dc.contributor.author | Williams, GM | |
dc.contributor.author | Long, AE | |
dc.contributor.author | Wilson, IV | |
dc.contributor.author | Aitken, RJ | |
dc.contributor.author | Wyatt, RC | |
dc.contributor.author | McDonald, TJ | |
dc.contributor.author | Wong, FS | |
dc.contributor.author | Hattersley, AT | |
dc.contributor.author | Williams, AJ | |
dc.contributor.author | Bingley, PJ | |
dc.contributor.author | Gillespie, KM | |
dc.date.accessioned | 2016-11-17T12:47:29Z | |
dc.date.issued | 2016-09-03 | |
dc.description.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. | en_GB |
dc.description.sponsorship | This study was funded by a JDRF grant (ref no. 6-2012-17), awarded to PJB, FSW and ATH. | en_GB |
dc.identifier.citation | December 2016, Vol. 59, Iss. 12, pp. 2722–2726 | en_GB |
dc.identifier.doi | 10.1007/s00125-016-4087-0 | |
dc.identifier.other | 10.1007/s00125-016-4087-0 | |
dc.identifier.uri | http://hdl.handle.net/10871/24488 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Verlag (Germany) | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/27591853 | en_GB |
dc.rights | This is the author accepted manuscript. This is an open access article. The final version is available from Springer Verlag (Germany) via the DOI in this record. | en_GB |
dc.subject | Autoantibodies | en_GB |
dc.subject | C-peptide | en_GB |
dc.subject | Type 1 diabetes | en_GB |
dc.title | Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2016-11-17T12:47:29Z | |
dc.identifier.issn | 0012-186X | |
exeter.place-of-publication | Germany | en_GB |
dc.description | Published online | en_GB |
dc.description | JOURNAL ARTICLE | en_GB |
dc.identifier.eissn | 1432-0428 | |
dc.identifier.journal | Diabetologia | en_GB |