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Increased Prevalence of Impaired Glucose Tolerance in Patients With Painful Sensory Neuropathy
Open accessAbstract
OBJECTIVE—To characterize a cohort of patients with neuropathy and impaired glucose tolerance (IGT) but no other identifiable cause of neuropathy. Of patients with diabetes, 10% have peripheral neuropathy at the time of their diagnosis, suggesting that axonal injury may occur early in the course of glucose intolerance. The American Diabetes Association (ADA) revised diagnostic criteria to recognize IGT (a serum glucose between 140 and 200 mg/dl in a 2-h oral glucose tolerance test [OGTT]) as a risk factor for cardiovascular disease independent of development of diabetes. RESEARCH DESIGN AND METHODS—Using revised ADA criteria for diabetes and IGT, we prospectively evaluated 107 sequential patients with idiopathic neuropathy. RESULTS—A total of 13 of the 107 patients had diabetes, whereas 36 (34%) had IGT, nearly three times the prevalence in age-matched control subjects (P < 0.01). OGTT was often elevated, whereas both fasting plasma glucose and HbA1c were normal. Comparing patients with diabetes, IGT, or normal OGTT, age and BMI were similar. However, painful sensory symptoms were more common in patients with IGT and diabetes, and family history of neuropathy was significantly more common in normoglycemic patients. Electrodiagnostic findings of axonal injury were less severe in patients with IGT and were more likely to be confined to sensory fibers than in patients with diabetes. CONCLUSIONS—Our results suggest that IGT may cause or contribute to small-fiber neuropathy, which is similar in phenotype to the painful sensory neuropathy commonly encountered in diabetes. Two-hour OGTT is more sensitive than other measures of glucose handling in screening these patients.
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“There is controversy regarding the effect of glucose dysmetabolism on small nerve fibers34,42 and symptom severity16,48,56 in FMS.”
From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [42]
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In the citing paper
“Other forms of diabetic neuropathies are mononeuritis such as cranial nerve palsies or entrapment neuropathies (eg, carpal tunnel syndrome, ulnar entrapment, and peroneal entrapment, among others).632–635”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [635]
Experimental — accuracy not yet measuredIn the citing paper
“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 [75]
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ResultTests and Expenditures in the Initial Evaluation of Peripheral Neuropathy
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“The prevalence of impaired glucose tolerance in otherwise idiopathic patients with neuropathy is higher compared with that of historical controls, and the type of neuropathy in these patients is different (more sensory and painful neuropathies).(9,10) Therefore, emerging data support impaired glucose tolerance as pote…”
Impaired glucose tolerance is associated with postganglionic sudomotor impairment
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MethodMeasurement of small fibre pain threshold values for the early detection of diabetic polyneuropathy
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EZSCAN™ a new technology to detect diabetes risk
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“Additionally, there is more and more evidence indicating that, among people with IGT, the prevalence of idiopathic polyneuropathy, painful sensory neuropathy [69–71], and small-fiber neuropathy [72,73] is higher, while the motor fibers are less often affected [67,71].”
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“However, standard nerve conduction studies are often normal in the presence of somatic small fiber neuropathy (SFN) which appears during the early stage of diabetes (Singleton et al., 2001).”
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Sural nerve biopsy may predict future nerve dysfunction
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S100B as a glial cell marker in diabetic peripheral neuropathy
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Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral neuropathy
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“On this basis a change in the sweat response may be a highly sensitive test in detecting small fiber neuropathy [18].”
BackgroundKoytak, P. K., Isak, B., Borucu, D., Uluç, K., Tanrıdağ, T., & Us, Ö. (2011) · Muscle & Nerve · doi:10.1002/mus.21877 · Cited by 25
Putz, Z., Németh, N., Istenes, I., Martos, T., Gandhi, R. A., Körei, A. E., Hermányi, Z., Szathmári, M., Jermendy, G., Tesfaye, S. H., et al. (2012) · Diabetic Medicine · doi:10.1111/dme.12111 · Cited by 25
Metabolic Syndrome in Small Fiber Sensory Neuropathy
Zhou, L., Li, J., Ontaneda, D., & Sperling, J. (2011) · Journal of Clinical Neuromuscular Disease · doi:10.1097/cnd.0b013e3182196e3c · Cited by 26
SFN-SIQ, SFNSL and skin biopsy of 55 cases with small fibre involvement
Sun, B., Li, Y., Liu, L., Chen, Z., Ling, L., Yang, F., Liu, J., Liu, H., & Huang, X. (2017) · International Journal of Neuroscience · doi:10.1080/00207454.2017.1398152 · Cited by 27
“IGT was the most prevalent neuropathy, which is consistent with previous research [18].”
