Lactate Acidosis Associated with Phenformin Therapy and Localized Tissue Hypoxia
Authors: GORDON A. EWY
Journal: Annals of Internal Medicine (1963)

Case Studies1 December 1963Lactate Acidosis Associated with Phenformin Therapy and Localized Tissue HypoxiaReport of a Case Treated by HemodialysisGORDON A. EWY, M.D., RUFINO C. PABICO, M.D., JOHN F. MAHER, M.D., DANIEL H. MINTZ, M.D.GORDON A. EWY, M.D.Search for more papers by this author, RUFINO C. PABICO, M.D.Search for more papers by this author, JOHN F. MAHER, M.D.Search for more papers by this author, DANIEL H. MINTZ, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-59-6-878 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe oral hypoglycemic agent phenformin (N1-β-phenethylbiguanide hydrochloride (DBI⌖*)) was greeted with hopeful anticipation when Ungar, Freedman, and Shapiro (1) demonstrated its mode of action to be different from the endogenous insulin-stimulating effect of sulfonylureas. Many investigators have reported on the therapeutic efficacy of phenformin, not only in ketoacidosis-resistant diabetes (2, 3), but also as an adjuvant to insulin therapy in juvenile diabetes (4) and in the treatment of insulin resistance (5, 6).It had been observed that patients prone to ketoacidosis could develop ketosis without associated hyperglycemia when treated with prenformin (3, 4, 7). Concern was occasioned by the reports...References1. UNGARFREEDMANSHAPIRO GLSL: Pharmacological studies of a new oral hypoglycemic drug. Proc. Soc. Exp. Biol. Med. 95: 190, 1957. CrossrefMedlineGoogle Scholar2. BEASER SB: Therapy of diabetes mellitus with combinations of drugs given orally. New Eng. J. Med. 259: 1207, 1958. CrossrefMedlineGoogle Scholar3. UNGERMADISONCARTER RHLLNW: Tolbutamide-phenformin in ketoacidosis-resistant patients. JAMA 174: 2132, 1960. CrossrefMedlineGoogle Scholar4. 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GOTTLIEBDUBERSTEINGELLER AJA: Phenformin acidosis. New Eng. J. Med. 267: 806, 1962. CrossrefMedlineGoogle Scholar12. TRANQUADABERNSTEINMARTIN RESHE: Irreversible lactic acidosis associated with phenformin therapy. JAMA 184: 37, 1963. CrossrefMedlineGoogle Scholar13. BERNIERMILLERSPRINGATE GMMCS: Lactic acidosis and phenformin hydrochloride. JAMA 184: 43, 1963. CrossrefMedlineGoogle Scholar14. DAUGHADAYLIPICKYRASINSKI WHRJDC: Lactic acidosis as a cause of nonketotic acidosis in diabetic patients. New Eng. J. Med. 267: 1010, 1962. CrossrefMedlineGoogle Scholar15. BARKERSUMMERSON SBWH: The colorimetric determination of lactic acid in biological material. J. Biol. Chem. 133: 585, 1940. Google Scholar16. BUEDINGWORTIS EH: The stabilization and determination of pyruvic acid in the blood. J. Biol. Chem. 133: 585, 1940. CrossrefGoogle Scholar17. CRAIGMILLERWOODWARDMERIK JWMHE: Influence of phenethylbiguanide on lactic, pyruvic, and citric acids in diabetic patients. Diabetes 9: 186, 1960. 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Med. 101: 211, 1958. CrossrefGoogle Scholar24. STEINERWILLIAMS DFRH: Respiratory inhibition and hypoglycemia by biguanides and decamethylenediguanidine. Biochim. Biophys. Acta 30: 329, 1958. CrossrefMedlineGoogle Scholar25. WICKLARSONSERIF ANERGS: A site of action of phenethylbiguanide, a hypoglycemic compound. J. Biol. Chem. 233: 296, 1958. CrossrefMedlineGoogle Scholar26. WILLIAMSTYBERGHEINHYDENIELSEN RHJMPMRL: Studies related to the hypoglycemic action of phenethylbiguanide. Metabolism 6: 311, 1957. MedlineGoogle Scholar27. KRUGERSKILLMANHAMWIGRUBBSDANFORTH FATGGJRCBA: The mechanism of action of hypoglycemic guanidine derivatives. Diabetes 9: 170, 1960. CrossrefMedlineGoogle Scholar28. WICKSTEWARTSERIF ANCJGS: Tissue distribution of C-14 labeled beta phenethylbiguanide. Diabetes 9: 163, 1960. CrossrefMedlineGoogle Scholar29. SALISBURYSELIGSONREESELKINTONGRENALLSCHREINER PFDBSBJRRGE: The nature of the uremic state. Trans. Amer. Soc. Artif. Intern. Organs 4: 178, 1958. Google Scholar30. SELIGSON D: Organic Acids and Renal Function. Consciousness and Chemical Environment of the Brain. Report of the Twenty-fifth Ross Pediatric Conference, Columbus, Ohio. Ross Laboratories, 1957, p. 66. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Washington, D. C.From the Department of Medicine, Georgetown University School of Medicine, The Georgetown University Medical Division, District of Columbia General Hospital, Washington, D. C.This work was supported in part by the John A. Hartford Foundation and the Georgetown Kidney Research Fund.Requests for reprints should be addressed to Daniel H. Mintz, M.D., The Georgetown University Medical Division, District of Columbia General Hospital, Washington 3, D. C.*Registered trademark of U. S. Vitamin and Pharmaceutical Corporation, New York, New York. 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OLSON, PH.D., M.D. 1 December 1963Volume 59, Issue 6Page: 878-883KeywordsHospital medicineHypoxiaInsulinInsulin resistanceLactatesLactic acidLesionsPathogenesisResearch fundingType 1 diabetes Issue Published: 1 December 1963 PDF DownloadLoading ...