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Exocrine Pancreatic Insufficiency and Diabetes: What You Need to Know

Do you have diabetes mellitus? Exocrine pancreatic insufficiency is an important condition which also affects the pancreas and can have significant health impacts. You may be surprised that it affects up to 50% of people with diabetes. And EPI is a condition that could go unnoticed or misattributed without actively screening for it.

Exocrine Pancreatic Insufficiency: The Role of the Pancreas

The pancreas plays an crucial role in digestion and metabolism. It has two functions : the endocrine cells which produce insulin and glucagon to serve in metabolism of glucose; and exocrine cells which produce amylases, proteases, and lipases which help digest carbohydrates, protein, and fat, respectively.

A loss of pancreatic function after a destructive or inflammatory disease can affect digestion and lead to systemic issues. The most important driver of severity of presentation is the loss of pancreatic lipase production, an enzyme required in the digestion of fat. As a consequence, excess fat remains within the intestines, leading to bloating and fatty, malodorous stools.

exocrine pancreatic insufficiency can lead to abdominal pain, bloating, gas, and fatty stools.
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EPI in Diabetes mellitus

Diabetes is associated with a decline of insulin production in the endocrine portions of the pancreas. It occurs after autoimmune-mediated pancreatic islet-cell destruction (Type I), or the development of dysfunction likely brought about by dietary-related hyperglycemia and obesity (Type II).

EPI is common in people with diabetes, particularly after a long duration of disease (Capurso, 2019). As many as 50% of people with type 1 diabetes and 30% of those with type 2 diabetes have pancreatic exocrine insufficiency.

Some individuals with pancreatic injury from multiple causes may develop diabetes. For example, people with chronic pancreatitis after alcohol-associated pancreatitis. They are classified as having Type 3c diabetes, which comprises about 10% of the total population with diabetes (Hart, 2016).

At Risk Groups for EPI (Capurso, et al., 2019)

Cystic Fibrosis80-90%
Inflammatory Bowel DiseaseUC: 10%
Crohn’s: 4%
Type I Diabetes
Type II Diabetes
Tobacco 10-20%
Aging (usually >70yo)10-30%
Acute pancreatitis (dep. on severity)
Chronic pancreatitis

Consequences of EPI

When the body is unable to produce a sufficient amount of enzymes to aide in digestion, an individual may develop signs and symptoms of exocrine pancreatic insufficiency (EPI). These include fatty stools, flatulence, vitamin deficiencies, and weight loss (Dieguez-Castillo, 2020). In diabetes, the symptoms of abdominal discomfort, diarrhea, and gas could be misconstrued as side effects of metformin or GLP-1 agonists.

Excess fat in the stools prevents the absorption of certain fat-soluble vitamins, like vitamins A, D, E, and K. Consequences of EPI include osteoporosis, malnutrition, and muscle atrophy.

Signs of EPI

Abdominal Fullness and Cramps
Weight Loss
Greasy Stools (Steatorrhea)

Consequences of EPI

Fat Soluble Vitamin Deficiencies (A,D,E,K)
Weight Loss
Weakening of bone (Osteopenia and Osteoporosis)
Muscle weaking (Sarcopenia)

Diagnosis of Exocrine Pancreatic Insufficiency

Newer methods have simplified the diagnosis of exocrine pancreatic insufficiency. In a patient at risk or with fatty stools, a doctors would order a stool test on solid stool looking for fecal elastace (fecal elastace-1 test). Not only does this enzyme concentrate heavily in stool, but it is also a surrogate marker for other pancreatic enzymes, like lipase.

The diagnosis of EPI is made when levels fall lower than that expected (100 to 200 micrograms/gram is consistent with mild to moderate EPI; <100 micrograms/gram of stool is severe EPI). The test is highly sensitive (virtually 100%) for moderate or severe EPI (Domínguez-Muñoz, 1995).

Treatment of Exocrine Pancreatic Insufficiency

Since EPI is caused by the decreased production of enzymes, the treatment is adding pancreatic enzymes replacement therapy (PERT) to food. These enzymes take the place of the pancreas and aide in the digestion and absorption of fats. The dose needs to be titrated to effect and adjusted depending on whether a person is eating a meal or a snack. Acid blocking medications may be useful to increase the efficacy of the enzymes by changing the pH in the foregut (Struyvenberg, 2017).

In addition to PERT, dietary counseling includes instruction of a high-fiber, low-fat diet.


Consider discussing exocrine pancreatic insufficiency with your provider the next visit if you have had diabetes for a long duration. It is common in diabetes and may lead to health consequences such as malabsorption, weight loss, and vitamin deficiencies. The condition is fairly easy to diagnose with newer methods of fecal elastace, particularly if it is a moderate to severe deficiency. Replacement with pancreatic enzymes targeted to the clinical remission of symptoms can improve a patient’s quality of life.

woman standing on sunflower field
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Capurso G, Traini M, et al. Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. Clin Exp Gastroenterol. 2019; 12: 129-139.

Dieguez-Castillo C, et. al. State of the Art in Exocrine Pancreatic Insufficiency. Medicine (Kaunas). 2020; 56(10): 523. doi: 10.3390/medicina56100523.

Domínguez-Muñoz JE, Hieronymus C, Sauerbruch T, Malfertheiner P. Fecal elastase test: evaluation of a new noninvasive pancreatic function test. Am J Gastroenterol. 1995;90(10):1834–1837. 

Hart P, et. al. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. Lancet Gastroenterol Hepatol. 2016. 1(3): 226-237. doi: 10.1016/S2468-1253(16)30106-6.

Radlinger B, Ramoser G, Kaser S. Exocrine Pancreatic Insufficiency in Type 1 and Type 2 Diabetes. Curr Diab Rep. 2020; 20(6): 18.

Struyvenberg M, et al. Practical guide to exocrine pancreatic insufficiency – Breaking the myths. BMC Medicine. 2017; 15(29).

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