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Med."],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital insulin resistance syndromes are caused by biallelic mutations within the insulin receptor gene (<jats:italic><jats:styled-content style=\"fixed-case\">INSR<\/jats:styled-content><\/jats:italic>). Recombinant human insulin\u2010like growth factor (rh<jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>1) has been used with mixed success; however, rigorous assessment of its efficacy is lacking. Here, we describe a child with a homozygous mutation in <jats:italic><jats:styled-content style=\"fixed-case\">INSR<\/jats:styled-content><\/jats:italic> successfully treated with rh<jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>1 for more than 5\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case report<\/jats:title><jats:p>The patient presented with osmotic diabetes symptoms and was noted to have dysplastic dentition, hypertrichosis, coarse and dysmorphic facial features. Acanthosis nigricans, skin tags and rugated hyperkeratosis were also evident on the posterior neck, axilla and groin. A homozygous <jats:italic><jats:styled-content style=\"fixed-case\">INSR<\/jats:styled-content><\/jats:italic> essential splice site mutation (c.1268\u00a0+\u00a02T\u00a0&gt;\u00a0C, p.G374\u00a0fs*12) was identified, for which both parents were found to be heterozygous. The patient was treated with twice daily injections of rh<jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>1 and metformin for more than 5\u00a0years with improvement in her acanthosis nigricans, hyperkeratosis and hypertrichosis. A dramatic fall in fasting insulin, <jats:styled-content style=\"fixed-case\">HOMA<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> and HbA<jats:sub>1c<\/jats:sub> has been maintained over the entire course of treatment without adverse effects. Her linear growth velocity has remained on target for her predicted adult height.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our case demonstrates the effectiveness of rh<jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>1 as an early treatment in a patient with a biallelic mutation within <jats:italic><jats:styled-content style=\"fixed-case\">INSR<\/jats:styled-content><\/jats:italic> without evidence of fluid retention, retinopathy, muscle pain, heart failure, cerebral infarcts or benign intracranial hypertension. Her case suggests rh<jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>1 can and should be considered as an initial treatment option instead of as a final option in those with <jats:italic><jats:styled-content style=\"fixed-case\">INSR<\/jats:styled-content><\/jats:italic> mutations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.12884","type":"journal-article","created":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T15:05:55Z","timestamp":1439305555000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Successful rh<scp>IGF<\/scp>1 treatment for over 5\u00a0years in a patient with severe insulin resistance due to homozygous insulin receptor mutation"],"prefix":"10.1111","volume":"33","author":[{"given":"D.","family":"Carmody","sequence":"first","affiliation":[{"name":"Departments of Medicine and Pediatrics Section\u00a0of Adult and Pediatric Endocrinology, Diabetes, &amp; Metabolism The University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. S.","family":"Ladsaria","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics Section\u00a0of Adult and Pediatric Endocrinology, Diabetes, &amp; Metabolism The University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. K.","family":"Buikema","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics Section\u00a0of Adult and Pediatric Endocrinology, Diabetes, &amp; Metabolism The University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. K.","family":"Semple","sequence":"additional","affiliation":[{"name":"University of Cambridge Wellcome Trust\u2010MRC Institute of Metabolic Science Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. A. W.","family":"Greeley","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics Section\u00a0of Adult and Pediatric Endocrinology, Diabetes, &amp; Metabolism The University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0787"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.02.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2012.27.5.565"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2011-0448"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2014.11.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp215"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000366225"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-07-0271"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2006.02678.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ11-0032"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2012.05665.x"},{"key":"e_1_2_8_13_1","first-page":"1237","article-title":"Continuous subcutaneous IGF\u20131 therapy via insulin pump in a patient with Donohue syndrome","volume":"27","author":"Weber DR","year":"2014","journal-title":"J Pediatr Endocrinol Metab"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0020"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)40889-1"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2850269"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2088"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116109"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2319\/0003-3219(2008)078[0745:DACCIA]2.0.CO;2"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)10384-1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.8.2623"}],"container-title":["Diabetic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdme.12884","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdme.12884","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.12884","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dme.12884","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.12884","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T10:25:27Z","timestamp":1693218327000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dme.12884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,11]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1111\/dme.12884"],"URL":"https:\/\/doi.org\/10.1111\/dme.12884","archive":["Portico"],"relation":{},"ISSN":["0742-3071","1464-5491"],"issn-type":[{"value":"0742-3071","type":"print"},{"value":"1464-5491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,11]]},"assertion":[{"value":"2015-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}