Obesity and Metabolic Complications in Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator gene, resulting in impaired chloride and bicarbonate transport across epithelial cells. This defect results in multisystem involvement, characterized primarily by chronic pulmonary infections, obstructive lung disease, and respiratory failure, alongside extrapulmonary manifestations including pancreatic insufficiency, CF-related diabetes, and liver disease. Historically, malnutrition represented a major clinical challenge due to chronic catabolism, increased energy expenditure, and malabsorption. Given the well-established association between nutritional status and both pulmonary function and survival, traditional CF management prioritized the prevention of undernutrition through high-calorie diets and nutritional supplementation.

This review examines the emerging epidemiology of overweight and obesity in CF, the associated metabolic complications, evolving nutritional recommendations, and pharmacologic and nonpharmacologic management strategies to optimize metabolic outcomes in the era of highly effective modulator therapy (HEMT).

With advances in multidisciplinary care, improved nutritional interventions, and the widespread adoption of HEMT, the CF population now experiences markedly improved health outcomes and life expectancy. These advances have concurrently contributed to a rising prevalence of overweight and obesity. Excess weight in CF is increasingly associated with metabolic complications including hypertension, dyslipidemia, insulin resistance, hepatic steatosis, and obstructive sleep apnea. Consequently, the nutritional landscape of CF care is transitioning from a predominant emphasis on weight gain toward individualized nutritional planning that prioritizes metabolic health. Pharmacologic therapies for weight management may be appropriate in selected individuals, though evidence specific to the CF population remains limited.

The widespread use of HEMT has fundamentally altered the trajectory of CF, shifting the primary nutritional concern from undernutrition to overweight and obesity-related metabolic disease. Optimizing metabolic outcomes in this evolving population requires individualized nutritional strategies that extend beyond caloric sufficiency. Further investigation into effective weight management interventions, including pharmacologic approaches, is needed to guide evidence-based care in this new era of CF management.