{"title":"二甲双胍相关性乳酸酸中毒可通过硫胺素治疗","authors":"Michael Ott , Ursula Werneke","doi":"10.1016/j.mehy.2024.111416","DOIUrl":null,"url":null,"abstract":"<div><p>Metformin is a biguanide antidiabetic and a first-line therapy for type-2 diabetes mellitus. It is highly effective, cheap, and easily available since taken in tablet form. Metformin-associated lactic acidosis (MALA) is a serious adverse event with high mortality. It is currently treated with bicarbonate and haemodialysis. The mechanism by which metformin can precipitate lactic acidosis remains subject to debate. Lactic acidosis has also been reported in thiamine (vitamin B1) deficiency. Thiamine deficiency results in a switch from aerobic to anaerobic metabolism with accumulation of lactate. MALA and thiamine-associated lactic acidosis are usually considered separate entities. Both, thiamine and metformin are competitive substrates of the organ cation and thiamine transporters. This way, metformin could cause thiamine deficiency in liver cells. We hypothesize that MALA may be treatable with thiamine. High-dose intravenous thiamine treatment is used routinely for the treatment of Wernicke’s encephalopathy and is regarded as safe. Thiamine has been reported to have improved MALA in four cases, who had been refractory to haemodialysis. Thiamine is widely available, easy to administer, and cheap. Thiamine could already be given while waiting for dialysis. Above all, thiamine could prove life-saving in the treatment of MALA in clinical settings in which dialysis is not available.</p></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"189 ","pages":"Article 111416"},"PeriodicalIF":2.1000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0306987724001592/pdfft?md5=15ab6e6ca33ec4c3f8c320c99c10bf60&pid=1-s2.0-S0306987724001592-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Metformin-associated lactic acidosis may be treatable with thiamine\",\"authors\":\"Michael Ott , Ursula Werneke\",\"doi\":\"10.1016/j.mehy.2024.111416\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Metformin is a biguanide antidiabetic and a first-line therapy for type-2 diabetes mellitus. It is highly effective, cheap, and easily available since taken in tablet form. Metformin-associated lactic acidosis (MALA) is a serious adverse event with high mortality. It is currently treated with bicarbonate and haemodialysis. The mechanism by which metformin can precipitate lactic acidosis remains subject to debate. Lactic acidosis has also been reported in thiamine (vitamin B1) deficiency. Thiamine deficiency results in a switch from aerobic to anaerobic metabolism with accumulation of lactate. MALA and thiamine-associated lactic acidosis are usually considered separate entities. Both, thiamine and metformin are competitive substrates of the organ cation and thiamine transporters. This way, metformin could cause thiamine deficiency in liver cells. We hypothesize that MALA may be treatable with thiamine. High-dose intravenous thiamine treatment is used routinely for the treatment of Wernicke’s encephalopathy and is regarded as safe. Thiamine has been reported to have improved MALA in four cases, who had been refractory to haemodialysis. Thiamine is widely available, easy to administer, and cheap. Thiamine could already be given while waiting for dialysis. Above all, thiamine could prove life-saving in the treatment of MALA in clinical settings in which dialysis is not available.</p></div>\",\"PeriodicalId\":18425,\"journal\":{\"name\":\"Medical hypotheses\",\"volume\":\"189 \",\"pages\":\"Article 111416\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0306987724001592/pdfft?md5=15ab6e6ca33ec4c3f8c320c99c10bf60&pid=1-s2.0-S0306987724001592-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medical hypotheses\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0306987724001592\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical hypotheses","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0306987724001592","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
二甲双胍是一种双胍类抗抑郁药,是治疗 2 型糖尿病的一线药物。二甲双胍是一种双胍类抗糖尿病药物,是治疗 2 型糖尿病的一线药物。二甲双胍相关性乳酸酸中毒(MALA)是一种严重的不良反应,死亡率很高。目前的治疗方法是使用碳酸氢盐和血液透析。二甲双胍导致乳酸酸中毒的机制仍有争议。硫胺素(维生素 B1)缺乏症也有乳酸酸中毒的报道。硫胺素缺乏会导致有氧代谢转为无氧代谢,乳酸蓄积。MALA和硫胺素相关性乳酸酸中毒通常被认为是两个不同的实体。硫胺素和二甲双胍都是器官阳离子和硫胺素转运体的竞争性底物。因此,二甲双胍可能会导致肝细胞硫胺素缺乏。我们推测,硫胺素可以治疗 MALA。大剂量静脉注射硫胺素是治疗韦尼克脑病的常规方法,被认为是安全的。据报道,硫胺素改善了四例血液透析治疗无效的 MALA 患者的病情。硫胺素供应广泛、易于使用且价格低廉。在等待透析期间就可以服用硫胺素。最重要的是,在无法进行透析的临床环境中,硫胺素可用于治疗MALA,从而挽救患者的生命。
Metformin-associated lactic acidosis may be treatable with thiamine
Metformin is a biguanide antidiabetic and a first-line therapy for type-2 diabetes mellitus. It is highly effective, cheap, and easily available since taken in tablet form. Metformin-associated lactic acidosis (MALA) is a serious adverse event with high mortality. It is currently treated with bicarbonate and haemodialysis. The mechanism by which metformin can precipitate lactic acidosis remains subject to debate. Lactic acidosis has also been reported in thiamine (vitamin B1) deficiency. Thiamine deficiency results in a switch from aerobic to anaerobic metabolism with accumulation of lactate. MALA and thiamine-associated lactic acidosis are usually considered separate entities. Both, thiamine and metformin are competitive substrates of the organ cation and thiamine transporters. This way, metformin could cause thiamine deficiency in liver cells. We hypothesize that MALA may be treatable with thiamine. High-dose intravenous thiamine treatment is used routinely for the treatment of Wernicke’s encephalopathy and is regarded as safe. Thiamine has been reported to have improved MALA in four cases, who had been refractory to haemodialysis. Thiamine is widely available, easy to administer, and cheap. Thiamine could already be given while waiting for dialysis. Above all, thiamine could prove life-saving in the treatment of MALA in clinical settings in which dialysis is not available.
期刊介绍:
Medical Hypotheses is a forum for ideas in medicine and related biomedical sciences. It will publish interesting and important theoretical papers that foster the diversity and debate upon which the scientific process thrives. The Aims and Scope of Medical Hypotheses are no different now from what was proposed by the founder of the journal, the late Dr David Horrobin. In his introduction to the first issue of the Journal, he asks ''what sorts of papers will be published in Medical Hypotheses? and goes on to answer ''Medical Hypotheses will publish papers which describe theories, ideas which have a great deal of observational support and some hypotheses where experimental support is yet fragmentary''. (Horrobin DF, 1975 Ideas in Biomedical Science: Reasons for the foundation of Medical Hypotheses. Medical Hypotheses Volume 1, Issue 1, January-February 1975, Pages 1-2.). Medical Hypotheses was therefore launched, and still exists today, to give novel, radical new ideas and speculations in medicine open-minded consideration, opening the field to radical hypotheses which would be rejected by most conventional journals. Papers in Medical Hypotheses take a standard scientific form in terms of style, structure and referencing. The journal therefore constitutes a bridge between cutting-edge theory and the mainstream of medical and scientific communication, which ideas must eventually enter if they are to be critiqued and tested against observations.