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The spectrum of neuropathy in diabetes and impaired glucose tolerance
Abstract
OBJECTIVE: To compare the neuropathy associated with impaired glucose tolerance (IGT) and diabetes mellitus (DM) determined by oral glucose tolerance testing (OGTT). METHODS: Patients with peripheral neuropathy of unknown cause were prescribed OGTT. Duration of neuropathic symptoms, neuropathic pain, neuropathy classification, nerve conduction test results, and intraepidermal nerve fiber densities (IENFD) were compared between IGT and DM groups. RESULTS: Seventy-three patients completed OGTT; 41 (56%) had abnormal results. Of these 41 patients, 26 had IGT and 15 had DM. Patients with IGT had less severe neuropathy than patients with diabetes, as measured by sural nerve amplitudes (p = 0.056), sural nerve conduction velocities (p = 0.03), and distal leg IENFD (p = 0.01). Patients with IGT had predominantly small fiber neuropathy, compared to patients with DM (p = 0.05), who had more involvement of large nerve fibers. CONCLUSIONS: The neuropathy associated with IGT is milder than the neuropathy associated with DM. Small nerve fibers are prominently affected and may be the earliest detectable sign of neuropathy in glucose dysmetabolism. OGTT is appropriate in patients with idiopathic neuropathy.
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“Finally, evidence is accumulating on increased prevalence of idiopathic polyneuropathy (eg, idiopathic sensory/painful neuropathy,73–78 and sensory/small fibre only neuropathy)73,75,78 among prediabetic individuals with IGT being more strongly related to painful than non-painful neuropathy.73,75,78”
From Prediabetes: a high-risk state for diabetes development (2012) · cites this paper as [78]
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Incidence and prevalence of small-fiber neuropathy
Peters, M. J. H., Bakkers, M., Merkies, I. S. J., Hoeijmakers, J. G. J., van Raak, E. P. M., & Faber, C. G. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a8236e · Cited by 151
Smith, S. M., Dworkin, R. H., Turk, D. C., Baron, R., Polydefkis, M. J., Tracey, I., Borsook, D., Edwards, R. R., Harris, R. E., Wager, T. D., et al. (2017) · Journal of Pain · doi:10.1016/j.jpain.2017.02.429 · Cited by 150
“biopsy detected neuropathy in individuals with impaired glucose tolerance or occult diabetes who had normal large fiber test results.(139,170,171,176) Patients with SFN followed for approximately 2.”
Self-citationBuysschaert, M., & Bergman, M. (2011) · Medical Clinics of North America · doi:10.1016/j.mcna.2010.11.002 · Cited by 159
A new simple method for assessing sudomotor function: Relevance in type 2 diabetes
Mayaudon, H., Miloche, P.-O., & Bauduceau, B. (2010) · Diabetes & Metabolism · doi:10.1016/j.diabet.2010.05.004 · Cited by 151
Myelinated nerve endings in human skin
Provitera, V., Nolano, M., Pagano, A., Caporaso, G., Stancanelli, A., & Santoro, L. (2007) · Muscle & Nerve · doi:10.1002/mus.20771 · Cited by 147
Lee, C. C., Perkins, B. A., Kayaniyil, S., Harris, S. B., Retnakaran, R. R., Gerstein, H. C., Zinman, B., & Hanley, A. J. (2015) · Diabetes Care · doi:10.2337/dc14-2585 · Cited by 153
Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres
Burgess, J., Frank, B., Marshall, A. G., Khalil, R. S., Ponirakis, G., Petropoulos, I. N., Cuthbertson, D. J., Malik, R. A., & Alam, U. (2021) · Diagnostics · doi:10.3390/diagnostics11020165 · Cited by 152
“Sudoscan on the other hand, is an FDA approved point of care device [205] which has been advocated as a screening tool for DPN [206].”
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“This has been based on a number of observations, including: 1) findings of altered thermal thresholds in patients with normal NCSs (7,8); 2) reduced intraepithelial nerve fiber density (IENFD) at the ankle and IENFD ratios in diabetic patientswithout symptoms or signs of peripheral neuropathy and normal NCSs (8,11); a…”
BackgroundSmall fiber neuropathy: Getting bigger!
Chan, A. C. Y., & Wilder-Smith, E. P. (2016) · Muscle & Nerve · doi:10.1002/mus.25082 · Cited by 141
“showed that 56% of patients with idiopathic neuropathy had abnormal OGTT results, and the neuropathy associated with impaired glucose tolerance (IGT) is milder than the neuropathy associated with diabetes mellitus (DM).(49) However, Kassardjian et al.”
