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. 2016 Dec;59(12):2722-2726.
doi: 10.1007/s00125-016-4087-0. Epub 2016 Sep 3.

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

Georgina M Williams  1   2 , Anna E Long  1 , Isabel V Wilson  1 , Rachel J Aitken  1 , Rebecca C Wyatt  1 , Timothy J McDonald  3 , F Susan Wong  4 , Andrew T Hattersley  3 , Alistair J K Williams  1 , Polly J Bingley  1 , Kathleen M Gillespie  5
Affiliations

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

Georgina M Williams et al. Diabetologia. 2016 Dec.

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.

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Conflict of interest statement

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

GMW, AEL, FSW, ATH, AJKW, PJB and KMG designed the study, performed data analysis and interpretation, and drafted, revised and approved the manuscript. IVW, RJA, RCW and TMcD performed data collection, analysis and interpretation, and revised and approved the manuscript. KMG is responsible for the integrity of the work as a whole.

Figures

Fig. 1
Fig. 1
Association between UCPCR and (a) age at diagnosis, (b) duration of disease (c, e, g) autoantibody levels at diagnosis or (d, f, h) at time of UCPCR measurement. For (g) and (h) black circles, ZnT8RA; white circles, ZnT8WA. Detectable C-peptide is shown >zero nmol/mmol. Dotted lines show minimal (0.03 nmol/mmol) and residual (0.2 nmol/mmol) C-peptide levels. Dashed lines show autoantibody positivity thresholds: GADA, 33 DK units/ml; IA-2A, 1.4 DK units/ml; ZnT8A, 1.8 AU
See this image and copyright information in PMC

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