Type 1 Diabetes Mellitus: Much Progress, Many Opportunities

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2021 Mar 24

PMID 33759815

Citations 41

Authors

Alvin C Powers

Affiliations

Soon will be listed here.

Abstract

As part of the centennial celebration of insulin's discovery, this review summarizes the current understanding of the genetics, pathogenesis, treatment, and outcomes in type 1 diabetes (T1D). T1D results from an autoimmune response that leads to destruction of the β cells in the pancreatic islet and requires lifelong insulin therapy. While much has been learned about T1D, it is now clear that there is considerable heterogeneity in T1D with regard to genetics, pathology, response to immune-based therapies, clinical course, and susceptibility to diabetes-related complications. This Review highlights knowledge gaps and opportunities to improve the understanding of T1D pathogenesis and outlines emerging therapies to treat or prevent T1D and reduce the burden of T1D.

Citing Articles

Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity.

Austin M, Muralidharan C, Roy S, Crowder J, Piganelli J, Linnemann A Front Immunol. 2025; 16:1504583.

PMID: 39944686 PMC: 11814175. DOI: 10.3389/fimmu.2025.1504583.

Regulation and function of insulin and insulin-like growth factor receptor signalling.

Choi E, Duan C, Bai X Nat Rev Mol Cell Biol. 2025; .

PMID: 39930003 DOI: 10.1038/s41580-025-00826-3.

Pancreatic β cell-secreted factor FGF23 attenuates Alzheimer's disease-related amyloid β-induced neuronal death.

Yazawa K, Nakashima M, Nakagawa T, Yanase Y, Yoda Y, Ozawa K PNAS Nexus. 2025; 4(1):pgae542.

PMID: 39876880 PMC: 11773612. DOI: 10.1093/pnasnexus/pgae542.

CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity.

Kong Y, Li J, Zhao X, Wu Y, Chen L Front Immunol. 2025; 15():1519671.

PMID: 39850899 PMC: 11754230. DOI: 10.3389/fimmu.2024.1519671.

Beneficial Actions of 4-Methylumbelliferone in Type 1 Diabetes by Promoting β Cell Renewal and Inhibiting Dedifferentiation.

Zhang W, Yang S, Yu X, Zhu S, Wang X, Sun F Biomedicines. 2025; 12(12.

PMID: 39767698 PMC: 11673412. DOI: 10.3390/biomedicines12122790.

References

Herold K, Bundy B, Long S, Bluestone J, DiMeglio L, Dufort M . An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019; 381(7):603-613. PMC: 6776880. DOI: 10.1056/NEJMoa1902226. View

Ruiz H, Ramasamy R, Schmidt A . Advanced Glycation End Products: Building on the Concept of the "Common Soil" in Metabolic Disease. Endocrinology. 2019; 161(1). PMC: 7188081. DOI: 10.1210/endocr/bqz006. View

Kaestner K, Powers A, Naji A, Atkinson M . NIH Initiative to Improve Understanding of the Pancreas, Islet, and Autoimmunity in Type 1 Diabetes: The Human Pancreas Analysis Program (HPAP). Diabetes. 2019; 68(7):1394-1402. PMC: 6609987. DOI: 10.2337/db19-0058. View

Ziegler A, Rewers M, Simell O, Simell T, Lempainen J, Steck A . Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013; 309(23):2473-9. PMC: 4878912. DOI: 10.1001/jama.2013.6285. View

Perkins B, Lovblom L, Lanctot S, Lamb K, Cherney D . Discoveries from the study of longstanding type 1 diabetes. Diabetologia. 2021; 64(6):1189-1200. DOI: 10.1007/s00125-021-05403-9. View

. 11. Microvascular Complications and Foot Care: . Diabetes Care. 2020; 44(Suppl 1):S151-S167. DOI: 10.2337/dc21-S011. View

Michels A, Landry L, McDaniel K, Yu L, Campbell-Thompson M, Kwok W . Islet-Derived CD4 T Cells Targeting Proinsulin in Human Autoimmune Diabetes. Diabetes. 2016; 66(3):722-734. PMC: 5319719. DOI: 10.2337/db16-1025. View

Thomas N, Jones S, Weedon M, Shields B, Oram R, Hattersley A . Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank. Lancet Diabetes Endocrinol. 2017; 6(2):122-129. PMC: 5805861. DOI: 10.1016/S2213-8587(17)30362-5. View

Korsgren S, Molin Y, Salmela K, Lundgren T, Melhus A, Korsgren O . On the etiology of type 1 diabetes: a new animal model signifying a decisive role for bacteria eliciting an adverse innate immunity response. Am J Pathol. 2012; 181(5):1735-48. PMC: 3483807. DOI: 10.1016/j.ajpath.2012.07.022. View

10.

Atkinson M, Eisenbarth G, Michels A . Type 1 diabetes. Lancet. 2013; 383(9911):69-82. PMC: 4380133. DOI: 10.1016/S0140-6736(13)60591-7. View

11.

Coppieters K, von Herrath M . The Development of Immunotherapy Strategies for the Treatment of Type 1 Diabetes. Front Med (Lausanne). 2018; 5:283. PMC: 6189286. DOI: 10.3389/fmed.2018.00283. View

12.

Babon J, DeNicola M, Blodgett D, Crevecoeur I, Buttrick T, Maehr R . Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes. Nat Med. 2016; 22(12):1482-1487. PMC: 5140746. DOI: 10.1038/nm.4203. View

13.

Rawshani A, Rawshani A, Franzen S, Eliasson B, Svensson A, Miftaraj M . Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes. N Engl J Med. 2017; 376(15):1407-1418. DOI: 10.1056/NEJMoa1608664. View

14.

Delong T, Wiles T, Baker R, Bradley B, Barbour G, Reisdorph R . Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion. Science. 2016; 351(6274):711-4. PMC: 4884646. DOI: 10.1126/science.aad2791. View

15.

Nathan D, Cleary P, Backlund J, Genuth S, Lachin J, Orchard T . Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005; 353(25):2643-53. PMC: 2637991. DOI: 10.1056/NEJMoa052187. View

16.

Virostko J, Williams J, Hilmes M, Bowman C, Wright J, Du L . Pancreas Volume Declines During the First Year After Diagnosis of Type 1 Diabetes and Exhibits Altered Diffusion at Disease Onset. Diabetes Care. 2018; 42(2):248-257. PMC: 6341292. DOI: 10.2337/dc18-1507. View

17.

Weng J, Zhou Z, Guo L, Zhu D, Ji L, Luo X . Incidence of type 1 diabetes in China, 2010-13: population based study. BMJ. 2018; 360:j5295. PMC: 5750780. DOI: 10.1136/bmj.j5295. View

18.

Vantyghem M, de Koning E, Pattou F, Rickels M . Advances in β-cell replacement therapy for the treatment of type 1 diabetes. Lancet. 2019; 394(10205):1274-1285. PMC: 6951435. DOI: 10.1016/S0140-6736(19)31334-0. View

19.

Chaimowitz N, Ebenezer S, Hanson I, Anderson M, Forbes L . STAT1 Gain of Function, Type 1 Diabetes, and Reversal with JAK Inhibition. N Engl J Med. 2020; 383(15):1494-1496. DOI: 10.1056/NEJMc2022226. View

20.

Haliyur R, Tong X, Sanyoura M, Shrestha S, Lindner J, Saunders D . Human islets expressing HNF1A variant have defective β cell transcriptional regulatory networks. J Clin Invest. 2018; 129(1):246-251. PMC: 6307934. DOI: 10.1172/JCI121994. View