Review of Genetic, Immunological and Clinical Differences in Type 1 Diabetes: A Comparison of Young and Adult Patients

The goal of this review article is to describe the differences in genetic, immunological, and clinical presentations of type 1 diabetes mellitus (T1DM) in children and adults. This can add to the knowledge of clinicians treating patients with DM and improve their management skills. T1DM has traditionally been associated with younger populations with onset below the age of 30. Recent epidemiological data have shown that more than half of all new cases of T1DM occur in adults. Key genetic, immune, and metabolic differences exist between adult- and childhood–adolescent-onset T1DM, many of which are not well understood. A substantial risk of misclassification of diabetes mellitus type can result. Notably, some adults with T1DM may not require insulin at diagnosis, their clinical disease can masquerade as type 2 diabetes mellitus (T2DM), and the consequent misclassification may result in inappropriate treatment. Here, the epidemiology and immunogenetic and metabolic characteristics of adult-onset T1DM was highlighted and summarized. In adult-onset, as compared with childhood-adolescent onset T1DM, HLA-associated risk is lower, with more protective genotypes and lower genetic risk scores. Multiple diabetes-associated autoantibodies are decreased, though Glutamic-acid decarboxylase antibody (GAD65) remains dominant although at lower titers than in children-adolescents with T1DM. After diagnosis, adult patients with T1DM progress more slowly, their serum C-peptide is higher, with ketoacidosis being less frequent. Tools to distinguish types of diabetes are discussed, including body phenotype, clinical course, genetic predisposition, autoantibodies, comorbidities, and C-peptide level. By providing this perspective, the aim is to improve the management of adults presenting with T1DM. Misdiagnosis in adult-onset T1DM is common due to overlapping features with T2DM, leading to inappropriate treatment. This mini-review integrates findings from recent studies to identify distinctions between T1DM in children and adolescents and adult-onset T1DM in genetic predispositions, autoimmunity, and clinical symptoms. Recognizing these differences is critical for timely diagnosis and personalized treatment strategies, ultimately improving patient outcomes.