The challenges of identifying and studying type 1 diabetes in adults

Abstract

Diagnosing type 1 diabetes in adults is difficult since type 2 diabetes is the predominant diabetes type, particularly with an older age of onset (approximately >30 years). Misclassification of type 1 diabetes in adults is therefore common and will impact both individual patient management and the reported features of clinically classified cohorts. In this article, we discuss the challenges associated with correctly identifying adult-onset type 1 diabetes and the implications of these challenges for clinical practice and research. We discuss how many of the reported differences in the characteristics of autoimmune/type 1 diabetes with increasing age of diagnosis are likely explained by the inadvertent study of mixed populations with and without autoimmune aetiology diabetes. We show that when type 1 diabetes is defined by high-specificity methods, clinical presentation, islet-autoantibody positivity, genetic predisposition and progression of C-peptide loss remain broadly similar and severe at all ages and are unaffected by onset age within adults. Recent clinical guidance recommends routine islet-autoantibody testing when type 1 diabetes is clinically suspected or in the context of rapid progression to insulin therapy after a diagnosis of type 2 diabetes. In this moderate or high prior-probability setting, a positive islet-autoantibody test will usually confirm autoimmune aetiology (type 1 diabetes). We argue that islet-autoantibody testing of those with apparent type 2 diabetes should not be routinely undertaken as, in this low prior-prevalence setting, the positive predictive value of a single-positive islet antibody for autoimmune aetiology diabetes will be modest. When studying diabetes, extremely high-specificity approaches are needed to identify autoimmune diabetes in adults, with the optimal approach depending on the research question. We believe that until these recommendations are widely adopted by researchers, the true phenotype of late-onset type 1 diabetes will remain largely misunderstood. Graphical Abstract

Type 1 diabetes: A new vision of the disease based on endotypes

“…77 Studies have speculated that patients who fall into the T1DE5 endotype (low GAD, high C-peptide LADA patients) may simply be a subset of misdiagnosed T2D patients. 71,111 -9 of 19 level than traditional T2D patients. 77 This suggests that there is an autoimmune component still at play, differing from the hypothesis that low GAD and high C-peptide patients simply represent a subset of misdiagnosed T2D patients.…”

Global burden of type 1 diabetes in adults aged 65 years and older, 1990-2019: population based study

“…Fourthly, we primarily relied on modelling processes for the estimates in this study, and the choice of models and parameter settings could have influenced the results. Finally, the diagnosis of T1DM in older people presents challenges, 40 41 and variations in healthcare systems, healthcare policies, and medical practices across countries may have an affect on disease burden. As a result, further high quality real world research is needed to validate the findings of this study.…”