Type 3c Diabetes (Pancreatogenic Diabetes)

Type 3c diabetes is a type of diabetes associated with exocrine diseases of the pancreas like chronic pancreatitis, cystic fibrosis, and other conditions. There is not a uniform terminology for “type 3c” diabetes.  This may also be called pancreatogenic diabetes, pancreatic diabetes, and post-pancreatitis diabetes. The exact number of people with type 3c diabetes is unknown; however, a 2008 study of 1,922 patients with diabetes at a specialty center found that 8% had type 3c diabetes. Because type 2 diabetes is the most common form of diabetes in adults, and type 3c diabetes may present like type 2 diabetes, type 3c diabetes is often misdiagnosed or mislabeled as type 2. Unlike type 2 diabetes, type 3c diabetes is caused by damage to the exocrine pancreas, which then also injures the islets. As a result, type 2 diabetes and type 3c diabetes can have different treatment needs.

What Is Type 3c Diabetes?

Type 3c diabetes is a type of diabetes caused by damage to the pancreasWhen the exocrine pancreas is inflamed or scarred by conditions like pancreatitis, that, in turn, can also harm the islet cells. This is different from other diabetes, like type 1 or type 2 diabetes, where the main problem is in the islet cells, either because the islets are destroyed (type 1) or don’t work as well as they need to in order to meet the body’s high insulin needs (type 2). 

In type 3c diabetes, the damaged pancreas causes dysfunction or destruction of the insulin-producing islets, so the pancreas can’t make enough insulin anymore, which makes it hard for your body to regulate blood sugar levels. This damage can also affect other hormones made by the pancreas that help regulate blood sugar. As a result, people with type 3c diabetes can experience both high blood sugar levels (hyperglycemia) and low blood sugar levels (hypoglycemia). Some patients also have maldigestion or malnutrition because of the injury to the digestive pancreas, and this can make blood glucose more unpredictable and challenging to manage.

The pancreas’s ability to produce insulin is referred to as its endocrine function. The other function of the pancreas is called the exocrine function. In the exocrine function, your pancreas creates and releases digestive enzymes that break down nutrients from the foods you eat. In addition to having trouble making insulin (endocrine function), people with type 3c diabetes also have issues with their exocrine function.

Learn more about the pancreas.

How Does Type 3c Diabetes Differ From Type 1 Diabetes and Type 2 Diabetes?

Type 3c diabetes is caused by damage to the exocrine pancreas, and that injury to the exocrine pancreas also damages the islets. In type 1 diabetes, the immune system destroys the islets, and the exocrine pancreas is either uninvolved or less involved. In type 2 diabetes, the islets don’t work well enough to make as much insulin as an individual needs to control blood sugars. Often, in type 2 diabetes, individuals are also ‘insulin resistant’ meaning that their body needs a lot of insulin to regulate blood sugars, and the islets just can’t keep up.

In type 1 and type 2 diabetes, the exocrine pancreas may have some damage, but it is not the primary cause of the diabetes.

Type 1 diabetes is an autoimmune condition that occurs when the pancreas isn’t able to secrete enough insulin to regulate blood sugar levels, along with other hormones in the islets that are present but may not be regulated normally. In comparison, type 3c diabetes reduces the body’s ability to make and secrete all hormones in the pancreas, including glucagon, gastrin, and amylin. Additionally, people with type 3c diabetes may have issues producing digestive enzymes (exocrine pancreatic insufficiency).

Type 2 diabetes occurs when the pancreas can produce insulin–in some cases, a little insulin and, in some cases, a lot of insulin–but the body cannot use it well enough. However, in type 3c diabetes, the body can use insulin to maintain stable blood sugar levels, but the damaged pancreas cannot produce enough insulin to do so.

What Causes Type 3c Diabetes?

Type 3c diabetes develops, in most cases, when the pancreas, which contains cells that make insulin and hormones to control blood sugar levels, becomes significantly damaged. This damage affects how well these cells (called islets) can work correctly. However, the term “type 3c” includes a wide range of diagnoses, and there may be other contributing factors. For example, in diabetes related to pancreatic cancer, often the region of the pancreas involved is small, and it is thought that neoplastic factors (signals from the tumor that circulates in the bloodstream) actually cause the diabetes rather than direct damage or loss of the islets. In some people with pancreatitis, insulin resistance (in addition to islet damage) may cause diabetes. 

