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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 inDiabetes 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%]).
 
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.”
 
Reference
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
 
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http://care.diabetesjournals.org/content/41/7/1486.long
 
C-Peptide Decline in Type 1 Diabetes Has Two Phases: An Initial Exponential Fall and a Subsequent Stable Phase
Beverley M. Shields1, Timothy J. McDonald2, Richard Oram1, Anita Hill1, Michelle Hudson1, Pia Leete3, Ewan R. Pearson4, Sarah J. Richardson3, Noel G. Morgan3 and Andrew T. Hattersley1⇑, on behalf of the TIGI Consortium*
 
Diabetes Care 2018 Jul; 41(7): 1486-1492. https://doi.org/10.2337/dc18-0465
 
Abstract
OBJECTIVE The decline in C-peptide in the 5 years after diagnosis of type 1 diabetes has been well studied, but little is known about the longer-term trajectory. We aimed to examine the association between log-transformed C-peptide levels and the duration of diabetes up to 40 years after diagnosis.
 
RESEARCH DESIGN AND METHODS We assessed the pattern of association between urinary C-peptide/creatinine ratio (UCPCR) and duration of diabetes in cross-sectional data from 1,549 individuals with type 1 diabetes using nonlinear regression approaches. Findings were replicated in longitudinal follow-up data for both UCPCR (n = 161 individuals, 326 observations) and plasma C-peptide (n = 93 individuals, 473 observations).
 
RESULTS We identified two clear phases of C-peptide decline: an initial exponential fall over 7 years (47% decrease/year [95% CI −51, −43]) followed by a stable period thereafter (+0.07%/year [−1.3, +1.5]). The two phases had similar durations and slopes in patients above and below the median age at diagnosis (10.8 years), although levels were lower in the younger patients irrespective of duration. Patterns were consistent in both longitudinal UCPCR (n = 162; ≤7 years duration: −48%/year [−55, −38]; >7 years duration −0.1% [−4.1, +3.9]) and plasma C-peptide (n = 93; >7 years duration only: −2.6% [−6.7, +1.5]).
 
CONCLUSIONS These data support two clear phases of C-peptide decline: an initial exponential fall over a 7-year period, followed by a prolonged stabilization where C-peptide levels no longer decline. Understanding the pathophysiological and immunological differences between these two phases will give crucial insights into understanding β-cell survival.
 
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