Objectives: Direct measurement of C-peptide has been
recommended to provide the most appropriate primary
outcome in trials evaluating the efficacy of therapies to
preserve beta-cell function. The aim of the present study was
to quantitatively characterize the natural history of disease
progression as assessed by stimulated C-peptide the first
12 months after diagnosis in children with new onset T1D in
two independent cohorts collected over a time interval of
6 years. Furthermore the purpose was to assess whether the
natural history of disease has changed over time.
Materials and methods: The International Hvidoere cohort, year
1999–2000: 275 children from 22 paediatric centers; the Danish
cohort, year 2005–2006: 130 children from 4 paediatric centers.
All patients went through a 90-minutes Boost-test 1, 3 (only the
Danish cohort), 6, 12 months to characterize the residual betacell
function. All samples were centrally analyzed. The linearity
of the slope of decline in stimulated C-peptide was analyzed
from 3–12 months on a logarithmic scale. Linear mixed-effect
models were used to determine cohort differences.
Results: Maximum values of stimulated C-peptide were reached
at a duration of three months. Thereafter there was a linear
decline in stimulated C-peptide for all age groups above 5 years
in both cohorts. The mean value for the disappearance rate in
stimulated C-peptide was 7.2 ± 0.9%/month for the Hvidoere
and 9.4 ± 0.8%/month for the Danish cohort (NS, P = 0.12). The
combined slope for both cohorts was calculated to 8.0 ± 0.7%/
month.This is in the same range as the value reported of
0.019 nmol/l/month (1982-1985) by Wallensteen corresponding
to a relative change of 9.5%/month.
Conclusion: Thus, the natural history of disease progression
during the first 12 months after diagnosis has not changed
considerably in new onset T1D populations during the last
20 years, despite more intensive insulin treatment regimens has
been introduced during this period.