Cystic Fibrosis Related Diabetes
Conditions
Keywords
Cystic Fibrosis Related Diabetes, cystic fibrosis transmembrane conductance regulator (CFTR), CFTR modulators, Elexacaftor/ tezacaftor/ivacaftor or ETI
Brief summary
The study aims to test whether use of CFTR modulators (ETI) improves fasting and post prandial glycemia by enhancing disposition index (DI) in individuals with CFRD with CFTR +ve mutation (at least one copy of F508del) on CFTR modulator (ETI) therapy (CFRDF508del+ETI). CFRD with a mutation that is not eligible for modulator therapy (CFRD-ETI) will be the control group.
Detailed description
This is a mechanistic observational study. It is NOT a clinical trial. A physiological challenge of a single mixed meal tolerance test (MMTT) is administered, which will enable a comprehensive assessment of multiple parameters of glucose turnover, insulin secretion, insulin sensitivity and lipolysis in individuals with CFRD. The MMTT is the gold standard for measuring both insulin action and secretion simultaneously with glucose kinetics. The pilot study aims to test whether use of CFTR modulators (ETI) improves fasting and post prandial glycemia by enhancing disposition index (DI) in individuals with CFRD with CFTR +ve mutation (at least one copy of F508del) on CFTR modulator (ETI) therapy (CFRDF508del+ETI). We plan to gather critical preliminary data on the following aspects of CFRD: 1. Abnormalities in specific components (basal vs. static vs. dynamic) of beta-cell function in CFRDF508del+ETI and in CFRD-ETI individuals. 2. Effects of ETI on components of beta cell function. 3. Effects of CFTR mutation and of CFTR modulators (CFRDF508del+ETI) on insulin sensitivity and post prandial glucose turnover in CFRD.
Interventions
None listed
Sponsors
University of Alabama at Birmingham
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Cystic Fibrosis Related Diabetes (CFRD) 2. Age 21-75 years at time of consent 3. BMI 19-50 kg/m2 (In Asians BMI is \~ 2 points lower for comparison so it is 17-48 kg/m2) 4. Creatinine ≤ 1.4 mg/dl in women and ≤ 1.5 mg/dl in men 5. HbA1c ≤ 11% lifestyle treatment or mono/combination therapy with oral hypoglycemic agents (e.g. metformin or sulphonylurea or SGLT2i) and preferably on insulin pump therapy (i.e., SAP, HCL) with or without CGM will be recruited. However, use of MDI (Multiple Daily Injections) of insulin, i.e., on basal-bolus insulin therapy will also be included. Most of our patients are on insulin therapy with very few on oral antidiabetes medications but we would like to offer them the choice of participation. 6. Subjects on FDA approved/recommended full doses of ETI will be offered participation. If dose adjustments of ETI are made after enrollment a discussion will be done with the primary care provider and HCSTOC as required. 7. Willing to be at a stable weight for duration of the study. 8. An understanding of and willingness to follow the protocol and sign the informed consent Subjects meeting any of the
Exclusion criteria
at baseline will be excluded from study participation:
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disposition Index in CFRD | Day 1 During the Mixed meal test | Disposition Index (DI - β-cell responsivity appropriate to the degree of insulin resistance) is higher in CFRDF508del+ETI when compared to CFRD with a mutation not eligible to be on ETI (CFRD-ETI). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post prandial glucose turnover | Day 1 During the mixed meal test | Post prandial glucose turnover is improved in CFRDF508del+ETI when compared to CFRD with a mutation not eligible to be on ETI (CFRD-ETI). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRita Basu, MD
UAB Medicine
Outcome results
None listed