BackgroundTreatment of diabetic peripheral neuropathy: a review
Khdour, M. R. (2020) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.13241 · Cited by 155
“The same is not the case for type-2 diabetes; several studies have demonstrated that aggressive glycaemic control has no meaningful impact on patient risk for polyneuropathy.([17,18]) A systemic review by Callaghan et al.”
BackgroundUse of Antiepileptic Drugs in the Treatment of Chronic Painful Diabetic Neuropathy
Vinik, A. I. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2376 · Cited by 141
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Skin biopsy for the diagnosis of peripheral neuropathy
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Skin biopsy in the management of peripheral neuropathy
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Assessment of Epidermal Nerve Fibers
Ebenezer, G. J., Hauer, P. E., Gibbons, C. H., McArthur, J. C., & Polydefkis, M. J. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31815c8989 · Cited by 137
“Differences between people with type I versus type II diabetes have not been identified although severity of IENF loss has been linked to the severity of glucose dysmetabolism (50).”
BackgroundInfluentialSelf-citationNew Insights Into Diabetic Polyneuropathy
Polydefkis, M. J. (2003) · JAMA · doi:10.1001/jama.290.10.1371 · Cited by 134
Self-citationThrainsdottir, S., Malik, R. A., Dahlin, L. B., Wiksell, P., Eriksson, K. F., Rosén, I., Petersson, J., Greene, D. A., & Sundkvist, G. (2003) · Diabetes · doi:10.2337/diabetes.52.10.2615 · Cited by 134
Dorsal root ganglia sensory neuronal cultures: a tool for drug discovery for peripheral neuropathies
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“The use of DRG sensory neurons has several advantages: i) they represent the main cellular target of diabetic neurotoxicity; ii) it is possible to enrich the neuronal population with nerve growth factor (NGF) dependent neurons that are often the most vulnerable ones clinically [34] and in animal models of type I diabe…”
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Biological and medical physics, biomedical engineering
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Body Mass Index, Weight Gain, and Incident Urinary Incontinence in Middle-Aged Women
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Diagnosing Diabetic Neuropathy: Something Old, Something New
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“[42] found a reduction in IENFD, sural nerve amplitude and conduction velocity in patients with IGT and DM, with more marked abnormalities in patients with DM with a predominantly small fiber neuropathy in the IGT group.”
BackgroundSmall-Fiber Neuropathy/Neuronopathy Associated With Celiac Disease
Brannagan, T. H., Hays, A. P., Chin, S. S., Sander, H. W., Chin, R. L., Magda, P., Green, P. H. R., & Latov, N. (2005) · Archives of Neurology · doi:10.1001/archneur.62.10.1574 · Cited by 5
“There is likely a spectrum of fiber involvement with CD as occurs with diabetes mellitus.(9) In our previous study, we noted that 8% of the patients in our center with symptoms of neuropathy and normal results of sensory nerve conduction studies that suggested small-fiber neuropathy had CD.”
Background
Metadata
- Authors
- Sumner, C. J., Sheth, S., Griffin, J. W., Cornblath, D. R., & Polydefkis, M.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Neurology
- Published
- 2003-01-14
- Volume
- 60
- Issue
- 1
- Pages
- 108-111
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W1978686107
- Cited by
- 708
- References
- 25
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 11 · 2023: 13 · 2022: 19 · 2021: 21 · 2020: 30 · 2019: 26 · 2018: 27 · 2017: 35 · 2016: 37 · 2015: 42 · 2014: 53 · 2013: 43 · 2012: 40
- FWCI
- 21.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k23ns041374-04)
- National Institute of Neurological Disorders and Stroke (K23NS41374-01)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- diabetic peripheral neuropathy, impaired glucose tolerance, oral glucose tolerance test, small fiber neuropathy, intraepidermal nerve fiber density, nerve conduction velocity, sural nerve, neuropathic pain, neuropathy classification
- MeSH terms
- Adult, Aged, Aged, 80 and over, Blood Glucose, Cell Count, Diabetic Nephropathies, Electrodiagnosis, Electromyography, Epidermis, Female, Glucose Tolerance Test, Humans, Male, Middle Aged, Nerve Fibers, Neural Conduction, Pain Measurement, Peripheral Nervous System Diseases, Sural Nerve, Cell Size
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