Credits

• Section Writer: Dr. Om J Lakhani
• Section Editor: Dr. Om J Lakhani

Important points:

• The diabetes in Cystic fibrosis is unique, having features of both type 1 and type 2 diabetes.
• However, patients with CF usually don't develop complete insulinopenia, making ketosis rare.
• Impaired glucose tolerance often develops first without accompanying fasting hyperglycemia. This progresses to impaired glucose tolerance with elevated fasting glucose levels, eventually leading to frank diabetes.
• The preferred screening method for patients with CF is the 2-hour 75-g oral glucose tolerance test.
• Hemoglobin A1c testing isn't sensitive and shouldn't be used for screening or diagnosing CFRD. #ClinicalPearl
• Consensus guidelines recommend screening for CFRD starting at age 10, though some CF centers begin screening at a younger age.

Q. What is the etiology of Cystic fibrosis?

• It results from a deficiency of the CFTR protein.
• This causes defective chloride transport.
• This defect makes secretions from various body organs thick and viscous.
• 

Q. How is the diagnosis of Cystic fibrosis established?

Q. List the systems involved in Cystic fibrosis.

• Pulmonary: bronchiectasis, sinusitis, recurrent pulmonary infections.
• GIT: recurrent pancreatitis, malabsorption.
• Endocrine: diabetes, osteoporosis.
• Genitourinary: absent vas deferens, infertility in both males and females.

Q. What is the mode of inheritance?

• Autosomal recessive.
• Multiple genes can lead to the clinical picture, resulting in variable clinical symptoms.

Q. Which is the primary investigation to diagnose cystic fibrosis?

• Elevated sweat chloride > 60 mmol/l confirms Cystic fibrosis.

Q. At what age does diabetes typically occur in cystic fibrosis?

• Middle school age and older.

Q. What is the etiology of diabetes in cystic fibrosis?

• Progressive destruction and fibrosis of the pancreas.

Q. Which clinical points are potentially related to Diabetes in cystic fibrosis?

• Presence of respiratory disease.
• Presence of pancreatic insufficiency.

Q. What are the consequences of diabetes on other manifestations of cystic fibrosis?

• Increased pulmonary infections and insufficiency.
• Increased mortality.
• Worsened nutritional status.

Q. How is screening for diabetes in cystic fibrosis conducted?

1. Annually using OGTT starting at 10 years of age.
   • HbA1c isn't used due to its low sensitivity in cystic fibrosis.
2. During pregnancy.
3. During pulmonary exacerbations.

Q. What is the clinical definition of diabetes in cystic fibrosis?

• Fasting >125 mg/dl – OGTT isn't needed.
• 2hr PG2BS in OGTT >200 mg/dl – confirms diabetes with or without fasting hyperglycemia.

Q. What is indeterminate hyperglycemia in cystic fibrosis?

• 1 hr OGTT >200.
• 2 hr <140.

Q. What is the management of choice for patients with CFRD?

• Insulin is the preferred treatment.

Q. Should insulin be used in patients with indeterminate hyperglycemia or IGT?

• In selected cases, insulin is initiated.
• Especially in those experiencing pulmonary exacerbations.
• It enhances nutritional status.

Q. Why are CFRD patients at a higher risk of hypoglycemia?

• Poor nutritional intake and glycogen stores lead to fasting hypoglycemia.
• Disordered insulin release results in reactive hypoglycemia post meals.
• Reduced glucagon response (though catecholamine response remains normal).

Q. What is the primary goal of therapy in CFRD with insulin?

1. The main objective is to maintain nutritional status (avoiding excessive catabolism).
2. To prevent pulmonary exacerbations.

• This contrasts with type 1 diabetes, where the primary therapy goal is preventing microvascular complications.

Q. What is the therapy goal?

• Keep HBA1c as low as possible (it's not used for diagnosis but for monitoring) – ideally below 5.5% if achievable without hypoglycemia.
• Reduce postprandial BG – ideally measured 1 hr post meal, aiming for <140 mg/dl.
• Maintain fasting levels between 70-90 mg/dl.

Q. How and when is screening for microvascular disease conducted?

• 5 years after diagnosing CFRD.

Q. True or false, does insulin treatment in CFRD improve the overall outcome and lung functions?

• True.