This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this recordOBJECTIVE: 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.This work was principally supported by the Juvenile Diabetes Research Foundation (JDRF) (ref 3-SRA-2014-314-M-R), with additional funding from the Department of Health and Wellcome Trust Health Innovation Challenge Award (HICF-1009-041; WT-091985). ATH is an NIHR Senior investigator and Wellcome Trust senior investigator. BS is a core member of the NIHR Exeter Clinical Research facility. ERP holds a Wellcome Trust New Investigator award (102820/Z/13/Z). TJM is funded by an NIHR clinical senior lecturer fellowship. 17 RO holds a Diabetes UK Harry Keen Fellowship award. We acknowledge further funding from the JDRF Career Development award to SJR (5-CDA-2014-221-A-N) and project grants from Diabetes UK (16/0005480; to NGM & SJR). This article/paper/report presents independent research supported by the JDRF, Diabetes UK, the Wellcome Trust and the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the JDRF, Diabetes UK, Wellcome Trust, NHS, the NIHR or the Department of Health.