C-peptide decline in type 1 diabetes has two phases: an initial exponential fall and a subsequent stable phase

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 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.