 

There are several potential causes of damage to the pancreas, which may result in type 3c diabetes. These include:

  • Chronic pancreatitis
  • Recurrent acute pancreatitis (RAP)
  • Pancreatic ductal adenocarcinoma (pancreatic cancer)
  • Hemochromatosis (too much iron in the body)
  • Cystic fibrosis
  • Pancreatic surgery

Who’s at Risk of Type 3c Diabetes?

Chronic pancreatitis is a leading risk factor for type 3c diabetes. A review of 1,868 people with type 3c diabetes showed the following underlying causes:

  • Chronic pancreatitis (and RAP): 79%
  • Pancreatic ductal adenocarcinoma (pancreatic exocrine cancer): 8%
  • Haemochromatosis: 7%
  • Cystic fibrosis: 4%
  • Previous pancreatic surgery: 2%

Chronic Pancreatitis

Chronic pancreatitis is a progressive disease in which the pancreas is persistently inflamed, leading to permanent damage and scarring. This damage can affect the pancreas’s ability to produce insulin, leading to type 3c diabetes. While people with chronic pancreatitis do not always develop type 3c diabetes, there is an increased risk of diabetes in CP patients. As a result, chronic pancreatitis patients should be monitored for type 3c diabetes.

Learn more about chronic pancreatitis.

Pancreatic Ductal Adenocarcinoma (Pancreatic Cancer) and Diabetes

Pancreatic ductal adenocarcinoma (PDAC) is a cancerous tumor that originates in the part of the pancreas that produces enzymes, the exocrine pancreas. These tumors develop in the pancreatic duct. The causes of diabetes in PDAC are not clear. Some cases may be due to loss of pancreas tissue from tumor destruction or surgery, but it is also thought that the cancer itself may produce a chemical that causes islet dysfunction. As a result, patients with PDAC may develop type 3c diabetes.

Hemochromatosis and Diabetes

Hemochromatosis occurs when an excess amount of iron accumulates in the body. These iron deposits accumulate in the liver and pancreas and can cause damage to islet cells, which may result in type 3c diabetes.

Cystic Fibrosis and Diabetes

Cystic fibrosis (CF) is a genetic disease that leads to dysfunction in various organs due to the buildup of thick, sticky mucus. In the pancreas, the buildup of mucus can cause damage to the pancreas, including the pancreatic islet cells, resulting in type 3c diabetes.  Most people with cystic fibrosis related diabetes (CFRD) also have pancreas exocrine insufficiency. Illness and corticosteroids (used for lung disease) can also contribute to high blood sugars. Some of the new medications used to treat CF might reduce the risk of type 3c diabetes (also referred to as CFRD in the CF patient population).

Pancreatic Surgery and Diabetes

Those who have pancreatic surgery may be at risk for developing type 3c diabetes. Surgeries that remove large amounts of pancreatic tissue, such as the Whipple procedure and the Frey procedure, may also remove large amounts of islet cells. This may cause less insulin secretion and increase the risk of developing type 3c diabetes.

Surgeries that may cause type 3c diabetes include:

  • Whipple procedure (Pancreaticoduodenectomy).The Whipple procedure is a surgery that removes inflammation and masses located on the head of the pancreas. It is most commonly used to treat pancreatic cancer but is also used to remove cysts in the bile duct and scarring in the pancreas. During this procedure, the surrounding tissue may be removed, increasing the risk of type 3c diabetes.
  • Frey Procedure. The Frey procedure is a surgery that involves a combination of draining the pancreatic duct along with the removal of pancreatic tissue. It is recommended for patients who have pancreatitis caused by blockage in the head of the pancreas. During this procedure, the surrounding tissue may be removed, increasing the risk of type 3c diabetes.
  • Total Pancreatectomy with Islet Auto Transplantation (TPIAT). The TPIAT is a surgery that involves the full removal of the pancreas and transplanting the patient’s pancreatic islet cells into the liver. It is primarily for people with debilitating recurrent acute and chronic pancreatitis. By transplanting the islet cells, the surgery hopes to reduce the risk of diabetes; however, it is not always successful, increasing the risk of type 3c diabetes.

Symptoms of Type 3c Diabetes

Regulating blood sugar levels is a key function of the pancreas. Type 3c diabetes hinders the secretion of insulin. Without insulin, the body’s blood sugar levels can become too high (hyperglycemia). This can cause both short and long-term symptoms of type 3c diabetes.

