Diabetes, unfortunately, goes hand in hand with stomach problems, for many different reasons. Type 1 diabetes has a well-known connection to celiac disease, and both types increase the incidence of thyroid conditions that can cause digestive problems. Gastroparesis, a type of very uncomfortable partial stomach paralysis, is a frequent complication of long-term diabetes. Some of the best type 2 diabetes medications, including metformin and semaglutide (Ozempic), are widely known for their unpleasant gastrointestinal effects.

If you’ve been struggling with belly issues, and none of those conditions above seem to fit, here’s another condition to consider: exocrine pancreatic insufficiency (EPI). Though EPI is not commonly associated with diabetes, a new study suggests that it is far more prevalent in people with diabetes than most endocrinologists and doctors realize.

What is Exocrine Pancreatic Insufficiency (EPI)?

According to Everyday Health, EPI is a condition in which the pancreas does not secrete enough digestive enzymes, which causes food to pass through your system without being fully digested. This results in uncomfortable symptoms like diarrhea, oily stools, and loss of appetite. EPI can cause malnutrition and is very bad for your health.

EPI is notoriously difficult to identify, leading frequently to “misdiagnosis and suboptimal treatment,” according to a 2019 review. The problem is that its symptoms overlap with those of many other common conditions, and the tests available for EPI are “generally difficult to perform, inaccurate, or non-specific.” It can take patients years to properly identify the cause of their troubles. A machine learning model has estimated that only one in twelve people with EPI has actually been diagnosed with the condition.

EPI is most strongly associated with conditions that are known to damage the pancreas, such as cystic fibrosis and chronic pancreatitis. Yet even in patients with these conditions and the signature symptoms of EPI, “diagnostic testing is rarely performed.”

How Often Do People with Diabetes Develop EPI?

Diabetes, of course, is also a disease of the pancreas. In type 1 diabetes, the body launches an auto-immune attack on the pancreatic Beta cells, which can completely eliminate the ability to secrete the vital hormone insulin. In type 2 diabetes, insulin resistance causes the same pancreatic cells to overwork and eventually fail. It is unknown exactly how diabetes might cause exocrine pancreatic insufficiency, or vice versa, but both are possible.

A new study argues that these mysteriously related two conditions coexist more often than almost anyone realizes. The paper is the work of a patient advocate with type 1 diabetes named Dana Lewis. Lewis is well known within the small but highly influential community of “loopers” — she led the development of the world’s first open-source do-it-yourself artificial pancreas. In 2021, Lewis learned that she also had EPI.

After diving into the medical literature to learn more about her condition, Lewis says that she “was a little dismayed that it was so clearly prevalent in diabetes, yet I had never ever heard of it. How can there be such a disconnect? Is there anything I can do about it?”

Published in Diabetes Technology & Therapeutics, Lewis’ study is a systematic review of the existing literature covering the connections between diabetes and EPI. (Though the paper is behind a paywall, Lewis shared an earlier draft on her blog.)

There have been many studies to examine pancreatic enzyme function in people with type 1 and type 2 diabetes, starting as early as the 1960s. Most studies employed the fecal elastase-1 (FE-1) test, which measures stool for a particular digestive enzyme that survives the passage through the gut, according to Mayo Clinic Laboratories. People with EPI have secrete less FE-1 when they eat, and have less FE-1 in their feces.

When Lewis tallied up all the data, she found that about 33 percent of people with type 1 diabetes and 29 percent of people with type 2 diabetes have lowered levels of FE-1, indicating some level of enzyme secretion abnormality. These results don’t necessarily mean that some 30 percent of people with diabetes have full-blown EPI — that would mean a hundred million new patients overnight. There is some evidence that diabetes leads to deceptively low FE-1 results, and many of the patients studied reported that they had no gastrointestinal symptoms. But Lewis’ paper is not the only recent work to argue that there’s an underdiscussed connection between the two conditions:

A 2020 review called EPI “highly prevalent in type 1 diabetes and common in type 2 diabetes,” although it is often symptomatic.
A 2021 analysis concluded that EPI is, in fact, more common in type 1 diabetes, but that EPI testing and therapy need to be limited to patients with overt symptoms.

Advocating for Yourself

Lewis explained that when she took the FE-1 test, her results were in an indeterminate “mild-to-moderate” range — below the regular healthy level, but above the “severe range” that automatically indicates a need for enzyme therapy. The standard test is less accurate in this gray area, and the severity of a patient’s symptoms may not match the tested enzyme deficiency.

This uncertain test, Lewis explains, “has been considered to be indicative of how severe the symptoms are, when in reality, somebody like me can be on the upper end of that test and have severe symptoms. There’s no standardized measure of symptom severity, there’s just this test and this loose categorization.”

After two years of searching for answers to her symptoms, Lewis wasn’t about to give up. She convinced her cautious doctor to prescribe medicine for EPI; when the medicine made “a remarkable difference,” it confirmed her diagnosis.

“But without my personal advocacy, I wouldn’t have necessarily gotten the treatment.”

Living with Diabetes and EPI

Readers that already manage diabetes are in a good position to understand the immense struggle of living with EPI. Exocrine pancreatic insufficiency is primarily treated with Pancreatic Enzyme Replacement Therapy (PERT), which delivers enzymes straight to the digestive system in the form of a pill. Patients swallow pills, sometimes a very large number of them, directly with the food that they eat.

It’s not easy to dial PERT therapy in. Patients need different amounts of enzymes depending on what they’re eating; taking too little is ineffective, and taking too much is wasteful. Just like insulin therapy, it takes a lot of practice to get management right. And just like insulin therapy, PERT can be extremely expensive.

Lewis believes that PERT is even more challenging to dose properly than insulin, and has gone so far as to design an iPhone app to help optimize dosing.

Takeaways:

Exocrine pancreatic insufficiency (EPI) is a condition in which the pancreas doesn’t make enough digestive enzymes, leading to gastrointestinal distress and even malnutrition. Though EPI is believed to be rare, it could be far more prevalent than most clinicians realize, especially in people with type 1 and type 2 diabetes. If you’ve had digestive issues that seem unrelated to common diabetes issues such as celiac disease or gastroparesis, it may be worth asking your doctor or endocrinologist about taking a diagnostic test for EPI.

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