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Diabetologia. 2016 Dec;59(12):2722-2726. Epub 2016 Sep 3.

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

Author information

1
Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, Level 2 Learning and Research Building, Bristol, BS10 5NB, UK.
2
National Institute for Health Research (NIHR) Biomedical Research Unit in Nutrition, Diet, and Lifestyle, University Hospitals Bristol National Health Service (NHS) Foundation Trust and University of Bristol, Bristol, UK.
3
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
4
Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK.
5
Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, Level 2 Learning and Research Building, Bristol, BS10 5NB, UK. k.m.gillespie@bristol.ac.uk.

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:

Autoantibodies; C-peptide; Type 1 diabetes

PMID:
27591853
DOI:
10.1007/s00125-016-4087-0
[Indexed for MEDLINE]

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