Painful diabetic peripheral neuropathy (pDPN) is associated with small nerve fiber degeneration and regeneration. This study investigated whether the presence of pDPN may influence nerve regeneration in patients with type 2 diabetes (T2D) undergoing intensive glycemic control.
This exploratory sub-study of an open-label randomized controlled trial undertook the Douleur Neuropathique en 4 (DN4) questionnaire and assessment of electrochemical skin conductance (ESC), vibration perception threshold (VPT) and corneal nerve morphology using corneal confocal microscopy in subjects 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.
Subjects with T2D, with (n=13) and without (n=28) pDPN had comparable corneal nerve fiber measures, ESC and VPT at baseline and pDPN was not associated with the severity of DPN. There was a significant HbA1c reduction (P<0.0001) and weight gain (P<0.005), irrespective of therapy. Subjects with pDPN showed a significant increase in corneal nerve fiber density (CNFD) (P<0.05), length (CNFL) (P<0.0001) and branch density (CNBD) (P<0.005) and a decrease in the DN4 score (P<0.01), but no change in ESC or VPT. Subjects without pDPN showed a significant increase in CNBD (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.
This study shows 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.

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