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Exploring C-peptide loss in type 1 diabetes using growth curve analysis
UCL, England; Oxford Univ Hosp NHS Fdn Trust, England; Churchill Hosp, England.
Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
UCL, England.
UCL, England.
2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 7, article id e0199635Article in journal (Refereed) Published
Abstract [en]

Objectives C-peptide (CP) loss in type 1 diabetes (T1D) is highly variable, and factors influencing it are poorly understood. We modelled CP values in T1D patients from diagnosis for up to 6 years, treating the serial data as growth curves plotted against time since diagnosis. The aims were to summarise the pattern of CP loss (i.e. growth curve shape) in individual patients in simple terms, and to identify baseline characteristics that predict this pattern in individuals. Materials and methods Between 1976 and 2011, 442 T1D patients initially aged amp;lt; 18y underwent 120-minute mixed meal tolerance tests (MMTT) to calculate area under the curve (AUC) CP, at 3, 9,18, 30, 48 and 72 months after diagnosis (n = 1537). The data were analysed using the novel SITAR mixed effects growth curve model (Superlmposition by Translation And Rotation). It fits a mean AUC growth curve, but also allows the curves mean level and rate of fall to vary between individuals so as to best fit the individual patient curves. These curve adjustments define individual curve shape. Results The square root (root) AUC scale provided the best fit. The mean levels and rates of fall for individuals were normally distributed and uncorrelated with each other. Age at diagnosis and root AUC at 3 months strongly predicted the patient-specific mean levels, while younger age at diagnosis (p amp;lt; 0.0001) and the 120-minute CP value of the 3-month MMTT (p = 0.002) predicted the patient-specific rates of fall. Conclusions SITAR growth curve analysis is a useful tool to assess CP loss in type 1 diabetes, explaining patient differences in terms of their mean level and rate of fall. A definition of rapid CP loss could be based on a quantile of the rate of fall distribution, allowing better understanding of factors determining CP loss and stratification of patients into targeted therapies.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE , 2018. Vol. 13, no 7, article id e0199635
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General Practice
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URN: urn:nbn:se:liu:diva-150272DOI: 10.1371/journal.pone.0199635ISI: 000437246700020PubMedID: 29969494OAI: oai:DiVA.org:liu-150272DiVA, id: diva2:1239716
Note

Funding Agencies|National Institute of Health Research (NIHR) from Academic Clinical Lectureship award; Barndiabetesfonden (The Swedish Child Diabetes Foundation); Swedish Research Council; UK Medical Research Council [MR/M012069/1]

Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-09-10

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Ludvigsson, Johnny
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Division of Children's and Women's healthFaculty of Medicine and Health SciencesH.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus
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