@article{e0c0c474106442ca8e6765275259ea5a,
title = "Longitudinal progression of diabetes mellitus in Wolfram syndrome: The Washington University Wolfram Research Clinic experience",
abstract = "Objective: (1) Describe the progression of diabetes mellitus over time in an observational study of Wolfram syndrome, a rare, genetic, neurodegenerative disorder, which often includes diabetes mellitus and is typically diagnosed during childhood or adolescence. (2) Determine whether C-peptide could be used as a marker of diabetes progression in interventional trials for Wolfram syndrome. Methods: N = 44 (25F/19M) participants with genetically confirmed Wolfram syndrome attended the Washington University Wolfram Research Clinic annually from 2010 to 2019. Medical history, physical examinations, blood sampling, and questionnaires were used to collect data about diabetes mellitus and other components of Wolfram syndrome. Beta-cell function was assessed by determination of C-peptide during a mixed meal tolerance test. Random coefficients models evaluated the rate of progression of C-peptide over time, and power analyses were used to estimate the number of subjects needed to detect a change in C-peptide decline during an intervention trial. Results: 93.2% of patients had diabetes mellitus. Mean HbA1c across all study visits was 7.9%. C-peptide significantly decreased with increasing duration of diabetes mellitus (p < 0.0001); an optimal break point in C-peptide decline was identified to occur between 0.1 and 2.3 years after diabetes mellitus diagnosis. Twenty patients per group (active vs. control) were estimated to be needed to detect a 60% slowing of C-peptide decline during the first 2.3 years following diabetes diagnosis. Conclusion: C-peptide declines over time in Wolfram syndrome and could potentially be used as a marker of diabetes progression in interventional studies for Wolfram syndrome, especially within the first 2 years after diabetes diagnosis.",
keywords = "C-peptide, DIDMOAD, Hb A1c, neurodegenerative disease",
author = "Ray, {Mary Katherine} and Ling Chen and White, {Neil H.} and Richard Ni and Tamara Hershey and Marshall, {Bess A.}",
note = "Funding Information: The authors would like to thank The Washington University Wolfram Study Group, Samantha Ranck for study coordination, and Heather Lugar, Tasha Doty, Anagha Narayanan for data management at Washington University in St. Louis. The work is funded by National Institute of Health (NIH) Eunice Kennedy Shriver National Institute of Child Health & Human Development (R01HD070855); Research reported in this publication was also supported by the Washington University Institute of Clinical and Translational Sciences (UL1TR002345) from the National Center for Advancing Translational Sciences (NCATS) of the NIH, the National Center for Research Resources (NCRR) Clinical and Translational Science Award (UL1RR024992), Washington University Diabetes Research Center (DK020579), Washington University Biomedical Research Training in Drug Abuse training grant (T32DA007261), Washington University Transdisciplinary Postdoctoral Training Program in Obesity and Cardiovascular Disease training grant (T32HL130357), National Center for Advancing Translational Sciences of the National Institutes of Health (KL2 TR002346). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Further funding includes Snow Foundation, George Decker and Julio V. Santiago Pediatric Diabetes Research Fund; Mallinckrodt Institute of Radiology; McDonnell Center for Systems Neuroscience. Funding Information: Eunice Kennedy Shriver National Institute of Child Health & Human Development, Grant/Award Number: R01HD070855; George Decker and Julio V. Santiago Pediatric Diabetes Research Fund; Mallinckrodt Institute of Radiology; McDonnell Center for Systems Neuroscience; National Center for Advancing Translational Sciences, Grant/Award Number: KL2 TR002346; National Center for Research Resources, Grant/Award Number: UL1RR024992; Snow Foundation; Washington University Biomedical Research Training in Drug Abuse, Grant/Award Number: T32DA007261; Washington University Diabetes Research Center, Grant/Award Number: DK020579; Washington University Transdisciplinary Postdoctoral Training Program in Obesity and Cardiovascular Disease, Grant/Award Number: T32HL130357; Washington University Institute of Clinical and Translational Sciences, Grant/Award Number: UL1TR002345 Funding information Publisher Copyright: {\textcopyright} 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2022",
month = mar,
doi = "10.1111/pedi.13291",
language = "English",
volume = "23",
pages = "212--218",
journal = "Pediatric Diabetes",
issn = "1399-543X",
number = "2",
}