Age of diagnosis does not alter the presentation or progression of robustly defined adult onset type 1 diabetes

This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record OBJECTIVE: To determine whether presentation, progression, and genetic susceptibility of robustly defined adult-onset type 1 diabetes (T1D) are altered by diagnosis age. RESEARCH DESIGN AND METHODS: We compared the relationship between diagnosis age and presentation, C-peptide loss (annual change in urine C-peptide-creatinine ratio [UCPCR]), and genetic susceptibility (T1D genetic risk score [GRS]) in adults with confirmed T1D in the prospective StartRight study, 1,798 adults with new-onset diabetes. T1D was defined in two ways: two or more positive islet autoantibodies (of GAD antibody, IA-2 antigen, and ZnT8 autoantibody) irrespective of clinical diagnosis (n = 385) or one positive islet autoantibody and a clinical diagnosis of T1D (n = 180). RESULTS: In continuous analysis, age of diagnosis was not associated with C-peptide loss for either definition of T1D (P > 0.1), with mean (95% CI) annual C-peptide loss in those diagnosed before and after 35 years of age (median age of T1D defined by two or more positive autoantibodies): 39 (31-46) vs. 44% (38-50) with two or more positive islet autoantibodies and 43 (33-51) vs. 39% (31-46) with clinician diagnosis confirmed by one positive islet autoantibody (P > 0.1). Baseline C-peptide and T1D GRS were unaffected by age of diagnosis or T1D definition (P > 0.1). In T1D defined by two or more autoantibodies, presentation severity was similar in those diagnosed before and after 35 years of age: unintentional weight loss, 80 (95% CI 74-85) vs. 82% (76-87); ketoacidosis, 24 (18-30) vs. 19% (14-25); and presentation glucose, 21 (19-22) vs. 21 mmol/L (20-22) (all P ≥ 0.1). Despite similar presentation, older adults were less likely to be diagnosed with T1D, insulin-treated, or admitted to hospital. CONCLUSIONS: When adult-onset T1D is robustly defined, the presentation characteristics, progression, and T1D genetic susceptibility are not altered by age of diagnosis.Diabetes UKNational Institute for Health Research (NIHR)European Foundation for the Study of Diabete

Routine islet autoantibody testing in clinically diagnosed adult-onset type 1 diabetes can help identify misclassification and the possibility of successful insulin cessation.

   Objective Recent joint American and European diabetes association guidelines recommend routine islet autoantibody testing in all adults newly diagnosed with type 1 diabetes. We aimed to assess the impact of routine islet autoantibody testing in this population. Research Design and Methods We prospectively assessed the characteristics and progression (annual change in Urine C-peptide Creatinine Ratio (UCPCR)) associated with islet autoantibody status (GAD, IA-2 and ZNT8) in 722 adults (≥ 18 years old at diagnosis) with clinically diagnosed type 1 diabetes and duration Results 24.8% (179/722) of participants diagnosed with type 1 diabetes were autoantibody negative. This group had genetic and C-peptide characteristics suggestive of a high prevalence of non-autoimmune diabetes: lower mean type 1 diabetes genetic risk score (islet autoantibody negative versus positive: 10.85 vs 13.09 (pp After median 24-months follow up, treatment change occurred in 36.6% (60/164) of autoantibody negative participants: 22.6% (37/164) discontinued insulin, with a HbA1c similar to those continuing insulin (57.5 vs 60.8mmol/mol [7.4 vs 7.7%], p=0.4) and 14.0% (23/164) added adjuvant agents to insulin.  Conclusions In adult-onset clinically diagnosed type 1 diabetes, negative islet autoantibodies should prompt careful consideration of other diabetes subtypes. When routinely measured negative antibodies are associated with successful insulin cessation. These findings support recent recommendations for routine islet autoantibody assessment in adult-onset type 1 diabetes.</p