{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:33:16Z","timestamp":1789421596641,"version":"build-2803163510"},"reference-count":40,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes and its Complications"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1016\/j.jdiacomp.2021.108111","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T02:06:57Z","timestamp":1640570817000},"page":"108111","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"title":["Neurological manifestations in m.3243A>G-related disease triggered by metformin"],"prefix":"10.1016","volume":"36","author":[{"given":"Hok-Fung","family":"Tong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Chih Hencher","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsz-Yan Tammy","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siu-Fung","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bun","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin-Wah","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June Kam-Yin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho-Kee Vicki","family":"Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chor-Kwan","family":"Ching","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jdiacomp.2021.108111_bb0005","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0010","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.2040-1124.2010.00047.x","article-title":"Mitochondrial metabolism and diabetes","volume":"1","author":"Kwak","year":"2010","journal-title":"J Diabetes Investig"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0015","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.mito.2006.12.004","article-title":"Population prevalence of the MELAS A3243G mutation","volume":"7","author":"Manwaring","year":"2007","journal-title":"Mitochondrion"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0020","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ymgme.2019.09.003","article-title":"Resolving complexity in mitochondrial disease: towards precision medicine","volume":"128","author":"Boggan","year":"2019","journal-title":"Mol Genet Metab"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0025","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1046\/j.1365-2265.2000.00989.x","article-title":"Mitochondrial DNA A3243G mutation in patients with early- or late-onset type 2 diabetes mellitus in Hong Kong chinese: mitochondrial mutation in chinese diabetics","volume":"52","author":"Ng","year":"2000","journal-title":"Clin Endocrinol (Oxf)"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0030","first-page":"480","article-title":"Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes","volume":"12","author":"King","year":"1992","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0035","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1093\/hmg\/ddn265","article-title":"The A3243G tRNALeu(UUR) MELAS mutation causes amino acid misincorporation and a combined respiratory chain assembly defect partially suppressed by overexpression of EFTu and EFG2","volume":"17","author":"Sasarman","year":"2008","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0040","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1080\/07853890510007188","article-title":"Molecular mechanisms of mitochondrial diabetes (MIDD)","volume":"37","author":"Maassen","year":"2005","journal-title":"Ann Med"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0045","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1007\/s00125-007-0779-9","article-title":"Prevalence and progression of diabetes in mitochondrial disease","volume":"50","author":"Whittaker","year":"2007","journal-title":"Diabetologia"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0050","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s004390100475","article-title":"Hearing impairment in patients with 3243A\u2192G mtDNA mutation: phenotype and rate of progression","volume":"108","author":"Uimonen","year":"2001","journal-title":"Hum Genet"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0055","doi-asserted-by":"crossref","first-page":"721","DOI":"10.7326\/0003-4819-134-9_Part_1-200105010-00008","article-title":"Maternally inherited diabetes and deafness: a multicenter study","volume":"134","author":"Guillausseau","year":"2001","journal-title":"Ann Intern Med"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0060","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0925-4439(95)00036-4","article-title":"Mitochondrial diabetes mellitus: a review","volume":"1271","author":"Gerbitz","year":"1995","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0065","first-page":"553","article-title":"Abnormal growth in mitochondrial disease","volume":"98","author":"Wolny","year":"2009","journal-title":"Acta Paediatr Oslo Nor 1992"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0070","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1210\/jc.2018-00957","article-title":"Height as a clinical biomarker of disease burden in adult mitochondrial disease","volume":"104","author":"Boal","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0075","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/j.1464-5491.2008.02359.x","article-title":"Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation","volume":"25","author":"Murphy","year":"2008","journal-title":"Diabet Med"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0080","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/s00415-013-7225-3","article-title":"The m.3243A>G mitochondrial DNA mutation and related phenotypes. A matter of gender?","volume":"261","author":"Mancuso","year":"2014","journal-title":"J Neurol"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0085","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1007\/s001250050950","article-title":"The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation","volume":"41","author":"Suzuki","year":"1998","journal-title":"Diabetologia"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0090","doi-asserted-by":"crossref","DOI":"10.1038\/gim.2017.107","article-title":"Patient care standards for primary mitochondrial disease: a consensus statement from the mitochondrial medicine society","volume":"19","author":"Parikh","year":"2017","journal-title":"Genet Med"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0095","doi-asserted-by":"crossref","first-page":"753","DOI":"10.3389\/fendo.2018.00753","article-title":"Metformin-induced mitochondrial complex I inhibition: facts, uncertainties, and consequences","volume":"9","author":"Fontaine","year":"2018","journal-title":"Front