Histopathological changes in the autonomic nervous system in patients with diabetes mellitus: a literature review
DOI:
https://doi.org/10.69849/1t38dj13Keywords:
diabetic neuropathy, autonomic nervous system, histopathology, diabetes mellitus, axonal degenerationAbstract
Diabetic autonomic neuropathy is a frequent and complex complication of diabetes mellitus, characterized by structural and functional alterations of the autonomic nervous system. This study aims to analyze the histopathological changes of the autonomic nervous system in patients with diabetes mellitus and their relationship with pathophysiological mechanisms and clinical manifestations. A descriptive and analytical literature review was conducted based on the selection of 26 scientific articles published between 2021 and 2026, obtained from indexed databases. The results indicate that chronic hyperglycemia triggers metabolic, inflammatory, and vascular processes that lead to progressive neuronal damage, including oxidative stress, microvascular dysfunction, Schwann cell injury, and axonal degeneration. From a histopathological perspective, a significant reduction in small nerve fiber density, segmental demyelination, and structural loss of neural tissue are observed. Furthermore, clinical autonomic manifestations reflect the multisystem involvement resulting from this structural damage. It is concluded that diabetic autonomic neuropathy has a well-defined and multifactorial anatomical basis, whose understanding requires an integrated approach combining structural, functional, and clinical aspects, which is essential for improving early diagnosis and management of this complication.
References
AKBAR, Muhammad et al. Sudomotor dysfunction in diabetic peripheral neuropathy (DPN) and its testing modalities: a literature review. Heliyon, 2023. Disponible en: https://doi.org/10.1016/j.heliyon.2023.e18184 Acceso en: 30 mar. 2026.
AL-KHAFAJI, Minnan; OTTI, Vanessa. Early diagnosis of diabetic neuropathy: a review of current diagnostic tests. Cureus, 2025. Disponible en: https://doi.org/10.7759/cureus.97880 Acceso en: 30 mar. 2026.
BAUM, Petra et al. Inflammatory mechanisms in the pathophysiology of diabetic peripheral neuropathy (DN) - new aspects. International Journal of Molecular Sciences, 2021. Disponible en: https://doi.org/10.3390/ijms221910835 Acceso en: 30 mar. 2026.
CAO, Ying; YANG, Jing. Mechanisms of pathological axonal degeneration. In: Handbook of Clinical Neurology. 2024. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK612540/ Acceso en: 30 mar. 2026.
CHESHIRE, William P. et al. Electrodiagnostic assessment of the autonomic nervous system: a consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology. Clinical Neurophysiology, 2021. Disponible en: https://doi.org/10.1016/j.clinph.2020.11.024 Acceso en: 30 mar. 2026.
COSMO, Eleonora et al. Corneal confocal microscopy as a quantitative imaging biomarker of diabetic peripheral neuropathy: a review. Journal of Clinical Medicine, 2022. Disponible en: https://doi.org/10.3390/jcm11175130 Acceso en: 30 mar. 2026.
DILLON, Brendan R.; ANG, Lynn; POP-BUSUI, Rodica. Spectrum of diabetic neuropathy: new insights in diagnosis and treatment. Annu Rev Med, 2024. Disponible en: https://pubmed.ncbi.nlm.nih.gov/38285516/ Acceso en: 30 mar. 2026.
GOGAN, Alexandra et al. Cardiac autonomic neuropathy in diabetes mellitus: pathogenesis, epidemiology, diagnosis and clinical implications: a narrative review. Journal of Clinical Medicine, 2025. Disponible en: https://pmc.ncbi.nlm.nih.gov/articles/PMC11818907/ Acceso en: 30 mar. 2026.
HASHIM, Mohd et al. Diabetic neuropathy: an overview of molecular pathways and protective mechanisms of phytobioactives. Bentham Science, 2024. Disponible en: https://pubmed.ncbi.nlm.nih.gov/37867264/ Acceso en: 30 mar. 2026.
HOSSEINI-MARNANI, Elham et al. Gastric autonomic neuropathy in diabetes. Endocrines, 2025. Disponible en: https://doi.org/10.3390/endocrines6030040 Acceso en: 30 mar. 2026.
HUSAIN, Masud. Mechanistic insights into allodynia in diabetic peripheral neuropathy. Brain, 2024. Disponible en: https://doi.org/10.1093/brain/awae280 Acceso en: 30 mar. 2026.
KEMPLER, Péter; KÖREI, Anna. Diabetic cardiovascular autonomic neuropathy: clinical significance, diagnosis and therapy. AK Journals, Orv Hetil, 2024. Disponible en: https://pubmed.ncbi.nlm.nih.gov/38643475/ Acceso en: 30 mar. 2026.
