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

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.