Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control

Abstract

Aims/Introduction: Painful diabetic peripheral neuropathy (pDPN) is associated with small nerve fiber degeneration and regeneration. This study investigated whether the presence of pDPN might influence nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control. Materials and Methods: This exploratory substudy of an open-label randomized controlled trial undertook the Douleur Neuropathique en 4 questionnaire and assessment of electrochemical skin conductance, vibration perception threshold and corneal nerve morphology using corneal confocal microscopy in participants 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.Results: Participants with type 2 diabetes, with (n = 13) and without (n = 28) pDPN had comparable corneal nerve fiber measures, electrochemical skin conductance and vibration perception threshold at baseline, and pDPN was not associated with the severity of DPN. There was a significant glycated hemoglobin reduction (P < 0.0001) and weight gain (P < 0.005), irrespective of therapy. Participants with pDPN showed a significant increase in corneal nerve fiber density (P < 0.05), length (P < 0.0001) and branch density (P < 0.005), and a decrease in the Douleur Neuropathique en 4 score (P < 0.01), but no change in electrochemical skin conductance or vibration perception threshold. Participants without pDPN showed a significant increase in corneal nerve branch density (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. Conclusions: This study showed 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.

Progressive loss of corneal nerve fibers is associated with physical inactivity and glucose lowering medication associated with weight gain in type 2 diabetes

“…However, a >3% reduction in HbA1c and weight loss of about 7 kg in type 2 diabetes over 4 years was associated with corneal nerve regeneration 40 , 41 . Furthermore, we showed previously that treatment with exenatide and pioglitazone or basal‐bolus insulin over 12 months resulted in about a 3% reduction in HbA1c, corneal nerve regeneration, and reduction in pain, particularly in those with painful DPN 42 , 43 .…”

Diabetic Corneal Neuropathy: Pathogenic Mechanisms and Therapeutic Strategies

“…Since chronic hyperglycemia can cause nerve damage through a variety of pathological mechanisms, strict glycemic control is believed to be an essential means to treat diabetes and reduce the progression of its related complications ( Ponirakis et al, 2021a ). Many drugs have been used to control blood glucose; they include oral drugs such as metformin, glucagon-like peptide-1 (GLP-1) receptor agonist or sodium–glucose cotransporter type 2 inhibitor, as well as injection drugs such as insulin.…”

Pioglitazone in diabetic kidney disease: forgotten but not gone

“…Early intensive triple therapy with MET, PIO and exenatide was shown to produce greater and more durable A1C reductions in patients with new-onset T2D compared to sequential add-on therapy with MET followed by SU and then basal insulin; patients treated with triple combination therapy experienced less hepatic steatosis and fibrosis compared to those in the conventional therapy group [ 162 , 163 ]. Improvement of painful diabetic neuropathy and corneal nerve regeneration were also demonstrated, while the generalizability of these results in other diabetic microvascular complications is anticipated [ 164 ].…”