Cause of Common Gastrointestinal Symptoms in Diabetes?

Miriam E. Tucker

August 11, 2023

Exocrine pancreatic insufficiency (EPI) may be more common in both type 1 and type 2 diabetes than is currently appreciated, a new literature review suggests.

The condition ― in which the pancreas fails to produce sufficient enzymes to fully digest food ― can cause gastrointestinal symptoms, including steatorrhea or other stool changes, bloating, and/or abdominal pain. The gold standard test for diagnosis is a 72-hour fecal fat quantification test, but fecal elastase-1 is a less invasive and reliable alternative; values of less than 200 Ig/g indicate EPI. Treatment is pancreatic enzyme replacement therapy (PERT), taken with every meal.

EPI occurs in up to 90% of people with cystic fibrosis and chronic pancreatitis and is commonly associated with acute pancreatitis, autoimmune pancreatitis, and pancreatic cancer. However, those conditions are relatively rare compared to diabetes, yet the EPI association with diabetes is less well-studied, Dana M. Lewis, BA, points out in her review article.

While the data vary across studies, owing to differences in inclusion and exclusion criteria, the overall median prevalence of EPI was 33% among patients with type 1 diabetes (range, 14% to 77.5%) and 29% among patients with type 2 diabetes (range, 16.8% to 49.2%), Lewis reports in the article, which was published recently in Diabetes Technology and Therapeutics.

"Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes who present with gastrointestinal symptoms ― such as steatorrhea or changes in stool, bloating, and/or abdominal pain ― should be screened for EPI. Diabetes specialists, gastroenterologists, and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms," Lewis writes.

Since the publication of her aricle, Lewis told Medscape, "I've gotten feedback from multiple diabetes and general providers that they will be changing their practice as a result of this paper, by screening people with diabetes who have GI symptoms for EPI, which is wonderful to hear."

In addition, she noted that since she began blogging about EPI and diabetes last year following her own delayed diagnosis, "I have had at least half a dozen people with diabetes tell me that they've since sought screening for EPI after years of GI symptoms and ended up being diagnosed with EPI as well."

Asked to comment, Romesh Khardori, MD, PhD, told Medscape Medical News, "it would be prudent to investigate EPI and treat it when confirmed. Consultation with a gastroenterologist colleague may be helpful. Treatment is quite rewarding."

Data Limitations; and Don't Forget Celiac Disease and Gastroparesis

However, as does Lewis, Khardori points to the limitations of the current literature.

"This review suffers from the lack of uniformity amongst the studies in terms of diagnosis and documentation of exocrine pancreatic insufficiency. Many studies lack a control group to draw any meaningful conclusions. Correlations with duration of diabetes, age of onset, symptoms and glycemic control were mostly lacking," says Khardori, now retired but formerly professor of medicine: endocrinology and metabolism at Eastern Virginia Medical School in Norfolk.

In general, the data suggest that PERT is safe and effective for people with diabetes and that it may reduce glycemic variability. However, "there are not many studies looking at glucose outcomes in detail, and only one study that has used CGM [continuous glucose monitoring] data, so this is a big area of need for future study," Lewis told Medscape.

Lewis also reviewed the literature on the prevalence of two other diabetes-related gastrointestinal conditions, celiac disease and gastroparesis, "because anecdotally, it seems as though diabetes care providers and people with diabetes are more aware of those as causes of GI symptoms."

In type 1 diabetes, the prevalence of both celiac disease and gastroparesis are reported at about 5%, in contrast to the 33% for EPI. Similarly, in type 2 diabetes, the reported prevalence of these two conditions are 1.3% and 1.6%, respectively, vs 29% for EPI.

"This suggests to me that there is likely disproportionate screening for things like celiac [disease] and gastroparesis in diabetes, and that screening for EPI when people with diabetes present with GI symptoms is warranted," Lewis said.

However, Khardori cautioned that those conditions may also be missed, noting, "Celiac disease often is undiagnosed and gastropathy or gastroparesis may be overlooked in a busy primary care clinic where most patients with diabetes mellitus get their care."

Lewis and Khardori have disclosed no relevant financial relationships.

Diabetes Technol Ther. Published online July 13, 2023. Abstract

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape. Other work of hers has appeared in the Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She can be found on Twitter @MiriamETucker.

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