patients were studied, with 66% having IR.
- Intensive glycemic control led to significant improvements in HbA1c, blood pressure, and cholesterol.
- Patients with lower HOMA-IR (<1.9) showed significant increases in corneal nerve fiber density, length, and branch density, while those with higher HOMA-IR (≥1.9) did not.
- Insulin resistance was negatively associated with changes in corneal nerve fiber density.
Conclusions:
- Insulin resistance may impede nerve regeneration in type 2 diabetes patients treated for glycemic control.
- The effectiveness of intensive glycemic control on neuropathy may be limited by the presence of insulin resistance.
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