{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:14:45Z","timestamp":1773828885321,"version":"3.50.1"},"reference-count":26,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>This case report discusses a 32-year-old woman with Friedreich ataxia (FA) and suboptimally managed diabetes mellitus (DM), focusing on a treatment strategy aimed at improving mitochondrial function for better glycemic control and symptom management. Her regimen included insulin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, neurotropic vitamins, and mitochondriotropic agents and antioxidants, specifically L-carnitine, coenzyme Q10 (CoQ10), and vitamin E. Imeglimin, a mitochondriotropic antihyperglycemic agent, was also part of her regimen. While glycemic stability initially fluctuated, it reached stability over 3 to 4 months. During the 3-year follow-up, her fasting C-peptide levels decreased from 1.15\u2005ng\/mL (SI: 0.38\u2005nmol\/L) to 0.5\u2005ng\/mL (SI: 0.17\u2005nmol\/L) (reference range, 0.78-1.89\u2005ng\/mL [SI: 0.26-0.62\u2005nmol\/L]), yet her glycemic stability improved significantly, and her International Cooperative Ataxia Rating Scale (ICARS) score improved from 85 to 71 points. These findings highlight the potential of mitochondriotropic agents in the management of FA and related DM, possibly improving insulin sensitivity and neurodegeneration and underscores the need for further studies on the efficacy of specific agents in improving metabolic and neurological outcomes.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf215","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:27:39Z","timestamp":1758788859000},"source":"Crossref","is-referenced-by-count":1,"title":["Friedreich Ataxia and Related Diabetes: Therapeutic Approach Targeting Mitochondrial Dysfunction"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2345-9493","authenticated-orcid":false,"given":"Pichakacheri","family":"Sureshkumar","sequence":"first","affiliation":[{"name":"Dr. Suresh\u2019s Diabcare India Diabetes Center , Calicut, Kerala 673017 ,","place":["India"]},{"name":"Department of Life Science, Calicut University , Kerala 673635 ,","place":["India"]},{"name":"Faculty of Medicine, Kerala University of Health Sciences , Thrissur, Kerala 680596 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidharth S","family":"Kumar","sequence":"additional","affiliation":[{"name":"Dr. Suresh\u2019s Diabcare India Diabetes Center , Calicut, Kerala 673017 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johny","family":"Cheriyan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korambayil Hospital and Diagnostic Center , Manjeri, Kerala 676122 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asif","family":"Masood","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Malabar Hospital , Manjeri, Kerala 676121 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"issue":"22","key":"2025100913171816400_luaf215-B1","doi-asserted-by":"crossref","first-page":"12239","DOI":"10.1073\/pnas.220403797","article-title":"Frataxin activates mitochondrial energy conversion and oxidative phosphorylation","volume":"97","author":"Ristow","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025100913171816400_luaf215-B2","author":"Williams"},{"issue":"16","key":"2025100913171816400_luaf215-B3","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1056\/NEJM199610173351601","article-title":"Clinical and genetic abnormalities in patients with Friedreich's ataxia","volume":"335","author":"D\u00fcrr","year":"1996","journal-title":"N Engl J Med"},{"key":"2025100913171816400_luaf215-B4","doi-asserted-by":"crossref","first-page":"109828","DOI":"10.1016\/j.diabres.2022.109828","article-title":"Friedreich's ataxia related diabetes: epidemiology and management practices","volume":"186","author":"Tamaroff","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"issue":"6","key":"2025100913171816400_luaf215-B5","first-page":"479","article-title":"Friedreich ataxia and diabetes mellitus-family study","volume":"18","author":"Melo","year":"2005","journal-title":"Acta Med Port"},{"issue":"1-2","key":"2025100913171816400_luaf215-B6","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jns.2014.04.015","article-title":"Cross-sectional analysis of glucose metabolism in Friedreich ataxia","volume":"342","author":"Greeley","year":"2014","journal-title":"J Neurol Sci"},{"issue":"9","key":"2025100913171816400_luaf215-B7","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/acn3.439","article-title":"Impact of diabetes in the Friedreich ataxia clinical outcome measures study","volume":"4","author":"McCormick","year":"2017","journal-title":"Ann Clin Transl Neurol"},{"issue":"11","key":"2025100913171816400_luaf215-B8","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1111\/pin.13008","article-title":"Two autopsy cases of mitochondrial disease (MELAS and MERRF) with special reference to the histological and immunohistochemical findings of the pancreatic islets","volume":"70","author":"Norose","year":"2020","journal-title":"Pathol Int"},{"issue":"5","key":"2025100913171816400_luaf215-B9","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.2337\/db06-0783","article-title":"Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients","volume":"56","author":"Befroy","year":"2007","journal-title":"Diabetes"},{"issue":"Suppl 1","key":"2025100913171816400_luaf215-B10","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/jnc.12216","article-title":"Diabetes in Friedreich ataxia","volume":"126","author":"Cnop","year":"2013","journal-title":"J