Abstract
Aims/hypothesisThis study aimed to determine the frequency of residual beta cell function in individuals with long-standing type 1 diabetes who were recruited at diagnosis, and relate this to baseline and current islet autoantibody profile.MethodsTwo hour post-meal urine C-peptide:creatinine ratio (UCPCR) and islet autoantibodies were measured in samples collected from 144 participants (median age at diagnosis: 11.7 years; 47% male), a median of 23 years (range 12–29 years) after diagnosis. UCPCR thresholds equivalent to mixed meal-stimulated serum C-peptide >0.001 nmol/l, ≥0.03 nmol/l and ≥0.2 nmol/l were used to define ‘detectable’, ‘minimal’ and ‘residual/preserved’) endogenous insulin secretion, respectively. Autoantibodies against GAD (GADA), islet antigen-2 (IA-2A), zinc transporter 8 (ZnT8A) and insulin (IAA) were measured by radioimmunoassay.ResultsEndogenous C-peptide secretion was detectable in 51 participants (35.4%), including residual secretion in seven individuals (4.9%) and minimal secretion in 14 individuals (9.7%). In the 132 samples collected more than 10 years after diagnosis, 86 participants (65.2%) had at least one islet autoantibody: 42 (31.8%) were positive for GADA, 69 (52.3%) for IA-2A and 14 of 104 tested were positive for ZnT8A (13.5%). The level of UCPCR was related to age at diagnosis (p = 0.002) and was independent of diabetes duration, and baseline or current islet autoantibody status.Conclusions/interpretationThere is evidence of ongoing autoimmunity in the majority of individuals with longstanding diabetes. Endogenous insulin secretion continues for many years after diagnosis in individuals diagnosed with autoimmune-mediated type 1 diabetes above age 5. These findings suggest that some beta cells are protected from continued autoimmune attack in longstanding type 1 diabetes.
Highlights
In type 1 diabetes, insulin producing beta cells are targeted for autoimmune destruction
Endogenous insulin secretion continues for many years after diagnosis in individuals diagnosed with autoimmune-mediated type 1 diabetes above age 5
Re-testing of baseline autoantibody samples was possible for 144 (47Q male) of these participants of whom 132 returned follow-up serum samples (Table 1). These participants were representative of the Bart’s Oxford (BOX) cohort for the average age at diagnosis and timing of initial sample for autoantibody testing, there was a higher proportion of female participants
Summary
In type 1 diabetes, insulin producing beta cells are targeted for autoimmune destruction. All beta cells were formerly assumed to be destroyed but increasing evidence indicates that endogenous insulin secretion occurs many years after diagnosis in some individuals with type 1 diabetes [1,2,3,4]. This phenomenon is associated with fewer complications, notably reduced incidence of severe hypoglycaemia [5]. These previous studies have been conducted on longstanding patients, but islet autoantibodies were not tested close to diagnosis. The aim of this study was to determine the frequency of residual C-peptide secretion in a cohort of patients with longstanding type 1 diabetes in whom islet autoantibody measurements were carried out within 2 years of diagnosis, to establish whether persistent beta cell function and baseline or current islet autoantibody status are associated
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