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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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Impaired Distal Thermoregulation in Diabetes and Diabetic Polyneuropathy
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“While sensory nerve conduction examines largefiber neuropathy, skin innervation is a parameter of smallfiber sensory neuropath (65).”
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“This is significant because it is similar to findings from prediabetic and obese human patients.(65) It should be noted that protocols often differ in the percent and source of fat, as well”
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“Without a gold standard for classifying SFN, a series of different definitions and classifications have therefore been suggested,(10,12-15) which in part may explain the large variation in frequency of SFN in different samples reported in the literature (7%-54%).(10,12,14) Based on the fact that there is no gold stand…”
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Association between visceral, cardiac and sensorimotor polyneuropathies in diabetes mellitus
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“Impaired glucose tolerance (IGT) is a transitional stage to DM, and many previous research studies have suggested that IGT plays a role in the development of neuropathy (10,11).”
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“There is an emerging consensus that small nerve fibers are earliest and most consistently affected in a length-dependent fashion (14, 23, 24).”
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“As IGT-related neuropathy is characterized by involvement of a heterogenous fiber population in which small nerve fiber injury predominates [12,21], our data showing IGT-PN induced deficits in UST and TREs are consistent with the idea that small fiber injury is associated with deficits in upright equilibrium.”
BackgroundResultPossible contribution of adipocytokines on diabetic neuropathy
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“The most common causes of polyneuropathy are diabetes mellitus and hereditary factors [7,17].”
BackgroundNeuropathy and impaired glucose tolerance: an updated review of the evidence
Rajabally, Y. A. (2010) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2010.01425.x · Cited by 34
“(26) described in 2003, 26 of 58 patients (45%) with neuropathy having IGT on GTT.”
BackgroundDiabetic neuropathy: Clinical features, etiology, and therapy
Podwall, D., & Gooch, C. L. (2004) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-004-0013-9 · Cited by 34
Valdivia, J. M. V., Weinand, M. E., Maloney, C. T., Blount, A. L., & Dellon, A. L. (2013) · Annals of Plastic Surgery · doi:10.1097/sap.0b013e3182764fb0 · Cited by 34
Diabetic Neuropathy and Axon Reflex-Mediated Neurogenic Vasodilatation in Type 1 Diabetes
Nouri, M. N., Ahmed, A., Bril, V., Orszag, A., Ng, E., Nwe, P., & Perkins, B. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034807 · Cited by 35
“The prevailing concept of the natural history of DSP is that early nerve damage begins in small thinly myelinated Ad and unmyelinated C-type nerve fibres [8,9], which can be examined morphologically by quantification of intraepidermal nerve fibre density from skin biopsy [10], or by Figure 1.”
Therapy Insight: neurological complications of prediabetes
Singleton, J. R., & Smith, A. G. (2006) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0172 · Cited by 34
High Energy Diets-Induced Metabolic and Prediabetic Painful Polyneuropathy in Rats
Xie, F., Han, F., Hou, J., Jiao, K., Costigan, M., & Chen, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057427 · Cited by 35
Chronic Microvascular Complications in Prediabetic States—An Overview
Baranowska-Jurkun, A., Matuszewski, W., & Bandurska-Stankiewicz, E. M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9103289 · Cited by 37
“Neuropathy in people with IGT seems to assume a milder course than in the case of DM patients because it affects mainly small not large nerve fibers [71].”
BackgroundLim, M. H., Lee, W., Jeon, B., & Kim, S. (2021) · IEEE Access · doi:10.1109/access.2021.3100007 · Cited by 31
“Diabetes mellitus is a chronic disorder of improper glucose metabolism that induces complications such as cardiovascular disease [1], and neuropathy [2].”
BackgroundIntraepidermal nerve fibre density at wrist level in diabetic and non‐diabetic patients
Thomsen, N., Englund, E. M., Thrainsdottir, S., Rosén, I., & Dahlin, L. B. (2009) · Diabetic Medicine · doi:10.1111/j.1464-5491.2009.02823.x · Cited by 33
Role of the Oral Glucose Tolerance Test (OGTT) in the idiopathic restless legs syndrome
Bosco, D., Plastino, M., Fava, A., Ettore, M., Bosco, F., Ermio, C., Tallarigo, F., Pirritano, D., & Consoli, D. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2009.09.008 · Cited by 32
“analyzing epidermal fibres on skin specimens, suggested that patients with IGT had less severe neuropathy with preferential small fibre involvement than patients with DM [15].”
