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

Georgios Ponirakis; Muhammad A. Abdul-Ghani; Amin Jayyousi; Mahmoud A. Zirie; Murtaza Qazi; Hamad Almuhannadi; Ioannis N. Petropoulos; Adnan Khan; Hoda Gad; Osama Migahid; Ayman Megahed; Salma Al-Mohannadi; Fatema AlMarri; Fatima Al-Khayat; Ziyad Mahfoud; Hanadi Al Hamad; Marwan Ramadan; Ralph DeFronzo; Rayaz A. Malik

doi:10.1111/jdi.13544

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

Georgios Ponirakis, Muhammad A. Abdul-Ghani, Amin Jayyousi, Mahmoud A. Zirie, Murtaza Qazi, Hamad Almuhannadi, Ioannis N. Petropoulos, Adnan Khan, Hoda Gad, Osama Migahid, Ayman Megahed, Salma Al-Mohannadi, Fatema AlMarri, Fatima Al-Khayat, Ziyad Mahfoud, Hanadi Al Hamad, Marwan Ramadan, Ralph DeFronzo, Rayaz A. Malik

Division of Diabetes

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1642-1650
Number of pages	9
Journal	Journal of Diabetes Investigation
Volume	12
Issue number	9
DOIs	https://doi.org/10.1111/jdi.13544
State	Published - Sep 2021

Keywords

Corneal confocal microscopy
Exenatide
Painful diabetic neuropathy

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

Access to Document

10.1111/jdi.13544

Cite this

Ponirakis, G., Abdul-Ghani, M. A., Jayyousi, A., Zirie, M. A., Qazi, M., Almuhannadi, H., Petropoulos, I. N., Khan, A., Gad, H., Migahid, O., Megahed, A., Al-Mohannadi, S., AlMarri, F., Al-Khayat, F., Mahfoud, Z., Al Hamad, H., Ramadan, M., DeFronzo, R., & Malik, R. A. (2021). Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control. Journal of Diabetes Investigation, 12(9), 1642-1650. https://doi.org/10.1111/jdi.13544

Ponirakis, G, Abdul-Ghani, MA, Jayyousi, A, Zirie, MA, Qazi, M, Almuhannadi, H, Petropoulos, IN, Khan, A, Gad, H, Migahid, O, Megahed, A, Al-Mohannadi, S, AlMarri, F, Al-Khayat, F, Mahfoud, Z, Al Hamad, H, Ramadan, M, DeFronzo, R & Malik, RA 2021, 'Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control', Journal of Diabetes Investigation, vol. 12, no. 9, pp. 1642-1650. https://doi.org/10.1111/jdi.13544

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title = "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.",

keywords = "Corneal confocal microscopy, Exenatide, Painful diabetic neuropathy",

author = "Georgios Ponirakis and Abdul-Ghani, {Muhammad A.} and Amin Jayyousi and Zirie, {Mahmoud A.} and Murtaza Qazi and Hamad Almuhannadi and Petropoulos, {Ioannis N.} and Adnan Khan and Hoda Gad and Osama Migahid and Ayman Megahed and Salma Al-Mohannadi and Fatema AlMarri and Fatima Al-Khayat and Ziyad Mahfoud and {Al Hamad}, Hanadi and Marwan Ramadan and Ralph DeFronzo and Malik, {Rayaz A.}",

note = "Funding Information: We thank all the participants for their efforts and commitment to be involved in the study. This work was funded by the Qatar National Research Fund (BMRP‐5726113101 & NPRP 5‐273‐3‐079). AstraZeneca provided exenatide for the Qatar Study. Publisher Copyright: {\textcopyright} 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.",

year = "2021",

month = sep,

doi = "10.1111/jdi.13544",

language = "English (US)",

volume = "12",

pages = "1642--1650",

journal = "Journal of Diabetes Investigation",

issn = "2040-1116",

publisher = "Blackwell Publishing Asia Pty Ltd",

number = "9",

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TY - JOUR

T1 - Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control

AU - Ponirakis, Georgios

AU - Abdul-Ghani, Muhammad A.

AU - Jayyousi, Amin

AU - Zirie, Mahmoud A.

AU - Qazi, Murtaza

AU - Almuhannadi, Hamad

AU - Petropoulos, Ioannis N.

AU - Khan, Adnan

AU - Gad, Hoda

AU - Migahid, Osama

AU - Megahed, Ayman

AU - Al-Mohannadi, Salma

AU - AlMarri, Fatema

AU - Al-Khayat, Fatima

AU - Mahfoud, Ziyad

AU - Al Hamad, Hanadi

AU - Ramadan, Marwan

AU - DeFronzo, Ralph

AU - Malik, Rayaz A.

N1 - Funding Information: We thank all the participants for their efforts and commitment to be involved in the study. This work was funded by the Qatar National Research Fund (BMRP‐5726113101 & NPRP 5‐273‐3‐079). AstraZeneca provided exenatide for the Qatar Study. Publisher Copyright: © 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

PY - 2021/9

Y1 - 2021/9

N2 - 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.

AB - 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.

KW - Corneal confocal microscopy

KW - Exenatide

KW - Painful diabetic neuropathy

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