Symptoms of type 3c diabetes include:

  • Being very thirsty
  • Tiredness and fatigue
  • Confusion
  • Frequently passing urine
  • Blurred vision
  • Headaches
  • Irritability
  • Unintentional weight loss
  • Slow wound healing
  • Frequent infections
  • Weakened immune system
  • Organ damage

People with type 3c diabetes can also have low blood sugar levels (hypoglycemia). This may be due to missing a meal, injecting too much insulin, or not taking enough pancreatic enzymes (see below) to properly digest food.

Symptoms of low blood sugar include:

  • Hunger
  • Trembling
  • Headache or becoming light-headed
  • Blurred vision
  • Paleness
  • Sweating, cold sweats
  • Mood changes, anxiety, aggression
  • Palpitations (racing, pounding heart)
  • Tingling lips
  • Feeling sick
  • Digestive problems (vomiting, diarrhea)
  • Difficulty concentrating

If your blood sugar is too low (below 70 mg/dL), it’s important to treat it right away. Experts suggest immediately taking 15-20 grams of quick-acting carbohydrate (glucose), with the guidance of your doctor.

How Is Type 3c Diabetes Diagnosed?

Type 3c diabetes is diagnosed using the same criteria as other forms of diabetes: A fasting blood sugar >/= 126 mg/dL, a hemoglobin A1c (average blood glucose level) of 6.5% or higher, or other standard tests will diagnose diabetes. Sometimes it is harder, though, for doctors to figure out that the type of diabetes is type 3c. Currently, there are no diagnostic criteria for type 3c diabetes that all doctors agree on. As a result, it can be hard for healthcare providers to recognize type 3c diabetes and tell the difference from type 2 diabetes. 

To diagnose type 3c diabetes physicians must confirm that the function of the exocrine pancreas (which produces insulin) has been damaged, that the patient has diabetes, and that the diabetes is a result of pancreatic damage. If you have been diagnosed with a risk factor like chronic pancreatitis or pancreatic cancer, or if your pancreas has been damaged and you are experiencing symptoms of diabetes, your doctor should check for type 3c diabetes.

Tests used to diagnose type 3c diabetes include:

  • Blood Glucose Tests. If you have symptoms of diabetes, your doctor may order a blood test, which can determine if your blood glucose levels are within normal range. Your doctor may also recommend an HbA1c test, which is a blood test that can determine your average blood glucose levels from the past two to three months. 
  • Pancreatic Imaging Tests. If you have not been diagnosed with a risk factor for type 3c diabetes, your physician may order a pancreatic imaging test. This can confirm if your exocrine pancreas has been damaged. There are several different pancreatic imaging tests, including an endoscopic ultrasound, a magnetic resonance imaging (MRI) scan, and a computed tomography (CT) scan. Ask your doctor if these would be right for you.

Treatments for Type 3c Diabetes

There are currently no generally accepted guidelines for treating type 3c diabetes. Treatment for type 3c diabetes is similar to type 2 diabetes treatment. It may include oral medication, synthetic insulin, and diet and exercise. However, type 3c diabetes patients may also have exocrine pancreatic insufficiency (EPI). If this is the case, they may need pancreatic enzyme supplementation (PERT) to improve digestion and help avoid malnutrition.

Oral Medication

Many people with type 3c diabetes take oral tablets to control their blood sugar. These pills work in different ways. Some pills work to make your body more sensitive to insulin secretion, while others help the pancreas secrete more insulin. These medications may also have side effects. Always talk with your doctor about which oral medication may be right for you.

Metformin

The first choice medication for type 3c diabetes is often metformin, which is recommended by the American Diabetes Association (ADA) to treat type 2 diabetes. Metformin works to reduce blood sugar levels by reducing the production of glucose in the liver and by increasing the body’s sensitivity to insulin.  Metformin might not be the right choice for people who have severe insulin deficiency, however, as it does not replace the function of the islets, only helps the body respond better to insulin. 

Pancreatic Enzyme Replacement Therapy

Pancreatic Enzyme Replacement Therapy (PERT) are pills that can improve the body’s ability to absorb fats and proteins. Patients with type 3c diabetes may also have issues producing digestive enzymes (exocrine pancreatic insufficiency) in addition to insulin. PERT replaces these enzymes and helps the body properly digest food.

Insulin

It is possible to inject synthetic insulin to treat high blood sugar. The pancreas secretes insulin constantly to regulate blood sugar levels. When the pancreas is damaged and cannot secrete insulin, it may be necessary to inject insulin into the bloodstream. 

