{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:26Z","timestamp":1784557046085,"version":"3.55.0"},"reference-count":18,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"\n Summary<\/jats:title>\n \n A 17-year-old boy was referred to our endocrinology clinic for a clinical investigation of hyperinsulinemia. An oral glucose tolerance test showed plasma glucose concentrations in the normal range. However, insulin concentrations were considerably elevated (0 min: 71 \u03bcU\/mL; 60 min: 953 \u03bcU\/mL), suggesting severe insulin resistance. An insulin tolerance test confirmed that he had insulin resistance. There was no apparent hormonal or metabolic cause, including obesity. The patient had no outward features of hyperinsulinemia, including acanthosis nigricans or hirsutism. However, his mother and grandfather also had hyperinsulinemia. Genetic testing showed that the patient (proband), his mother, and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (\n INSR<\/jats:italic>\n ). Although all three family members have the same mutation, their clinical courses have been different. The onset of the mother\u2019s diabetes was estimated at 50 years, whereas the grandfather developed diabetes at 77 years.\n <\/jats:p>\n <\/jats:sec>\n \n Learning points<\/jats:title>\n \n \n \n Type A insulin resistance syndrome is caused by mutations in the insulin receptor (\n INSR<\/jats:italic>\n ) gene and results in severe insulin resistance.\n <\/jats:p>\n <\/jats:list-item>\n \n Genetic evaluation should be considered in adolescents or young adults with dysglycemia when an atypical phenotype, such as severe insulin resistance, or a relevant family history is observed.<\/jats:p>\n <\/jats:list-item>\n \n Clinical courses may differ even if the same genetic mutation is found in a family.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-22-0362","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T07:38:47Z","timestamp":1681285127000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":5,"title":["A family with type A insulin resistance syndrome caused by a novel insulin receptor mutation"],"prefix":"10.1530","volume":"2023","author":[{"given":"Osamu","family":"Horikawa","sequence":"first","affiliation":[{"name":"Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-0666","authenticated-orcid":true,"given":"Satoshi","family":"Ugi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan"},{"name":"Department of Medicine, Omihachiman Community Medical Center, Omihachiman, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomofumi","family":"Takayoshi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Omura","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kohka Public Hospital, Kohka, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Yonishi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Fuke","sequence":"additional","affiliation":[{"name":"Department of Medicine, Saiseikai Shiga Hospital, Ritto, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Maegawa","sequence":"additional","affiliation":[{"name":"Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Endocrine Reviews","first-page":"498","article-title":"Genetic syndromes of severe insulin resistance","volume":"32","author":"Semple","year":"2011","unstructured":"Semple RKSavage DBCochran EKGorden P & O'Rahilly S. Genetic syndromes of severe insulin resistance. Endocrine Reviews201132498\u2013514. (https:\/\/doi.org\/10.1210\/er.2010-0020)"},{"key":"bib2","series-title":"Diabetes Care","first-page":"3117","article-title":"Monogenic diabetes: from genetic insights to population-based precision in care. Reflections from a 2020","volume":"43","author":"Riddle","year":"2020","unstructured":"Riddle MCPhilipson LHRich SSCarlsson AFranks PWGreeley SAWNolan JJPearson ERZeitler PS & Hattersley AT. Monogenic diabetes: from genetic insights to population-based precision in care. Reflections from a 2020. Diabetes Care2020433117\u20133128. (https:\/\/doi.org\/10.2337\/dci20-0065)"},{"key":"bib3","series-title":"Journal of Diabetes Investigation","first-page":"603","article-title":"Clinical characteristics of insulin resistance syndromes: a nationwide survey in