Cystic Fibrosis-Related Diabetes Workshop: research priorities spanning disease pathophysiology, diagnosis, and outcomes
Open accessAbstract
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.
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Pancreatic exocrine damage in cystic fibrosis ultimately manifests as pancreatic exocrine insufficiency that begins as early as infancy.
“Pancreatic exocrine damage ultimately manifests as pancreatic exocrine insuf fi ciency that begins as early as infancy (124).”
From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [124]
The Model Systems section states that destruction of pancreatic acinar cells leads to pancreatic insufficiency, supporting the link between exocrine damage and insufficiency. It describes pancreatic damage in young people with CF and loss of exocrine function during the first months of life in CF ferrets, but does not establish that exocrine insufficiency begins in infancy in humans. Page numbers are not available in our copy. (LLM, conf=0.86)
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Self-citationCystic Fibrosis–Related Diabetes
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Self-citationGenetic Modifiers Play a Substantial Role in Diabetes Complicating Cystic Fibrosis
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CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells
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Self-citationIvacaftor Reverses Airway Mucus Abnormalities in a Rat Model Harboring a Humanized G551D-CFTR
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Increased expression of anion transporter SLC26A9 delays diabetes onset in cystic fibrosis
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Cystic fibrosis–related diabetes onset can be predicted using biomarkers measured at birth
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Self-citationDefective exocytosis and processing of insulin in a cystic fibrosis mouse model
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Self-citationOxidative stress and impaired insulin secretion in cystic fibrosis pig pancreas
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Self-citationDiagnostic Testing in Cystic Fibrosis
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An Update in Cystic Fibrosis-Related Diabetes in Children and Adolescents
Anton-Păduraru, D.-T., Murgu, A. M., Donos, M. A., Trofin, F., Azoicai, A. N., Popovici, P., Stana, B. A., Gheorghiescu, I., & Trandafir, L. M. (2023) · Children · doi:10.3390/children10121879 · Cited by 9 · see citing works
GLP-1 Receptor Agonist Therapy in Cystic Fibrosis-Related Diabetes: A Case Report
Ayada, G., Zolotov, S., Cohen, R., Lavi, T., Abdul‐Ghani, M. A., Shehadeh, N., & Nakhleh, A. (2024) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2024.0367 · Cited by 8 · see citing works
Approach to the Patient With Pancreatogenic Diabetes
Ode, K. L., Imai, Y., & Norris, A. W. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf623 · Cited by 11 · see citing works
Self-citationOrganoid-on-a-chip (OrgOC): Advancing cystic fibrosis research
Zheng, M., Erice, E., Wang, H., Zhang, L., & Lawrie, C. H. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.102148 · Cited by 8 · see citing works
Spin State Modulation Strategies for Transition Metal-Based MRI Contrast Agents
Chen, Y.-X., Ge, A.-W., Guo, X. Y., Yu, M., & Tao, J. (2025) · Chemical & Biomedical Imaging · doi:10.1021/cbmi.5c00161 · Cited by 6 · see citing works
The endocrine complications of cystic fibrosis
Moheet, A. A., Scully, K. J., Harindhanavudhi, T., Steinmetz-Wood, S., Guzman, H., Story, L., & Putman, M. S. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01196-8 · Cited by 5 · see citing works
Self-citationSex disparities in cystic fibrosis in the era of highly effective modulator treatment
McNally, E., & Casey, M. (2025) · BMC Pulmonary Medicine · doi:10.1186/s12890-025-03621-0 · Cited by 7 · see citing works
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Self-citationCystic fibrosis related diabetes - current situation and perspective
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Scoping review: relationship between glucose tolerance and pulmonary decline in cystic fibrosis
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Persistence of Residual Insulin Secretion in Long-Standing Cystic Fibrosis-Related Diabetes
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Self-citationImpact of Genetics on Endocrine Manifestations of Cystic Fibrosis
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Self-citationUnravelling the developmental origins of cystic fibrosis-related diabetes
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Nutrition Therapy for Cystic Fibrosis–Related Diabetes
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Self-citationSleep patterns and glycemia in adults with cystic fibrosis-related diabetes: a remote pilot study
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Self-citationCystic Fibrosis–Related Diabetes
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- Authors
- Putman, M. S., Norris, A. W., Hull, R. L., Rickels, M. R., Sussel, L., Blackman, S. M., Chan, C. L., Ode, K. L., Daley, T., Stecenko, A. A., Moran, A., Helmick, M. J., Cray, S., Alvarez, J. A., Stallings, V. A., Tuggle, K. L., Clancy, J. P., Eggerman, T. L., Engelhardt, J. F., & Kelly, A.
- Affiliations
- Boston Children's Hospital (US)
- University of Iowa (US)
- University of Washington (US)
- University of Pennsylvania (US)
- University of Colorado Anschutz (US)
- Johns Hopkins University (US)
- Emory University (US)
- University of Minnesota (US)
- Cystic Fibrosis Foundation (US)
- Children's Hospital of Philadelphia (US)
- National Institutes of Health (US)
- Corresponding author
- Engelhardt, John F.
- Kelly, Andrea
- ORCID
- Putman, Melissa S.
- Norris, Andrew W.
- Hull, Rebecca L.
- Rickels, Michael R.
- Sussel, Lori
- Blackman, Scott M.
- Chan, Christine L.
- Ode, Katie Larson
- Daley, Tanicia
- Stecenko, Arlene A.
- Moran, Antoinette
- Helmick, Meagan J.
- Alvarez, Jessica A.
- Stallings, Virginia A.
- Tuggle, Katherine L.
- Clancy, John P.
- Engelhardt, John F.
- Kelly, Andrea
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2023-05-01
- Volume
- 46
- Issue
- 6
- Pages
- 1112-1123
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC10234745
- OpenAlex
- W4367600780
- Cited by
- 35
- References
- 147
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 6 · 2023: 4
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CFF
- NIH (P30DK125013, R01 DK133523, R01DK101402)
- AAS
- CF Foundation (P30 DK054759, R01 DK115791, R01DK119699, RC2 DK124207)
- Public Health Service (R01 DK97830)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- cystic fibrosis-related diabetes, cystic fibrosis, CFTR, exocrine pancreatic insufficiency, insulin secretion defect, CFTR modulators, pathogenesis, research priorities, glucose tolerance
- MeSH terms
- Adolescent, Adult, Cystic Fibrosis, Diabetes Mellitus, Humans, Male, Research, Glucose Intolerance, Cystic Fibrosis Transmembrane Conductance Regulator
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