ResultPrediabetes, diabetes, metabolic syndrome, and small fiber neuropathy
Thaisetthawatkul, P., Lyden, E. R., Fernandes, J. A., & Herrmann, D. N. (2020) · Muscle & Nerve · doi:10.1002/mus.26825 · Cited by 24
Drug therapy for chronic idiopathic axonal polyneuropathy
Warendorf, J. K., Vrancken, A. F. J. E., van Schaik, I. N., Hughes, R. A., & Notermans, N. C. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003456.pub3 · Cited by 23
Thermal Threshold: Research Study on Small Fiber Dysfunction in Distal Diabetic Polyneuropathy
Jiménez-Cohl, P., Grekin, C., Leyton, C., Vargas, C., & Villaseca, R. (2012) · Journal of Diabetes Science and Technology · doi:10.1177/193229681200600122 · Cited by 23
Sé, A., Novikov, I. A., Махотин, С. С., & Сурнина, З. В. (2015) · Russian Annals of Ophthalmology · doi:10.17116/oftalma201513145-14 · Cited by 22
Abduljawad, S. H., El‐Refaei, M. F., & El-Nashar, N. N. G. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.06.019 · Cited by 22
“1016 E D P R O O F defined as diabetic when their non-fasting blood glucose level (BGL) reached more than 200 mg/dl in two consecutive readings [22].”
The Evaluation of Distal Symmetric Polyneuropathy
Callaghan, B. C. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.1735 · Cited by 22
“This finding may be the result of the fact that there is controversy about whether IGT causes DSP.14,16,18-20 In con- trast, MRI scans are used frequently without a clear indication.”
BackgroundInfluentialAn Approach to the Evaluation of Peripheral Neuropathies
Bromberg, M. B. (2005) · Seminars in Neurology · doi:10.1055/s-2005-871323 · Cited by 22
Self-citationIs there cardiac autonomic neuropathy in prediabetes?
Zilliox, L. A., & Russell, J. W. (2020) · Autonomic Neuroscience · doi:10.1016/j.autneu.2020.102722 · Cited by 23
Kamel, J. T., Vogrin, S. J., Knight-Sadler, R., Willems, N. K., Seiderer, L., Cook, M. J., MacIsaac, R. J., & Roberts, L. J. (2014) · Clinical Neurophysiology · doi:10.1016/j.clinph.2014.09.011 · Cited by 20
“fibers can be detected by standard techniques (Singleton et al., 2001; Lacomis, 2002).”
MethodA Rational Diagnostic Approach to Peripheral Neuropathy
Smith, A. G., & Bromberg, M. B. (2003) · Journal of Clinical Neuromuscular Disease · doi:10.1097/00131402-200306000-00005 · Cited by 20
“Likewise, hemoglobin Alc (HbAlc) provides a useful measure of overall glucose control over a 3-month period but is a poor diagnostic test.(37) For patients with neuropathy, an OGTT is the preferred diagnostic test.”
BackgroundSelf-citationPourhamidi, K., Dahlin, L. B., Englund, E., & Rolandsson, O. (2013) · Diabetes Care · doi:10.2337/dc12-1331 · Cited by 21
“When addressing the question of whether ‘IGT neuropathy’ truly exists, objective measures of nerve dysfunction are frequently crude and focused on large nerve fibers, while small nerve fiber dysfunction is often overlooked (1, 4, 6)”
BackgroundRelations between Metabolic Homeostasis, Diet, and Peripheral Afferent Neuron Biology
Dunn, T. N., & Adams, S. H. (2014) · Advances in Nutrition · doi:10.3945/an.113.005439 · Cited by 19
Gwathmey, K. G. (2017) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000518 · Cited by 19
The Effects of C‐peptide on Type 1 Diabetic Polyneuropathies and Encephalopathy in the BB/Wor‐rat
Sima, A. A. F., Zhang, W., Li, Z.-G., & Kamiya, H. (2008) · Journal of Diabetes Research · doi:10.1155/2008/230458 · Cited by 19
“Impaired insulin and/or NGF support may also explain the occurrence of painful diabetic neuropathy in prediabetic patients with impaired insulin function [59, 60], and nociceptive neuropathy in prediabetic rats with impaired glucose tolerance but without overt hyperglycemic diabetes [61].”
