Complications and Comorbidities> Pulmonary>

DEFINITION

• Cystic fibrosis (CF): an autosomal recessive disease, diagnosed if : (1) clinical symptoms consistent with CF in at least one organ system AND (2) evidence of CF transmembrane conductance regulator (CFTR) dysfunction, which can include elevated sweat chloride >60 mmol/L on 2 occasions, presence of two disease-causing mutations in the CFTR (most common mutation is delta F508), or abnormal nasal potential difference.
• Manifestations: include respiratory tract disease, sinus disease, exocrine pancreatic insufficiency, meconium ileus and distal ileal obstruction, biliary disease, infertility, musculoskeletal disorders (reduced bone mineral content, hypertrophic osteoarthropathy), nephrolithiasis and nephrocalcinosis, and recurrent venous thrombosis.
• Cystic fibrosis-related diabetes (CFRD): distinct from types 1 or 2 diabetes, with evidence of beta cell dysfunction but conflicting results regarding insulin resistance. Because basal insulin secretion is retained, patients with CFRD are not ketosis prone.

EPIDEMIOLOGY

• CFRD present in 2% of children, 19% of adolescents, and 40-50% of adults with CF (Moran, 2009).
• Prevalence of CFRD rises steadily with age through 30-39 years and remains stable at 40-50% after age 40 (Moran, 2009).
• Incidence estimated at 2.7 cases per 100 patient-years (Moran, 2009).
• Estimated prevalence of impaired glucose tolerance (IGT) among all individuals with CF is 15-30% (Moran, 2009).
• Risk factors for CFRD: homozygosity for the delta F508 mutation, older age, female sex, pancreatic insufficiency, more severe pulmonary disease, greater number of pulmonary exacerbations, impaired nutritional status, use of oral/implanted contraceptives, presence of Pseudomonas aeruginosa or Bacteroides cepacia complex in the sputum, liver disease, and allergic bronchopulmonary aspergillosus (ABPA)(Marshall, 2005).

DIAGNOSIS

• Diagnostic criteria for CFRD are the same as those for diabetes.
• Type1 diabetes can occur independently of CF, and should be suspected in a child who presents with ketosis prior to the age of 10 years.

SIGNS AND SYMPTOMS

• Polyuria or polydipsia in person with CF
• Failure to gain or maintain weight despite appropriate nutritional intervention
• Poor growth velocity
• Delayed progression of puberty
• Unexplained chronic decline in pulmonary function

CLINICAL TREATMENT

• Nutritional insulin initiated for post-prandial hyperglycemia, which is seen most often in patients with CFRD. Dosed based on carbohydrate intake (e.g. 1 unit/10 grams carbohydrate). Administered as short-acting insulin (aspart or lispro). Goal is 2-hour post-prandial glucose <180 mg/dL. (See Bolus insulin) (Moran, 1999)
• If patient does not have fasting hyperglycemia, basal insulin is not necessary for initial therapy (Moran, 1999).
• Basal insulin initiated for patients with fasting hyperglycemia, providing 40-50% of patient's total daily insulin dose. Administered as once daily basal insulin analog (glargine or detemir) or NPH in the morning and at bedtime. Goal is a fasting glucose of 80-120 mg/dL.
• Oral agents are not effective in the management of CFRD.

• Due to increased metabolic demands of CF, total energy intake is 120-150% of recommended daily allowance to restore growth, achieve a weight 100% of that predicted based on height, and to achieve a body mass index of at least 21 kg/m2 (Moran, 1999)
• Forty percent of energy intake is from fat to compensate for malabsorption (Moran, 1999).
• Intake of complex carbohydrates is promoted and refined carbohydrates are allowed liberally (except sugary drinks between meals).
• Do not reduce protein even in setting of nephropathy. 
• Fiber intake is discouraged due to malabsorption and malnutrition.
• Salt intake is increased.

FOLLOW UP

• Hemoglobin A1c to monitor average glycemic control.
• Optimal care of CRFD requires a diabetes specialist, diabetes nurse educator, and/or nutritionist every 3 months.
• CRFD without fasting hyperglycemia: start medical nutrition therapy, exercise, and screening for complications; monitor closely to detect progression to fasting hyperglycemia; and monitor glucose levels more frequently during acute illness (Moran, 1999).
• Indications for insulin therapy: weight loss, poor growth, delayed puberty and unexplained deterioration of lung capacity (Moran, 1999).
• Nutritional insulin should be considered in patients with post-prandial hyperglycemia (2-hour glucose >180 mg/dL).

EXPERT COMMENTS

• Unlike patients with type 1 diabetes patients with CRFD have residual beta-cell function and often do not present with fasting hyperglycemia.
• Typically, post-prandial glucoses are elevated at diagnosis so the initial insulin therapy is most often nutritional insulin, not basal.
• Nutritional requirements for CF are greatly increased, so the medical nutrition therapy is different from that of most patients with diabetes.

Basis for Recommendations

• Brennan AL, Gyi KM, Wood DM, et al.; Relationship between glycosylated haemoglobin and mean plasma glucose concentration in cystic fibrosis.; J Cyst Fibros; 2006; Vol. 5; pp. 27-31;
  ISSN: 1569-1993;
  PUBMED: 16202666
  Rating: Basis for recommendation
  Comments:This study determined whether hemoglobin A1c was an accurate measure of glycemic control in patients with CFRD. The study showed that hemoglobin A1c correlated with mean plasma glucose in patients with CFRD just as it does in patients with type 1 diabetes.
  
  
• Moran A, Hardin D, Rodman D, et al.; Diagnosis, screening and management of cystic fibrosis related diabetes mellitus: a consensus conference report.; Diabetes Res Clin Pract; 1999; Vol. 45; pp. 61-73;
  ISSN: 0168-8227;
  PUBMED: 10499886
  Rating: Basis for recommendation
  Comments:This comprehensive consensus statement provides current guidelines regarding the diagnosis, screening, and treatment of CFRD.
  
  

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