Mary Katherine Ray1, Ling Chen2, Neil H White3,4, Richard Ni1, Tamara Hershey1,5, Bess A Marshall3,4,6. 1. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. 2. Division of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA. 3. Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA. 4. Saint Louis Children's Hospital, One Children's Place, St. Louis, Missouri, USA. 5. Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. 6. Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
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.
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.
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Simin Lu; Kohsuke Kanekura; Takashi Hara; Jana Mahadevan; Larry D Spears; Christine M Oslowski; Rita Martinez; Mayu Yamazaki-Inoue; Masashi Toyoda; Amber Neilson; Patrick Blanner; Cris M Brown; Clay F Semenkovich; Bess A Marshall; Tamara Hershey; Akihiro Umezawa; Peter A Greer; Fumihiko Urano Journal: Proc Natl Acad Sci U S A Date: 2014-11-24 Impact factor: 11.205
Authors: Agnieszka Zmyslowska; Michal Ciborowski; Maciej Borowiec; Wojciech Fendler; Karolina Pietrowska; Ewa Parfieniuk; Karolina Antosik; Aleksandra Pyziak; Arleta Waszczykowska; Adam Kretowski; Wojciech Mlynarski Journal: J Proteome Res Date: 2017-11-03 Impact factor: 4.466
Authors: Tamara Hershey; Heather M Lugar; Joshua S Shimony; Jerrel Rutlin; Jonathan M Koller; Dana C Perantie; Alex R Paciorkowski; Sarah A Eisenstein; M Alan Permutt Journal: PLoS One Date: 2012-07-11 Impact factor: 3.240
Authors: Kristen A Pickett; Ryan P Duncan; James Hoekel; Bess Marshall; Tamara Hershey; Gammon M Earhart Journal: Orphanet J Rare Dis Date: 2012-12-08 Impact factor: 4.123
Authors: Agnieszka Zmyslowska; Wojciech Fendler; Arleta Waszczykowska; Anna Niwald; Maciej Borowiec; Piotr Jurowski; Wojciech Mlynarski Journal: Acta Diabetol Date: 2017-08-30 Impact factor: 4.280