Japan","volume":"11","author":"Takeuchi","year":"2020","unstructured":"Takeuchi TIshigaki YHirota YHasegawa YYorifuji TKadowaki HAkamizu TOgawa W & Katagiri H. Clinical characteristics of insulin resistance syndromes: a nationwide survey in Japan. Journal of Diabetes Investigation202011603\u2013616. (https:\/\/doi.org\/10.1111\/jdi.13171)"},{"key":"bib4","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"374","article-title":"Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies","volume":"68","author":"Bonora","year":"1989","unstructured":"Bonora EMoghetti PZancanaro CCigolini MQuerena MCacciatori VCorgnati A & Muggeo M. Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies. Journal of Clinical Endocrinology and Metabolism198968374\u2013378. (https:\/\/doi.org\/10.1210\/jcem-68-2-374)"},{"key":"bib5","series-title":"Journal of Diabetes Investigation","first-page":"305","article-title":"Usefulness of the insulin tolerance test in patients with type 2 diabetes receiving insulin therapy","volume":"5","author":"Okita","year":"2014","unstructured":"Okita KIwahashi HKozawa JOkauchi YFunahashi TImagawa A & Shimomura I. Usefulness of the insulin tolerance test in patients with type 2 diabetes receiving insulin therapy. Journal of Diabetes Investigation20145305\u2013312. (https:\/\/doi.org\/10.1111\/jdi.12143)"},{"key":"bib6","series-title":"Diabetology International","first-page":"337","article-title":"New classification and diagnostic criteria for insulin resistance syndrome","volume":"13","author":"Ogawa","year":"2022","unstructured":"Ogawa WAraki EIshigaki YHirota YMaegawa HYamauchi TYorifuji T & Katagiri H. New classification and diagnostic criteria for insulin resistance syndrome. Diabetology International202213337\u2013343. (https:\/\/doi.org\/10.1007\/s13340-022-00570-5)"},{"key":"bib7","series-title":"New England Journal of Medicine","first-page":"739","article-title":"The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man","volume":"294","author":"Kahn","year":"1976","unstructured":"Kahn CRFlier JSBar RSArcher JAGorden PMartin MM & Roth J. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. New England Journal of Medicine1976294739\u2013745. (https:\/\/doi.org\/10.1056\/NEJM197604012941401)"},{"key":"bib8","series-title":"Medicine (Baltimore)","first-page":"209","article-title":"Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective","volume":"83","author":"Musso","year":"2004","unstructured":"Musso CCochran EMoran SASkarulis MCOral EATaylor S & Gordon P. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective. Medicine (Baltimore)200483209\u2013222. (https:\/\/doi.org\/10.1097\/01.md.0000133625.73570.54)"},{"key":"bib9","series-title":"Diabetes","first-page":"2713","article-title":"Structural basis and genotype-phenotype correlations of INSR mutations causing severe insulin resistance","volume":"66","author":"Hosoe","year":"2017","unstructured":"Hosoe JKadowaki HMiya FAizu KKawamura TMiyata ISatomura KIto THara KTanaka M, Structural basis and genotype-phenotype correlations of INSR mutations causing severe insulin resistance. Diabetes2017662713\u20132723. (https:\/\/doi.org\/10.2337\/db17-0301)"},{"key":"bib10","series-title":"Diabetes","first-page":"1837","article-title":"Ala1048-->Asp mutation in the kinase domain of insulin receptor causes defective kinase activity and insulin resistance","volume":"42","author":"Haruta","year":"1993","unstructured":"Haruta TTakata YIwanishi MMaegawa HImamura TEgawa KItazu T & Kobayashi M. Ala1048-->Asp mutation in the kinase domain of insulin receptor causes defective kinase activity and insulin resistance. Diabetes1993421837\u20131844. (https:\/\/doi.org\/10.2337\/diab.42.12.1837)"},{"key":"bib11","series-title":"Science","first-page":"63","article-title":"Human diabetes associated with a deletion of the tyrosine kinase domain of the insulin receptor","volume":"245","author":"Taira","year":"1989","unstructured":"Taira MTaira MHashimoto NShimada FSuzuki YKanatsuka ANakamura FEbina YTatibana MMakino H, Human diabetes associated with a deletion of the tyrosine kinase domain of the insulin receptor. Science198924563\u201366. (https:\/\/doi.org\/10.1126\/science.2544997)"},{"key":"bib12","series-title":"Pediatric