REFERENCES
2. Paschou SA, Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C. On type 1 diabetes mellitus pathogenesis. Endocr Connect 2018;7:R38-46.
3. Greenbaum CJ, Speake C, Krischer J, et al. Strength in numbers: opportunities for enhancing the development of effective treatments for type 1 diabetes-the trialnet experience. Diabetes 2018;67:1216-25.
4. Gregory GA, Robinson TIG, Linklater SE, et al. International Diabetes Federation Diabetes Atlas Type 1 Diabetes in Adults Special Interest Group. Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study. Lancet Diabetes Endo 2022;10:741-60.
5. Neumann M, Arnould T, Su BL. Encapsulation of stem-cell derived β-cells: a promising approach for the treatment for type 1 diabetes mellitus. J Colloid Interface Sci 2023;636:90-102.
6. Chen S, Du K, Zou C. Current progress in stem cell therapy for type 1 diabetes mellitus. Stem Cell Res Ther 2020;11:275.
8. Infante M, Baidal DA, Rickels MR, et al. Dual-hormone artificial pancreas for management of type 1 diabetes: recent progress and future directions. Artif Organs 2021;45:968-86.
9. Moon SJ, Jung I, Park CY. Current advances of artificial pancreas systems: a comprehensive review of the clinical evidence. Diabetes Metab J 2021;45:813-39.
10. Infante M, Ricordi C. Editorial - moving forward on the pathway of targeted immunotherapies for type 1 diabetes: the importance of disease heterogeneity. Eur Rev Med Pharmacol Sci 2019;23:8702-4.
11. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann Intern Med 1998;128:517-23.
12. Steffes MW, Sibley S, Jackson M, Thomas W. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 2003;26:832-6.
13. Jeyam A, Colhoun H, McGurnaghan S, et al. SDRNT1BIO Investigators. Clinical impact of residual C-peptide secretion in type 1 diabetes on glycemia and microvascular complications. Diabetes Care 2021;44:390-8.
14. Suh J, Lee HI, Lee M, et al. Insulin requirement and complications associated with serum C-peptide decline in patients with type 1 diabetes mellitus during 15 years after diagnosis. Front Endocrinol 2022;13:869204.
15. Liu W, Ma Y, Cai X, et al. Preserved C-peptide secretion is associated with higher time in range (TIR) on intermittently scanned continuous glucose monitoring in Chinese adults with type 1 diabetes. Endocr Connect 2022:11.
16. Deligne C, You S, Mallone R. Personalized immunotherapies for type 1 diabetes: who, what, when, and how? J Pers Med 2022;12:542.
17. Oram RA, Jones AG, Besser RE, et al. The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells. Diabetologia 2014;57:187-91.
18. Evans-Molina C, Oram RA. Teplizumab approval for type 1 diabetes in the USA. Lancet Diabetes Endo 2023;11:76-7.
19. 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;381:603-13.
20. 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.
21. Atkinson MA, Mirmira RG. The pathogenic "symphony" in type 1 diabetes: a disorder of the immune system, β cells, and exocrine pancreas. Cell Metab 2023;35:1500-18.
22. Mallone R, Halliez C, Rui J, Herold KC. The β-cell in type 1 diabetes pathogenesis: a victim of circumstances or an instigator of tragic events? Diabetes 2022;71:1603-10.
23. Leete P, Oram RA, McDonald TJ, et al. TIGI study team. Studies of insulin and proinsulin in pancreas and serum support the existence of aetiopathological endotypes of type 1 diabetes associated with age at diagnosis. Diabetologia 2020;63:1258-67.
24. Sims EK, Syed F, Nyalwidhe J, et al. Abnormalities in proinsulin processing in islets from individuals with longstanding T1D. Transl Res 2019;213:90-9.
25. Arbelaez AM, Xing D, Cryer PE, et al. Diabetes Research in Children Network (DirecNet) Study Group. Blunted glucagon but not epinephrine responses to hypoglycemia occurs in youth with less than 1 yr duration of type 1 diabetes mellitus. Pediatr Diabetes 2014;15:127-34.
26. Farhy LS, McCall AL. Optimizing reduction in basal hyperglucagonaemia to repair defective glucagon counterregulation in insulin deficiency. Diabetes Obes Metab 2011;13 Suppl 1:133-43.
27. Mundinger TO, Mei Q, Foulis AK, Fligner CL, Hull RL, Taborsky GJ Jr. Human type 1 diabetes is characterized by an early, marked, sustained, and islet-selective loss of sympathetic nerves. Diabetes 2016;65:2322-30.
28. Alexandre-Heymann L, Mallone R, Boitard C, Scharfmann R, Larger E. Structure and function of the exocrine pancreas in patients with type 1 diabetes. Rev Endocr Metab Disord 2019;20:129-49.
29. Foster TP, Bruggeman B, Campbell-Thompson M, Atkinson MA, Haller MJ, Schatz DA. Exocrine pancreas dysfunction in type 1 diabetes. Endocr Pract 2020;26:1505-13.
