{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:15:07Z","timestamp":1792800907127,"version":"4.5.0"},"reference-count":11,"publisher":"Walter de Gruyter GmbH","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n Rabson\u2013Mendenhall syndrome (RMS) is a rare monogenic insulin resistance disorder characterized by progressive dysglycemia and early mortality. Management of diabetic ketoacidosis (DKA) in RMS is particularly challenging because standard insulin doses may be inadequate, and pediatric-specific experience is limited.<\/jats:p>\n <\/jats:sec>\n \n Case presentation<\/jats:title>\n \n We report two siblings with genetically confirmed RMS. The index child, a 7-year-old girl, presented with severe refractory DKA requiring progressive escalation of intravenous insulin to 12\u202fIU\/kg\/h before meaningful metabolic response was achieved. Insulin was titrated according to serial glycemic and acid\u2013base responses, without bicarbonate therapy, with close potassium monitoring. Her 3-year-old brother was evaluated proactively after the diagnosis in his sister and was found to have hyperglycemia and the same homozygous\n INSR<\/jats:italic>\n variant before an episode of metabolic decompensation. He was treated with subcutaneous insulin and insulin sensitizers. At 1-year follow-up, HbA\n 1c<\/jats:sub>\n was 10.4\u202f% in the index child and 8.9\u202f% in the sibling.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Refractory DKA in RMS may require rapid, response-guided escalation of insulin beyond conventional pediatric dosing. The detailed temporal relationship between insulin dose and metabolic response in this child provides practical clinical insight, while early recognition of RMS permits evaluation and treatment of affected siblings before presentation with acute metabolic decompensation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1515\/jpem-2026-0389","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:55:48Z","timestamp":1791035748000},"source":"Crossref","is-referenced-by-count":1,"title":["Refractory diabetic ketoacidosis in Rabson\u2013Mendenhall syndrome due to a novel mutation: contrasting outcomes in a sibling\u00a0\u2013\u00a0case series"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0259-8412","authenticated-orcid":false,"given":"J. Mohammed","family":"Azarudeen","sequence":"first","affiliation":[{"name":"Department of Paediatrics , Velammal Medical College Hospital and Research Institute , Madurai , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics , All India Institute of Medical Science , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjana","family":"Kar","sequence":"additional","affiliation":[{"name":"Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics , Hyderabad , Telangana , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gowri","family":"Rao","sequence":"additional","affiliation":[{"name":"Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics , Hyderabad , Telangana , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwin","family":"Dalal","sequence":"additional","affiliation":[{"name":"Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics , Hyderabad , Telangana , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxi","family":"Vairavan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics , Velammal Medical College Hospital and Research Institute , Madurai , India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"2026100313553940655_j_jpem-2026-0389_ref_001","doi-asserted-by":"crossref","unstructured":"Ogawa, W, Araki, E, Ishigaki, Y, Hirota, Y, Maegawa, H, Yamauchi, T, et al.. New classification and diagnostic criteria for insulin resistance syndrome. Endocr J 2022;69:107\u201313. https:\/\/doi.org\/10.1507\/endocrj.ej21-0725.","DOI":"10.1507\/endocrj.EJ21-0725"},{"key":"2026100313553940655_j_jpem-2026-0389_ref_002","unstructured":"Brown, RJ, Cochran, E, Gorden, P. Syndromes of severe insulin resistance and\/or lipodystrophy. Pediatr Diabetes 2011;12:154\u201364."