{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:14:30Z","timestamp":1785762870836,"version":"3.56.0"},"reference-count":124,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder which affects the motor neurons. Growing evidence suggests that ALS may impact the metabolic system, including the glucose metabolism. Several studies investigated the role of Diabetes Mellitus (DM) as risk and\/or prognostic factor. However, a clear correlation between DM and ALS has not been defined. In this review, we focus on the role of DM in ALS, examining the different hypotheses on how perturbations of glucose metabolism may interact with the pathophysiology and the course of ALS. Methods: We undertook an independent PubMed literature search, using the following search terms: ((ALS) OR (Amyotrophic Lateral Sclerosis) OR (Motor Neuron Disease)) AND ((Diabetes) OR (Glucose Intolerance) OR (Hyperglycemia)). Review and original articles were considered. Results: DM appears not to affect ALS severity, progression, and survival. Contrasting data suggested a protective role of DM on the occurrence of ALS in elderly and an opposite effect in younger subjects. Conclusions: The actual clinical and pathophysiological correlation between DM and ALS is unclear. Large longitudinal prospective studies are needed. Achieving large sample sizes comparable to those of common complex diseases like DM is a challenge for a rare disease like ALS. Collaborative efforts could overcome this specific issue.<\/jats:p>","DOI":"10.3390\/biom11060867","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T13:31:39Z","timestamp":1623331899000},"page":"867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Diabetes Mellitus and Amyotrophic Lateral Sclerosis: A Systematic Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2105-5038","authenticated-orcid":false,"given":"Laura","family":"Ferri","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8173-1723","authenticated-orcid":false,"given":"Paola","family":"Ajdinaj","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6709-3489","authenticated-orcid":false,"given":"Marianna Gabriella","family":"Rispoli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Carrarini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Barbone","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano","family":"D\u2019Ardes","sequence":"additional","affiliation":[{"name":"Department of Medicine and Aging Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Capasso","sequence":"additional","affiliation":[{"name":"Department of Neurology, \u201cSS Annunziata\u201d Hospital, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Di","family":"Muzio","sequence":"additional","affiliation":[{"name":"Department of Neurology, \u201cSS Annunziata\u201d Hospital, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cipollone","sequence":"additional","affiliation":[{"name":"Department of Medicine and Aging Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Onofrj","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7443-9233","authenticated-orcid":false,"given":"Laura","family":"Bonanni","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University G. d\u2019Annunzio of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nrneurol.2013.203","article-title":"The epidemiology of ALS: A conspiracy of genes, environment and time","volume":"9","author":"Hardiman","year":"2013","journal-title":"Nat. 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