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 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.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

Shields BM,McDonald TJ,Oram R,Hill A,Hudson M,Leete P,Pearson ER,Richardson SJ,Morgan NG,Hattersley AT,TIGI Consortium.

doi

10.2337/dc18-0465

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

1486-1492

issue

7

eissn

0149-5992

issn

1935-5548

pii

dc18-0465

journal_volume

41

pub_type

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