{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:12:46Z","timestamp":1773288766874,"version":"3.50.1"},"reference-count":14,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2017,11,25]],"date-time":"2017-11-25T00:00:00Z","timestamp":1511568000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Chicago Diabetes Research and Training Center","award":["P30DK020595"],"award-info":[{"award-number":["P30DK020595"]}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["K23DK094866"],"award-info":[{"award-number":["K23DK094866"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["R01 DK104942"],"award-info":[{"award-number":["R01 DK104942"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["CTSA UL1 TR000430"],"award-info":[{"award-number":["CTSA UL1 TR000430"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although mutations in the proinsulin gene (INS) are the second most common cause of neonatal diabetes mellitus, the natural history of \u03b2-cell death and the most appropriate treatments remains unknown. We describe the management and outcome of two sisters with INS-mediated diabetes (S1 and S2) and suggest that more intensive insulin treatment of S2 may have resulted in better clinical outcomes. S1 was diagnosed with diabetes after presenting with serum glucose of 404 mg\/dL (22.4 mmol\/L) and started multiple daily insulin injections at age 4 months, followed by continuous subcutaneous insulin infusion (CSII) at age 42 months. S1 had positive genetic testing at age 4 months for the GlyB8Ser or Gly32Ser mutation in proinsulin. S2 had positive research-based genetic testing, age 1 month, before she had consistently elevated blood glucose levels. Continuous glucose monitoring revealed abnormal excursions to 200 mg\/dL. Low-dose insulin therapy was initiated at age 2.5 months via CSII. At age-matched time points, S2 had higher C-peptide levels, lower hemoglobin A1c values, and lower estimated doses of insulin as compared with S1. Earlier, more intensive insulin treatment was associated with higher C-peptide levels, decreased insulin dosing, and improved glycemic control. Initiating exogenous insulin before overt hyperglycemia and maintaining intensive insulin management may reduce the demand for endogenous insulin production and may preserve \u03b2-cell function. Studies accumulating data on greater numbers of participants will be essential to determine whether these associations are consistent for all INS gene mutations.<\/jats:p>","DOI":"10.1210\/js.2017-00356","type":"journal-article","created":{"date-parts":[[2017,11,24]],"date-time":"2017-11-24T19:06:14Z","timestamp":1511550374000},"page":"1-8","source":"Crossref","is-referenced-by-count":12,"title":["Early Intensive Insulin Use May Preserve \u03b2-Cell Function in Neonatal Diabetes Due to Mutations in the Proinsulin Gene"],"prefix":"10.1210","volume":"2","author":[{"given":"Lisa R","family":"Letourneau","sequence":"first","affiliation":[{"name":"Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Carmody","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Singapore General Hospital, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis H","family":"Philipson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siri Atma W","family":"Greeley","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Illinois"},{"name":"Department of Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2017,11,24]]},"reference":[{"issue":"6","key":"2020071621584921500_B1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s11892-011-0234-7","article-title":"Neonatal diabetes: an expanding list of genes allows for improved diagnosis and treatment","volume":"11","author":"Greeley","year":"2011","journal-title":"Curr Diab Rep"},{"issue":"4","key":"2020071621584921500_B2","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.2337\/db07-1405","article-title":"Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood","volume":"57","author":"Edghill","year":"2008","journal-title":"Diabetes"},{"issue":"14","key":"2020071621584921500_B3","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1056\/NEJM199309303291401","article-title":"The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus","volume":"329","author":"Nathan","year":"1993","journal-title":"N Engl J Med"},{"issue":"38","key":"2020071621584921500_B4","doi-asserted-by":"crossref","first-page":"15040","DOI":"10.1073\/pnas.0707291104","article-title":"Insulin gene mutations as a cause of permanent neonatal diabetes","volume":"104","author":"St\u00f8y","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071621584921500_B5","unstructured":"Centers for Disease Control and Prevention NC for HS. CDC growth charts: United States. 2000 Available at: http:\/\/www.cdc.gov\/growthcharts\/. Accessed 8 November 2017."},{"issue":"1","key":"2020071621584921500_B6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1172\/JCI4431","article-title":"A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse","volume":"103","author":"Wang","year":"1999","journal-title":"J Clin Invest"},{"issue":"3","key":"2020071621584921500_B7","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.bbrc.2009.12.090","article-title":"Mutant proinsulin proteins associated with neonatal diabetes are retained in the endoplasmic reticulum and not efficiently secreted","volume":"391","author":"Park","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"issue":"2","key":"2020071621584921500_B8","doi-asserted-by":"crossref","first-page":"e54351","DOI":"10.1371\/journal.pone.0054351","article-title":"Insulin therapy for pre-hyperglycemic beta-cell endoplasmic reticulum crowding","volume":"8","author":"Absood","year":"2013","journal-title":"PLoS One"},{"issue":"11","key":"2020071621584921500_B9","doi-asserted-by":"crossref","first-page":"E1780","DOI":"10.1210\/jc.2013-1764","article-title":"Improvement in insulin sensitivity after human islet transplantation for type 1 diabetes","volume":"98","author":"Rickels","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2020071621584921500_B10","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1464-5491.2007.02311.x","article-title":"Comparison of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) in paediatric Type 1 diabetes: a multicentre matched-pair cohort analysis over 3 years","volume":"25","author":"Jakisch","year":"2008","journal-title":"Diabet Med"},{"issue":"6","key":"2020071621584921500_B11","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.2337\/dc07-9922","article-title":"Use of insulin pump therapy in the pediatric age-group: consensus statement from the European Society for Paediatric Endocrinology, the Lawson Wilkins Pediatric Endocrine Society, and the International Society for Pediatric and Adolescent Diabetes, endorsed by the American Diabetes Association and the European Association for the Study of Diabetes","volume":"30","author":"Phillip","year":"2007","journal-title":"Diabetes Care"},{"issue":"10","key":"2020071621584921500_B12","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.2337\/dc17-1145","article-title":"Diabetes presentation in infancy: high risk of diabetic ketoacidosis","volume":"40","author":"Letourneau","year":"2017","journal-title":"Diabetes Care"},{"issue":"6","key":"2020071621584921500_B13","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.2337\/diacare.27.6.1399","article-title":"Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up","volume":"27","author":"Barker","year":"2004","journal-title":"Diabetes Care"},{"issue":"5","key":"2020071621584921500_B14","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1056\/NEJMoa061759","article-title":"Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations","volume":"355","author":"Pearson","year":"2006","journal-title":"N Engl J Med"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/2\/1\/1\/23434684\/js.2017-00356.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/2\/1\/1\/23434684\/js.2017-00356.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T09:42:36Z","timestamp":1594978956000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/2\/1\/1\/4657103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,24]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/js.2017-00356","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,1,1]]},"published":{"date-parts":[[2017,11,24]]}}}