},{"key":"2026100313553940655_j_jpem-2026-0389_ref_003","doi-asserted-by":"crossref","unstructured":"Melvin, A, O\u2019Rahilly, S, Savage, DB. Genetic syndromes of severe insulin resistance. Curr Opin Genet Dev 2018;50:60\u20137. https:\/\/doi.org\/10.1016\/j.gde.2018.02.002.","DOI":"10.1016\/j.gde.2018.02.002"},{"key":"2026100313553940655_j_jpem-2026-0389_ref_004","unstructured":"Rabson, SM, Mendenhall, EN. Insulin-resistant diabetes mellitus: report of a case. Am J Dis Child 1956;91:603\u201311."},{"key":"2026100313553940655_j_jpem-2026-0389_ref_005","doi-asserted-by":"crossref","unstructured":"Semple, RK, Savage, DB, Cochran, EK, Gorden, P, O\u2019Rahilly, S. Genetic syndromes of severe insulin resistance. Endocr Rev 2011;32:498\u2013514. https:\/\/doi.org\/10.1210\/er.2010-0020.","DOI":"10.1210\/er.2010-0020"},{"key":"2026100313553940655_j_jpem-2026-0389_ref_006","doi-asserted-by":"crossref","unstructured":"Moore, MM, Bailey, AM, Flannery, AH, Baum, RA. Treatment of diabetic ketoacidosis with intravenous U-500 insulin in a patient with Rabson-Mendenhall syndrome: a case report. J\u00a0Pharm Pract 2017;30:468\u201375. https:\/\/doi.org\/10.1177\/0897190016645036.","DOI":"10.1177\/0897190016645036"},{"key":"2026100313553940655_j_jpem-2026-0389_ref_007","doi-asserted-by":"crossref","unstructured":"Robinson, C, Cochran, E, Gorden, P, Brown, RJ. Management of diabetic ketoacidosis in severe insulin resistance. Diabetes Care 2016;39:e116\u201318. https:\/\/doi.org\/10.2337\/dc16-0635.","DOI":"10.2337\/dc16-0635"},{"key":"2026100313553940655_j_jpem-2026-0389_ref_008","doi-asserted-by":"crossref","unstructured":"Aftab, S, Shaheen, T, Asif, R, Anjum, MN, Saeed, A, Manzoor, J, et al.. Management challenges of Rabson Mendenhall syndrome in a resource limited country: a case report. J\u00a0Pediatr Endocrinol Metab 2022;35:1429\u201332. https:\/\/doi.org\/10.1515\/jpem-2022-0214.","DOI":"10.1515\/jpem-2022-0214"},{"key":"2026100313553940655_j_jpem-2026-0389_ref_009","doi-asserted-by":"crossref","unstructured":"Sinnarajah, K, Dayasiri, MBKC, Dissanayake, NDW, Kudagammana, ST, Jayaweera, AHHM. Rabson Mendenhall syndrome caused by a novel missense mutation. Int J Pediatr Endocrinol 2016;2016:3. https:\/\/doi.org\/10.1186\/s13633-016-0039-1.","DOI":"10.1186\/s13633-016-0039-1"},{"key":"2026100313553940655_j_jpem-2026-0389_ref_010","doi-asserted-by":"crossref","unstructured":"Ardon, O, Procter, M, Tvrdik, T, Longo, N, Mao, R. Sequencing analysis of insulin receptor defects and detection of two novel mutations in INSR gene. Mol Genet Metab Rep 2014;1:53\u20137. https:\/\/doi.org\/10.1016\/j.ymgmr.2013.12.006.","DOI":"10.1016\/j.ymgmr.2013.12.006"},{"key":"2026100313553940655_j_jpem-2026-0389_ref_011","doi-asserted-by":"crossref","unstructured":"Okawa, MC, Cochran, E, Lightbourne, M, Brown, RJ. Long-term effects of metreleptin in Rabson-Mendenhall syndrome on glycemia, growth, and kidney function. J\u00a0Clin Endocrinol Metab 2022;107:e1032\u201346. https:\/\/doi.org\/10.1210\/clinem\/dgab782.","DOI":"10.1210\/clinem\/dgab782"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2026-0389\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2026-0389\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:55:56Z","timestamp":1791035756000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2026-0389\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":11,"alternative-id":["10.1515\/jpem-2026-0389"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2026-0389","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"value":"0334-018X","type":"print"},{"value":"2191-0251","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]}}}