The beginning of the end for insulin? – enter immunotherapy for T1DM

Bonifacio E, Achenbach P. Birth and coming of age of islet autoantibodies. Clin Exp Immunol 2019;198(3):294-305. https://doi.org/ 10.1111/cei.13360. Epub 2019 Sep 12. PMID: 31397889; PMCID: PMC6857083.

ONS data: https://www.nomisweb.co.uk/query/select/getdatasetbytheme. asp?theme=73

NPDA report: https://www.rcpch.ac.uk/work-we-do/quality-improvement- patient-safety/national-paediatric-diabetes-audit; NDA report: https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-a udit

Fisher L, Hessler D, Polonsky W, Strycker L, Masharani U, Peters A. Diabetes distress in adults with type 1 diabetes: Prevalence, incidence and change over time. J Diabetes Complications 2016;30(6):1123-8. https://doi.org/10.1016/j.jdiacomp.2016.03.032. Epub 2016 Apr 4. PMID: 27118163; PMCID: PMC4949147.

Tanaka Y, Luo Y, O'Shea JJ, Nakayamada S. Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach. Nat Rev Rheumatol 2022;18(3):133-45. https://doi.org/10.1038/s41584-021-00726-8. Epub 2022 Jan 5. PMID: 34987201; PMCID: PMC8730299.

Allen LA, Dayan CM. Immunotherapy for type 1 diabetes. Br Med Bull 2021;140(1):76-90. https://doi.org/10.1093/bmb/ldab027. PMID: 34893820.

Tatovic D, Dayan CM. Replacing insulin with immunotherapy: Time for a paradigm change in Type 1 diabetes. Diabet Med 2021;38(12):e14696. https://doi.org/10.1111/dme.14696. Epub 2021 Sep 29. PMID: 34555209.

Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care 2015;38(10):1964-74. https://doi.org/10.2337/dc15-1419. PMID: 26404926; PMCID: PMC5321245.

American Diabetes Association Professional Practice Committee; 2. Classifi- cation and Diagnosis of Diabetes: Standards of Medical Care in Diabetes— 2022. Diabetes Care; 45 (Supplement_1): S17–S38. https://doi.org/10.2337/dc22-S002

Dayan CM, Korah M, Tatovic D, Bundy BN, Herold KC. Changing the land- scape for type 1 diabetes: the first step to prevention. Lancet 2019; 394(10205):1286-96. https://doi.org/10.1016/S0140-6736(19)32127-0.

Epub 2019 Sep 15. PMID: 31533907.

Herold KC, Bundy BN, Long SA, et al; Type 1 Diabetes TrialNet Study Group. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med 2019;381(7):603-13. https://doi.org/10.1056/NEJMoa1902226. Epub 2019 Jun 9. Erratum in: N Engl J Med 2020;382(6):586. PMID: 31180194; PMCID: PMC6776880.

Sims EK, Bundy BN, Stier K, et al; Type 1 Diabetes TrialNet Study Group. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med 2021;13(583):eabc8980. https://doi.org/10.1126/scitranslmed.abc8980. PMID: 33658358; PMCID: PMC8610022.

Perdigoto AL, Preston-Hurlburt P, Clark P, et al; Immune Tolerance Network. Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis. Diabetologia 2019;62(4):655-64. https://doi.org/10.1007/s00125-018-4786-9. Epub 2018 Dec 19. PMID:30569273; PMCID: PMC6402971.

Dayan CM, Besser REJ, Oram RA, et al. Preventing type 1 diabetes in childhood. Science 2021;373(6554):506-510. https://doi.org/10.1126/ science.abi4742. PMID: 34326231.

https://www.fda.gov/news-events/press-announcements/fda-approves- first-drug-can-delay-onset-type-1-diabetes

Ziegler AG, Kick K, Bonifacio E, et al; Fr1da Study Group. Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany. JAMA 2020;323(4):339-351. https://doi.org/10.1001/jama.2019.21565. PMID: 31990315; PMCID: PMC6990943.

