The Effects of a Low Glycemic Load Diet on Dysglycemia and Body Composition in Adults With Cystic Fibrosis-Related Diabetes

Study Overview
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Brief Summary
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This study will evalute the effect of a low glycemic load (LGL diet on dysglycemia, insulin requirements, DXA-derived body composition, gastrointestinal symptoms and quality of life measures in adults with cystic fibrosis-related diabetes (CFRD). We will use continuous glucose monitors (CGM) to assess the LGL diet both in a controlled setting (via a meal delivery company) and in free-living conditions.

Detailed Description
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Maintenance of a healthy body mass index (BMI) is a well-established marker of improved morbidity and mortality in patients with cystic fibrosis (CF). To achieve and maintain adequate weight, patients with CF are encouraged to consume a caloric intake of 120-150% of the dietary reference intake (DRI) for the typical healthy adult. However, dietary recommendations for children and adults with CF are based entirely on consensus and expert opinion. High carbohydrate intake is typical for patients with CF, but this may lead to multiple complications including post-prandial hyperglycemia, increased inflammation, and abnormal GI motility and may predispose to obesity and metabolic syndrome. Dietary changes are a commonly used treatment approach for CF-related diabetes (CFRD), despite the fact that there are no data establishing whether dietary interventions are helpful in preventing and/or treating CFRD. Particularly as patients with CF live longer with highly effective modulator therapy and as the prevalence of cardiovascular and metabolic disease increases in this population, it is crucial to understand the effects of dietary composition on short and long-term endocrine, GI, and pulmonary outcomes. In patients with both type 1 and type 2 diabetes mellitus, a low glycemic load (LGL) diet has been shown to improve glycemic variability, A1c level, insulin sensitivity, and quality of life without increasing hypoglycemic events. Significant glycemic variability is associated with increased markers of inflammation in adolescents with T1DM, possibly serving as a mechanistic link to the development of cardiovascular disease. Particularly as rates of obesity and cardiovascular disease continue to increase, this diet may be particularly useful in patients with CF, altered glucose homeostasis, and/or obesity. There are currently no prospective studies evaluating the impact of diet quality on glycemic control and body composition in patients with CF. The gold standard approach for assessing the safety and efficacy of dietary interventions is a food delivery study. The investigators will conduct a prospective, open-label study in adults with CFRD to determine the effects of an LGL diet on dysglycemia and body composition. Participants will initially follow their standard diet for a 10-day run-in period. They will then transition to an LGL diet provided by a meal delivery company for 8 weeks. During this period, they will wear a continuous glucose monitor (CGM) for 2 10-day periods. Finally, participants will adhere to an LGL diet under free-living conditions with close nutritionist follow-up for a period of 4 months. Serum studies, DXA-body composition, anthropometric data, GI symptoms and quality of life measures will be obtained at baseline, after the meal-delivery phase and at study completion. The investigators hypothesize that an LGL diet will result in improved CGM-derived measures of hyperglycemia, a decrease in insulin requirements, and reductions in fat-mass index on DXA analysis in adults with CFRD over an 8-week period during a meal delivery period. Furthermore, they hypothesize that these changes will be sustainable under free-living conditions during a 4-month period.

Official Title
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The Effects of a Low Glycemic Load Diet on Dysglycemia and Body Composition in Adults With Cystic Fibrosis-Related Diabetes

Conditions
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Cystic Fibrosis, Cystic Fibrosis-related Diabetes, Cystic Fibrosis With Intestinal Manifestations

