{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:29:40Z","timestamp":1793255380571,"version":"4.5.0"},"reference-count":15,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A young girl with type 1 diabetes mellitus (T1D) developed exogenous insulin antibody syndrome (EIAS) characterized by daytime hyperglycemia and ketosis alternating with prolonged severe nocturnal hypoglycemia. EIAS was diagnosed after the exclusion of other causes of hypoglycemia and with confirmation of very high insulin autoantibody levels, high plasma levels of bound insulin, and abnormal insulin clearance. Treatment with different insulin analogues, subcutaneous (SC) insulin pump, immunomodulation using corticosteroids, and intravenous (IV) immunoglobulin were not effective. She responded well to B-lymphocyte depletive therapy (rituximab) with a fall in insulin antibody levels and returned to usual T1D management with a marked improvement in severity of hypoglycemia. One year later she developed hyperglycemia and ketosis and showed no glycemic effect from SC insulin. She became dependent on IV insulin and was diagnosed with severe subcutaneous insulin resistance (SIR). She managed IV insulin at home but developed episodes of sepsis and central line blockage. Many treatment strategies failed, but successful management was finally achieved with the addition of heparin to insulin lispro via SC pump. EIAS and SIR are both extremely rare and, in this case, responded to very different treatment approaches.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf300","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T12:54:30Z","timestamp":1763816070000},"source":"Crossref","is-referenced-by-count":2,"title":["Exogenous Insulin Antibody Syndrome and Subsequent Severe Subcutaneous Insulin Resistance Complicating Type 1 Diabetes"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5596-6029","authenticated-orcid":false,"given":"Vicki","family":"Cunningham","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Te Whatu Ora\u2013Health New Zealand , Whangarei 0148 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1405-9890","authenticated-orcid":false,"given":"Leo","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Te Whatu Ora\u2013Health New Zealand , Auckland 1010 ,","place":["New Zealand"]},{"name":"Pathology, Surgical and Support Services, Te Whatu Ora\u2013Health New Zealand , Whangarei 0148 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Chih","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Paediatric Immunology, Starship Child Health, Te Whatu Ora\u2013Health New Zealand , Auckland 1050 ,","place":["New Zealand"]},{"name":"Department of Paediatrics, The University of Auckland , Auckland 1050 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Ayers","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Te Whatu Ora\u2013Health New Zealand , Whangarei 0148 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0498-3473","authenticated-orcid":false,"given":"Benjamin","family":"Albert","sequence":"additional","affiliation":[{"name":"Liggins Institute, The University of Auckland , Auckland 1050 ,","place":["New Zealand"]},{"name":"Department of Paediatric Endocrinology, Starship Child Health, Te Whatu Ora\u2013Health New Zealand , Auckland 1050 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Jefferies","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The University of Auckland , Auckland 1050 ,","place":["New Zealand"]},{"name":"Liggins Institute, The University of Auckland , Auckland 1050 ,","place":["New Zealand"]},{"name":"Department of Paediatric Endocrinology, Starship Child Health, Te Whatu Ora\u2013Health New Zealand , Auckland 1050 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"issue":"3","key":"2025122922045752900_luaf300-B1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.33176\/AACB-20-00008","article-title":"Clinical and laboratory aspects of insulin autoantibody-mediated glycaemic dysregulation and hyperinsulinaemic hypoglycaemia: insulin autoimmune syndrome and exogenous insulin antibody syndrome","volume":"41","author":"Huynh","year":"2020","journal-title":"Clin Biochem Rev"},{"issue":"1","key":"2025122922045752900_luaf300-B2","doi-asserted-by":"crossref","first-page":"R47","DOI":"10.1530\/EC-17-0309","article-title":"Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients","volume":"7","author":"Hu","year":"2018","journal-title":"Endocr Connect"},{"key":"2025122922045752900_luaf300-B3","first-page":"130086","article-title":"Analytical and clinical challenges in a patient with concurrent type 1 diabetes, subcutaneous insulin resistance and insulin autoimmune