LIMA DE PAULA, Ana Vitoria et al. The association of diabetic peripheral neuropathy with cardiac autonomic neuropathy in individuals with diabetes mellitus: a systematic review. Journal of Diabetes and its Complications, 2024. Disponible en: https://pubmed.ncbi.nlm.nih.gov/38971002/ Acceso en: 30 mar. 2026.
LIN, Qingxia et al. Oxidative stress in diabetic peripheral neuropathy: pathway and mechanism-based treatment. Mol Neurobiol, 2023. Disponible en: https://pubmed.ncbi.nlm.nih.gov/37115404/ Acceso en: 30 mar. 2026.
PATEL, Kamakshi; HORAK, Holli; TIRYAKI, Ezgi. Diabetic neuropathies. Muscle & Nerve, 2021. Disponible en: https://doi.org/10.1002/mus.27014 Acceso en: 30 mar. 2026.
POP-BUSUI, Rodica. Autonomic diabetic neuropathies: a brief overview. Diabetes Research and Clinical Practice, 2023. Disponible en: https://doi.org/10.1016/j.diabres.2023.110762 Acceso en: 30 mar. 2026.
RAICHER, Irina et al. Investigation of nerve fibers in the skin by biopsy: technical aspects, indications, and contribution to diagnosis of small-fiber neuropathy. Einstein, 2022. Disponible en: https://doi.org/10.31744/einstein_journal/2022MD8044 Acceso en: 30 mar. 2026.
RAJPUT, Jay Prakash S. et al. Therapeutic and diagnostic landscape of diabetic neuropathy: a systematic review of clinical studies. Cureus, 2026. Disponible en: https://pmc.ncbi.nlm.nih.gov/articles/PMC12958784/ Acceso en: 30 mar. 2026.
SHARMA, Sanjeev; VAS, Prashanth; RAYMAN, Gerry. Small fiber neuropathy in diabetes polyneuropathy: is it time to change? Journal of Diabetes Science and Technology, 2021. Disponible en: https://doi.org/10.1177/1932296821996434 Acceso en: 30 mar. 2026.
STIRBAN, Ovidiu Alin. Diabetic autonomic neuropathy. MMW Fortschr Med, 2024. Disponible en: https://pubmed.ncbi.nlm.nih.gov/38637392/ Acceso en: 30 mar. 2026.
STRAND, Natalie et al. Diabetic neuropathy: pathophysiology review. Curr Pain Headache Rep, 2024. Disponible en: https://pubmed.ncbi.nlm.nih.gov/38558164/ Acceso en: 30 mar. 2026.
TANNUS, Lucianne Righeti Monteiro; COBAS, Roberta Arnoldi. Autonomic neuropathy in diabetes. Arch Endocrinol Metab, 2025. Disponible en: https://pmc.ncbi.nlm.nih.gov/articles/PMC12671339/ Acceso en: 30 mar. 2026.
WANG, Nan; ZHANG, Jie. Recent advances in the study of diabetic cardiac autonomic neuropathy. Rev. Cardiovasc. Med., 2026. Disponible en: https://doi.org/10.31083/RCM45579 Acceso en: 30 mar. 2026.
WU, Lijiao et al. Diabetic peripheral neuropathy based on Schwann cell injury: mechanisms of cell death regulation and therapeutic perspectives. Frontiers in Endocrinology, 2024. Disponible en: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1427679/full Acceso en: 30 mar. 2026.
YANG, Yang et al. Diabetic neuropathy: cutting-edge research and future directions. Signal Transduction and Targeted Therapy, 2025. Disponible en: https://www.nature.com/articles/s41392-025-02175-1 Acceso en: 30 mar. 2026.
ZHU, Jinxi et al. Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment. Frontiers in Endocrinology, 2023. Disponible en: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1265372/full Acceso en: 30 mar. 2026.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Gabriella Rocha Barros, Amanda Vitoria Oliveira Cruz, Kayra Francine Kupske, Cleuza Maria de Lima, Thaline Lima Manhães, Thomas Andrade Moreira, Nicolle Naara Antunes da Silva, Anne Karoline de Freitas Teles (Autor)
This work is licensed under a Creative Commons Attribution 4.0 International License.
"Os Autores que publicam nesta revista concordam com os seguintes termos:
-
Os Autores mantêm os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a licença Creative Commons Attribution 4.0 International (CC BY 4.0). Esta licença permite que o trabalho seja compartilhado, copiado e adaptado em qualquer suporte ou formato, para qualquer fim, inclusive comercial, desde que seja atribuído o devido crédito de autoria e de publicação inicial nesta revista.
-
Os Autores têm autorização para assumir compromissos contratuais adicionais separadamente, para a distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.
-
A revista permite e incentiva os autores a publicar e distribuir seu trabalho online (ex.: em repositórios institucionais ou na sua página pessoal) após o processo de edição e publicação, pois isso pode gerar alterações produtivas, bem como aumentar o impacto e a citação do trabalho publicado."
