Research

The prompt matters when using Large Language Models (LLMs) and AI in healthcare

by Dana Lewis

I see more and more research papers coming out these days about different uses of large language models (LLMs, a type of AI) in healthcare. There are papers evaluating it for supporting clinicians in decision-making, aiding in note-taking and improving clinical documentation, and enhancing patient education. But I see a wide-sweeping trend in the titles and conclusions of these papers, exacerbated by media headlines, making sweeping claims about the performance of one model versus another. I challenge everyone to pause and consider a critical fact that is less obvious: the prompt matters just as much as the model.

As an example of this, I will link to a recent pre-print of a research article I worked on with Liz Salmi (pre-print here).

Liz nerd-sniped me about an idea of a study to have a patient and a neuro-oncologist evaluate LLM responses related to patient-generated queries about a chart note (or visit note or open note or clinical note, however you want to call it). I say nerd-sniped because I got very interested in designing the methods of the study, including making sure we used the APIs to model these ‘chat’ sessions so that the prompts were not influenced by custom instructions, ‘memory’ features within the account or chat sessions, etc. I also wanted to test something I’ve observed anecdotally from personal LLM use across other topics, which is that with 2024-era models the prompt matters a lot for what type of output you get. So that’s the study we designed, and wrote with Jennifer Clarke, Zhiyong Dong, Rudy Fischmann, Emily McIntosh, Chethan Sarabu, and Catherine (Cait) DesRoches, and I encourage you to check out the pre-print and enjoy the methods section, which is critical for understanding the point I’m trying to make here. 

In this study, the data showed that when LLM outputs were evaluated for a healthcare task, the results varied significantly depending not just on the model but also on how the task was presented (the prompt). Specifically, persona-based prompts—designed to reflect the perspectives of different end users like clinicians and patients—yielded better results, as independently graded by both an oncologist and a patient.

The Myth of the “Best Model for the Job”

Many research papers conclude with simplified takeaways: Model A is better than Model B for healthcare tasks. While performance benchmarking is important, this approach often oversimplifies reality. Healthcare tasks are rarely monolithic. There’s a difference between summarizing patient education materials, drafting clinical notes, or assisting with complex differential diagnosis tasks.

But even within a single task, the way you frame the prompt makes a profound difference.

Consider these three prompts for the same task:

  • “Explain the treatment options for early-stage breast cancer.”
  • “You’re an oncologist. Explain the treatment options for early-stage breast cancer.”
  • “You’re an oncologist. Explain the treatment options for early-stage breast cancer as you would to a newly diagnosed patient with no medical background.”

The second and third prompt likely result in a more accessible and tailored response. If a study only tests general prompts (e.g. prompt one), it may fail to capture how much more effective an LLM can be with task-specific guidance.

Why Prompting Matters in Healthcare Tasks

Prompting shapes how the model interprets the task and generates its output. Here’s why it matters:

  • Precision and Clarity: A vague prompt may yield vague results. A precise prompt clarifies the goal and the speaker (e.g. in prompt 2), and also often the audience (e.g. in prompt 3).
  • Task Alignment: Complex medical topics often require different approaches depending on the user—whether it’s a clinician, a patient, or a researcher.
  • Bias and Quality Control: Poorly constructed prompts can inadvertently introduce biases

Selecting a Model for a Task? Test Multiple Prompts

When evaluating LLMs for healthcare tasks—or applying insights from a research paper—consider these principles:

  1. Prompt Variation Matters: If an LLM fails on a task, it may not be the model’s fault. Try adjusting your prompts before concluding the model is ineffective, and avoid broad sweeping claims about a field or topic that aren’t supported by the test you are running.
  2. Multiple Dimensions of Performance: Look beyond binary “good” vs. “bad” evaluations. Consider dimensions like readability, clinical accuracy, and alignment with user needs, as an example when thinking about performance in healthcare. In our paper, we saw some cases where a patient and provider overlapped in ratings, and other places where the ratings were different.
  3. Reproducibility and Transparency: If a study doesn’t disclose how prompts were designed or varied, its conclusions may lack context. Reproducibility in AI studies depends not just on the model, but on the interaction between the task, model, and prompt design. You should be looking for these kinds of details when reading or peer reviewing papers. Take results and conclusions with a grain of salt if these methods are not detailed in the paper.
  4. Involve Stakeholders in Evaluation: As shown in the preprint mentioned earlier, involving both clinical experts and patients in evaluating LLM outputs adds critical perspectives often missing in standard evaluations, especially as we evolve to focus research on supporting patient needs and not simply focusing on clinician and healthcare system usage of AI.