BackgroundArimura, A., Deguchi, T., Sugimoto, K., Uto, T., Nakamura, T., Arimura, Y., Arimura, K., Yagihashi, S., Nishio, Y., & Takashima, H. (2012) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2012.09.026 · Cited by 33
Garoushi, S., Johnson, M. I., & Tashani, O. A. (2019) · BMC Public Health · doi:10.1186/s12889-018-6374-9 · Cited by 32
Insulin resistance increases risk of carpal tunnel syndrome: a case‐control study
Plastino, M., Fava, A., Colica, C., Bartolo, M. D., Ermio, C., Cristiano, D., Ettore, M., Abenavoli, L., & Bosco, D. (2011) · Journal of the Peripheral Nervous System · doi:10.1111/j.1529-8027.2011.00344.x · Cited by 31
Mok, T. (2010) · The HKU Scholars Hub (University of Hong Kong) · Cited by 31
dell’Omo, R., Cifariello, F., Turris, S. D., Romano, V., Renzo, F. D., Taranto, D. D., Coclite, G., Agnifili, L., Mastropasqua, L., & Costagliola, C. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.06.010 · Cited by 31
Määttä, L. L., Charles, M., Witte, D. R., Bjerg, L., Jørgensen, M. E., Jensen, T. S., & Andersen, S. T. (2019) · Diabetes Care · doi:10.2337/dc19-0869 · Cited by 31
“, peoplewith impaired glucose tolerance, people with overt and often long-standing diabetes) (4,6,11,13).”
BackgroundCoppey, L. J., Davidson, E. P., Lu, B., Gerard, C. J., & Yorek, M. A. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.09.008 · Cited by 30
“It is known that painful sensory neuropathy is also associated with impaired glucose tolerance or metabolic syndrome (Singleton et al., 2001a; b; Sumner et al., 2003; Pittenger et al., 2005).”
BackgroundDeng, W., Dong, X., Zhang, Y., Jiang, Y., Lu, D., Wu, Q., Liang, Z., Yang, G., & Chen, B. (2014) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2014.05.012 · Cited by 32
“[24] Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis M.”
BackgroundInflammation role in sensory neuropathy in Chinese patients with diabetes/prediabetes
Zeng, J., Xu, Y., Shi, Y. F., & Jiang, C. (2018) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2018.01.031 · Cited by 32
State of the art paper APOE gene polymorphisms and diabetic peripheral neuropathy
Monastiriotis, C., Παπάνας, Ν., Veletza, S. V., & Maltezos, E. S. (2012) · Archives of Medical Science · doi:10.5114/aoms.2012.30279 · Cited by 29
“It has also been noted that some patients show minor or no clinical signs of neuropathy even after many years of diabetes, while others suffer from severe neuropathy by the time of, or before, the diagnosis of DM [7-10].”
BackgroundWu, L.-Y., Li, M., Qu, M., Li, X., Pi, L., Chen, Z., Zhou, S., Yi, X., Shi, X., Wu, J., et al. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.11.025 · Cited by 31
A method to quantify autonomic nervous system function in healthy, able-bodied individuals
Debnath, S., Levy, T. J., Bellehsen, M. H., Schwartz, R. M., Barnaby, D. P., Zanos, S. P., Volpe, B. T., & Zanos, T. P. (2021) · Bioelectronic Medicine · doi:10.1186/s42234-021-00075-7 · Cited by 30
“…response (SSR), silicone impressions, the acetylcholine sweat-spot test, and quantitative direct and indirect reflex testing (QDIRT), which also belong to the standard range of provocative autonomic tests (Sumner et al., 2003; Pittenger et al., 2005; Low et al., 2006; Illigens & Gibbons, 2008).”
BackgroundMethodLarge and Small Fiber Dysfunction in Peripheral Nerve Injuries With or Without Spontaneous Pain
Kleggetveit, I. P., & Jørum, E. (2010) · Journal of Pain · doi:10.1016/j.jpain.2010.03.004 · Cited by 29
Cheng, J., Daftari, A. P., & Zhou, L. (2012) · Case Reports in Anesthesiology · doi:10.1155/2012/285328 · Cited by 31
A 52-Year-Old Woman With Disabling Peripheral Neuropathy
Rutkove, S. B. (2009) · JAMA · doi:10.1001/jama.2009.1377 · Cited by 29
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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