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Aim To examine the hypothesis that the quality, magnitude and breadth of helper T-lymphocyte responses to β cells differ in Type 1 diabetes according to diagnosis in childhood or adulthood. Methods We studied helper T-lymphocyte reactivity against β-cell autoantigens by measuring production of the pro-inflammatory cytokine interferon-γ and the anti-inflammatory cytokine interleukin-10, using enzyme-linked immunospot assays in 61 people with Type 1 diabetes (within 3 months of diagnosis, positive for HLA DRB1*0301 and/or *0401), of whom 33 were children/adolescents, and a further 91 were unaffected siblings. Results Interferon-γ responses were significantly more frequent in children with Type 1 diabetes compared with adults (85 vs 61%; P = 0.04). Insulin and proinsulin peptides were preferentially targeted in children ( P = 0.0001 and P = 0.04, respectively) and the breadth of the interferon-γ response was also greater, with 70% of children having an interferon-γ response to three or more peptides compared with 14% of adults ( P < 0.0001). Islet β-cell antigen-specific interleukin-10 responses were similar in children and adults in terms of frequency, breadth and magnitude, with the exception of responses to glutamic acid decarboxylase 65, which were significantly less frequent in adults. Conclusions At diagnosis of Type 1 diabetes, pro-inflammatory autoreactivity is significantly more prevalent, focuses on a wider range of targets, and is more focused on insulin/proinsulin in children than adults. We interpret this as indicating a more aggressive immunological response in the younger age group that is especially characterized by loss of tolerance to proinsulin. These findings highlight the existence of age-related heterogeneity in Type 1 diabetes pathogenesis that could have relevance to the development of immune-based therapies. [ABSTRACT FROM AUTHOR]

Aims To determine if urine C-peptide/creatinine ratio is a useful tool for monitoring β-cell function in new-onset Type 1 diabetes. Methods Data were obtained from a prospective immunomodulation study in people with Type 1 diabetes ≤ 3 months from diagnosis, with a standard mixed-meal tolerance test and measurement of urine C-peptide/creatinine ratio carried out at 0, 3, 6, 9 and 12 months. The change in the insulin-dose-adjusted HbA1c level was also correlated with the change in serum/urine C-peptide level during the 12-month follow-up period. Results A significant reduction in urine C-peptide/creatinine ratio, measured after a mixed-meal, was reached at 9 months (−45.4%), whilst the reduction in stimulated serum C-peptide level reached significance after 3 months (−54.7%) in placebo-treated participants. Neither change in stimulated serum C-peptide nor change in urine C-peptide level correlated with each other, and nor did change in insulin-dose-adjusted HbA1c level in the first 6 months, but all measures correlated significantly in the second half of the 12-month follow-up period. Conclusion Mixed-meal-stimulated urine C-peptide/creatinine ratio was similar to, although less sensitive than, stimulated serum C-peptide level in monitoring β-cell function during the first year after diagnosis. Because the former is significantly less invasive, it warrants inclusion in further studies in Type 1 diabetes and may represent an attractive alternative outcome measure in cohort studies and in children. [ABSTRACT FROM AUTHOR]