{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T07:06:15Z","timestamp":1779865575110,"version":"3.53.1"},"reference-count":16,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Barnstable Brown Diabetes Center."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Type B insulin resistance syndrome (TBIRS) is a rare autoimmune condition characterized by insulin receptor autoantibodies, often in association with systemic lupus erythematosus (SLE). It can cause extreme insulin resistance, with fewer than 200 cases described worldwide. A 24-year-old man with no prior autoimmune history presented with diabetic ketoacidosis and severe insulin resistance, requiring up to 215 000 units of insulin daily. Laboratory studies revealed high-titer antinuclear antibodies, hypocomplementemia, lupus-specific autoantibodies, and mesangial proliferative lupus nephritis, confirming new-onset SLE. His management was complicated by latent tuberculosis, neutropenia, and cyclophosphamide-induced hearing loss. Despite intensive therapy with corticosteroids, rituximab, cyclophosphamide, obinutuzumab, plasmapheresis, and intravenous immunoglobulin, he remained profoundly insulin resistant, requiring very high daily insulin doses, with persistently elevated insulin receptor antibody titers. Initiation of daratumumab, a CD38 monoclonal antibody, resulted in marked clinical improvement, with progressive decline in insulin requirements and eventual discontinuation of insulin 17 months after presentation. He achieved durable remission with normalization of hemoglobin A1c. This unusually severe case of TBIRS highlights the limitations of conventional B-cell\u2013directed therapies, where long-lived plasma cells sustain pathogenic autoantibodies. Plasma cell\u2013targeted strategies such as daratumumab may represent an effective therapeutic option in refractory cases.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag145","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:38:39Z","timestamp":1778153919000},"source":"Crossref","is-referenced-by-count":0,"title":["Refractory severe type B insulin resistance treated with daratumumab"],"prefix":"10.1210","volume":"4","author":[{"given":"Samhitha","family":"Munugoti","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, University of Kentucky , Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maneesh","family":"Gaddam","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Appalachian Regional Healthcare , Hazard, KY 41701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Rasool","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Kentucky , Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Shevtsov","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Kentucky , Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paramarajan","family":"Piranavan","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Kentucky , Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4761-7417","authenticated-orcid":false,"given":"Philip A","family":"Kern","sequence":"additional","affiliation":[{"name":"Division of 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