a pilot and feasibility study to evaluate high vs low glycemic index mixed meal tolerance test in adolescents and young adults with cystic fibrosis

Conditions: Cystic Fibrosis

Summary: the goal of this study is to determine the extent to which excess dietary simple sugars serve as a secondary mediating factor in cystic fibrosis-related diabetes (cfrd) development. the main questions it aims to answer are: * whether conducting a randomized 2x2 factorial design that evaluates acute postprandial changes in glucose over 2 hours following ingestion of a mixed meal challenge that varies by glycemic index and consumption of a sugar-sweetened beverage is acceptable and feasible. * what are the preliminary changes in postprandial hyperglycemia, islet cell function, and incretin response to a high or low glycemic index mixed meal tolerance test (mmtt) with and without sugar-sweetened beverages (ssb) in adolescents and young adults with cf participants will be randomized to a mixed diet and blood will be drawn before and after the mixed meal challenge.

cystic fibrosis-related diabetes (cfrd) is one of the most common co-morbidities seen in cf and significantly increases morbidity and mortality. the prevalence of cfrd increases with age with approximately 20% of adolescents and 50% of adults in the 3rd and 4th decade of life carrying the diagnosis. although a diagnosis of cfrd is uncommon in children less than 10 years of age, research studies show that abnormal glucose tolerance is found in about 40% of cf toddlers and school-age children. mechanisms leading to the development of cfrd are incompletely understood. for several years, the predominant theory of pancreatic endocrine dysfunction was based on the theory of "collateral damage" which results in impairment of β-cell function due to loss of islet cells. in addition to experiencing reduced beta cell mass, individuals with cf have a diminished incretin effect that contributes to impaired insulin secretion. postprandial hyperglycemia is not uncommon for individuals with cf irrespective of their glucose tolerance and during an ogtt failure to suppress glucagon results in hyperglycemia. unfortunately, mechanisms involved in dysregulated glucagon release and its contribution to hyperglycemia in cf are poorly understood. the cf diet is typically high in energy-dense, nutrient-poor foods. individuals with cf require high-energy, high-fat diets to maintain their hypermetabolic state and offset malabsorption, with current cf dietary guidelines recommending an energy intake of 1.2 to 1.5 times that of the general population. to date, there is a paucity of studies that rigorously investigate the metabolic sequelae that high gi foods and ssb have on the metabolic profile of individuals with cf. the study team proposes that a diet high is ssbs and high gi foods induces more oxidative stress due to postprandial hyperglycemia, impairs insulin secretion, and exacerbates glucose abnormalities in cf.

Eligibility criteria:
inclusion criteria: * english speaking * diagnosis of cf based on the presence of two known cf causing mutations and/or positive sweat test * pancreatic insufficiency * baseline dietary consumption of \>10% total kcal from added sugars and self-reported consumption of \>/= sugar-sweetened beverages per week exclusion criteria: * current use or anticipated use of medication that is known to raise or lower blood glucose in the past 4 weeks. * oral or iv glucocorticoid current or previous use in the past 4 weeks will prohibit enrollment in the study. * recent pulmonary exacerbation within 3 weeks of enrollment and/or an acute illness requiring a change in antibiotics will also exclude participants. * bmi below the 5th percentile or greater than the 95th percentile for age and sex * fev1 \<40% or awaiting a lung transplant; * prior lung or liver transplant or kidney or liver dysfunction. * use of cftr modulators is not an exclusion criterion. rather, for patients recently started on cftr modulators, we will wait to enroll in the study until on cftr modulator for at least 2 months. * diagnosis of cf liver disease. * uncontrolled exocrine pancreatic insufficiency/malabsorption * diagnosis of cfrd * g-tube feeds (bolus and/or continuous) * current enrollment in another intervention study * changes in diet to lose or gain weight * gluten allergy or intolerance * current pregnancy or lactation or plans to become pregnant during study period * history of drug or alcohol abuse * restrictive dietary patterns (e.g, vegan, ketogenic, intermittent fasting) for more than one month within the last two months prior to screening. * more than 5% body weight change within 2 months of screening visit or day 1 of mixed meal tolerance test

Keywords: cystic fibrosis glycemic index cystic fibrosis related diabetes