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

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.

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.

Eligibility Criteria:
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)