Type 1 diabetes presenting in adults: Trends, diagnostic challenges and unique features.

Type 1 diabetes (T1D) has been historically regarded as a childhood-onset disease; however, recent epidemiological data indicate that adult-onset T1D accounts for a substantial proportion of cases worldwide. There is evidence that adult-onset T1D is associated with the classic T1D triad of elevated genetic risk, the presence of islet-specific autoantibodies and progression to severe insulin deficiency. In this article, we review our understanding of the commonalities and differences between childhood and adult-onset T1D, and we highlight significant knowledge gaps in our understanding of the diagnosis, incidence, trajectory and treatment of adult-onset T1D. Compared to children, adults presenting with T1D exhibit differences in genetic risk, immunologic profiles and metabolic outcomes, including differences in the type and number of autoantibodies present, genetic associations and total genetic burden, rates of C-peptide decline, the persistence of C-peptide in long-duration disease and glycaemic control. In addition, obesity and metabolic syndrome are increasingly common in adults, which not only blurs the clinical distinction of adult-onset T1D from type 2 diabetes (T2D) but also likely contributes to differences in metabolic outcomes and rates of progression. Because T2D is so prevalent in the adult population, adult-onset T1D is misclassified as T2D in at least one in three cases, leading to delays in appropriate treatment. Current diagnostic tools, including autoantibody testing and C-peptide measurement, are underutilised or lack specificity in distinguishing adult-onset T1D from atypical T2D. Additionally, the impact of different responses to disease-modifying therapy between adults and children is unclear. Addressing these knowledge gaps requires expanded epidemiological studies, diverse patient registries and refined classification criteria to improve early detection and treatment strategies. A deeper understanding of adult-onset T1D will be critical to reduce the burden of misdiagnosis, lead to earlier diagnosis and treatment and optimise population-based screening approaches in this under-recognised population. PLAIN LANGUAGE SUMMARY: Type 1 diabetes (T1D) is an autoimmune disease that causes metabolic and nutritional complications due to the destruction of insulin-producing pancreatic β cells. T1D was formerly known as "juvenile diabetes" because it was assumed that most cases occurred in childhood; however, recent epidemiological data show that nearly half of all T1D cases are diagnosed in adulthood. Despite the high prevalence of adult-onset T1D, there are challenges with correctly diagnosing T1D in adulthood, and significant knowledge gaps remain regarding the incidence, trajectory, and treatment of adult-onset T1D. In this article, we summarize the current understanding of commonalities and differences between childhood and adult-onset T1D. Particularly, we highlight age-related differences in genetic risk, immunologic profiles, and metabolic outcomes and complications. Finally, we highlight key gaps in our understanding of adult-onset T1D that need to be addressed to reduce the burden of misdiagnosis and allow for better screening and treatment of T1D in adulthood.