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ALA is widely prescribed in patients with diabetic polyneuropathy due to its positive effects on nerve conduction and alleviation of symptoms. It is, moreover, also prescribed in other insulin resistance conditions such as metabolic syndrome (SM), polycystic ovary syndrome (PCOS) and obesity. However, several cases of Insulin Autoimmune Syndrome (IAS) have been reported in subjects taking ALA. The aim of the present review is to describe the main chemical and biological functions of ALA in glucose metabolism, focusing on its antioxidant activity, its role in modulating insulin sensitivity and secretion and in symptomatic peripheral diabetic polyneuropathy. We also provide a potential explanation for increased risk for the development of IAS.<\/jats:p>","DOI":"10.3390\/nu15010018","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T04:28:55Z","timestamp":1671596935000},"page":"18","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Alpha-Lipoic Acid and Glucose Metabolism: A Comprehensive Update on Biochemical and Therapeutic Features"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8048-8664","authenticated-orcid":false,"given":"Umberto","family":"Capece","sequence":"first","affiliation":[{"name":"Endocrinology and Diabetology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Moffa","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Improta","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4506-5193","authenticated-orcid":false,"given":"Gianfranco","family":"Di Giuseppe","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico Celestino","family":"Nista","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8665-8406","authenticated-orcid":false,"given":"Chiara M. A.","family":"Cefalo","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-7055","authenticated-orcid":false,"given":"Francesca","family":"Cinti","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gasbarrini","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7462-7792","authenticated-orcid":false,"given":"Andrea","family":"Giaccari","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Mezza","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/mnfr.201200608","article-title":"Direct and indirect antioxidant properties of alpha-lipoic acid and therapeutic potential","volume":"57","author":"Rochette","year":"2013","journal-title":"Mol. 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