{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T19:18:45Z","timestamp":1786475925956,"version":"build-2736575974"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,2,16]],"date-time":"2014-02-16T00:00:00Z","timestamp":1392508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"Medical Council"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet. Med."],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatocyte nuclear factor 4\u03b1 (HNF4A) is a member of the nuclear receptor family of ligand\u2010activated transcription factors. <jats:italic>HNF4A<\/jats:italic> mutations cause hyperinsulinaemic hypoglycaemia in early life and maturity\u2010onset diabetes of the young. Regular screening of <jats:italic>HNF4A<\/jats:italic> mutation carriers using the oral glucose tolerance test has been recommended to diagnose diabetes mellitus at an early stage. Glucagon\u2010like peptide\u20101 and glucose\u2010dependent insulinotropic polypeptide are incretin hormones, responsible for up to 70% of the secreted insulin after a meal in healthy individuals. We describe, for the first time, gradual alteration of glucose homeostasis in a patient with <jats:italic>HNF4A<\/jats:italic> mutation after resolution of hyperinsulinaemic hypoglycaemia, on serial oral glucose tolerance testing. We also measured the incretin response to a mixed meal in our patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case report<\/jats:title><jats:p>Our patient was born with macrosomia and developed hyperinsulinaemic hypoglycaemia in the neonatal period. Molecular genetic analysis confirmed <jats:italic>HNF4A<\/jats:italic> mutation (p.M116I, c.317G&gt;A) as an underlying cause of hyperinsulinaemic hypoglycaemia. Serial oral glucose tolerance testing, after the resolution of hyperinsulinaemic hypoglycaemia, confirmed the diagnosis of maturity\u2010onset diabetes of the young at the age of 10\u00a0years. Interestingly, the intravenous glucose tolerance test revealed normal glucose disappearance rate and first\u2010phase insulin secretion. Incretin hormones showed a suboptimal rise in response to the mixed meal, potentially explaining the discrepancy between the oral glucose tolerance test and the intravenous glucose tolerance test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Maturity\u2010onset diabetes of the young can develop as early as the first decade of life in persons with an <jats:italic>HNF4A<\/jats:italic> mutation. Impaired incretin response might be contributory in the early stages of <jats:italic>HNF4A<\/jats:italic> maturity\u2010onset diabetes of the young.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.12369","type":"journal-article","created":{"date-parts":[[2013,12,3]],"date-time":"2013-12-03T08:50:19Z","timestamp":1386060619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["<i>HNF4A<\/i> mutation: switch from hyperinsulinaemic hypoglycaemia to maturity\u2010onset diabetes of the young, and incretin response"],"prefix":"10.1111","volume":"31","author":[{"given":"V. B.","family":"Arya","sequence":"first","affiliation":[{"name":"Department of Paediatric Endocrinology Great Ormond Street Hospital for Children NHS Trust London"},{"name":"The Institute of Child Health University College London Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Rahman","sequence":"additional","affiliation":[{"name":"The Institute of Child Health University College London Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Senniappan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology Great Ormond Street Hospital for Children NHS Trust London"},{"name":"The Institute of Child Health University College London Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. E.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ellard","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology Great Ormond Street Hospital for Children NHS Trust London"},{"name":"The Institute of Child Health University College London Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.9.3807"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.4.12b.2353"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/355457a0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1089769"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006612200"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/384458a0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040118"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1657"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30076"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22279"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000073557"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0861"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmr.5610050705"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.43.1.40"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01648.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2003.11.011"},{"key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.33549\/physiolres.931995","article-title":"Gut peptide hormones and pediatric type\u00a01 diabetes mellitus","volume":"60","author":"Huml M","year":"2011","journal-title":"Physiol Res"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115865"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116596"}],"container-title":["Diabetic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdme.12369","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdme.12369","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.12369","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T03:16:44Z","timestamp":1696303004000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dme.12369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,16]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1111\/dme.12369"],"URL":"https:\/\/doi.org\/10.1111\/dme.12369","archive":["Portico"],"relation":{},"ISSN":["0742-3071","1464-5491"],"issn-type":[{"value":"0742-3071","type":"print"},{"value":"1464-5491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,16]]},"assertion":[{"value":"2013-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}