Serial dried blood spot c-peptide sampling, but not urine c-peptide-to-creatinine ratio, detects early preservation of β-cell function in new-onset type 1 diabetes: experience from the USTEKID trial

Dunseath, Gareth J., Cheung, Wai-Yee, Luzio, Stephen D., Carter, Kym, Tatovic, Danijela ORCID: https://orcid.org/0000-0002-3879-2686, Taylor, Peter N. ORCID: https://orcid.org/0000-0002-3436-422X, Gregory, John W. ORCID: https://orcid.org/0000-0001-5189-3812 and Dayan, Colin M. ORCID: https://orcid.org/0000-0002-6557-3462 2026. Serial dried blood spot c-peptide sampling, but not urine c-peptide-to-creatinine ratio, detects early preservation of β-cell function in new-onset type 1 diabetes: experience from the USTEKID trial. Diabetes Care 49 (7) , pp. 1-8. 10.2337/dc25-2896

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Abstract

OBJECTIVE To determine whether less invasive C-peptide tests, urine C-peptide–to–creatinine ratio (UCPCR) and dried blood spot (DBS), could replace the mixed-meal tolerance test (MMTT) in the context of an interventional clinical trial (USTEKID). RESEARCH DESIGN AND METHODS C-peptide was assessed at screening and weeks 28 and 52 using a 2-h MMTT. UCPCR samples were taken after each MMTT. Fasting and 60-min postmeal DBS samples were collected weekly to week 28 and then monthly to week 52. UCPCR and glucose-adjusted DBS results were compared with MMTT results. Weekly DBS averages were calculated and differences between treatment groups assessed using a mixed linear model, bootstrap one-sample t tests, and autoregressive integrated moving averages. Six months of weekly DBS data were used to predict 12-month C-peptide levels. RESULTS Unlike MMTT C-peptide, UCPCR did not change in the first 6 months, before decreasing by 12 months. The DBS area under the curve from 0 to 60 min declined steadily over 12 months. The DBS C-peptide decline in the intervention group was significantly less than that in the control group by week 20 (P < 0.05). This was not apparent with UCPCR and did not become evident until 52 weeks with MMTT. The slope from 6 months of DBS could predict 12-month MMTT C-peptide in the control but not in the intervention group, consistent with the increasing impact of the intervention from 6 to 12 months indicated by the MMTT data. CONCLUSIONS Frequently sampled glucose-adjusted DBS was more sensitive to early change than MMTT and could serve as a home-based marker of β-cell function, whereas UCPCR was not sensitive to change in the early period.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Medicine
Publisher:	American Diabetes Association
ISSN:	0149-5992
Date of Acceptance:	2 April 2026
Last Modified:	21 May 2026 15:30
URI:	https://orca.cardiff.ac.uk/id/eprint/187090

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