Type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, is a chronic disease characterized by insulin deficiency due to pancreatic β-cell loss and leads to hyperglycaemia. Although the age of symptomatic onset is usually during childhood or adolescence, symptoms can sometimes develop much later. Although the aetiology of T1DM is not completely understood, the pathogenesis of the disease is thought to involve T cell-mediated destruction of β-cells. Islet-targeting autoantibodies that target insulin, 65 kDa glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter 8 — all of which are proteins associated with secretory granules in β-cells — are biomarkers of T1DM-associated autoimmunity that are found months to years before symptom onset, and can be used to identify and study individuals who are at risk of developing T1DM. The type of autoantibody that appears first depends on the environmental trigger and on genetic factors. The pathogenesis of T1DM can be divided into three stages depending on the absence or presence of hyperglycaemia and hyperglycaemia-associated symptoms (such as polyuria and thirst). A cure is not available, and patients depend on lifelong insulin injections; novel approaches to insulin treatment, such as insulin pumps, continuous glucose monitoring and hybrid closed-loop systems, are in development. Although intensive glycaemic control has reduced the incidence of microvascular and macrovascular complications, the majority of patients with T1DM are still developing these complications. Major research efforts are needed to achieve early diagnosis, prevent β-cell loss and develop better treatment options to improve the quality of life and prognosis of those affected.
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The authors were supported by the US NIH (grants K12DK097696 and R21DK106505 to B.J.A.; DK60987, DK60987, DK104216 and UL1TR001427 to D.A.S. and L.M.J.; and DK063861 to Å.L.), The Leona M. and Harry B. Helmsley Charitable Trust (grants 2015PG-T1D084 and 2016PG-T1D011 to B.J.A.) and the Swedish Research Council (Å.L., S.G. and A.R.).
Å.L. is a member of the Scientific Advisory Board of Diamyd Medical, Stockholm, Sweden. All other authors declare no conflicts of interest.
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Katsarou, A., Gudbjörnsdottir, S., Rawshani, A. et al. Type 1 diabetes mellitus. Nat Rev Dis Primers 3, 17016 (2017). https://doi.org/10.1038/nrdp.2017.16
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