Intervention / Treatment
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* Behavioral: Low Glycemic Load Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years and above Genetically confirmed diagnosis of CF Diagnosis of pancreatic insufficiency, requiring pancreatic enzyme replacement Criteria for CFRD: A.) Most recent OGTT 2-hour glucose >200 mg/dL within the past two years, and/or; B.) HbA1c >6.5% in the past two years, and/or; C.) Current use of insulin Exclusion Criteria: FEV1 <50% predicted on most recent pulmonary function testing BMI <18 kg/m2 Currently receiving enteral nutrition support via GT feeds Pregnancy, plan to become pregnant in the next 3-months, or sexually active without use of contraception Use of IV antibiotics or systemic supraphysiologic glucocorticoids for CF exacerbation within 1 month Started or stopped treatment with a CFTR modulator within 3 months of enrollment Currently adhering to an LGL or other carbohydrate-restricted diet (carbohydrate intake <30% of total daily caloric intake)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Single dietary treatment with a meal-delivery phase and free-living conditions phase, as well as a run-in period as a control
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Glycemic Load Diet<br>Feeding study with dietary composition (approximately) 50% fat, 20% protein, 30% carbohydrate. | Behavioral: Low Glycemic Load Diet<br>* Food delivery service will provide a low glycemic load diet for 8 weeks, followed by a 4-month period of self-adherence to a low glycemic load diet with close nutritionist follow up<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percent time in target range 70-180 mg/dL | Continuous glucose monitoring | Baseline, post-meal delivery phase (8 weeks), post-free-living conditions phase (4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CGM average glucose (AG) mg/dL | Continuous glucose monitoring | Baseline, post-meal delivery phase (8 weeks), post-free-living conditions phase (4 months) | 
| Change in percent time >180 mg/dL | Continuous glucose monitoring | Baseline, post-meal delivery phase (8 weeks), post-free-living conditions phase (4 months) | 
| Change in percent time >250 mg/dL | Continuous glucose monitoring | Baseline, post-meal delivery phase (8 weeks), post-free-living conditions phase (4 months) | 
| Change in CGM standard deviation (SD) | Continuous glucose monitoring | Baseline, post-meal delivery phase (8 weeks), post-free-living conditions phase (4 months) | 
| Change in CGM coefficient of variation (CV) | Continuous glucose monitoring | Baseline, post-meal delivery phase (8 weeks), post-free-living conditions phase (4 months) | 
| Change in percent time <70 mg/dL | Continuous glucose monitoring | Baseline, post-meal delivery phase (8 weeks), post-free-living conditions phase (4 months) | 
| Change in percent time <54 mg/dL | Continuous glucose monitoring | Baseline, post-meal delivery phase (8 weeks), post-free-living conditions phase (4 months) | 
| Change in number of episodes of symptomatic hypoglycemia (average per week) | Weekly emailed survey | Baseline (weeks 1-2), visit 2 (post-meal delivery phase, weeks 2-10), visit 3 (post-free living conditions phase, weeks 11-26)) | 
| Change in total daily dose of insulin (TDD) | Weekly emailed survey | Baseline (weeks 1-2), visit 2 (post-meal delivery phase, weeks 2-10), visit 3 (post-free living conditions phase, weeks 11-26) | 
| Change in body mass index (BMI, kg/m2) | Every other week emailed survey | Baseline (weeks 1-2), visit 2 (post-meal delivery phase, weeks 2-10), visit 3 (post-free living conditions phase, weeks 11-26) | 
| Change in weight (kg) | Every other week emailed survey | Baseline (weeks 1-2), visit 2 (post-meal delivery phase, weeks 2-10), visit 3 (post-free living conditions phase, weeks 11-26) | 
| Change fat-mass index (FMI, fat mass kg/ height m^2) | DXA body composition measures | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in percent body fat (%) | DXA body composition measures | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in appendicular lean mass index (ALMI, lean mass kg/ height m^2) | DXA body composition measures | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in Patient Assessment of Constipation (PAC) questionnaire score | Likert scale questionnaire with 12 items, each scored 0-4, total score ranging from 0-48 with higher scores related to worse outcomes | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in Patient Assessment of Gastrointestinal Symptoms (PAGI-Sym) questionnaire score | Likert scale questionnaire with 20 items, each scored 0-5, total score ranging from 0-100 with higher scores related to worse outcomes | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) score | Likert scale questionnaire with 50 items, each scored 0-4, total score ranging from 0-100 with higher scores reflecting better outcomes | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in Diet Tolerability Questionnaire | Likert scale questionnaire with 5 items, each scored 0-10, total score ranging from 0-50 with higher scores reflecting better diet tolerability | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in Bristol stool chart data | Chart depicting 7 types of stool patterns, ranging from constipation to diarrhea | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in erythrocyte sedimentation rate (ESR) | Laboratory test, measured in mm/hr | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in c-reactive protein (CRP) | Laboratory test, measured in mg/L | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in hemoglobin A1c | Laboratory test, measured in % | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in total cholesterol | Laboratory test, measured in mg/dL | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in high-density lipoprotein (HDL) | Laboratory test, measured in mg/dL | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in low-density lipoprotein (LDL) | Laboratory test, measured in mg/dL | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in triglyceride level | Laboratory test, measured in mg/dL | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 
| Change in intestinal fatty acid binding protein (I-FABP) | Laboratory test, measured in ng/mL | Baseline (week 1), visit 2 (post-meal delivery phase, week10), visit 3 (post-free living conditions phase, week 26) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis-Related Diabetes, Low Glycemic Load, Continuous Glucose Monitoring, Body Composition