We assessed the prevalence and characteristics of type 1 diabetes defined by early insulin requirement and severe endogenous insulin deficiency in an insulin-treated population cohort.
Participants
583 participants from the population-based Exeter Diabetes Alliance for Research in England (DARE) cohort met the following inclusion criteria: diagnosed with diabetes after 30 years of age, insulin treated and with a C-peptide measurement available. Participants with previous pancreatic pathology (n = 2) were excluded from analysis. To allow for comparison with young-onset type 1 diabetes, we assessed a further cohort of 220 DARE participants with age of diabetes diagnosis ≤30 years who met the study criteria for type 1 diabetes (ESM Fig. 1; see below).
The DARE study was approved by the South West ethics committee (UK). Participants gave informed consent.
Assessment of clinical characteristics
Clinical history was self-reported by participants in an interview with a research nurse, and height and weight were measured at a median diabetes duration of 13 years. Time to insulin was defined as immediate if within 2 weeks of diagnosis.
Laboratory analysis
Non-fasting (random) C-peptide, islet autoantibodies (GAD, zinc transporter protein 8 [ZnT8], islet antigen 2 [IA2]) and a type 1 diabetes genetic risk score (T1DGRS) were assessed in all included participants, as previously described (see ESM methods) [6, 7]. Where multiple C-peptide measurements were available (70% of participants, median 3 values per participant), the median value was used. Median duration at islet autoantibody and C-peptide assessment was 13 and 16 years respectively (ESM Methods).
Definition of diabetes type
Type 1 diabetes was defined as continuous insulin treatment commenced within 3 years of diagnosis and severe insulin deficiency defined by a non-fasting C-peptide <200 pmol/l. Insulin-treated type 2 diabetes was defined as current insulin treatment with a C-peptide ≥600 pmol/l and a duration of diabetes of over 3 years at C-peptide measurement. Participants who were insulin treated and with a C-peptide level ≥200–<600 pmol/l (n = 115, median 48 months from diagnosis to insulin therapy) were considered indeterminate and were not included in analysis (ESM Fig. 1) [5].
Statistical analysis
Data were assessed visually for distribution. Data for all continuous variables except age were not normally distributed; therefore, data are presented as median and interquartile range (IQR), unless otherwise stated. We compared the clinical characteristics, islet autoantibody status and T1DGRS of participant groups defined by C-peptide, initial insulin treatment (within 2 weeks of diagnosis) and age at diagnosis using the Wilcoxon rank-sum test for continuous variables and χ2 analysis for comparison of categorical characteristics. All analyses were performed using Stata 15 (StataCorp LP, College Station, TX, USA).