C-peptide decline in type 1 diabetes has two phases: an initial exponential fall and a subsequent stable phase
Shields, B; McDonald, T; Oram, R; et al.Hill, A; Hudson, M; Leete, P; Pearson, E; Richardson, S; Morgan, N; Hattersley, A
Date: 7 June 2018
Article
Journal
Diabetes Care
Publisher
American Diabetes Association
Publisher DOI
Abstract
OBJECTIVE: The decline in C-peptide in the five 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 duration of diabetes
up to 40 years after diagnosis
RESEARCH DESIGN AND METHODS: We ...
OBJECTIVE: The decline in C-peptide in the five 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 duration of diabetes
up to 40 years after diagnosis
RESEARCH DESIGN AND METHODS: We assessed the pattern of association between urinary Cpeptide
creatinine ratio (UCPCR) and duration of diabetes in cross sectional data from 1549
individuals with Type 1 diabetes using non-linear regression approaches. Findings were
replicated in longitudinal follow-up data in 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 per year [95%CI -50%,-43%]) followed by a stable period thereafter
(+0.09% [-1.3,+1.5] per year). The two phases had similar duration and slope 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) <7y duration: -48% per year [-55%,-38%]; >7y duration -0.1% [-4.1%,+3.9%])
and plasma C-peptide ((n=93) >7y 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 beta-cell
survival.
Institute of Biomedical & Clinical Science
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