Sims EK, Besser REJ, Dayan C, et al; NIDDK Type 1 Diabetes TrialNet Study Group. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes 2022;71(4):610-23. https://doi.org/10.2337/dbi20-0054. PMID: 35316839; PMCID: PMC9114719.

Besser REJ, Ng SM, Gregory JW, Dayan CM, Randell T, Barrett T. General population screening for childhood type 1 diabetes: is it time for a UK strat- egy? Arch Dis Child 2022;107(9):790-5. https://doi.org/10.1136/archdis- child-2021-321864. Epub 2021 Nov 5. PMID: 34740879.

Besser REJ, Ng SM, Robertson EJ. Screening children for type 1 diabetes. BMJ 2021;375:e067937. https://doi.org/10.1136/bmj-2021-067937. PMID: 34965925.

Ferrat LA, Vehik K, Sharp SA, et al; TEDDY Study Group. A combined risk score enhances prediction of type 1 diabetes among susceptible children. Nat Med 2020;26(8):1247-55. https://doi.org/10.1038/s41591-020-0930-

Epub 2020 Aug 7. Erratum in: Nat Med 2022;28(3):599. PMID:32770166; PMCID: PMC7556983.

Barker JM, Goehrig SH, Barriga K, et al; DAISY study. Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up. Diabetes Care 2004;27(6):1399-404. https://doi.org/10.2337/ diacare.27.6.1399. PMID: 15161795.

Triolo TM, Chase HP, Barker JM; DPT-1 Study Group. Diabetic subjects diagnosed through the Diabetes Prevention Trial-Type 1 (DPT-1) are often asymptomatic with normal A1C at diabetes onset. Diabetes Care 2009; 32(5):769-73. https://doi.org/10.2337/dc08-1872. PMID: 19407074; PMCID: PMC2671125.

Elding Larsson H, Vehik K, et al; TEDDY Study Group; SEARCH Study Group; Swediabkids Study Group; DPV Study Group; Finnish Diabetes Reg- istry Study Group. Reduced prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in young children participating in longitudinal follow- up. Diabetes Care 2011;34(11):2347-52. https://doi.org/10.2337/dc11- 1026. Epub 2011 Oct 4. PMID: 21972409; PMCID: PMC3198296.

Winkler C, Schober E, Ziegler AG, Holl RW. Markedly reduced rate of dia- betic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies. Pediatr Diabetes 2012;13(4):308-13. https://doi.org/ 10.1111/j.1399-5448.2011.00829.x. Epub 2011 Nov 8. PMID: 22060727.

Lundgren M, Sahlin Å, Svensson C, et al; DiPiS study group. Reduced mor- bidity at diagnosis and improved glycemic control in children previously en- rolled in DiPiS follow-up. Pediatr Diabetes 2014;15(7):494-501. https://doi.org/10.1111/pedi.12151. Epub 2014 May 13. PMID: 24823816; PMCID: PMC4190091.

Quattrin T, Haller MJ, Steck AK, et al; T1GER Study Investigators. Goli- mumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes. N Engl J Med 2020;383(21):2007-17. https://doi.org/10.1056/ NEJ- Moa2006136. PMID: 33207093.

Gitelman SE, Bundy BN, Ferrannini E, et al; Gleevec Trial Study Group. Ima- tinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol 2021;9(8):502-514. https://doi.org/10.1016/S2213- 8587(21)00139-X. Epub 2021 Jun 29. PMID: 34214479; PMCID: PMC8494464.

Ovalle F, Grimes T, Xu G, et al. Verapamil and beta cell function in adults with recent-onset type 1 diabetes. Nat Med 2018;24(8):1108-12. https://doi.org/10.1038/s41591-018-0089-4. Epub 2018 Jul 9. PMID:29988125; PMCID: PMC6092963.

Xu G, Grimes TD, Grayson TB, et al. Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes. Nat Commun 2022;13(1):1159. https://doi.org/10.1038/s41467- 022-28826-3. PMID: 35241690; PMCID: PMC8894430.