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

AIMS/INTRODUCTION This study aimed to investigate whether insulin resistance (IR) in subjects with T2D undergoing intensive glycemic control determines the extent of improvement in neuropathy. MATERIALS AND METHODS This is an exploratory sub-study of an open-label, randomized controlled trial of subjects with poorly controlled T2D treated with exenatide and pioglitazone or insulin to achieve an HbA1c <7.0% (<53 mmol/mol). Baseline IR was defined using HOMA-IR and change in neuropathy was assessed using corneal confocal microscopy. RESULTS Thirty-eight subjects with T2D aged 50.2 ± 8.5 years with (n=25, 66%) and without (n=13, 34%) IR were studied. There was a significant decrease in HbA1c (P<0.0001), diastolic blood pressure (P<0.0001), total cholesterol (P<0.01) and LDL (P=0.05) and an increase in body weight (P<0.0001) with treatment. Subjects with HOMA-IR <1.9 showed a significant increase in corneal nerve fiber density (CNFD) (P≤0.01), length (P≤0.01) and branch density (P≤0.01) whilst subjects with HOMA-IR ≥1.9 showed no change. IR was negatively associated with change in CNFD after adjusting for change in body weight (P<0.05). CONCLUSIONS Nerve regeneration may be limited in subjects with T2D and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control.