Skip to main content

Advertisement

SpringerLink
Log in

Assessment of small nerve fiber function as an early marker of peripheral neuropathy in children and adolescents with type 1 diabetes mellitus (T1DM)

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

This study aimed to assess subclinical peripheral diabetic neuropathy (PDN) in adolescents with type 1 diabetes mellitus (T1DM).

Methods

Subjects included 53 T1DM patients (age (mean ± SE): 15.8 ± 0.54 years, disease duration: 6.0 ± 0.51 years and HbA1c: 7.9 ± 0.19%), and 37 healthy gender matched controls (age: 15.6 ± 0.52 years). PDN was assessed by vibration perception threshold (VPT) and by quantitative sensory testing (QST). In controls, 95% confidence intervals were calculated.

Results

Among patients, VPT prevalence of abnormality ranged from 60–73.4% on different sites. Higher VPT was found in patients on all examined sites (p < 0.01). In controls, VPT correlated with height (r = 0.48, p = 0.05). Regarding QST prevalence of abnormality, cold detection threshold (CDT) ranged 7.3–39.0%, cold pain threshold (CPT) ranged 22.22–29.63%, hot detection threshold (HDT) ranged 34.14–63.41%, and hot pain threshold (HPT) ranged 15.79–36.84%. In patients, CPT correlated with BMI (r = 0.42, p = 0.05) and diabetes duration, (r = 0.40, p = 0.05), HPT correlated with age (r = 0.36, p = 0.05) and height (r = 0.35, p = 0.05), while in controls with BMI (r = 0.51, p = 0.05). No correlation of VPT or QST with HbA1c was observed.

Conclusion

Adolescents with T1DM in this study, although asymptomatic, showed a high prevalence of impaired indices of PDN, highlighting potential clinical implications of early identification of PDN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. R. Pop-Busui, A.J.M. Boulton, E.L. Feldman et al. Diabetic neuropathy: A position statement by the American Diabetes Association. Diab. Care 40(1), 136–154 (2017)

    Article  CAS  Google Scholar 

  2. M. Louraki, C. Tsentidis, D. Kallinikou, M. Katsalouli, C. Kanaka-Gantenbein, N. Kafassi, A. Papathanasiou, K. Karavanaki, Reproducibility of vibration perception threshold values in children and adolescents with type 1 diabetes mellitus and associated factors. Prim. Care Diab 8(2), 147–157 (2014)

    Article  CAS  Google Scholar 

  3. D. Lacomis, Small fiber neuropathy. Muscle Nerve 26, 173–188 (2002)

    Article  PubMed  Google Scholar 

  4. F.W. Bertelsmann, J.J. Heimans, J.C. van Rooy et al. Reproducibility of vibratory perception thresholds in patients with diabetic neuropathy. Diab. Res 3, 463–466 (1986)

    CAS  Google Scholar 

  5. F. Abad, N.M. Diaz-Gomez, I. Rodriguez, R. Perez, J.A. Delgado, Subclinical pain and thermal sensory dysfunction in children and adolescents with type 1 diabetes mellitus. Diabet. Med. 19, 827–831 (2002)

    Article  PubMed  CAS  Google Scholar 

  6. S.J. Bird, M.J. Brown, C. Spino, S. Watling, H.L. Foyt, Value of repeated measures of nerve conduction and quantitative sensory testing in a diabetic neuropathy trial. Muscle Nerve 34(2), 214–224 (2006)

    Article  PubMed  Google Scholar 

  7. J. Fagius, L.K. Wahren, Variability of sensory thresholddetermination in clinical use. J. Neurol. Sci. 51, 11–27 (1981)

    Article  PubMed  CAS  Google Scholar 

  8. G. Gruener, P.J. Dyck, Quantitative sensory testing: methodology, applications, and future directions. J. Clin. Neurophysiol. 11, 568–583 (1994)

    Article  PubMed  CAS  Google Scholar 

  9. H. Nodera et al. Epidermal reinnervation concomitant with symptomatic improvement in a sensory neuropathy. Muscle Nerve 27, 507–509 (2003)

    Article  PubMed  Google Scholar 

  10. K.A. Sveen, B. Karime, E. Jorum, S.I. Mellgren, M.W. Fagerland, V.M. Monnier, K. Dahl-Jorgensen, K.F. Hanssen, Small and large fiber neuropathy after 40 years of T1DM. Diabet. Care 36, 3712–3717 (2013)

    Article  CAS  Google Scholar 

  11. N. Weintrob, I. Amitay, P. Lilos, S. Shalitin, L. Lazar, Z. Josefsberg, Bedside neuropathy disability score compared to quantitative sensory testing for measurement of diabetic neuropathy in children, adolescents and young adults with type 1 diabetes. J. Diab. Complic. 21, 13–17 (2007)

    Article  Google Scholar 

  12. M. Louraki, M. Katsalouli, C. Kanaka-Gantenbein, N. Kafasi, E. Critselis, D. Kallinikou, C. Tsentidis, K. Karavanaki, The prevalence of early subclinical somatic neuropathy in children and adolescents with type 1 dibetes mellitus and its association with the persistence of autoantibodies to glutamic acid decarboxylase (GAD) and islet antigen-2 (IA-2). Diab Res Clin. Pr. 117, 82–90 (2016)

    Article  CAS  Google Scholar 

  13. K.E. Galluzzi, Managing neuropathic pain. J. Am. Osteopath Assoc. 107(suppl 6), ES39–ES48 (2007)

    PubMed  Google Scholar 

  14. B.S. Olsen, A. Sjolie, P. Hougaard, J. Johannesen, K. Borch-Johnsen, K. Marinelli et al. A 6-year nationwide cohort study of glycaemic control in young people with type 1 diabetes. Risk markers for the development of retinopathy, nephropathy and neuropathy. Danish Study Group of Diabetes in Childhood. J. Diab. Compl 14, 295–300 (2000)