30. Riddle MC. Rediscovery of the second β-cell hormone: co-replacement with pramlintide and insulin in type 1 diabetes. Diabetes Care 2020;43:518-21.
31. Greenbaum CJ, Schatz DA, Haller MJ, Sanda S. Through the fog: recent clinical trials to preserve β-cell function in type 1 diabetes. Diabetes 2012;61:1323-30.
32. Battaglia M, Ahmed S, Anderson MS, et al. Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes. Diabetes Care 2020;43:5-12.
33. Woittiez NJ, Roep BO. Impact of disease heterogeneity on treatment efficacy of immunotherapy in Type 1 diabetes: different shades of gray. Immunotherapy 2015;7:163-74.
34. Infante M, Alejandro R, Fabbri A, Ricordi C. The heterogeneity of type 1 diabetes: From immunopathology to immune intervention. Translational Autoimmunity. Elsevier; 2022. pp. 83-104.
35. Gotfredsen CF, Buschard K, Frandsen EK. Reduction of diabetes incidence of BB Wistar rats by early prophylactic insulin treatment of diabetes-prone animals. Diabetologia 1985;28:933-5.
36. Bowman MA, Campbell L, Darrow BL, Ellis TM, Suresh A, Atkinson MA. Immunological and metabolic effects of prophylactic insulin therapy in the NOD-scid/scid adoptive transfer model of IDDM. Diabetes 1996;45:205-8.
37. McVean J, Forlenza GP, Beck RW, et al. CLVer Study Group. Effect of tight glycemic control on pancreatic beta cell function in newly diagnosed pediatric type 1 diabetes: a randomized clinical trial. JAMA 2023;329:980-9.
38. Boughton CK, Allen JM, Ware J, et al. CLOuD Consortium. Closed-loop therapy and preservation of C-peptide secretion in type 1 diabetes. N Engl J Med 2022;387:882-93.
39. Haller MJ, Gitelman SE, Gottlieb PA, et al. Anti-thymocyte globulin/G-CSF treatment preserves β cell function in patients with established type 1 diabetes. J Clin Invest 2015;125:448-55.
40. Foster TP, Jacobsen LM, Bruggeman B, et al. Low-dose antithymocyte globulin: a pragmatic approach to treating stage 2 type 1 diabetes. Diabetes Care 2024;47:285-9.
41. Pinheiro MM, Pinheiro FMM, de Arruda MM, et al. Association between sitagliptin plus vitamin D3 (VIDPP-4i) use and clinical remission in patients with new-onset type 1 diabetes: a retrospective case-control study. Arch Endocrinol Metab 2023;67:e000652.
42. Yan X, Li X, Liu B, et al. Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial. Signal Transduct Target Ther 2023;8:158.
43. Pinheiro MM, Pinheiro FMM, Diniz SN, Fabbri A, Infante M. Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes. Int Immunopharmacol 2021;95:107518.
44. Vella A. Mechanism of action of DPP-4 inhibitors--new insights. J Clin Endocrinol Metab 2012;97:2626-8.
45. Dicker D. DPP-4 inhibitors: impact on glycemic control and cardiovascular risk factors. Diabetes Care 2011;34 Suppl 2:S276-8.
46. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab 2018;27:740-56.
47. Rabinovitch A, Koshelev D, Lagunas-Rangel FA, et al. Efficacy of combination therapy with GABA, a DPP-4i and a PPI as an adjunct to insulin therapy in patients with type 1 diabetes. Front Endocrinol 2023;14:1171886.
48. Hartig SM, Cox AR. Paracrine signaling in islet function and survival. J Mol Med 2020;98:451-67.
49. Tian J, Dang HN, Yong J, et al. Oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice. PLoS One 2011;6:e25338.
50. Téllez N, Joanny G, Escoriza J, Vilaseca M, Montanya E. Gastrin treatment stimulates β-cell regeneration and improves glucose tolerance in 95% pancreatectomized rats. Endocrinology 2011;152:2580-8.
51. Buteau J. GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival. Diabetes Metab 2008;34 Suppl 2:S73-7.
52. Hare KJ, Vilsbøll T, Asmar M, Deacon CF, Knop FK, Holst JJ. The glucagonostatic and insulinotropic effects of glucagon-like peptide 1 contribute equally to its glucose-lowering action. Diabetes 2010;59:1765-70.
53. Suarez-Pinzon WL, Power RF, Yan Y, Wasserfall C, Atkinson M, Rabinovitch A. Combination therapy with glucagon-like peptide-1 and gastrin restores normoglycemia in diabetic NOD mice. Diabetes 2008;57:3281-8.
54. Suarez-Pinzon WL, Lakey JR, Rabinovitch A. Combination therapy with glucagon-like peptide-1 and gastrin induces beta-cell neogenesis from pancreatic duct cells in human islets transplanted in immunodeficient diabetic mice. Cell Transplant 2008;17:631-40.
