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No standardized treatment regimen exists.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate an analytic approach to IAS and responses to different treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Setting<\/jats:title><jats:p>Observational study in the UK Severe Insulin Resistance Service.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Six patients with hyperinsulinemic hypoglycemia and detectable circulating anti\u2013insulin antibody (IA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>Glycemia, plasma insulin, and C-peptide concentrations by immunoassay or mass spectrometry (MS). Immunoreactive insulin was determined in the context of polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC). IA quantification using ELISA and RIA, and IA were further characterized using radioligand binding studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients were diagnosed with IAS (five IgG, one IgA) based on a high insulin\/C-peptide ratio, low insulin recovery after PEG precipitation, and GFC evidence of antibody-bound insulin. Neither ELISA nor RIA result proved diagnostic for every case. MS provided a more robust quantification of insulin in the context of IA. One patient was managed conservatively, four were treated with diazoxide without sustained benefit, and four were treated with immunosuppression with highly variable responses. IA affinity did not appear to influence presentation or prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IAS should be considered in patients with hyperinsulinemic hypoglycemia and a high insulin\/C-peptide ratio. Low insulin recovery on PEG precipitation supports the presence of insulin-binding antibodies, with GFC providing definitive confirmation. Immunomodulatory therapy should be customized according to individual needs and clinical response.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2018-00972","type":"journal-article","created":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T21:50:00Z","timestamp":1533073800000},"page":"3845-3855","source":"Crossref","is-referenced-by-count":40,"title":["Assessment and Management of Anti-Insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome"],"prefix":"10.1210","volume":"103","author":[{"given":"David","family":"Church","sequence":"first","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Wellcome Trust\u2013MRC Institute of Metabolic Science, Cambridge, United Kingdom"},{"name":"National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, United Kingdom"},{"name":"Department of Clinical Biochemistry and Immunology, Cambridge University Hospitals, NHS Foundation Trust, Cambridge, United 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