syndrome","volume":"2014","author":"Jassam","year":"2014","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"issue":"3","key":"2025122922045752900_luaf300-B4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1034\/j.1399-5448.2002.30305.x","article-title":"Insulin autoantibodies are of less value compared with islet antibodies in the clinical diagnosis of autoimmune type 1 diabetes in children older than 3\u2005yr of age: insulin autoantibodies","volume":"3","author":"Borg","year":"2002","journal-title":"Pediatr Diabetes"},{"issue":"2","key":"2025122922045752900_luaf300-B5","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1016\/j.diabres.2009.02.007","article-title":"Characteristics of the antibodies of two patients who developed daytime hyperglycemia and morning hypoglycemia because of insulin antibodies","volume":"84","author":"Ishizuka","year":"2009","journal-title":"Diabetes Res Clin Pract"},{"issue":"1","key":"2025122922045752900_luaf300-B6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/pedi.12522","article-title":"Therapeutic plasma exchange normalizes insulin-mediated response in a child with type 1 diabetes and insulin autoimmune syndrome","volume":"19","author":"Sharwood","year":"2018","journal-title":"Pediatr Diabetes"},{"issue":"1","key":"2025122922045752900_luaf300-B7","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/j.1600-6143.2009.02881.x","article-title":"Extreme subcutaneous, intramuscular and inhaled insulin resistance treated by pancreas transplantation alone","volume":"10","author":"Sa","year":"2010","journal-title":"Am J Transplant"},{"issue":"6","key":"2025122922045752900_luaf300-B8","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1399-5448.2009.00597.x","article-title":"Successful treatment of severe subcutaneous insulin resistance with inhaled insulin therapy","volume":"11","author":"van Alfen-van der Velden","year":"2010","journal-title":"Pediatr Diabetes"},{"issue":"5","key":"2025122922045752900_luaf300-B9","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/S1262-3636(07)70221-5","article-title":"Subcutaneous insulin resistance successfully circumvented on long term by peritoneal insulin delivery from an implantable pump in four diabetic patients","volume":"31","author":"Riveline","year":"2005","journal-title":"Diabetes Metab"},{"issue":"9","key":"2025122922045752900_luaf300-B10","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.2337\/diacare.27.9.2243","article-title":"Beta-cell transplantation restores metabolic control and quality of life in a patient with subcutaneous insulin resistance","volume":"27","author":"Gillard","year":"2004","journal-title":"Diabetes Care"},{"issue":"3","key":"2025122922045752900_luaf300-B11","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0168-8227(01)00314-X","article-title":"A patient with subcutaneous-insulin resistance treated by insulin lispro plus heparin","volume":"54","author":"Tokuyama","year":"2001","journal-title":"Diabetes Res Clin Pract"},{"issue":"5","key":"2025122922045752900_luaf300-B12","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1111\/jdi.13266","article-title":"Insulin and heparin challenge tests are useful for choosing an optimal insulin regimen in a case of subcutaneous insulin resistance","volume":"11","author":"Nakamura","year":"2020","journal-title":"J Diabetes Investig"},{"issue":"3","key":"2025122922045752900_luaf300-B13","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.2337\/dc07-2161","article-title":"Dramatic improvement of subcutaneous insulin resistance with nafamostat ointment treatment","volume":"31","author":"Kawashima","year":"2008","journal-title":"Diabetes Care"},{"issue":"7","key":"2025122922045752900_luaf300-B14","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1056\/NEJM198108133050702","article-title":"Diabetes responsive to intravenous but not subcutaneous insulin: effectiveness of aprotinin","volume":"305","author":"Freidenberg","year":"1981","journal-title":"N Engl J Med"},{"issue":"3","key":"2025122922045752900_luaf300-B15","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/jdi.13667","article-title":"Case of subcutaneous insulin resistance syndrome treated with ultra-rapid insulin lispro","volume":"13","author":"Ishii","year":"2022","journal-title":"J Diabetes Investig"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/1\/luaf300\/66149358\/luaf300.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/1\/luaf300\/66149358\/luaf300.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T03:05:06Z","timestamp":1767063906000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luaf300\/8407079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,3]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12,3]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luaf300","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,12,3]]},"article-number":"luaf300"}}