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

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)2722-2726
Number of pages5
JournalDiabetologia
Volume59
Issue number12
Early online date3 Sep 2016
DOIs
DateAccepted/In press - 5 Aug 2016
DateE-pub ahead of print - 3 Sep 2016
DatePublished (current) - Dec 2016

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.

    Research areas

  • Autoantibodies, Type 1 diabetes, C-peptide

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Springer at http://doi.org/10.1007/s00125-016-4087-0. Please refer to any applicable terms of use of the publisher.

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