A 20-year-old woman with cystic fibrosis comes to the clinic for routine follow-up. She has no concerns since her last visit 3 months ago. Vital signs are normal. Examination shows a hyperexpanded chest with equal aeration bilaterally. Fasting glucose level is 90 mg/dL. Plasma glucose level 2 hours after oral glucose tolerance testing is 185 mg/dL (normal:

Question

A 20-year-old woman with cystic fibrosis comes to the clinic for routine follow-up.  She has no concerns since her last visit 3 months ago.  Vital signs are normal.  Examination shows a hyperexpanded chest with equal aeration bilaterally.  Fasting glucose level is 90 mg/dL.  Plasma glucose level 2 hours after oral glucose tolerance testing is 185 mg/dL (normal: <140).  Which of the following is the primary mechanism responsible for this patient's abnormal test result?

Quizplus · Accepted Answer

Cystic fibrosis (CF) is an autosomal recessive disorder caused by a mutation (eg, ΔF508) in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. CFTR normally regulates the transport of chloride ions across secretory epithelial cells; a defect in this protein leads to the accumulation of thick, inspissated secretions in ducts throughout the body (eg, lungs, pancreas, gastrointestinal tract, vas deferens). In the pancreas, dehydrated, viscous secretions block the lumen of the pancreatic ducts, causing both exocrine (ie, malabsorption) and endocrine dysfunction. Endocrine dysfunction is due to pancreatic fibrosis and fat infiltration, which cause progressive encroachment, disruption, and destruction of pancreatic islet cells. This injury results in decreased insulin production and CF-related diabetes (CFRD). In the initial stages, glucose is typically normal when fasting (ie, able to produce some insulin) but elevated after a glycemic load, as seen in this patient. As the disease progresses, there is fasting hyperglycemia and increasing hemoglobin A1c levels. Because early diagnosis and treatment with insulin are associated with improved pulmonary status and overall survival, all CF patients should undergo regular screening with oral glucose tolerance tests. (Choice B) Decreased insulin production due to pancreatic islet cell autoantibodies describes the pathogenesis of type 1 diabetes mellitus. Islet cell destruction in CFRD is not an autoimmune process. (Choice C) Although glucagon increases in response to starvation, chronic malnutrition is likely to result in glucagon resistance. In addition, glucagon-producing alpha islet cells are damaged along with beta cells in patients with CF, resulting in decreased glucagon secretion. (Choices D and E) Stress-induced hyperglycemia and insulin resistance can occur in times of acutely increased metabolic demand (eg, trauma, burn, sepsis) due to the release of cortisol, epinephrine, and glucagon. Patients with late-stage CFRD may have a component of insulin resistance during times of acute stress and inflammation (eg, pulmonary exacerbation); however, this is not the primary mechanism of CFRD. Educational objective: Cystic fibrosis (CF) causes the accumulation of thick, viscous secretions in ducts throughout the body. CF-related diabetes occurs after the progressive destruction of pancreatic islet cells leads to decreased insulin production. __________ References: Cystic fibrosis related diabetes: pathophysiology, screening and diagnosis. (http://www.ncbi.nlm.nih.gov/pubmed/31679726)

A 20-Year-Old Woman with Cystic Fibrosis Comes to the Clinic