ESPE Yearbook of Paediatric Endocrinology

Diabetes Care. 2025 May 22:dc250214. PMID: 40402094 Online ahead of print. doi: 10.2337/dc25-0214.

Brief summary: This observational study, in a subgroup of the INNODIA cohort (n= 292, age 1-45 years-old) with a recent diagnosis of stage 3 type 1 diabetes (T1D), assessed the feasibility of measuring dried blood spot (DBS) C-peptide levels, collected at home, as an alternative to the gold standard mixed-meal tolerance test (MMTT) to assess β-cell function during the first 12 months post-diagnosis. Liquid meal stimulated DBS C-peptide levels in the first 6 months post-diagnosis predicted MMTT stimulated C-peptide levels at 12 months.

The need for early detection of β-cell decline in people with newly diagnosed clinical T1D is particularly important in the context of emerging immunotherapy trials. The area under the curve (AUC) of stimulated C-peptide during a 2-h MMTT is the accepted gold standard measure of β-cell function (1). However, MMTT is an invasive and time-consuming procedure that requires attendance at clinical/research settings. Previous clinical trials have shown the need of a minimum follow-up of 12 months to detect an effect of interventions on MMTT C-peptide. Thus, there is a need for biomarkers that can capture differences in β-cell function earlier.

This study assessed an alternative method, monthly DBS C-peptide measurements collected at home, both fasting and 60 min after a liquid meal. Data were collected from 292 people (mean age 12.7 years) with newly diagnosed stage 3 T1D from the INNODIA Natural history study (2). The slopes of post-load DBS C-peptide levels in the first 6 months post-diagnosis predicted MMTT AUC C-peptide and peak C-peptide levels at 12 months. In contrast, the 6-month fasting DBS C-peptide slope did not predict 12-month MMTT AUC C-peptide.

The study results support the feasibility and potential clinical utility of home DBS C-peptide assessment for monitoring β-cell function in individuals with newly diagnosed stage 3 T1D. The ability to collect DBS samples at home enables frequent monitoring without the need for repeated clinic visits. This method has the potential to streamline clinical trials by reducing the follow-up period needed to assess drug efficacy. However, additional validation is required to establish its reliability and wider applicability in both research and clinical settings.

References: 1. Palmer JP, Fleming GA, Greenbaum CJ, et al. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes 2004;53(1):250-64.2. Marcovecchio ML, Hendriks AEJ, Delfin C, et al. The INNODIA Type 1 Diabetes Natural History Study: a European cohort of newly diagnosed children, adolescents and adults. Diabetologia 2024;67(6):995-1008.