BackgroundLysy, Z., Lovblom, L. E., Halpern, E. M., Ngo, M., Ng, E., Orszag, A., Breiner, A., Bril, V., & Perkins, B. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106995 · Cited by 19
“The hypothesis on the pathophysiology and progression of DSP in subjects with diabetes is that nerve fiber damage is progressive and affects small thinly myelinated Ad and unmyelinated C fibers at the onset.[6,11] By virtue of this hypothesis, there may exist a subset of subjects who have established evidence of nerve…”
BackgroundThe heterogeneity of diabetic neuropathy
Anders, A. F. S. (2008) · Frontiers in bioscience · doi:10.2741/3040 · Cited by 18
Dyslipidaemia in chronic acquired distal axonal polyneuropathy
Rajabally, Y. A., & Shah, R. S. (2011) · Journal of Neurology · doi:10.1007/s00415-011-5950-z · Cited by 18
“Although our controls had not been investigated for IGT by OGTT, we found a high proportion of patients with IGT and no other cause of neuropathy (about 35%), in accordance with several other studies [16–19].”
ResultThe Efficacy of Pregabalin in the Treatment of Prediabetic Neuropathic Pain
González‐Duarte, A., Lem‐Carrillo, M., Díaz‐Díaz, E., Castillo, C., & Cárdenas‐Soto, K. (2015) · Clinical Journal of Pain · doi:10.1097/ajp.0000000000000339 · Cited by 17
Peripheral Neuropathy With Impaired Glucose Tolerance
Kissel, J. T. (2006) · Archives of Neurology · doi:10.1001/archneur.63.8.1055 · Cited by 18
The Epidemiology of Diabetic Neuropathy
Hansen, C. S., Määttä, L. L., Andersen, S. T., & Charles, M. H. (2023) · Contemporary Diabetes · doi:10.1007/978-3-031-15613-7_2 · Cited by 17
Wei, M., Zhu, J., Wang, N., Xue, Q., Liu, F., Hu, B., Junchu, F., & Zhang, Y. (2012) · Muscle & Nerve · doi:10.1002/mus.23418 · Cited by 17
Hube, L., Dohrn, M. F., Karsai, G., Hirshman, S., Damme, P. V., Schulz, J. B., Weis, J., Hornemann, T., & Claeys, K. G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0170583 · Cited by 17
“Previous studies indicate a higher prevalence of metabolic risk factors such as IGT [6, 7], hypercholesterolemia [5], hypertriglyceridemia [4, 5], abdominal obesity and arterial hypertension [3] in CIAP-patients.”
BackgroundMethodBril, V., Perkins, B. A., & Toth, C. C. (2013) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2013.01.039 · Cited by 18
Ferreira‐da‐Silva, F. W., da Silva‐Alves, K. S., Lemos-dos-Santos, M., de Oliveira, K. A., Joca, H. C., do Vale, O. C., Coelho‐de‐Souza, A. N., & Leal‐Cardoso, J. H. (2013) · ISRN Endocrinology · doi:10.1155/2013/638028 · Cited by 17
“It is also in coherence with the clinical findings, which have documented important sensory alterations, including hyperalgesia, allodynia, and pain in cases of human glucose intolerance [34, 35] without fasting glycemic values characteristic of DM.”
ResultDetermination of nerve conduction abnormalities in patients with impaired glucose tolerance
Şahin, Ş., Karşıdağ, S., Ayalp, S., Şengül, A. M., Us, Ö., & Karşıdağ, K. (2009) · Neurological Sciences · doi:10.1007/s10072-009-0089-8 · Cited by 17
“2% for individuals aged 60–75 years, and later gradually reduces [1, 24].”
A comparison of sural nerve conduction studies in patients with impaired oral glucose tolerance test
Koçer, A., Domaç, F. M., Boylu, E., Us, Ö., & Tanrıdağ, T. (2007) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2007.00886.x · Cited by 17
Metadata
- Authors
- Singleton, J. R., Smith, A. G., & Bromberg, M. B.
- Affiliations
- University of Utah (US)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2001-08-01
- Volume
- 24
- Issue
- 8
- Pages
- 1448-1453
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2095995150
- Cited by
- 364
- References
- 32
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 7 · 2022: 12 · 2021: 7 · 2020: 21 · 2019: 9 · 2018: 17 · 2017: 20 · 2016: 14 · 2015: 22 · 2014: 28 · 2013: 25 · 2012: 21
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- 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
- impaired glucose tolerance, small fiber neuropathy, peripheral neuropathy, diabetes mellitus, oral glucose tolerance test, axonal injury, electrodiagnostic findings
- MeSH terms
- Adult, Aged, Arsenic, Blood Glucose, Cardiovascular Diseases, Diabetic Neuropathies, Electromyography, Glucose Tolerance Test, Glycated Hemoglobin, Humans, Lead, Mercury, Middle Aged, Neural Conduction, Neuralgia, Peripheral Nervous System Diseases, Prospective Studies, Risk Factors, Body Mass Index, Prevalence, Glucose Intolerance
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