Two Phases of C-Peptide Decline Identified in Type I Diabetes

C-peptide test tube
C-peptide test tube
Identifying phases of C-peptide decline may be valuable for understanding β-cell survival.

There are 2 phases of C-peptide decline that occur during the first 4 decades following a diagnosis of type 1 diabetes (T1D), and further understanding of the pathophysiologic and immunologic differences between these two phases may help increase knowledge of β-cell survival, according to a study published in Diabetes Care.

The decline in C-peptide during the first 5 years following the diagnosis of T1D has been well studied, but much less is known about long-term sequelae. In this study, the investigators evaluated the trajectory of C-peptide levels in a large cohort of 1549 patients up to 40 years after receiving a diagnosis of T1D. The cross-sectional study assessed the pattern of association between urinary C-peptide/creatinine ratio (UCPCR) and duration of diabetes using nonlinear regression approaches, and then the investigators replicated their results in longitudinal follow-up data for both UCPCR (n=161 individuals, 326 observations) and plasma C-peptide (n=93 individuals, 473 observations).

In the cohort, 2 clear phases of C-peptide decline were identified. The first decline occurred over a 7-year period (47% decrease/year [95% CI, −51% to −43%]) and that was followed by a period of stability (+0.07%/year [−1.3 to +1.5]). The durations and slopes in patients above and below the median age at diagnosis (10.8) were similar in both phases, but levels were lower in younger patients irrespective of duration. Patterns also remained consistent for both longitudinal UCPCR (n=162; ≤7 years duration: −48%/year [−55% to −38%]; >7 years duration −0.1% [−4.1% to +3.9%]) and plasma C-peptide (n=93; >7 years duration only: −2.6% [−6.7% to +1.5%]).

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The investigators note that the stabilization of C-peptide levels 7 years after diagnosis “suggests that there are important and previously unrecognized changes in immune function and/or β-cell viability around this time that may have critical implications for future pharmaceutical interventions.”


Shields BM, McDonald TJ, Oram R, et al; TIGI Consortium. C-peptide decline in type 1 diabetes has two phases: An initial exponential fall and a subsequent stable phase [published online Jun 7, 2018]. Diabetes Care. doi:10.2337/dc18-0465