What This Means for Healthcare Providers, Researchers, and Patients

  • For healthcare providers, understand that the way you frame a question can improve the usefulness of AI tools in practice. A carefully constructed prompt, adding a persona or requesting information for a specific audience, can change the output.
  • For researchers, especially those developing or evaluating AI models, it’s essential to test prompts across different task types and end-user needs. Transparent reporting on prompt strategies strengthens the reliability of your findings.
  • For patients, recognizing that AI-generated health information is shaped by both the model and the prompt. This can support critical thinking when interpreting AI-driven health advice. Remember that LLMs can be biased, but so too can be humans in healthcare. The same approach for assessing bias and evaluating experiences in healthcare should be used for LLM output as well as human output. Everyone (humans) and everything (LLMs) are capable of bias or errors in healthcare.

Prompts matter, so consider model type as well as the prompt as a factor in assessing LLMs in healthcare. Blog by Dana M. LewisTLDR: Instead of asking “Which model is best?”, a better question might be:

“How do we design and evaluate prompts that lead to the most reliable, useful results for this specific task and audience?”

I’ve observed, and this study adds evidence, that prompt interaction with the model matters.

Best practices in communication related to writing a journal article and sharing it with co-authors

by Dana Lewis

I’ve been a single author, a lead author, a co-author, a corresponding author, AND a last author. Basically, I have written a lot of journal articles myself, solo / single, and with other people. One area in this process that I observe frequently gets overlooked is what happens during and after the submission process, as it relates to communicating about the article itself.

I’m not talking about disseminating the article to your target audience or the public, either (although that is important as well). I’m talking about making sure all authors know the article has been accepted; when it is live; have access to a copy of the article (!); etc.

Most people don’t know that by default, not all journals give all authors access to their own articles for free.

Here are some tips about the process of submitting and saving published articles that will help all authors – even solo authors – in the future.

Basically, help you help your future self! (As well as help your co-authors).

Journals typically only notify the lead/corresponding/submitting author about where the manuscript is in terms of revision, acceptance, and publication. That puts the responsibility on the lead/corresponding/submitting author to notify the full team of authors of where the article is in the process. Similarly, some journals will send a PDF/final copy of the proofed, final, version of record article to the lead author (not always, but usually), but that often does not go out to the full author team by default.

This means that it is the lead author’s responsibility to forward the copy of the final, PDF, proofed article to the entire authorship team so everyone has a copy.

(No, most of the time authors do not have free access to the journal they are submitting to. No, most authors do not have budget to make articles open access and free to all, which means unless they manage to snag and save this PDF article when it is sent to them at the time of publication, in the future, they may not have access to their very own article! Just because you, as the lead/corresponding author do have access, this does not mean everyone on your article team will.

I’m a good example of someone who authors frequently but is not at an institution and has zero access to any paywalled journals. If I’m not given a copy of my articles at the time of publication, I have to phone-a-friend (thanks, Liz Salmi, for being the go-to for me here) to help pull articles. There are things like S c i H u b, but they more often than not do not have super recent, fresh off the press articles. So yes, people like me exist on your authorship teams.)

Best practices for authors include:

  • Once you submit a manuscript, mark your file name (somehow) with “Submitted”. This way you know this is the version that was submitted. This is a useful step related to the below, we’ll come back to why we may want to use only the ‘submitted’ version.

    Example: “JournalAcronym-Article-Blah-Blah-SUBMITTED.docx”.

    Even as the non-lead author, when co-writing articles, as any type of author I prefer to have access to this submitted version. This way, I can see all incorporated edits and the ‘final’ version we submitted. There’s also cases where, see below, I need this for sharing it with other people.

  • Usually, the article goes through peer review and you get comments, so you make revisions and re-submit your article. Again, once submitted, make sure you’ve marked this as ‘revision’ somehow (usually people do) and that is was submitted.

