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Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes

Williams, Georgina M., Long, Anna E., Wilson, Isabel V., Aitken, Rachel J., Wyatt, Rebecca C., McDonald, Timothy J., Wong, Florence Susan, Hattersley, Andrew T., Williams, Alistair J. K., Bingley, Polly J. and Gillespie, Kathleen M. 2016. Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes. Diabetologia 59 (12) , pp. 2722-2726. 10.1007/s00125-016-4087-0

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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; 47Q 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 (35.4Q), including residual secretion in seven individuals (4.9Q) and minimal secretion in 14 individuals (9.7Q). In the 132 samples collected more than 10 years after diagnosis, 86 participants (65.2Q) had at least one islet autoantibody: 42 (31.8Q) were positive for GADA, 69 (52.3Q) for IA-2A and 14 of 104 tested were positive for ZnT8A (13.5Q). 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Autoantibodies . C-peptide . Type 1 diabetes
Publisher: Springer
ISSN: 0012-186X
Date of First Compliant Deposit: 21 November 2016
Date of Acceptance: 5 August 2016
Last Modified: 04 Jun 2017 09:31

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