title: Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, Level 2 Learning and Research Building, Bristol, BS10 5NB, UK.|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.
authors: Georgina M
authors: GM
authors: Williams
authors: Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, Level 2 Learning and Research Building, Bristol, BS10 5NB, UK.
authors: Anna E
authors: AE
authors: Long
authors: Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, Level 2 Learning and Research Building, Bristol, BS10 5NB, UK.
authors: Isabel V
authors: IV
authors: Wilson
authors: Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, Level 2 Learning and Research Building, Bristol, BS10 5NB, UK.
authors: Rachel J
authors: RJ
authors: Aitken
authors: Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, Level 2 Learning and Research Building, Bristol, BS10 5NB, UK.
authors: Rebecca C
authors: RC
authors: Wyatt
authors: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
authors: Timothy J
authors: TJ
authors: McDonald
authors: Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK.
authors: F Susan
authors: FS
authors: Wong
authors: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
authors: Andrew T
authors: AT
authors: Hattersley
authors: Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, Level 2 Learning and Research Building, Bristol, BS10 5NB, UK.
authors: Alistair J K
authors: AJ
authors: Williams
authors: Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, Level 2 Learning and Research Building, Bristol, BS10 5NB, UK.
authors: Polly J
authors: PJ
authors: Bingley
authors: 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.
authors: Kathleen M
authors: KM
authors: Gillespie
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology / Q000502:physiology*; D002096:C-Peptide / Q000652:urine; D002648:Child; D003401:Creatine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism* / Q000652:urine; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D011863:Radioimmunoassay; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D000949:Histocompatibility Antigens Class II; D003401:Creatine
keywords: Autoantibodies; C-peptide; Type 1 diabetes