Exocrine pancreatic insufficiency (EPI) occurs when the pancreas does not make enough of the enzymes that the body uses to digest food. People with diabetes have an increased risk of developing EPI, but the condition is treatable.

EPI is a condition in which the pancreas fails to produce enough of the pancreatic enzymes necessary to digest food and absorb nutrients.

This can lead to deficiencies in important vitamins and minerals and uncomfortable gastrointestinal symptoms.

People with diabetes have a higher risk of EPI, and people with EPI may also have a higher risk of diabetes.

This article explains the prevalence, symptoms, and treatment of EPI, and its link with diabetes.

EPI is a condition in which the pancreas does not produce enough of the enzymes that the body needs to digest food. People may also refer to it as pancreatic exocrine insufficiency (PEI) or exocrine pancreatic dysfunction (EPD).

The body needs various digestive enzymes, including amylase, proteases, and lipase, to help digest carbohydrates, proteins, and fats.

If the pancreas does not produce enough of these enzymes, the body cannot break food down properly and absorb it into the body. This can cause:

  • fatty stool
  • diarrhea
  • abdominal pain
  • gas and bloating
  • unexplained weight loss
  • nutritional deficiencies

Chronic pancreatitis, or inflammation of the pancreas, is a leading cause of EPI.

Diabetes is a condition that involves high levels of blood glucose, or sugar. Glucose is the body’s main energy source, and it comes from the foods in the diet.

The pancreas makes a hormone called insulin that helps move glucose from the bloodstream into cells, where it provides energy.

In people with type 1 diabetes, the pancreas does not make insulin. In those with type 2 diabetes, the pancreas either does not make enough insulin or the body cannot use insulin properly.

If there is not enough insulin to move glucose into cells, glucose instead stays in the blood. Over time, too much glucose in the blood can lead to health problems, such as:

  • heart disease
  • kidney disease
  • nerve damage
  • eye and vision problems

More research is necessary to fully understand the connection between EPI and diabetes, but a 2020 article suggests the following factors may play a role:

  • Lack of trophic action of insulin: When insulin does not function properly, this can result in a smaller pancreas size.
  • Inflammation: Diabetes can increase inflammation in the pancreas, damaging pancreatic tissue.
  • Fibrosis: The article suggests that 59.4% of people with type 1 and type 2 diabetes may have scarring in the exocrine part of the pancreas.
  • Steatosis: Researchers associate diabetes with fat deposition in the pancreas. However, the role this plays in EPI remains unclear.

Pancreatitis seems to be a common link between diabetes and EPI. People with type 2 diabetes have an increased risk of pancreatitis, which can cause EPI. Damage to the pancreas from pancreatitis may also cause diabetes in people with EPI.

Research shows an overlap in dysfunction of both the endocrine and exocrine parts of the pancreas following pancreatitis.

Endocrine glands secrete substances directly into the blood, whereas exocrine glands have ducts that transport their secretions.

Can diabetes cause EPI?

The National Institute of Diabetes and Digestive and Kidney Diseases lists type 1 and 2 diabetes as a less common cause of EPI.

People with diabetes may have a significantly higher risk of EPI than people without diabetes. Factors that may contribute to this risk include:

  • reduced pancreas size
  • reduction of insulin production
  • inflammation

However, more research is necessary to fully understand the link between these two conditions.

A 2023 systematic review found the following prevalence rates of EPI in people with diabetes:

  • type 1 diabetes — 14–77.5%
  • type 2 diabetes — 16.8–49.2%
  • non-specified type — 5.4–77%

The review author highlights the fact that many people with diabetes may also have undiagnosed EPI.

Nearly every person living with pancreatogenic diabetes also has EPI. Pancreatogenic diabetes, also known as type 3c diabetes, occurs when the pancreas stops producing enough insulin due to conditions or factors affecting the exocrine pancreas. These include:

  • chronic pancreatitis
  • pancreatic cancer
  • surgery on the pancreas
  • removal of the pancreas

Treatment for EPI primarily involves lifestyle changes and pancreatic enzyme replacement therapies (PERT).

Pancreatic enzyme replacement therapy

PERT is the main treatment option for EPI. People with EPI take PERT medications orally with each meal and snack.

These supplements replace the enzymes that the body lacks. They help the body break down food and absorb the necessary nutrients.

Dosage varies among individuals and meals. A meal that is large or high in fat may require the affected person to take more enzyme supplements than a meal that is small or low in fat.

Dietary interventions

A 2020 study notes that there is currently no specific dietary recommendation based on interventional studies for those living with diabetes and EPI. However, doctors may advise against a diet that is very high in fiber.

Eating several smaller meals throughout the day rather than fewer big meals may make it easier for the body to absorb the necessary nutrients from food.

Foods that are too high in fat may make symptoms such as fatty stools worse, but people should not avoid fats entirely.

Sources of healthy fats include:

  • olives and olive oil
  • fatty fish
  • nuts
  • seeds

People with EPI, especially those who also have diabetes, should work with a doctor or dietitian to establish the best dietary approach to manage the condition.

Supplements

In people with EPI, the body does not always absorb the nutrients that it needs to function well. In some cases, a doctor may prescribe vitamins or mineral supplements.

These may include:

  • vitamin A
  • vitamin D
  • vitamin E
  • vitamin K

A doctor may also recommend avoiding or limiting alcohol and smoking.

The treatment options for diabetes depend on the type of diabetes.

Type 1 diabetes

People with type 1 diabetes need to take insulin to replace the insulin their pancreas does not make.

They may use a needle and syringe or an insulin pen to administer insulin. Some people may use an insulin pump, a wearable device that delivers insulin through a needle that sits under the skin.

There are several types of insulin that differ by how quickly they start to work and how long they last:

  • Rapid-acting insulin starts to work within 15 minutes and lasts 2–4 hours.
  • Short-acting insulin starts to work within 30 minutes and lasts 3–6 hours.
  • Intermediate-acting insulin starts to work within 2–4 hours and lasts 12–18 hours.
  • Long-acting insulin starts to work within several hours and lasts 24 hours or longer.

Type 2 diabetes

Some people with type 2 diabetes may be able to manage the condition with lifestyle changes, such as eating balanced meals and exercising regularly.

However, others may also need to take medications. There are different classes of type 2 diabetes medications, which work in different ways to lower blood sugar:

  • metformin (Glucophage) is a first-line medication for type 2 diabetes
  • sulfonylureas
  • alpha-glucosidase inhibitors
  • DPP-4 inhibitors
  • SGLT2 inhibitors

People may need to take a combination of medications. Some people with type 2 diabetes may also need to take insulin.

People living with diabetes have a higher risk of developing EPI. EPI prevalence may vary depending on the type of diabetes a person has, and some people with diabetes may have undiagnosed EPI.

EPI symptoms in people with diabetes are often mild to moderate. Currently, there is no specific dietary recommendation for those living with diabetes and EPI.

Treatment options for EPI include dietary interventions and PERT. Treatments for diabetes include lifestyle changes, medications, and insulin.