Cystic Fibrosis-Related Diabetes - Cause, Symptoms, Pathophysiology, and Management

Introduction

There are different types of diabetes. Cystic fibrosis diabetes is one of the types of diabetes occurring among those affected with cystic fibrosis. Type 1 and type 2 diabetes may present among people with cystic fibrosis. Type 2 diabetes is caused by either insufficient insulin production by the pancreas, improper insulin utilization by the body, or both. This is not the same as Type 1 diabetes, which arises from a complete lack of insulin production due to an autoimmune attack on the pancreas. Cystic fibrosis diabetes is one of the most common types seen among people with cystic fibrosis.

What Is Cystic Fibrosis?

Cystic fibrosis is a genetic condition in which mucus builds up in organs like the lungs, pancreas, and others. It is caused by transferring a defective CFTR gene from both parents. Cystic fibrosis may be identified before the age of one.

What Is Cystic Fibrosis-Related Diabetes?

The thick and sticky mucus produced in the case of cystic fibrosis may cause inflammation and scarring of the pancreas. Due to this reason, there may be damage to the cells in the pancreas. When cells producing insulin get damaged, they cannot produce enough insulin, which causes high blood sugar levels in the blood. If this continues, it may keep increasing the sugar levels in the blood, resulting in cystic fibrosis diabetes.

Cystic fibrosis diabetes is also called cystic fibrosis-related diabetes (CFRD). In 2019, it was estimated that 20 percent of cystic fibrosis patients suffer from CFRD. CFRD shows characteristics of both type 1 and type 2 diabetes. People with CFRD might not respond to insulin the same way people with other types of diabetes, such as type 2, do. This is known as insulin resistance. Insulin resistance is widespread in those on certain medications or pregnant women.

What Is the Cause of Cystic Fibrosis-Related Diabetes?

CFRD is considered a multifactorial condition in which beta cell dysfunction exists in the pancreas and a decrease in the size and number of islet cells in the pancreas.

What Is the Pathophysiology of Cystic Fibrosis-Related Diabetes?

CFRD is caused by the transfer of a defective gene called CFTR. The CFTR gene is expressed in beta cells of the pancreas. Whenever there is a mutation in a gene, it causes dysfunction of beta cells. This causes decreased insulin secretion, causing increased blood glucose levels.

The CFTR mutation also causes damage to the structure of the islet cells of the pancreas. The CFTR protein is located in the ductal cells of the pancreas. When there is a mutation in this protein, it affects normal chloride channel function. Because of this, pancreatic secretion is affected. Pancreatic secretion becomes viscous and contains less water. This leads to the autodigestion of enzymes in the pancreas. This situation leads to cyst formation and slowly progresses to fibrosis of the pancreas. If there is a premature loss of the function of the exocrine gland, there may be an increased risk of getting CFRD.

What Are the Symptoms of Cystic Fibrosis-Related Diabetes?

Many cases of cystic fibrosis diabetes may be identified before the onset of symptoms. Screening for diabetes is very important.

Symptoms of cystic fibrosis diabetes include

• Occurrence of chest infections frequently.

• A loss of weight is observed.

• Experiencing thirst.

• Frequent urination.

• Getting tired easily.

In pediatric patients, growth and weight observation is to be done.

What Are the Complications of Cystic Fibrosis-Related Diabetes?

If not treated early, it may lead to complications like:

• Retinopathy (problems related to eyes).

• Neuropathy (damage to nerves).

• Damage to many organs like legs, feet, heart, etc.

How to Diagnose Cystic Fibrosis-Related Diabetes?

Diabetes symptoms may not always be present in people with CFDR. For this reason, people with cystic fibrosis must undergo routine screening for CFRD. The only approved screening test for cystic fibrosis is the 2-hour 75-gram oral glucose tolerance test (or 1.75 gm glucose/kg for those under 42 kg body weight), according to guidelines released by the American Diabetes Association and the Cystic Fibrosis Foundation. Any person with cystic fibrosis should start yearly screening for CFRD by the age of ten.

Due to its reduced sensitivity, additional screening techniques like monitoring hemoglobin A1c levels, fructosamine testing, random blood glucose tests, and urine glucose testing are not advised.

The standard American Diabetes Association criteria are employed to diagnose CFRD at baseline health. These criteria are as follows: HbA1c (glycated hemoglobin) greater than or equal to 6.5 percent, fasting blood sugar level higher than or equal to 126 mg/dL, two-hour plasma glucose level higher than or equal to 200 mg/dL on an oral glucose tolerance test, and random glucose higher than or comparable to 200 mg/dL with symptoms. Diagnostic criteria in an acute illness state include a two-hour postprandial blood sugar level of 200 mg/dL or a persistent 48-hour fasting plasma glucose level of 126 mg/dL. Studies are attempting to establish screening protocols using continuous glucose monitoring (CGM), which is becoming increasingly popular.

How to Treat Cystic Fibrosis-Related Diabetes?

There are different treatments available to treat CFRD.

Diet:

A dietician may help plan a diet that should include high-calorie, protein, and fat. The diet given to those with CFRD differs from those given to other types of diabetes. This may be due to the difficulty of maintaining weight in CFRD. This is because of the use of more energy in fighting infections and the functioning of the lungs. If CFTR modulators are given as a treatment, it may increase the weight. In such conditions, the diet should be modified.

Insulin:

Insulin therapy is the common treatment for CFRD. This treatment helps reduce glucose, improve weight gain, and improve the functioning of the lungs. Individuals with CFRD are advised to continue taking the same calories as before treatment with insulin. Treatment of CFRD without fasting hyperglycemia requires only rapid-acting insulin. The premeal dosage depends on the ratio of insulin to carbohydrates. Treatment of CFRD with fasting hyperglycemia requires long-acting basal insulin and rapid-acting insulin for meals.

Treatment of CFRD patients who receive overnight continuous gastrostomy tube feeding needs

intermediate-acting insulin and NPH (neutral protamine Hagedorn) insulin to handle the continuous carbohydrate load.

CFRD patients may need more insulin during acute illness as they develop insulin resistance. The requirement for insulin may come down after the acute illness resolves.

Based on current guidelines, the fasting glucose requirement is 70-130 mg/dL, and the 3-hour postprandial glucose requirement is below 180 mg/dL.

Physical Activity:

Physical activity provides many benefits, even in the case of CFRD. Regular exercise may benefit.

What Is the Differential Diagnosis of Cystic Fibrosis-Related Diabetes?

Some characteristics are similar to those of type 1 and type 2 diabetes. But these can be differentiated.

What Is the Prognosis of Cystic Fibrosis-Related Diabetes?

CFRD is considered a disease that will remain for life but can be treated with insulin therapy. Individuals with cystic fibrosis with CFRD have a higher risk of early death than those with only cystic fibrosis. Regular screening tests and early treatment of CFRD with insulin therapy may reduce the risk of death.

Conclusion

CFRD is a genetic disorder that causes mucus to accumulate in various organs, causing scarring of the pancreas. This leads to high blood sugar levels. Hence, it is important to know about cystic fibrosis, or CFRD, its cause, symptoms, complications, management, and prognosis. Knowing this helps an individual identify the disease and seek help from a healthcare provider early. Early diagnosis helps in getting effective treatment. This, in turn, helps achieve a good quality of life.