Cystic Fibrosis, Cystic Fibrosis-related Diabetes
Conditions
Brief summary
The goal of this study is to determine the extent to which excess dietary sugars serve as a precipitating factor in glucose intolerance in adults with cystic fibrosis (CF), a population at especially high risk for a unique form of diabetes (CF-related diabetes, CFRD) and with standard-of-care dietary recommendations (high-calorie, high-fat) that conflict with recommendations for other forms of diabetes. This trial will investigate if the typical high-sugar, high-fat CF diet plays a role in diabetes risk and visceral fat accumulation in people with CF. A total of 30 participants will get a low-added sugar, high-fat diet and the other 30 will get a standard CF diet with no sugar restrictions. Participants will be randomized to the diet group they are assigned. All foods will be provided for 8 weeks.
Detailed description
Approximately half of adults with cystic fibrosis (CF), a genetic disease, will develop diabetes. Dietary strategies shown to be successful in preventing or treating other forms of diabetes in people without CF contradict current nutritional recommendations for people with CF. The nutrition standard-of-care in CF is prescription of an unrestricted high-calorie, high-fat diet because of malnutrition. However, the standard CF diet translates to low-quality diets, with excess added sugars well-above general population recommendations. Also the investigators have shown that people with CF have more fat around their abdominal organs (called visceral fat) compared to healthy controls. The hypothesis is that the typical high-sugar, high-fat CF diet plays a role in diabetes risk and visceral fat accumulation in people with CF. In this study, the investigators will test if a low-added sugar diet improves risk markers for diabetes and decreases visceral fat over 8 weeks. The study will recruit 60 participants with CF. A total of 30 participants will get a low-added sugar, high-fat diet and the other 30 will get a standard CF diet with no sugar restrictions. Participants will be randomized to the diet group they are assigned. All foods will be provided for 8 weeks. There will be a total of 4 study visits at the Emory Hospital clinical research unit. These will include: 1) a screening visit with an oral glucose tolerance test with blood draws to determine if they already have diabetes, 2) a baseline visit for an insulin secretion test (called glucose-potentiated arginine (GPA) stimulation test) to assess risk for diabetes, as well as magnetic resonance imaging (MRI) testing to measure visceral fat, 3) a 4-week visit for another oral glucose tolerance test and in-person check-in, and 4) an 8-week visit for another GPA and MRI. Blood samples will be collected and banked. In addition to all meals provided for 8 weeks, participants will be compensated for their time and effort. Participants will be recruited from patients seen at the Emory CF Clinic. Informed consent will be performed prior to any study testing. The investigators hope this study will contribute to the development of new standardized nutrition guidelines for people living with CF.
Interventions
OTHERLow-added sugar, high-fat diet
Consist of \<5% kcal from added sugars as recommended by the American Heart Association, and the glycemic index will be 45 or lower (25% lower than typical CF diet). The macronutrient composition of both study diets will reflect the general CF recommendations for macronutrients: 35-40% of total kcal from fat and 15-20% total kcal from protein.
OTHERHigh-added sugar, high-fat CF diet
Consist of ≥13% kcal from added sugars and the glycemic index will be \>60. The macronutrient composition of both study diets will reflect the general CF recommendations for macronutrients: 35-40% of total kcal from fat and 15-20% total kcal from protein.
Sponsors
Emory University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The study team, including the investigators, statistician, and coordinator, will be blinded to diet allocation throughout. All major assessments and assays will be performed by individuals who will be blinded to the diet. Participants will not be informed of their allocated diet.
Intervention model description
A double-blind, randomized, parallel-group design clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Confirmed CF diagnosis 2. Ages 18 years and older 3. Baseline estimated daily total added sugar intake \>16 tsp, as estimated from the Dietary Screener Questionnaire (DSQ).
Exclusion criteria
1. Nocturnal tube feeds 2. BMI \<18.5 kg/m2 3. Life expectancy \< 12 months 4. Confirmed diagnosis of CFRD 5. Screening OGTT showing fasting hyperglycemia (≥126 mg/dL) 6. Chronic steroid use 7. Current pregnancy or lactation 8. Inability/unwillingness to consume the majority of foods on the menu during the study period 9. MRI-incompatible metal that cannot be removed for testing 10. Uncontrolled exocrine pancreatic insufficiency/malabsorption 11. Clinically instability, defined as no changes in medical regimen (including medications and pulmonary exacerbations) for at least 21 days prior to study visit 12. Initiation of CFTR modulator within previous 8 weeks OR unstable changes in weight and lung function due to CFTR modulator use 13. Actively trying to gain or lose weight 14. Any food allergies or intolerances that cannot be accommodated 15. Any medical condition deemed by the a study physician or PI that may preclude completion of the study or interfere with primary end points.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in acute insulin response to arginine (AIRarg) from baseline | Baseline and 8 weeks post intervention | Participants will undergo a Glucose-Potentiated Arginine Stimulation (GPA) Test after a 10-12 hour overnight fast to measure acute insulin (AIRarg) responses during a 230 and 340 mg/dl glucose clamp. This test will measure changes in beta cell secretory capacity. |
| Change in acute C-peptide (ACRarg) from baseline | Baseline and 8 weeks post intervention | Participants will undergo a Glucose-Potentiated Arginine Stimulation (GPA) Test after a 10-12 hour overnight fast to measure acute C-peptide (ACRarg) responses during a 230 and 340 mg/dl glucose clamp. This test will measure changes in beta cell secretory capacity. |
| Change in visceral adipose tissue from baseline | Baseline and 8 weeks post intervention | Dual energy X-ray absorptiometry (DEXA)-derived measurement of visceral adipose tissue (VAT) will be assessed with a GE Lunar iDXA machine. This will enable assessment of changes in body composition over the study. |
| Change in fasted plasma Eh[CySS] from baseline | Baseline and 8 weeks post intervention | Change in plasma Cysteine/Cystine Redox Potential (Eh\[CySS\]) will be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gastrointestinal Symptom Rating Scale (GSRS) scale | Baseline and 8 weeks post intervention | The GSRS is a 15 items combine into five symptom clusters: Reflux, Abdominal pain, Indigestion, Diarrhea and Constipation. Possible score range is 0-7, with 7 being the worst and 0 being the best (no symptoms). |
| Change in hepatic and pancreatic fat volume | Baseline and 8 weeks post intervention | Dual energy X-ray absorptiometry (DEXA)-derived measurement of visceral adipose tissue (VAT) for hepatic and pancreatic fat volume. Will be assessed with a GE Lunar iDXA machine. |
| Change in fasted plasma Eh[GSSG] | Baseline and 8 weeks post intervention | Change in plasma glutathione disulfide (GSSG) (Eh\[CySS\]) will be measured. |
Countries
United States
Contacts
CONTACTJessica A Alvarez, PhD, RD
CONTACTSwati Zaveri, PhD
PRINCIPAL_INVESTIGATORJessica A Alvarez, PhD, RD
Emory University
Outcome results
None listed