    Example: “JournalAcronym-Article-Blah-Blah-SUBMITTED-R1.docx”.

    Again, best practice would be to send out this re-submitted revision version to all authors so everyone has it.

  • You may end up with multiple rounds of revisions and peer review (moving to R2, etc), or you may get an acceptance notice. Your article will then move to copyediting stage and you get proofs. It’s useful to save these for your own purpose, such as making sure that the edits you make are actually executed in the final article. This is less important for dissemination, though, although I do recommend giving all co-authors the ability to edit/review/proof and request changes.
  • Accepted, proofed, published! THIS is the step that I see most people miss, so pay attention.If you are the lead or solo author, you will probably get an email saying your article is now online, either online first or published. You may get an attachment PDF of your article. If not, you should be able to click on your access link and go to access the article online.

    IMPORTANT STEP HERE: go ahead and download the PDF of the article then. Right then, go ahead and save it.

    Example: “JournalAcronym-Article-Blah-Blah-Year.PDF”.

    (Why do you care about this if you are a solo author? Because the link may expire and you may lose access to this article. More on sharing your article below.)

  • Email your entire author team (if you’re not a solo author). Tell them the article was published; provide a link and/or the DOI link; and attach the PDF to the email so everyone on the team has a copy of the final article. Not all of your co-authors will work at an institution that has unlimited library access; if they do, that might change in the future. Give everyone a copy of the article to save for themselves.You can also remind everyone what the sharing permissions (or limitations) are for the article.

    For example, some articles are paywalled but authors have permission to store the final copy (PDF of the final version) on their own repository or not-for-profit website. For an example, see my research page of DIYPS.org/research – you’ll notice how sometimes I link to an “author copy” PDF, which is what this is – the final article PDF like you would get by accessing the paywalled journal.

    Other times, though, you are specifically not permitted to share the final/proofed/formatted copy. Instead, you’ll be allowed to share the “submitted” manuscript (usually prior to the revision stage). Remember how step 1 that I told you was to save a SUBMITTED copy? This is why! You can PDF this up; add a note to the top that references the final version of record (usually, journals give you recommended language for this) and a link/DOI link to it, and share away on your own site. Again, look at DIYPS.org/research and you’ll notice some of my “author copy” versions are these submitted versions rather than the final versions.

    You’ll also notice that sometimes I link to articles that are open access and then also have a link to a PDF author copy. This is in case something changes in the future with open access links breaking, the journal changing, etc. I have actually had free non-paywalled articles get turned into paywalled journal articles years later, which is why I do point to both places (the open access version and a back up author copy).

    Regardless of what the permissions are for sharing on your own website/repository/institutional repository: you as the author always have permission to give this PDF out when you are asked directly. For example, someone emails you and asks for a copy: you can email back and attach the PDF! This is true even if the permissioning for your own website is the submitted version (not the final version), you can still hand out the final, formatted, pretty PDF version when asked directly.

    As a related tip, this is a great way to disseminate your research and build relationships, so if someone does email you and ask for an author copy…please reply and send them a copy. (Saying this as someone without access to articles who sends requests to many authors to get access to their research, and I only get responses from 50% of authors. Sad panda.) Again, this is why it is helpful to get in the habit of saving your articles as you submit and have them published; it makes it easy to jump into the “Published copy” folder (or however you name it) and attach the PDF to the email and send it.

To recap, as a best practice, you should disseminate various versions of articles to your entire co-author team at the following points in time:

  • Original submission.

    Suggestion: Write an email, say you’ve successfully submitted, remind everyone which journal this was submitted to, and attached a copy of your “JournalAcronym-Article-Blah-Blah-SUBMITTED.docx”(If you end up getting a desk rejection, and you are re-submitting elsewhere, it is also nice to email co-authors and tell them so. You don’t necessarily need to send out a newly retitled version, unless there’s new changes to the submission, such as if you did go through a partial round of peer review before getting rejected and you are submitting the revised version to the new target journal.)

  • Revision submission.

    Suggestion: Write an email, say you’ve successfully submitted the revisions, remind everyone which journal this was submitted to, and attached a copy of your “JournalAcronym-Article-Blah-Blah-SUBMITTED-R1.docx” and the reviewer response document so everyone can see how edits/feedback were incorporated (or not).