Neurochem"},{"issue":"4","key":"2025100913171816400_luaf215-B11","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s13410-022-01156-2","article-title":"Maternally inherited diabetes and deafness (MIDD)\u2014a series of case reports","volume":"43","author":"Sureshkumar","year":"2023","journal-title":"Int J Diabetes Dev Ctries"},{"key":"2025100913171816400_luaf215-B12","first-page":"1","article-title":"Clinical profile of monogenic diabetes: a case series from a single south Indian diabetes clinic","volume":"13","author":"Sureshkumar","year":"2024","journal-title":"Int J Diabetes Dev Ctries"},{"issue":"1","key":"2025100913171816400_luaf215-B13","doi-asserted-by":"crossref","first-page":"6934394","DOI":"10.1155\/2017\/6934394","article-title":"Role of mitochondrial genome mutations in pathogenesis of carotid atherosclerosis","volume":"2017","author":"Sazonova","year":"2017","journal-title":"Oxid Med Cell Longev"},{"issue":"3","key":"2025100913171816400_luaf215-B14","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1007\/s12010-020-03275-0","article-title":"Novel point mutations in mitochondrial Mt-Co2 gene may be risk factors for coronary artery disease","volume":"191","author":"Heidari","year":"2020","journal-title":"Appl Biochem Biotechnol"},{"issue":"1","key":"2025100913171816400_luaf215-B15","doi-asserted-by":"crossref","first-page":"191171","DOI":"10.1098\/rsos.191171","article-title":"Modelling of dysregulated glucagon secretion in type 2 diabetes by considering mitochondrial alterations in pancreatic \u03b1-cells","volume":"7","author":"Grubelnik","year":"2020","journal-title":"R Soc Open Sci"},{"issue":"3","key":"2025100913171816400_luaf215-B16","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/dom.14277","article-title":"Mechanism of action of imeglimin: a novel therapeutic agent for type 2 diabetes","volume":"23","author":"Hallakou-Bozec","year":"2021","journal-title":"Diabetes Obes Metab"},{"key":"2025100913171816400_luaf215-B17","doi-asserted-by":"crossref","first-page":"1359618","DOI":"10.3389\/fphar.2024.1359618","article-title":"Emerging antioxidant therapies in Friedreich's ataxia","volume":"15","author":"Edzeamey","year":"2024","journal-title":"Front Pharmacol"},{"issue":"13","key":"2025100913171816400_luaf215-B18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fj.03-0240fje","article-title":"Mitochondria-targeted antioxidants protect Friedreich ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants","volume":"17","author":"Jauslin","year":"2003","journal-title":"FASEB J"},{"issue":"12","key":"2025100913171816400_luaf215-B19","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1111\/j.1468-1331.2008.02318.x","article-title":"Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy","volume":"15","author":"Cooper","year":"2008","journal-title":"Eur J Neurol"},{"issue":"2","key":"2025100913171816400_luaf215-B20","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.gene.2013.10.017","article-title":"L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders","volume":"533","author":"Ribas","year":"2014","journal-title":"Gene"},{"issue":"2","key":"2025100913171816400_luaf215-B21","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.3390\/ijms13022078","article-title":"Neuroprotective effects of pre-treatment with l-carnitine and acetyl-L-carnitine on ischemic injury in vivo and in vitro","volume":"13","author":"Zhang","year":"2012","journal-title":"Int J Mol Sci"},{"issue":"6","key":"2025100913171816400_luaf215-B22","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s00702-004-0216-x","article-title":"L-carnitine and creatine in Friedreich's ataxia: a randomized, placebo-controlled crossover trial","volume":"112","author":"Sch\u00f6ls","year":"2005","journal-title":"J Neural Transm (Vienna)"},{"issue":"5","key":"2025100913171816400_luaf215-B23","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/gt.2016.89","article-title":"Deletion of the GAA repeats from the human frataxin gene using the CRISPR-Cas9 system in YG8R-derived cells and mouse models of Friedreich ataxia","volume":"24","author":"Ouellet","year":"2017","journal-title":"Gene Ther"},{"issue":"13-14","key":"2025100913171816400_luaf215-B24","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1089\/hum.2023.020","article-title":"Identification of safe and effective intravenous dose of AAVrh.10hFXN to treat the cardiac manifestations of Friedreich's ataxia","volume":"34","author":"Munoz-Zuluaga","year":"2023","journal-title":"Hum Gene Ther"},{"issue":"13","key":"2025100913171816400_luaf215-B25","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/S1474-4422(16)30287-3","article-title":"Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 2 year cohort study","volume":"15","author":"Reetz","year":"2016","journal-title":"Lancet Neurol"},{"issue":"12","key":"2025100913171816400_luaf215-B26","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1002\/acn3.51686","article-title":"Harmonizing results of ataxia rating scales: mFARS, SARA, and ICARS","volume":"9","author":"Rummey","year":"2022","journal-title":"Ann Clin Transl Neurol"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/11\/luaf215\/64378790\/luaf215.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/11\/luaf215\/64378790\/luaf215.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:17:27Z","timestamp":1760030247000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luaf215\/8263379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":26,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,9,25]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luaf215","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,9,25]]},"article-number":"luaf215"}}