{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:59:32Z","timestamp":1793365172814,"version":"4.5.0"},"reference-count":67,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK105448"],"award-info":[{"award-number":["R01-DK105448"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetes mellitus (DM) in children is most often caused by impaired insulin secretion (type 1 DM). In some children, the underlying mechanism for DM is increased insulin resistance, which can have different underlying causes. While the majority of these children require insulin dosages less than 2.0 U\/kg\/day to achieve normoglycemia, higher insulin requirements indicate severe insulin resistance. Considering the therapeutic challenges in patients with severe insulin resistance, early diagnosis of the underlying cause is essential in order to consider targeted therapies and to prevent diabetic complications. Although rare, several disorders can attribute to severe insulin resistance in pediatric patients. Most of these disorders are diagnosed through advanced diagnostic tests, which are not commonly available in low- or middle-income countries. Based on a case of DM with severe insulin resistance in a Surinamese adolescent who was later confirmed to have autosomal recessive congenital generalized lipodystrophy, type 1 (Berardinelli\u2013Seip syndrome), we provide a systematic approach to the differential diagnosis and work-up. We show that a thorough review of medical history and physical examination generally provide sufficient information to diagnose a child with insulin-resistant DM correctly, and, therefore, our approach is especially applicable to low- or middle-income countries.<\/jats:p>","DOI":"10.1210\/clinem\/dgab549","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T11:20:28Z","timestamp":1627471228000},"source":"Crossref","is-referenced-by-count":1,"title":["Approach to Diagnosing a Pediatric Patient With Severe Insulin Resistance in Low- or Middle-income Countries"],"prefix":"10.1210","author":[{"given":"Alise A","family":"van Heerwaarde","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Academic Pediatric Center Suriname, Academic Hospital Paramaribo, Paramaribo, Suriname"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renz C W","family":"Klomberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Academic Pediatric Center Suriname, Academic Hospital Paramaribo, Paramaribo, Suriname"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conny M A","family":"van Ravenswaaij-Arts","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Academic Pediatric Center Suriname, Academic Hospital Paramaribo, Paramaribo, Suriname"},{"name":"Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Kristian","family":"Ploos van Amstel","sequence":"additional","affiliation":[{"name":"Department of Genetics, Utrecht University, University Medical Center Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aartie","family":"Toekoen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Academic Pediatric Center Suriname, Academic Hospital Paramaribo, Paramaribo, Suriname"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariza","family":"Jessurun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Academic Pediatric Center Suriname, Academic Hospital Paramaribo, Paramaribo, Suriname"},{"name":"Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-6986","authenticated-orcid":false,"given":"Abhimanyu","family":"Garg","sequence":"additional","affiliation":[{"name":"Division of Nutrition, and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6408-1717","authenticated-orcid":false,"given":"Dani\u00eblle C M","family":"van der Kaay","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Erasmus Medical Center-Sophia Children\u2019s Hospital, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"issue":"Suppl 27","key":"2021092414522232000_CIT0001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/pedi.12773","article-title":"ISPAD Clinical Practice Consensus Guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents","volume":"19","author":"Mayer-Davis","year":"2018","journal-title":"Pediatr Diabetes."},{"issue":"9922","key":"2021092414522232000_CIT0002","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/S0140-6736(13)62219-9","article-title":"The many faces of diabetes: a disease with increasing heterogeneity","volume":"383","author":"Tuomi","year":"2014","journal-title":"Lancet."},{"key":"2021092414522232000_CIT0003","doi-asserted-by":"crossref","first-page":"107842","DOI":"10.1016\/j.diabres.2019.107842","article-title":"Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas, 9th edition","volume":"(157)","author":"Patterson","year":"2019","journal-title":"Diabetes Res Clin Pract."},{"issue":"5","key":"2021092414522232000_CIT0004","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/S0022-3476(96)80124-7","article-title":"Increased incidence of non-insulin- dependent diabetes mellitus among adolescents","volume":"128","author":"Pinhas-Hamiel","year":"1996","journal-title":"J. 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