  • Acceptance.

    Suggestion:

    A) Forward the email if it has the PDF attached to your full author team. Say congratulations; the article was accepted; and point out the article is attached as PDF.

    B) If you don’t have a PDF attachment in your email already, go to the online access link the journal gave you and save a copy of the PDF. Then, email the author team with the FYI that the article is live; provide the link to the online version; and attach the PDF directly to that email so everyone has a final version.

    Regardless of A or B, remind everyone what the permissions are for sharing to their own/institution repository (eg final PDF or use the submitted version, which you previously shared or could also re-share here).

Bonus tip:

Depending on the content of your article, you may also want to think about sending copies of the final PDF article to certain people who are not co-authors with you.

For example, if you are heavily citing someone’s work or talking about their work in a constructive way – you could email them and give them a heads up and provide a copy of the article. It’s a great way to contribute to your relationship (if you have an existing relationship) and/or foster a relationship. Remember that many people will have Google Scholar Alerts or similar with their name and/or citation alerts from various services, so people are likely to see when you talk about them or their work or are heavily citing their work. Again, some of those people may not have access to your article and may reach out to ask for an article; you can (and should) send them a copy! (And again, consider thinking about it as a relationship building opportunity rather than a transactional thing related to this single article.)

I would particularly flag this as something to pay attention to and do if you are someone working in the space of patient engagement in healthcare. For example, if you write an article and mention them or their body of work by name, it would be courteous to email them, let them know about the article, and send them a PDF.

Otherwise, I can speak from the experience of being talked about as a patient like I’m an ant under the microscope where someone cites an article where my work is mentioned; talks about me by name and references my perspective; and I get a notification about this article….but I can’t access it because it’s in a paywalled journal. Awkward, and a little weird in some cases when the very subject of the article(s) are about patient engagement and involving patients in research. Remember, research involvement should include all stages from design, planning, doing the research, and then disseminating the research. So this meta point is that if there is scholarly literature of any kind (whether original research articles or reviews, commentaries, letters in response to other articles, etc) talking about specific patients and their bodies of work – best practice should be to email them and send a copy of the article. Again, think less transactional and more about relationships – it will likely give you benefit in the long run! Plus, less awkward, a short-term benefit.

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best practices for communicating with co-authors about published articles, by Dana M. Lewis from DIYPS.orgAs an example for how I like to disseminate my articles personally, every time a journal article is published and I have access to it, I updated DIYPS.org/research with the title, journal, a DOI link (to help people find it online and/or cite it), and a link to the open access version if available and if not, an author copy PDF of the final or submitted version. So, if you’re ever looking for any of my articles, you can head there (DIYPS.org/research) first and grab copies any time!

If you are looking for a particular article and can’t find it or it’s not listed there yet (e.g. likely because it just came out and I haven’t been sent my own copy by my co-authors yet…), you can always email me directly (Dana@OpenAPS.org) and I’m more than happy to send you a copy of whatever version I have available and/or the final PDF once I have access to it.

Assessing the Impact of Diabetes on Gastrointestinal Symptom Severity in Exocrine Pancreatic Insufficiency (EPI/PEI): A Diabetes Subgroup Analysis of EPI/PEI-SS Scores – Poster at #ADA2024

by Dana Lewis

Last year, I recognized that there was a need to improve the documentation of symptoms of exocrine pancreatic insufficiency (known as EPI or PEI). There is no standardized way to discuss symptoms with doctors, and this influences whether or not people get the right amount of enzymes (pancreatic enzyme replacement therapy; PERT) to treat EPI and eliminate symptoms completely. It can be done, but like insulin, it requires matching PERT to the amount of food you’re consuming. I also began observing that EPI is underscreened and underdiagnosed, whether that’s in the general population or in people with diabetes. I thought that if we could create a list of common EPI symptoms and a standardized scale to rate them, this might help address some of these challenges.

I developed this scale to address these needs. It is called the “Exocrine Pancreatic Insufficiency Symptom Score” or “EPI/PEI-SS” for short.