    Article  CAS  Google Scholar 

  15. D. Lacomis, Small-fiber neuropathy. Muscle Nerve 26, 173–188 (2002)

    Article  PubMed  Google Scholar 

  16. G.L. Pittenger et al. Intraepidermal nerve fibers are indicators of small – fiber neuropathy in both diabetic and nondiabetic patients. Diab. Care 27, 1974–1979 (2004)

    Article  Google Scholar 

  17. C.T. Shun et al. Skin denervation in type 2 diabetes : correlation with diabetic duration and functional impairments. Brain 127, 1593–1605 (2004)

    Article  PubMed  Google Scholar 

  18. K.A. Sveen et al. Small- and large- fiber neuropathy after 40 years of type 1 diabetes: associations with glycemic control and advanced protein glycation: the Oslo Study. Diab. Care 36(11), 3712d pro (2013)

    Article  Google Scholar 

  19. S.-L. Lv, C. Fang, J. Hu, Y. Huang, B. Yang, R. Zou et al. https://doi.org/10.1016/j.diabres.2015.04.018

  20. The DCCT Research Group. Factors in development of diabetic neuropathy, Baseline analysis of neuropathy in feasibility phase of diabetes control and complications trial (DCCT). Diabetes 37, 476–481 (1988)

    Article  Google Scholar 

  21. H.H. Kramer, R. Rolke, A. Bickel, F. Birklein, Thermal thresholdw predict painfulness of diabetic neuropathies 2386–2391 (2004).

  22. D.S. Kim, C.H. Yoon, S.J. Lee, S.Y. Park, H.J. Yoo, H.J. Cho, Changes in voltage-gated calcium channel alpha (1) gene expression in rat dorsal root ganglia following peripheral nerve injury. Brain Res. Mol. Brain Res 96, 151–156 (2001)

    Article  PubMed  CAS  Google Scholar 

  23. G.M. Pitcher, J.L. Henry, Cellular mechanisms of hyperalgesia and spontaneous pain in spinalized rat model of peripheral neuropathy : changes in myelinated afferent inputs implicated. Eur. J. Neurosci. 12, 2006–2020 (2000)

    Article  PubMed  CAS  Google Scholar 

  24. S. Fitzek, U. Baumgartner, C. Fitzek, W. Margerl, P. Urban, F. Thomke, J. Marx, R.D. Treede, P. Stoeter, H.C. Hopf, Mechanisms and predictors of chronic facial pain in lateral medullary infarction. Ann. Neurol. 49, 493–500 (2001)

    Article  PubMed  CAS  Google Scholar 

  25. A.E. Panerai, P. Sacerdote, A. Brini, M. Bianchi, P. Mantegazza, Autonomy and central nervous system neuropeptides aftersection of the sciatic nerve in rats of different strains. Pharm. Biochem Behav. 28, 385–388 (1987)

    Article  CAS  Google Scholar 

  26. U. Breitinger, H.G. Breitinger, Excitatory and inhibitory neuronal signaling in inflammatory and diabetic neuropathic pain. Mol. Med. 29(1), 53 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. H. Chen, T.J. Lamer, R.H. Rho et al. Contemporary management of neuropathic pain for the primary care physician. Mayo Clin. Proc. 79, 1533–1545 (2004)

    Article  PubMed  Google Scholar 

  28. W.C. Kwowler, E. Barrett – Connor, S.E. Fowler et al. Reduction in the incidence of type 2 diabetes with life style intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002)

    Article  Google Scholar 

  29. S.T. Britland, R.J. Young, A.K. Sharma, B.F. Clarke, Acute and remitting painful diabetic polyneuropathy: a comparison of peripheral nerve fibre pathology. Pain 48, 361–370 (1992)

    Article  PubMed  Google Scholar 

  30. X. Zhang et al. Clinical characteristics and risk factors of diabetic peripheral neuropathy of type 1 diabetes mellitus patients. Diab. Res. Clin. Pract. 129, 97ts (2017)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Diabetes and Metabolism Unit, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, “P&A Kyriakou” Childrens Hospital, Athens, Greece

    Argyropoulou Stavroula, Paltoglou George, Karanasios Spyridon, Sakou Irine-Ikbale & Karavanaki Kyriaki

  2. Laboratory of Clinical Neurophysiology, First Department of Neurology, National and Kapodistrian University of Athens, “Aeginitio” University Hospital, Athens, Greece

    Kokotis Panagiotis, Boutziouka Chrysanthi & Karamatzianni Georgia

Authors
  1. Argyropoulou Stavroula
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kokotis Panagiotis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paltoglou George
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Boutziouka Chrysanthi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karamatzianni Georgia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Karanasios Spyridon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sakou Irine-Ikbale
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Karavanaki Kyriaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization/visualization, A.S., P.K. and K.K.; methodology, P.K., G.P., K.K. ; validation, X.X., Y.Y. and Z.Z.; formal analysis, K.P., P.G., K.K.; data acquisition, A.S., K.P., B.C., K.G., S.I-I., K.K.; writing—original draft preparation, A.S., B.C., K.G., K.S., S.I-I.; writing—review and editing, K.P., P.G., K.K.; supervision, P.K., K.K. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Paltoglou George.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stavroula, A., Panagiotis, K., George, P. et al. Assessment of small nerve fiber function as an early marker of peripheral neuropathy in children and adolescents with type 1 diabetes mellitus (T1DM). Endocrine (2024). https://doi.org/10.1007/s12020-024-03991-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12020-024-03991-1

Keywords

Search

Navigation