Adult-Onset Type 1 Diabetes: Current Understanding and Challenges

R David Leslie, Carmella Evans-Molina, Jacquelyn Freund-Brown, Raffaella Buzzetti, Dana Dabelea, Kathleen M Gillespie, Robin Goland, Angus G Jones, Mark Kacher, Lawrence S Phillips, Olov Rolandsson, Jana L Wardian, Jessica L Dunne

Research output: Contribution to journalArticle (Academic Journal)peer-review

77 Citations (Scopus)

Abstract

Recent epidemiological data have shown that more than half of all new cases of type 1 diabetes occur in adults. Key genetic, immune, and metabolic differences exist between adult- and childhood-onset type 1 diabetes, many of which are not well understood. A substantial risk of misclassification of diabetes type can result. Notably, some adults with type 1 diabetes may not require insulin at diagnosis, their clinical disease can masquerade as type 2 diabetes, and the consequent misclassification may result in inappropriate treatment. In response to this important issue, JDRF convened a workshop of international experts in November 2019. Here, we summarize the current understanding and unanswered questions in the field based on those discussions, highlighting epidemiology and immunogenetic and metabolic characteristics of adult-onset type 1 diabetes as well as disease-associated comorbidities and psychosocial challenges. In adult-onset, as compared with childhood-onset, type 1 diabetes, HLA-associated risk is lower, with more protective genotypes and lower genetic risk scores; multiple diabetes-associated autoantibodies are decreased, though GADA remains dominant. Before diagnosis, those with autoantibodies progress more slowly, and at diagnosis, serum C-peptide is higher in adults than children, with ketoacidosis being less frequent. Tools to distinguish types of diabetes are discussed, including body phenotype, clinical course, family history, autoantibodies, comorbidities, and C-peptide. By providing this perspective, we aim to improve the management of adults presenting with type 1 diabetes.

Original languageEnglish
Pages (from-to)2449-2456
Number of pages8
JournalDiabetes Care
Volume44
Issue number11
DOIs
Publication statusPublished - Nov 2021

Bibliographical note

Funding Information:
Acknowledgments. Sharon Saydah, Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, attended the workshop and participated in subsequent discussions of the manuscript. Elizabeth Seaquist, Division of Diabetes, Endocrinology, and Metabolism at the University of Minnesota, participated in the workshop. The authors acknowledge Marilyn L. Wales for her assistance with formatting the manuscript. Funding and Duality of Interest. This manuscript is the result of a one-day meeting held at JDRF headquarters in New York, NY. Financial support for the workshop was provided by JDRF and Janssen Research and Development, LLC. Financial support from Janssen Research and Development, LLC, for the workshop was in an unrestricted grant to JDRF. JDRF provided participants with transportation, lodging, and meals to attend the workshop. No additional support was provided for the writing of the manuscript. R.D.L. is supported by a grant from the European Union (contract no. QLGi-CT-2002-01886). C.E.-M. is supported by National Institute for Health Research grants R01 DK093954, R21DK11 9800, U01DK127786, R01DK127308, and P30DK 097512; VA Merit Award I01BX001733; JDRF grant 2-SRA-2019-834-S-B; and gifts from the Sigma Beta Sorority, the Ball Brothers Foundation, and the George and Frances Ball Foundation. R.B. is supported in part by the Italian Ministry of University and Research (project code 20175L9H7H). A.G.J. is funded by a National Institute for Health Research (NIHR) Clinician Scientist fellowship (CS-2015-15-018). L.S.P. is supported in part by U.S. Department of Veterans Affairs (VA) awards CSP #2008, I01 CX001899, I01 CX001737, and Health Services Research & Development IIR 07-138; National Institute for Health Research awards R21 DK099716, R18 DK066204, R03 AI133172, R21 AI156161, U01 DK091958, U01 DK098246, and UL1 TR002378; and Cystic Fibrosis Foundation award PHILLI12A0.

Funding Information:
R.D.L. received unrestricted educational grants from Novo Nordisk, Sanofi, MSD, and AstraZeneca. C.E.-M. has participated in advisory boards for Dompé Pharmaceuticals, Pro-vention Bio, MaiCell Technologies, and ISLA Technologies. C.E.M. is the recipient of in-kind research support from Nimbus Pharmaceuticals and Bristol Myers Squibb and an investigator-initiated research grant from Eli Lilly and Company. J.F.-B. and J.L.D. were employed by JDRF during the workshop and early stages of writing. J.F.-B. is currently an employee of Provention Bio, and J.L.D. is currently an employee of Janssen Research and Development, LLC. R.B. participated in advisory boards for Sanofi and Eli Lilly and received honoraria for speaker bureaus from Sanofi, Eli Lilly, AstraZeneca, Novo Nordisk, and Abbott. L.S.P. has served on scientific advisory boards for Janssen and has or had research support from Merck, Pfizer, Eli Lilly, Novo Nordisk, Sanofi, PhaseBio, Roche, AbbVie, Vascular Pharmaceuticals, Janssen, GlaxoSmithKline, and the Cystic Fibrosis Foundation. L.S.P. is also a cofounder and officer and board member and stockholder for a company, Diasyst, Inc., that markets software aimed to help improve diabetes management. No other potential conflicts of interest relevant to this article were reported.

Publisher Copyright:
© 2021 by the American Diabetes Association.

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