55. Ludvigsson J. Autoantigen treatment in type 1 diabetes: unsolved questions on how to select autoantigen and administration route. Int J Mol Sci 2020;21:1598.
56. Peakman M, von Herrath M. Antigen-specific immunotherapy for type 1 diabetes: maximizing the potential. Diabetes 2010;59:2087-93.
57. Morales AE, Thrailkill KM. GAD-alum immunotherapy in type 1 diabetes mellitus. Immunotherapy 2011;3:323-32.
58. Ludvigsson J, Routray I, Elluru S, et al. Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset type I diabetes: lessons from the DIABGAD randomized pilot trial. Future Sci OA 2020;6:FSO604.
59. Ludvigsson J, Routray I, Vigård T, et al. Combined etanercept, GAD-alum and vitamin D treatment: an open pilot trial to preserve beta cell function in recent onset type 1 diabetes. Diabetes Metab Res Rev 2021;37:e3440.
60. Hannelius U, Beam CA, Ludvigsson J. Efficacy of GAD-alum immunotherapy associated with HLA-DR3-DQ2 in recently diagnosed type 1 diabetes. Diabetologia 2020;63:2177-81.
61. Ludvigsson J, Sumnik Z, Pelikanova T, et al. Intralymphatic glutamic acid decarboxylase with vitamin d supplementation in recent-onset type 1 diabetes: a double-blind, randomized, placebo-controlled phase IIb trial. Diabetes Care 2021;44:1604-12.
62. Barcenilla H, Pihl M, Wahlberg J, Ludvigsson J, Casas R. Intralymphatic GAD-alum injection modulates B cell response and induces follicular helper T cells and PD-1+ CD8+ T cells in patients with recent-onset type 1 diabetes. Front Immunol 2021;12:797172.
63. Puente-Marin S, Dietrich F, Achenbach P, Barcenilla H, Ludvigsson J, Casas R. Intralymphatic glutamic acid decarboxylase administration in type 1 diabetes patients induced a distinctive early immune response in patients with DR3DQ2 haplotype. Front Immunol 2023;14:1112570.
64. Dandona P, Chaudhuri A, Ghanim H. Semaglutide in early type 1 diabetes. N Engl J Med 2023;389:958-9.
65. Ovalle F, Grimes T, Xu G, et al. Verapamil and beta cell function in adults with recent-onset type 1 diabetes. Nat Med 2018;24:1108-12.
66. Forlenza GP, McVean J, Beck RW, et al. CLVer Study Group. Effect of verapamil on pancreatic beta cell function in newly diagnosed pediatric type 1 diabetes: a randomized clinical trial. JAMA 2023;329:990-9.
67. 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;13:1159.
68. Padda IS, Bhatt R, Parmar M. Golimumab. Available from: https://www.ncbi.nlm.nih.gov/books/NBK576392/ [Last accessed on 13 May 2024].
69. Quattrin T, Haller MJ, Steck AK, et al. T1GER Study Investigators. Golimumab and beta-cell function in youth with new-onset type 1 diabetes. N Engl J Med 2020;383:2007-17.
70. Rigby MR, Hayes B, Li Y, Vercruysse F, Hedrick JA, Quattrin T. Two-year follow-up from the T1GER study: continued off-therapy metabolic improvements in children and young adults with new-onset T1D treated with golimumab and characterization of responders. Diabetes Care 2023;46:561-9.
71. Ahmad A, Zaheer M, Balis FJ. Baricitinib. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572064/ [Last accessed on 13 May 2024].
72. Waibel M, Wentworth JM, So M, et al. BANDIT Study Group. Baricitinib and β-cell function in patients with new-onset type 1 diabetes. N Engl J Med 2023;389:2140-50.
73. Priotto G, Pinoges L, Fursa IB, et al. Safety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort study. BMJ 2008;336:705-8.
74. LoGiudice N, Le L, Abuan I, Leizorek Y, Roberts SC. Alpha-difluoromethylornithine, an irreversible inhibitor of polyamine biosynthesis, as a therapeutic strategy against hyperproliferative and infectious diseases. Med Sci 2018;6:12.
75. Sims EK, Kulkarni A, Hull A, et al. Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes. Cell Rep Med 2023;4:101261.
76. Tersey SA, Colvin SC, Maier B, Mirmira RG. Protective effects of polyamine depletion in mouse models of type 1 diabetes: implications for therapy. Amino Acids 2014;46:633-42.
77. Krogvold L, Mynarek IM, Ponzi E, et al. Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial. Nat Med 2023;29:2902-8.
78. Dunne JL, Richardson SJ, Atkinson MA, et al. Rationale for enteroviral vaccination and antiviral therapies in human type 1 diabetes. Diabetologia 2019;62:744-53.
79. Krogvold L, Edwin B, Buanes T, et al. Detection of a low-grade enteroviral infection in the islets of langerhans of living patients newly diagnosed with type 1 diabetes. Diabetes 2015;64:1682-7.
