PMID- 29969494
OWN - NLM
STAT- MEDLINE
DCOM- 20190101
LR  - 20210109
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 7
DP  - 2018
TI  - Exploring C-peptide loss in type 1 diabetes using growth curve analysis.
PG  - e0199635
LID - 10.1371/journal.pone.0199635 [doi]
LID - e0199635
AB  - 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 <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 (SuperImposition by Translation And Rotation). It fits a mean 
      AUC growth curve, but also allows the curve's 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 ( radical) 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  radicalAUC 
      at 3 months strongly predicted the patient-specific mean levels, while younger 
      age at diagnosis (p<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.
FAU - Besser, Rachel E J
AU  - Besser REJ
AUID- ORCID: 0000-0002-4645-6324
AD  - Genetics and Epigenetics in Health and Disease, University College London, Great 
      Ormond Street Institute of Child Health, London, United Kingdom.
FAU - Ludvigsson, Johnny
AU  - Ludvigsson J
AD  - Department of Clinical and Experimental Medicine, Division of Pediatrics, Medical 
      Faculty, Linkoping University, Linkoping, Sweden.
FAU - Hindmarsh, Peter C
AU  - Hindmarsh PC
AD  - Developmental Endocrinology Research Group, University College London Great 
      Ormond Street Institute of Child Health, London, United Kingdom.
FAU - Cole, Tim J
AU  - Cole TJ
AD  - Population, Policy and Practice Programme, University College London Great Ormond 
      Street Institute of Child Health, London, United Kingdom.
LA  - eng
GR  - MR/M012069/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/R010692/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180703
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (C-Peptide)
SB  - IM
MH  - Adolescent
MH  - Area Under Curve
MH  - Biomarkers
MH  - C-Peptide/*blood/deficiency
MH  - Cell Count
MH  - Child
MH  - Diabetes Mellitus, Type 1/*blood/*diagnosis
MH  - Female
MH  - Humans
MH  - Insulin-Secreting Cells/metabolism
MH  - Male
PMC - PMC6029769
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/07/04 06:00
MHDA- 2019/01/02 06:00
PMCR- 2018/07/03
CRDT- 2018/07/04 06:00
PHST- 2018/03/14 00:00 [received]
PHST- 2018/06/11 00:00 [accepted]
PHST- 2018/07/04 06:00 [entrez]
PHST- 2018/07/04 06:00 [pubmed]
PHST- 2019/01/02 06:00 [medline]
PHST- 2018/07/03 00:00 [pmc-release]
AID - PONE-D-18-07895 [pii]
AID - 10.1371/journal.pone.0199635 [doi]
PST - epublish
SO  - PLoS One. 2018 Jul 3;13(7):e0199635. doi: 10.1371/journal.pone.0199635. 
      eCollection 2018.