Corneal confocal microscopy identifies small-fiber neuropathy in subjects with impaired glucose tolerance who develop type 2 diabetes

Shazli Azmi, Maryam Ferdousi, Ioannis N. Petropoulos, Georgios Ponirakis, Uazman Alam, Hassan Fadavi, Omar Asghar, Andrew Marshall, Andrew J. Atkinson, Wendy Jones, Andrew J.M. Boulton, Mitra Tavakoli, Maria Jeziorska, Rayaz Malik

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

OBJECTIVE Impaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management. RESEARCH DESIGN AND METHODS Thirty subjects with IGT and 17 age-matched control subjects underwent an oral glucose tolerance test, assessment of neuropathic symptoms and deficits, quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and annually for 3 years. RESULTS Ten subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), andmean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjectswho returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P < 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years. CONCLUSIONS CCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status.

Original languageEnglish
Pages (from-to)1502-1508
Number of pages7
JournalDiabetes Care
Volume38
Issue number8
DOIs
Publication statusPublished - 1 Aug 2015

Fingerprint

Glucose Intolerance
Nerve Fibers
Confocal Microscopy
Type 2 Diabetes Mellitus
Biopsy
Glucose
Skin
Neurophysiology
Symptom Assessment
Glucose Tolerance Test
Small Fiber Neuropathy

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

Cite this

Corneal confocal microscopy identifies small-fiber neuropathy in subjects with impaired glucose tolerance who develop type 2 diabetes. / Azmi, Shazli; Ferdousi, Maryam; Petropoulos, Ioannis N.; Ponirakis, Georgios; Alam, Uazman; Fadavi, Hassan; Asghar, Omar; Marshall, Andrew; Atkinson, Andrew J.; Jones, Wendy; Boulton, Andrew J.M.; Tavakoli, Mitra; Jeziorska, Maria; Malik, Rayaz.

In: Diabetes Care, Vol. 38, No. 8, 01.08.2015, p. 1502-1508.

Research output: Contribution to journalArticle

Azmi, S, Ferdousi, M, Petropoulos, IN, Ponirakis, G, Alam, U, Fadavi, H, Asghar, O, Marshall, A, Atkinson, AJ, Jones, W, Boulton, AJM, Tavakoli, M, Jeziorska, M & Malik, R 2015, 'Corneal confocal microscopy identifies small-fiber neuropathy in subjects with impaired glucose tolerance who develop type 2 diabetes', Diabetes Care, vol. 38, no. 8, pp. 1502-1508. https://doi.org/10.2337/dc14-2733
Azmi, Shazli ; Ferdousi, Maryam ; Petropoulos, Ioannis N. ; Ponirakis, Georgios ; Alam, Uazman ; Fadavi, Hassan ; Asghar, Omar ; Marshall, Andrew ; Atkinson, Andrew J. ; Jones, Wendy ; Boulton, Andrew J.M. ; Tavakoli, Mitra ; Jeziorska, Maria ; Malik, Rayaz. / Corneal confocal microscopy identifies small-fiber neuropathy in subjects with impaired glucose tolerance who develop type 2 diabetes. In: Diabetes Care. 2015 ; Vol. 38, No. 8. pp. 1502-1508.
@article{09aeabf9402348ef9573cf512fc8bd50,
title = "Corneal confocal microscopy identifies small-fiber neuropathy in subjects with impaired glucose tolerance who develop type 2 diabetes",
abstract = "OBJECTIVE Impaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management. RESEARCH DESIGN AND METHODS Thirty subjects with IGT and 17 age-matched control subjects underwent an oral glucose tolerance test, assessment of neuropathic symptoms and deficits, quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and annually for 3 years. RESULTS Ten subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), andmean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjectswho returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P < 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years. CONCLUSIONS CCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status.",
author = "Shazli Azmi and Maryam Ferdousi and Petropoulos, {Ioannis N.} and Georgios Ponirakis and Uazman Alam and Hassan Fadavi and Omar Asghar and Andrew Marshall and Atkinson, {Andrew J.} and Wendy Jones and Boulton, {Andrew J.M.} and Mitra Tavakoli and Maria Jeziorska and Rayaz Malik",
year = "2015",
month = "8",
day = "1",
doi = "10.2337/dc14-2733",
language = "English",
volume = "38",
pages = "1502--1508",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "8",

}

TY - JOUR

T1 - Corneal confocal microscopy identifies small-fiber neuropathy in subjects with impaired glucose tolerance who develop type 2 diabetes

AU - Azmi, Shazli

AU - Ferdousi, Maryam

AU - Petropoulos, Ioannis N.

AU - Ponirakis, Georgios

AU - Alam, Uazman

AU - Fadavi, Hassan

AU - Asghar, Omar

AU - Marshall, Andrew

AU - Atkinson, Andrew J.

AU - Jones, Wendy

AU - Boulton, Andrew J.M.

AU - Tavakoli, Mitra

AU - Jeziorska, Maria

AU - Malik, Rayaz

PY - 2015/8/1

Y1 - 2015/8/1

N2 - OBJECTIVE Impaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management. RESEARCH DESIGN AND METHODS Thirty subjects with IGT and 17 age-matched control subjects underwent an oral glucose tolerance test, assessment of neuropathic symptoms and deficits, quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and annually for 3 years. RESULTS Ten subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), andmean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjectswho returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P < 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years. CONCLUSIONS CCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status.

AB - OBJECTIVE Impaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management. RESEARCH DESIGN AND METHODS Thirty subjects with IGT and 17 age-matched control subjects underwent an oral glucose tolerance test, assessment of neuropathic symptoms and deficits, quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and annually for 3 years. RESULTS Ten subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), andmean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjectswho returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P < 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years. CONCLUSIONS CCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status.

UR - http://www.scopus.com/inward/record.url?scp=84962368256&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962368256&partnerID=8YFLogxK

U2 - 10.2337/dc14-2733

DO - 10.2337/dc14-2733

M3 - Article

VL - 38

SP - 1502

EP - 1508

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 8

ER -