Cystic Fibrosis–Related Diabetes Workshop: Research Priorities Spanning Disease Pathophysiology, Diagnosis, and Outcomes

• Authors: Melissa S. Putman, Boston Children's Hospital; Andrew W. Norris, University of Iowa; Rebecca L. Hull, University of Washington School of Medicine; Michael R. Rickels, University of Pennsylvania Perelman School of Medicine; Lori Sussel, University of Colorado Anschutz Medical Campus; Scott M. Blackman, Johns Hopkins School of Medicine; Christine L. Chan, University of Colorado Anschutz Medical Campus; Katie Larson Ode, University of Iowa; Tanicia Daley Jean Pierre, Emory University; Arlene Stecenko, Emory University; Antoinette Moran, University of Minnesota Twin Cities; Meagan J. Helmick, Cystic Fibrosis Foundation; Sharon Cray, Cystic Fibrosis Foundation; Jessica Alvarez, Emory University; Virginia A. Stallings, The Children's Hospital of Philadelphia; Katherine L. Tuggle, Cystic Fibrosis Foundation; John P. Clancy, Cystic Fibrosis Foundation; Thomas L. Eggerman, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); John F. Engelhardt, University of Iowa; Andrea Kelly, University of Pennsylvania
• Journal Title: Diabetes
• Volume: Volume 72, Number 6
• Publisher: American Diabetes Association | 2023-06-01, Pages 677-689
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.2337/db22-0949
• Subjects: Health Sciences, Nutrition; Health Sciences, Public Health
• Keywords: Adult; Adolescent; Male; Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Diabetes Mellitus; Glucose Intolerance; Research

Abstract

Cystic fibrosis (CF) is a recessive disorder arising from mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is expressed in numerous tissues, with high expression in the airways, small and large intestine, pancreatic and hepatobiliary ducts, and male reproductive tract. CFTR loss in these tissues disrupts regulation of salt, bicarbonate, and water balance across their epithelia, resulting in a systemic disorder with progressive organ dysfunction and damage. Pancreatic exocrine damage ultimately manifests as pancreatic exocrine insufficiency that begins as early as infancy. Pancreatic remodeling accompanies this early damage, during which abnormal glucose tolerance can be observed in toddlers. With increasing age, however, insulin secretion defects progress such that CF-related diabetes (CFRD) occurs in 20% of teens and up to half of adults with CF. The relevance of CFRD is highlighted by its association with increased morbidity, mortality, and patient burden. While clinical research on CFRD has greatly assisted in the care of individuals with CFRD, key knowledge gaps on CFRD pathogenesis remain. Furthermore, the wide use of CFTR modulators to restore CFTR activity is changing the CFRD clinical landscape and the field’s understanding of CFRD pathogenesis. For these reasons, the National Institute of Diabetes and Digestive and Kidney Diseases and the Cystic Fibrosis Foundation sponsored a CFRD Scientific Workshop, 23–25 June 2021, to define knowledge gaps and needed research areas. This article describes the findings from this workshop and plots a path for CFRD research that is needed over the next decade.