Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, Glucose Intolerance, Muscle Accrual, Cystic Fibrosis-related Diabetes, Healthy Controls, Healthy Participants
Brief summary
This study will investigate the link between glucose abnormalities and elements critical to muscle function including mass, composition and energy metabolism. the primary goal of the study is to determine whether Cystic Fibrosis (CF) disease is associated with muscle dysfunction, especially in the presence of glucose intolerance. This is a longitudinal cohort study of 3 main groups: CF subjects without Cystic Fibrosis-related diabetes (CFRD), healthy matched controls and CF subjects with newly diagnosed CFRD started on insulin therapy.
Detailed description
Cystic Fibrosis (CF) is a lethal inherited disease that primarily affects the lungs but also confers a high risk of diabetes, with up to 40-50% of adults experiencing Cystic Fibrosis-related diabetes (CFRD). CFRD is associated with an accelerated decline in lung function, nutritional status and survival and despite treatment mortality in patients with CFRD remains high. Airway inflammation and susceptibility to infections caused by hyperglycemia, and the catabolic effect of insulin deficiency are posited mechanisms of CFRD-associated morbidity. Respiratory failure caused by airway disease is well known but the contribution of respiratory muscle dysfunction may be critical. In Type 2 Diabetes Mellitus (T2DM) glucose and insulin defects are closely correlated with muscle function. The pulmonary muscles are crucial to respiration and airway clearance in CF. Muscle function is dependent on its mass, composition, and energy metabolism. Lean body mass (LBM) deficits are present in CF and improvement in LBM improves pulmonary function. Using T2DM as a model for muscle dysfunction, the study hypothesis is that glucose intolerance exacerbates LBM deficits, negatively affects muscle composition, and alters muscle metabolism leading to respiratory muscle dysfunction and a decline in pulmonary function. CF subjects without CFRD and healthy controls will undergo 3 study visits (baseline then annually for 2 years) and CFRD subjects will undergo 2 study visits (baseline and 6 months after baseline). Evaluations will include neurologic exams, anthropometric assessments, 3-day dietary recall, MRI scans, oral glucose tolerance tests (CF subjects only), blood work, pulmonary function testing, muscle strength testing, exercise testing, bone density scans, and adverse event assessment.
Interventions
None listed
Sponsors
National Institutes of Health (NIH)
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Children's Hospital of Philadelphia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for CF subjects without CFRD: 1. Males or females age 16 to 22 years. 2. Confirmed diagnosis of CF per CF Foundation guidelines 3. Parental/guardian permission (informed consent) and if appropriate, child assent.
Exclusion criteria
for CF subjects without CFRD 1. Chronic systemic glucocorticoid use e.g. for allergic bronchopulmonary aspergillosis 2. Organ transplantation 3. Forced Expiratory Volume (FFEV) 1%-predicted \< 40% 4. Established diagnosis of CFRD and treatment with insulin or hypoglycemic agent 5. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures. 6. Pregnancy or breastfeeding (if female) 7. Pre-existing neurological or neuromuscular disease All study visits for CF subjects will be scheduled during periods of baseline health. Visits will not be performed within 4 weeks of an acute respiratory illness or pulmonary exacerbation. Inclusion Criteria for healthy controls 1. Age-, sex-, ethnicity-, and BMI-matched at time of enrollment to CF subjects without CFRD 2. Parental/guardian permission (informed consent) and if appropriate, child assent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compare change in mean lean body mass (LBM) from baseline to end of study | 24 months (CF without CFRD subjects & healthy controls); 6 months for CF subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare Intramyocellular lipid (IMCL) accumulation from baseline to end of study | 24 months (CF without CFRD subjects & healthy controls); 6 months for CF subjects | Proton magnetic resonance spectroscopy will be used to measure IMCL per previously published methods. |
Countries
United States
Outcome results
None listed