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Cited by 148Pain Mechanisms and TreatmentsOcular Surface and Contact LensPeripheral Neuropathies and Disorders

Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes

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Azmi, Shazli, Ferdousi, Maryam, Petropoulos, Ioannis N., Ponirakis, Georgios, Alam, Uazman, Fadavi, Hassan, Asghar, Omar, Marshall, Andrew +6 more·2015·Diabetes Care
DOI 10.2337/dc14-2733PMC PMC4512140
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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), and mean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjects who 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.

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  • There are data showing a relationship between glucose tolerance and alterations in IENFD as well as corneal nerve fiber morphology.

    “However, there are data showing a relationship between glucose tolerance and alterations in IENFD as well as corneal nerve fiber morphology.3”

    From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [3]

    The Results section (“Change in Neuropathy Measures in Relation to Change in Glucose Tolerance”) reports that corneal nerve morphology worsened in subjects who developed type 2 diabetes and improved in those who returned to normal glucose tolerance. It also reports decreased IENFD in all three groups, including those who returned to normal glucose tolerance. The Conclusions section therefore describes corneal morphology, but not IENFD, as responsive to changes in glucose-tolerance status. (LLM, conf=0.83)

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Authors
Azmi, S., Ferdousi, M., Petropoulos, I. N., Ponirakis, G., Alam, U., Fadavi, H., Asghar, O., Marshall, A., Atkinson, A. J., Jones, W., Boulton, A. J. M., Tavakoli, M., Jeziorska, M., & Malik, R. A.
Affiliations
  • Manchester Academic Health Science Centre (GB)
  • Department of Clinical Neurophysiology, Central Manchester NHS Foundation Trust, Manchester, U.K.
Corresponding author
Malik, Rayaz A.
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2015-04-15
Volume
38
Issue
8
Pages
1502-1508
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc14-2733
PMC
PMC4512140
OpenAlex
W2123471547
Cited by
148
References
7
Citations by year
2026: 7 · 2025: 13 · 2024: 8 · 2023: 10 · 2022: 16 · 2021: 20 · 2020: 23 · 2019: 18 · 2018: 13 · 2017: 8 · 2016: 9 · 2015: 2
FWCI
7.86
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/site/license (vor, 292 d)
Locations
  • Diabetes Care (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
Funders
National Institute for Health Research (R1-05991)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
Keywords
corneal confocal microscopy, small fiber neuropathy, impaired glucose tolerance, type 2 diabetes, corneal nerve fiber density, intraepidermal nerve fiber density, diabetic neuropathy, risk stratification
MeSH terms
Biopsy, Needle, Blood Glucose, Cornea, Diabetes Mellitus, Type 2, Diabetic Neuropathies, Erythromelalgia, Female, Glucose Tolerance Test, Humans, Male, Middle Aged, Nerve Fibers, Prediabetic State, Prospective Studies, Skin, Case-Control Studies, Glucose Intolerance, Microscopy, Confocal

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