{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:09:51Z","timestamp":1779426591477,"version":"3.53.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Type B insulin resistance (TBIR) is a rare autoimmune disorder caused by immunoglobulin G (IgG) autoantibodies targeting the insulin receptor. These antibodies act as partial agonists, resulting in severe insulin resistance and hyperglycemia at high titer, and hypoglycemia at low titer. TBIR typically affects middle-aged women with autoimmune diseases but may occur in younger individuals and across diverse ethnic groups. Early recognition and timely immunosuppressive therapy are crucial for remission and prevention of metabolic complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case<\/jats:title>\n                    <jats:p>We report a 20-year-old Hispanic woman who presented with diabetic ketoacidosis (DKA), severe refractory hyperglycemia, and extreme insulin resistance requiring high doses of U-500 insulin. She had cachexia, acanthosis nigricans, and persistent hyperglycemia despite intravenous insulin infusion exceeding 4 units\/kg\/day. A detailed clinical evaluation, biochemical testing, and immunologic studies were conducted to establish the diagnosis. Laboratory findings showed elevated C-peptide and adiponectin, with positive antinuclear and anti-Smith ribonucleoprotein antibodies. Insulin receptor antibody testing confirmed TBIR. The therapeutic approach included high-dose insulin therapy, adjunctive metabolic agents such as incretin agonists (GLP1 receptor agonist semaglutide), and immunosuppressive therapy, with continuous glucose monitoring (CGM) used for dynamic glucose assessment and titration. Adjunctive therapy with metformin and low-dose semaglutide reduced daily insulin requirements from over 5,000 units to 200 units. Subsequent treatment with rituximab and azathioprine led to complete discontinuation of insulin within one week. However, the course was complicated by serum sickness-like illness and recurrent fasting hypoglycemia, which was managed with glucocorticoids and diazoxide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case illustrates a rare presentation of TBIR in a young Hispanic female, initially manifesting as refractory DKA and extreme insulin resistance, followed by antibody-induced hypoglycemia, highlighting the spectrum of TBIR. This biphasic glycemic course underscores the complex immunopathophysiology of TBIR. To our knowledge, this is the first reported case describing the use of a GLP-1 receptor agonist (semaglutide) to reduce insulin requirements in TBIR prior to immunosuppressive therapy. Continuous glucose monitoring proved essential in guiding therapy and preventing severe hypoglycemia. This case emphasizes the need for early diagnosis, individualized immunosuppressive regimens, and vigilant metabolic monitoring to optimize outcomes in patients with TBIR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1852784","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:53:45Z","timestamp":1779425625000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Type B insulin resistance with glycemic extremes: a case report and literature review"],"prefix":"10.3389","volume":"17","author":[{"given":"Emmeline Monique T.","family":"Ngo","sequence":"first","affiliation":[{"name":"University of Missouri-Kansas City School of Medicine","place":["Kansas, MO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan M.","family":"Rowe","sequence":"additional","affiliation":[{"name":"University of Missouri-Kansas City School of Medicine","place":["Kansas, MO, United States"]},{"name":"University of Missouri-Kansas City School of Pharmacy","place":["Kansas, MO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo Samson","family":"Chillon","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Odense University Hospital","place":["Odense, Denmark"]},{"name":"Institute for Experimental Endocrinology, Charit\u00e9-Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Schomburg","sequence":"additional","affiliation":[{"name":"Institute for Experimental Endocrinology, Charit\u00e9-Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J","family":"Brown","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shourya","family":"Tadisina","sequence":"additional","affiliation":[{"name":"University of Missouri-Kansas City School of Medicine","place":["Kansas, MO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ21\u20130725","article-title":"New classification and diagnostic criteria for insulin resistance syndrome","volume":"69","author":"Ogawa","year":"2022","journal-title":"Endocr J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000263","article-title":"Type B insulin resistance syndrome","volume":"23","author":"Willard","year":"2016","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26125669","article-title":"Severe insulin resistance syndromes: Clinical spectrum and management","volume":"26","author":"Pliszka","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.20945\/2359\u20133997000000257","article-title":"Type B insulin resistance syndrome: a systematic review","volume":"64","author":"Martins","year":"2020","journal-title":"Arch Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-012-2098-x","article-title":"Type B insulin resistance syndrome induced by systemic lupus erythematosus and successfully treated with intravenous immunoglobulin: case report and systematic review","volume":"32","author":"Zhang","year":"2013","journal-title":"Clin Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2337\/dc18\u20130884","article-title":"Combined immunosuppressive therapy induces remission in patients with severe type B insulin resistance: a prospective cohort study","volume":"41","author":"Klubo-Gwiezdzinska","year":"2018","journal-title":"Diabetes Care"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-58-1\u2013182","article-title":"Anti-receptor antibodies mimic the effect of insulin to down-regulate insulin receptors in cultured human lymphoblastoid (IM-9) cells","volume":"58","author":"Taylor","year":"1984","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108861","article-title":"Effects of autoantibodies to the insulin receptor on isolated adipocytes. 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