Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes
Open Access
- 3 September 2016
- journal article
- research article
- Published by Springer Science and Business Media LLC in Diabetologia
- Vol. 59 (12), 2722-2726
- https://doi.org/10.1007/s00125-016-4087-0
Abstract
Aims/hypothesis This 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. Methods Two 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. Results Endogenous 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/interpretation There 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.Keywords
Funding Information
- Juvenile Diabetes Research Foundation (#6-2012-17)
This publication has 10 references indexed in Scilit:
- Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1 diabetesDiabetologia, 2015
- Low levels of C‐peptide have clinical significance for established Type 1 diabetesDiabetic Medicine, 2015
- Most People With Long-Duration Type 1 Diabetes in a Large Population-Based Study Are Insulin MicrosecretorsDiabetes Care, 2014
- The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cellsDiabetologia, 2013
- Persistence of Prolonged C-peptide Production in Type 1 Diabetes as Measured With an Ultrasensitive C-peptide AssayDiabetes Care, 2012
- Residual Insulin Production and Pancreatic β-Cell Turnover After 50 Years of Diabetes: Joslin Medalist StudyDiabetes, 2010
- Harmonization of Glutamic Acid Decarboxylase and Islet Antigen-2 Autoantibody Assays for National Institute of Diabetes and Digestive and Kidney Diseases ConsortiaJournal of Clinical Endocrinology & Metabolism, 2010
- Stability and Reproducibility of a Single-Sample Urinary C-Peptide/Creatinine Ratio and Its Correlation with 24-h Urinary C-PeptideClinical Chemistry, 2009
- Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration?Diabetologia, 2005
- Incidence of insulin dependent diabetes in England: a study in the Oxford region, 1985-6.BMJ, 1989