{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:36:45Z","timestamp":1793932605184,"version":"4.8.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T00:00:00Z","timestamp":1651536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Despite advances in the characterization of partial clinical remission (PR) of type 1 diabetes, an accurate definition of PR remains problematic. Two recent studies in children with new-onset T1D demonstrated serious limitations of the present gold standard definition of PR, a stimulated C-peptide (SCP) concentration of &amp;gt;300 pmol\/L. The first study employed the concept of insulin sensitivity score (ISS) to show that 55% of subjects with new-onset T1D and a detectable SCP level of &amp;gt;300 pmol\/L had low insulin sensitivity (IS) and thus might not be in remission when assessed by insulin-dose adjusted A1c (IDAA1c), an acceptable clinical marker of PR. The second study, a randomized controlled trial of vitamin D (ergocalciferol) administration in children and adolescents with new-onset T1D, demonstrated no significant difference in SCP between the ergocalciferol and placebo groups, but showed a significant blunting of the temporal trend in both A1c and IDAA1c in the ergocalciferol group. These two recent studies indicate the poor specificity and sensitivity of SCP to adequately characterize PR and thus call for a re-examination of current approaches to the definition of PR. They demonstrate the limited sensitivity of SCP, a static biochemical test, to detect the complex physiological changes that occur during PR such as changes in insulin sensitivity, insulin requirements, body weight, and physical activity. These shortcomings call for a broader definition of PR using a combination of functional markers such as IDAA1c and ISS to provide a valid assessment of PR that reaches beyond the static changes in SCP alone.<\/jats:p>","DOI":"10.3389\/fendo.2022.884219","type":"journal-article","created":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T06:15:10Z","timestamp":1651558510000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Partial Clinical Remission of Type 1 Diabetes: The Need for an Integrated Functional Definition Based on Insulin-Dose Adjusted A1c and Insulin Sensitivity Score"],"prefix":"10.3389","volume":"13","author":[{"given":"Benjamin Udoka","family":"Nwosu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,3]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.33590\/emj\/10310168","article-title":"Partial Clinical Remission of Type 1 Diabetes Mellitus in Children: Clinical Applications and Challenges With Its Definitions","volume":"4","author":"Nwosu","year":"2019","journal-title":"Eur Med J Diabetes"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1756","article-title":"Insulin Resistance in Adolescents With Type 1 Diabetes and Its Relationship to Cardiovascular Function","volume":"95","author":"Nadeau","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60931-8","article-title":"Teplizumab for Treatment of Type 1 Diabetes (Protege Study): 1-Year Results From a Randomised, Placebo-Controlled Trial","volume":"378","author":"Sherry","year":"2011","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062103","article-title":"Immunotherapy Strategies for the Prevention and Treatment of Distinct Stages of Type 1 Diabetes: An Overview","volume":"21","author":"Rapini","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2020.1727885","article-title":"CTLA4-Ig (Abatacept): A Promising Investigational Drug for Use in Type 1 Diabetes","volume":"29","author":"Rachid","year":"2020","journal-title":"Expert Opin Investig Drugs"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2020.101510","article-title":"Decreased Interleukin-35 Levels and CD4(+)EBI3(+) T Cells in Patients With Type 1 Diabetes and the Effects of the Antibody Against CD20 (Rituximab)","volume":"17","author":"Ouyang","year":"2021","journal-title":"Arch Med Sci: AMS"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-0360","article-title":"Fall in C-Peptide During First 4 Years From Diagnosis of Type 1 Diabetes: Variable Relation to Age, HbA1c, and Insulin Dose","volume":"39","author":"Hao","year":"2016","journal-title":"Diabetes Care"},{"key":"B8","first-page":"e14702","article-title":"Differences in Insulin Sensitivity in the Partial Remission Phase of Childhood Type 1 Diabetes; a Longitudinal Cohort Study","author":"Mork","year":"2021","journal-title":"Diabet. 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