Diabetes","first-page":"835","article-title":"Diagnostic and management challenges from childhood, puberty through to transition in severe insulin resistance due to insulin receptor mutations","volume":"18","author":"Wei","year":"2017","unstructured":"Wei C & Burren CP. Diagnostic and management challenges from childhood, puberty through to transition in severe insulin resistance due to insulin receptor mutations. Pediatric Diabetes201718835\u2013838. (https:\/\/doi.org\/10.1111\/pedi.12486)"},{"key":"bib13","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1840","article-title":"A 3-basepair in-frame deletion (delta Leu999) in exon 17 of the insulin receptor gene in a family with insulin resistance","volume":"79","author":"Awata","year":"1994","unstructured":"Awata TMatsumoto CMomomura KTakahashi YOdawara MKasuga MKadowaki T & Iwamoto Y. A 3-basepair in-frame deletion (delta Leu999) in exon 17 of the insulin receptor gene in a family with insulin resistance. Journal of Clinical Endocrinology and Metabolism1994791840\u20131844. (https:\/\/doi.org\/10.1210\/jcem.79.6.7989492)"},{"key":"bib14","series-title":"Endocrine Journal","first-page":"509","article-title":"Phenotypical variety of insulin resistance in a family with a novel mutation of the insulin receptor gene","volume":"57","author":"Takahashi","year":"2010","unstructured":"Takahashi IYamada YKadowaki HHorikoshi MKadowaki TNarita TTsuchida SNoguchi AKoizumi A & Takahashi T. Phenotypical variety of insulin resistance in a family with a novel mutation of the insulin receptor gene. Endocrine Journal201057509\u2013516. (https:\/\/doi.org\/10.1507\/endocrj.k09e-339)"},{"key":"bib15","series-title":"Journal of Medical Case Reports","article-title":"Type A insulin resistance syndrome misdiagnosed as polycystic ovary syndrome: a case report","volume":"13","author":"Lin","year":"2019","unstructured":"Lin LChen CFang TChen DChen K & Quan H. Type A insulin resistance syndrome misdiagnosed as polycystic ovary syndrome: a case report. Journal of Medical Case Reports201913 347. (https:\/\/doi.org\/10.1186\/s13256-019-2304-4)"},{"key":"bib16","series-title":"Diabetologia","first-page":"1577","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","unstructured":"Rena GHardie DG & Pearson ER. The mechanisms of action of metformin. Diabetologia2017601577\u20131585. (https:\/\/doi.org\/10.1007\/s00125-017-4342-z)"},{"key":"bib17","series-title":"Endocrinology, Diabetes and Metabolism Case Reports","first-page":"21","article-title":"Monogenic diabetes due to an INSR mutation in a child with severe insulin resistance","volume":"2022","author":"Sanderson","unstructured":"Sanderson EEShah MHooper AJBell DA & Choong CS. Monogenic diabetes due to an INSR mutation in a child with severe insulin resistance. Endocrinology, Diabetes and Metabolism Case Reports202221\u20130114. (https:\/\/doi.org\/10.1530\/EDM-21-0114)"},{"key":"bib18","series-title":"Diabetologia","first-page":"385","article-title":"Effects of metformin on androgens and insulin concentrations in type A insulin resistance syndrome","volume":"43","author":"Rique","year":"2000","unstructured":"Rique SIb\u00e1\u00f1ez LMarcos MVCarrascosa A & Potau N. Effects of metformin on androgens and insulin concentrations in type A insulin resistance syndrome. Diabetologia200043385\u2013386. (https:\/\/doi.org\/10.1007\/s001250050059)"}],"container-title":["Endocrinology, Diabetes & Metabolism Case Reports"],"original-title":[],"link":[{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2023\/2\/EDM22-0362.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2023\/2\/EDM22-0362.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2023\/2\/EDM22-0362.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:48:05Z","timestamp":1784555285000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/edm\/article\/3577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,1]]},"references-count":18,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/edm-22-0362","relation":{},"ISSN":["2052-0573"],"issn-type":[{"value":"2052-0573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,1]]}}}