{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:44:09Z","timestamp":1788194649789,"version":"build-2803163510"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Mitochondrial disease, most cases of which are caused by mitochondrial DNA (mtDNA) mutation, is present with multiple phenotypes including diabetes mellitus, sensorineural hearing loss, cardiomyopathy, muscle weakness, renal dysfunction, and encephalopathy, depending on the degree of heteroplasmy. While mitochondria play an important role in intracellular glucose and lactate metabolism in insulin-sensitive tissues such as muscles, appropriate strategies for glycemic control have not yet been established in a patient with mitochondrial disease, which is often complicated by myopathy. Here, we describe the history of a 40-year-old man with mtDNA 3243A\u2009&amp;gt;\u2009G who had sensorineural hearing loss, cardiomyopathy, muscle wasting, and diabetes mellitus with stage 3 chronic kidney disease. He developed mild diabetic ketoacidosis (DKA) in the process of treatment for poor glycemic control with severe latent hypoglycemia. According to the standard therapy for DKA, he was treated with continuous intravenous insulin infusion therapy, which unexpectedly resulted in an abrupt and transient elevation in blood lactate levels without exacerbation of heart failure and kidney function. Since blood lactate levels are determined by the balance between lactate production and consumption, an abrupt and transient lactate elevation following intravenous insulin injection therapy may reflect not only enhanced glycolysis in insulin-sensitive tissues with mitochondrial dysfunction but also decreased lactate consumption in the sarcopenic skeletal muscle and failing heart. Intravenous insulin infusion therapy in patients with mitochondrial disease may unmask derangements of intracellular glucose metabolism in response to insulin signaling.<\/jats:p>","DOI":"10.3389\/fcvm.2023.1144925","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T04:29:42Z","timestamp":1681705782000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case report: Transient lactate elevation by intravenous insulin infusion therapy for diabetic ketoacidosis in a patient with mitochondrial DNA 3243 A\u2009&gt;\u2009G mutation: A glycolysis rebooting syndrome?"],"prefix":"10.3389","volume":"10","author":[{"given":"Wataru","family":"Ohwada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemichi","family":"Kouzu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kahomi","family":"Sazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azumi","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Nagano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Koyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Ogasawara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akifumi","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Yano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Furuhashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1002\/1873-3468.14049","article-title":"The molecular pathology of pathogenic mitochondrial tRNA variants","volume":"595","author":"Richter","year":"2021","journal-title":"FEBS Lett"},{"key":"B2","doi-asserted-by":"publisher","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\u2009>\u2009G mitochondrial point mutation","volume":"25","author":"Murphy","year":"2008","journal-title":"Diabet Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/nrg3966","article-title":"The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease","volume":"16","author":"Stewart","year":"2015","journal-title":"Nat Rev Genet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"951185","DOI":"10.3389\/fgene.2022.951185","article-title":"Pathogenic mitochondrial DNA 3243A\u2009>\u2009G mutation: from genetics to phenotype","volume":"13","author":"Li","year":"2022","journal-title":"Front Genet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/s41392-022-01151-3","article-title":"Lactate metabolism in human health and disease","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B6","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.jamda.2013.11.025","article-title":"Sarcopenia in Asia: consensus report of the Asian working group for sarcopenia","volume":"15","author":"Chen","year":"2014","journal-title":"J Am Med Dir Assoc"},{"key":"B7","doi-asserted-by":"publisher","first-page":"516","DOI":"10.2337\/dc13-0600","article-title":"Relationship between hypoglycemic episodes and ventricular arrhythmias in patients with type 2 diabetes and cardiovascular diseases: silent hypoglycemias and silent arrhythmias","volume":"37","author":"Stahn","year":"2014","journal-title":"Diabetes Care"},{"key":"B8","doi-asserted-by":"publisher","first-page":"S267","DOI":"10.2337\/dc23-S016","article-title":"16. 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Review of monogenic, mitochondrial, and syndromic diabetes","volume":"19","author":"Yeung","year":"2018","journal-title":"Rev Endocr Metab Disord"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1111\/jdi.12992","article-title":"\u201cSwitched\u201d metabolic acidosis in mitochondrial diabetes mellitus","volume":"10","author":"Keidai","year":"2019","journal-title":"J Diabetes Investig"},{"key":"B12","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/s42255-020-0238-1","article-title":"Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality","volume":"2","author":"Legouis","year":"2020","journal-title":"Nat Metab"},{"key":"B13","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.cmet.2018.03.008","article-title":"The science and translation of lactate shuttle theory","volume":"27","author":"Brooks","year":"2018","journal-title":"Cell Metab"},{"key":"B14","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/s42255-020-0243-4","article-title":"Lactate: the ugly duckling of energy metabolism","volume":"2","author":"Rabinowitz","year":"2020","journal-title":"Nat Metab"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e136055","DOI":"10.1172\/JCI136055","article-title":"Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity","volume":"131","author":"Sharma","year":"2021","journal-title":"J Clin Invest"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0219628","DOI":"10.1371\/journal.pone.0219628","article-title":"Appendicular skeletal muscle mass: a more sensitive biomarker of disease severity than BMI in adults with mitochondrial diseases","volume":"14","author":"Hou","year":"2019","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"E578","DOI":"10.1152\/ajpendo.00093.2009","article-title":"The Randle cycle revisited: a new head for an old hat","volume":"297","author":"Hue","year":"2009","journal-title":"Am J Physiol Endocrinol Metab"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1144925\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T04:29:43Z","timestamp":1681705783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1144925\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,17]]},"references-count":17,"alternative-id":["10.3389\/fcvm.2023.1144925"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2023.1144925","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,17]]},"article-number":"1144925"}}