Endocrinol"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0100","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nature13270","article-title":"Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase","volume":"510","author":"Madiraju","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0105","series-title":"Adult onset MELAS syndrome presenting as a mimic of herpes simplex encephalitis","first-page":"6","volume":"28","author":"Chen","year":"2019"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0110","doi-asserted-by":"crossref","first-page":"124","DOI":"10.7326\/L20-0292","article-title":"MELAS syndrome and MIDD unmasked by metformin use: a case report","volume":"174","author":"Kim","year":"2021","journal-title":"Ann Intern Med"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0115","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11154-018-9446-3","article-title":"Not quite type 1 or type 2, what now? Review of monogenic, mitochondrial, and syndromic diabetes","volume":"19","author":"Yeung","year":"2018","journal-title":"Rev Endocr Metab Disord"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0120","first-page":"157","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition","author":"Saeedi","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0125","first-page":"69","article-title":"Genetics of type 2 diabetes mellitus","volume":"6","author":"So","year":"2000","journal-title":"Hong Kong Med J"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0130","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201708262","article-title":"mtDNA heteroplasmy level and copy number indicate disease burden in m.3243A>G mitochondrial disease","volume":"10","author":"Grady","year":"2018","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0135","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3390\/molecules23020323","article-title":"Recent advances in detecting mitochondrial DNA heteroplasmic variations","volume":"23","author":"Duan","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0140","series-title":"GeneReviews\u00ae","article-title":"MELAS","author":"El-Hattab","year":"2001"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0145","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1001\/archneur.64.11.1625","article-title":"Wolff-parkinson-white syndrome in patients with MELAS","volume":"64","author":"Sproule","year":"2007","journal-title":"Arch Neurol"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0150","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13023-018-0949-5","article-title":"A retrospective analysis of health care utilization for patients with mitochondrial disease in the United States: 2008\u20132015","volume":"13","author":"Cohen","year":"2018","journal-title":"Orphanet J Rare Dis"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0155","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ajo.2020.01.013","article-title":"Progression of retinopathy secondary to maternally inherited diabetes and deafness \u2013 evaluation of predicting parameters","volume":"213","author":"M\u00fcller","year":"2020","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0160","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S0140-6736(18)31868-3","article-title":"Mitochondrial donation: from test tube to clinic","volume":"392","author":"Gorman","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0165","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1007\/s004310050663","article-title":"Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy","volume":"156","author":"Lam","year":"1997","journal-title":"Eur J Pediatr"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0170","doi-asserted-by":"crossref","first-page":"S168","DOI":"10.1016\/j.mito.2007.03.002","article-title":"Coenzyme Q10 and statins: biochemical and clinical implications","volume":"7","author":"Littarru","year":"2007","journal-title":"Mitochondrion"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0175","doi-asserted-by":"crossref","first-page":"152","DOI":"10.4103\/0970-2113.80343","article-title":"Adverse drug reaction and causality assessment scales","volume":"28","author":"Zaki","year":"2011","journal-title":"Lung India"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0180","doi-asserted-by":"crossref","DOI":"10.1016\/j.jdiacomp.2020.107584","article-title":"Management of mitochondrial diabetes in the era of novel therapies","volume":"35","author":"Yeung","year":"2021","journal-title":"J Diabetes Complicat"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0185","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3109\/01480540903207076","article-title":"Drugs interfering with mitochondrial disorders","volume":"33","author":"Finsterer","year":"2010","journal-title":"Drug Chem Toxicol"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0190","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1007\/s13300-019-00680-5","article-title":"Cardiorenal protection: potential of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes","volume":"10","author":"Nagahisa","year":"2019","journal-title":"Diabetes Ther"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0195","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12933-019-0964-4","article-title":"Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet\/streptozotocin-induced diabetic rats","volume":"18","author":"Shao","year":"2019","journal-title":"Cardiovasc Diabetol"},{"key":"10.1016\/j.jdiacomp.2021.108111_bb0200","doi-asserted-by":"crossref","unstructured":"M Igoillo-Esteve AF Oliveira C Cosentino , et al. Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia. JCI Insight. 5:e134221. doi:10.1172\/jci.insight.134221.","DOI":"10.1172\/jci.insight.134221"}],"container-title":["Journal of Diabetes and its Complications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1056872721003354?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1056872721003354?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:14:00Z","timestamp":1761005640000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1056872721003354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["S1056872721003354"],"URL":"https:\/\/doi.org\/10.1016\/j.jdiacomp.2021.108111","relation":{},"ISSN":["1056-8727"],"issn-type":[{"value":"1056-8727","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Neurological manifestations in m.3243A>G-related disease triggered by metformin","name":"articletitle","label":"Article Title"},{"value":"Journal of Diabetes and its Complications","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jdiacomp.2021.108111","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108111"}}