Types of synthetic insulin used to treat type 3c diabetes include:

  • Long-Acting Insulin. Long-acting insulin works to reduce blood sugar levels for up to 24 hours. It is injected once or twice per day. It takes about two to three hours to function and may not be suitable for treating a blood sugar spike. 
  • Quick-Acting Insulin. Quick-acting insulin works to lower blood sugar spikes that may happen after eating a meal. It should be taken at mealtime, and the dose should be adjusted depending on the meal. 

Injecting too much insulin can result in hypoglycemia, which occurs when the body’s blood sugar levels drop dangerously low. Talk to your doctor about correctly dosing synthetic insulin. 

Other Medications

There are other newer medications that are widely used in type 2 diabetes, including GLP1 analogs (Ozempic, Victoza), DPP-4 inhibitors (Januvia, Onglyza), and SGLT2 inhibitors (Invokana, Farxiga). The use of these in type 3c diabetes is not clear. GLP-1 analogs and DPP-4 inhibitors might increase the risk for pancreatitis, so they are not recommended for recurrent acute or chronic pancreatitis. If someone is very insulin deficient, SGLT2 inhibitors might increase the risk of a condition called diabetic ketoacidosis. Other older diabetes drugs include TZDs (Actos), which has not been studied yet for this form of diabetes. 

Lifestyle Changes

Lifestyle changes have also been shown to improve symptoms of type 3c diabetes. Consider some of the following practices:

  • Monitor Blood Sugar. Regularly monitoring your blood sugar may help decrease diabetes symptoms. This can be done using an over-the-counter blood glucose monitor, which takes a small blood sample from your finger. Depending on the monitor’s reading, you may need to alter your blood sugar levels by taking medication for diabetes, synthetic insulin, or consuming foods that are high or low in sugar. 
  • Adjust Diet. Type 3c diabetes can make it difficult to ensure your body is getting all the nutrients it needs. In general, it is recommended to eat a diet that includes protein, fruits, and vegetables and is low in sugar and fat. Avoid eating large portions and, instead, space your meals throughout the day. This can help prevent spikes in blood sugar levels. 
  • Physical Exercise. Physical exercise has been shown to improve overall physical and mental health and can include various activities such as jogging, stretching, swimming, yoga, and dancing. Additionally, guidelines for treating type 3c diabetes recommend about 150 minutes of moderate exercise per week.  If you are on insulin, you may need to work with your doctor to adjust your doses or set up a snack plan to prevent low blood sugar around exercise. 

Remember to always consult your doctor before making any changes to your lifestyle. 

Frequently Asked Questions

Type 3c diabetes can be dangerous if it is not properly managed. If type 3c diabetes is left untreated or blood sugar levels are regularly too high for a long time, permanent damage can occur to your organs, including nerve cells, blood vessels, kidneys, and eyes. 

Ask your doctor about which treatment options may be right for you. 

Because there is not enough research on type 3c diabetes, the life expectancy for those with type 3c diabetes is unknown. However, since type 3c diabetes occurs due to a pancreatic condition, life expectancy may be dependent on the specific pancreatic condition causing type 3c diabetes.

Currently, type 3c diabetes is not reversible. Since type 3c diabetes is caused by pancreatic conditions such as chronic pancreatitis and cystic fibrosis, there has been significant damage to pancreatic tissue and islet cells, which are necessary for the body to produce insulin. Mission: Cure is working with partners to find a therapy to regenerate pancreatic tissue. Stay tuned! However, type 3c diabetes can be managed through treatments such as oral medications and synthetic insulin.

Key Takeaways

  • Type 3c diabetes is a type of diabetes that occurs when the endocrine pancreas is damaged and cannot secrete insulin. Symptoms of type 3c diabetes can include thirst, headaches, and a weakened immune system.
  • Pancreatic islet cells are groups of endocrine cells located in the pancreas. Islet cells produce important hormones such as glucagon and insulin, which work to regulate blood sugar levels.
  • Type 3c diabetes can be caused by conditions that damage the pancreas, such as chronic pancreatitis, pancreatic cancer, hemochromatosis, cystic fibrosis, and pancreatic surgery.
  • Chronic pancreatitis is strongly associated with type 3c diabetes; 79% of those with type 3c diabetes also have chronic pancreatitis.
  • Type 3c diabetes can be diagnosed through blood tests that measure the body’s glucose levels and imaging tests that can determine if the pancreas has been damaged.
  • Treatments for type 3c diabetes include oral medications, synthetic insulin, and PERT. 
  • Lifestyle changes, such as monitoring blood sugar levels, exercising regularly, and eating a balanced diet, can help reduce the severity of type 3c diabetes symptoms.

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