ESPEYB19 10. Type 1 Diabetes New paradigms (4 abstracts)
10.7. Circulating C-peptide levels in living children and young people and pancreatic beta cell loss in pancreas donors across type 1 diabetes disease duration
Carr ALJ , Inshaw JRJ , Flaxman CS , Leete P , Wyatt RC , Russell LA , Palmer M , Prasolov D , Worthington T , Hull B , Wicker LS , Dunger DB , Oram RA , Morgan NG , Todd JA , Richardson SJ & Besser REJ
Diabetes. 2022;71:1591-1596. https://pubmed.ncbi.nlm.nih.gov/35499624/
Brief Summary: This cross-sectional study compared trends in plasma C-peptide decline in 4,076 young people with type 1 diabetes (T1D), with trends in beta-cell loss in 235 pancreas donors. As expected, C-peptide declined over time, and this was particularly marked in children with T1D younger than 7 years. Of interest, plasma C-peptide profiles were mirrored by trends of loss of islets containing beta-cells within pancreas sections.
C-peptide is a useful indicator of beta-cell function, whose levels can be detected even after many years after the onset of T1D (1). This residual beta cell function has been associated with better glycemic control and reduced risk of severe hypoglycemia, as well as reduced long-term complications (2). Although several studies have shown a decline in C-peptide over time, measuring residual C-peptide alone cannot distinguish between loss of beta cell mass and reduced functionality. Clarifying this is important in view of the development of interventions to preserve residual beta cell function.
This is the first study comparing pancreatic histology with patterns of C-peptide loss according to age at diagnosis (<7, 7–12, ≥13 years) and duration (<1, 1–5, 5–10, ≥10 years) in young people with T1D. This study adds to the existing evidence by showing that progressive loss of insulin-containing beta cells is the main contributory factor to the decline in endogenous insulin secretion, as measured by C-peptide. This supports the utility of C-peptide as marker of residual beta cell mass for clinical indications and in the context of clinical studies.
The study also highlights that a younger age at T1D diagnosis is associated with a steeper decline in circulating C-peptide and beta cell mass. An additional interesting finding was that up to 5% of young children can retain C-peptide production 10 years after diabetes onset, reiterating the concept of heterogeneity not only across age groups but also within each age group. This heterogeneity is a key factor to consider when designing clinical trials aiming at preserving residual beta cell function and still needs further clarification of the underlying mechanisms.
References: 1. Shields BM, McDonald TJ, Oram R, Hill A, Hudson M, Leete P, Pearson ER, Richardson SJ, Morgan NG, Hattersley AT; TIGI Consortium. C-Peptide Decline in Type 1 Diabetes Has Two Phases: An Initial Exponential Fall and a Subsequent Stable Phase. .Diabetes Care. 2018;41:1486–1492. 2. Jeyam A, Colhoun H, McGurnaghan S, Blackbourn L, McDonald TJ, Palmer CNA, et al. Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications. Diabetes Care. 2021;44:390–398.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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