Age of Diagnosis Does Not Alter the Presentation or Progression of Robustly Defined Adult-Onset Type 1 Diabetes

Abstract

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 mmol/L (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.

Conflict of interest statement

Conflict of interest statement

RA is a co-Investigator on a Randox R&D research grant. The study has received translational industry-academic funding from Randox R&D relating to autoimmune genetic risk scores for prediction and classification of disease. There are no established patents, loyalties or licensing agreements relating to this grant. It is a 3 year grant (Feb 2022-2025). The approximate value is a £2.2m program grant on genetic risk scores across autoimmune disease.

All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

© 2023 by the American Diabetes Association.

Figures

Figure 1. Comparison of type 1 diabetes genetic susceptibility (T1DGRS) (a) and recruitment blood C-peptide (b) in participants with type 1 diabetes defined by both study definitions aged below and above age 35 at diabetes diagnosis.

Horizontal lines represent the mean, error bars represent 95% confidence intervals. Comparisons by age group are shown for each definition and across all definitions and age groups.

Figure 2. Progression of change in log UCPCR from mixed effect models with age as an interaction term for a) type 1 diabetes defined by multi-antibody (≥2) positivity and b) a single positive antibody in the context of a clinical diagnosis of type 1 diabetes.

Error bars represent 95% confidence intervals. Comparison type 2 diabetes group shown for reference.