I had a handful of people with and without EPI help me test the scale last year, and then I opened up a survey to the entire world and asked people to share their experiences with GI-related symptoms. I specifically sought people with EPI diagnoses as well as people who don’t have EPI, so that we could compare the symptom burden and experiences to people without EPI. (Thank you to everyone who contributed their data to this survey!)

After the first three weeks, I started analyzing the first set of data. While doing that, I realized that (both because of my network of people with diabetes and because I also posted in at least one diabetes-specific group), I had a large sub-group of people with diabetes who had contributed to the survey, and I was able to do a full subgroup analyses to assess whether having diabetes seemed to correlate with a different symptom experience of EPI or not.

Here’s what I found, and what my poster is about (you can view my poster as a PDF here), presented at ADA Scientific Sessions 2024 (#ADA2024):

1985-LB at #ADA2024, “Assessing the Impact of Diabetes on Gastrointestinal Symptom Severity in Exocrine Pancreatic Insufficiency (EPI/PEI): A Diabetes Subgroup Analysis of EPI/PEI-SS Scores”

Exocrine pancreatic insufficiency has a high symptom burden and is present in as many as 3 of 10 people with diabetes. (See my systematic review from last year here). To help improve conversations about symptoms of EPI, which can then be used to improve screening, diagnosis, and treatment success with EPI, I created the Exocrine Pancreatic Insufficiency Symptom Score (EPI/PEI-SS), which consists of 15 individual symptoms that people separately rate the frequency (0-5) and severity (0-3) for which they experience those symptoms, if at all. The frequency and severity get multiplied for an individual symptom score (0-15 possible) and these get added up for a total EPI/PEI-SS score (0-225 possible, because 15 symptoms times 15 possible points per symptom is 225).

I conducted a real-world study of the EPI/PEI-SS in the general population to assess the gastrointestinal symptom burden in individuals with (n=155) and without (n=169) EPI. Because there was a large cohort of PWD within these groups, I separately analyzed them to evaluate whether diabetes contributes to a difference in EPI/PEI-SS score.

Methods:

I calculated EPI/PEI-SS scores for all survey participants. Previously, I had analyzed the differences of people with and without EPI overall. For this sub-analysis, I analyzed and compared between PWD (n=118 total), with EPI (T1D: n=14; T2D: n=20) or without EPI (T1D: n=78; T2D: n=6), and people without diabetes (n=206 total) with and without EPI.

I also looked at sub-groups within the non-EPI cohorts and broke them into two groups to see whether other GI conditions contributed to a higher EPI/PEI-SS score and whether we could distinguish EPI from other GI and non-GI conditions.

Results:

People with EPI have a much higher symptom burden than people without EPI. This can be assessed by looking at the statistically significant higher mean EPI/PEI-SS score as well as the average number of symptoms; the average severity score of individual symptoms; and the average frequency score of individual symptoms.

This remains true irrespective of diabetes. In other words, diabetes does not appear to influence any of these metrics.

People with diabetes with EPI had statistically significant higher mean EPI/PEI-SS scores (102.62 out of 225, SD: 52.46) than did people with diabetes without EPI (33.64, SD: 30.38), irrespective of presence of other GI conditions (all group comparisons p<0.001). As you can see below, that is the same pattern we see in people without diabetes. And the stats confirm what you can see: there is no significant difference overall or in any of the subgroups between people with and without diabetes.

Box plot showing EPI/PEI-SS scores for people with and without diabetes, and with and without EPI or other GI conditions. The scores are higher in people with EPI regardless of whether they have diabetes. The plot makes it clear that the scores are distinct between the groups with and without EPI, even when the people without EPI have other GI conditions. This suggests the EPI/PEI-SS can be useful in distinguishing between EPI and other conditions that may cause GI symptoms, and that the EPI/PEI-SS could be a useful screening tool to help identify people who need screening for EPI.

T1D and T2D subgroups were similar
(but because the T2D cohort is small, I did not break them out separately in this graph).

For example, people with diabetes with EPI had an average of 12.59 (out of 15) symptoms, with an average frequency score of 3.06 and average severity score of 1.79, and an average individual symptom score of 5.48. This is a pretty clear contrast to people with diabetes without EPI who had had an average of 7.36 symptoms, with an average frequency score of 1.4 and average severity score of 0.8, and an average individual symptom score of 1.12. All comparisons are statistically significant (p<0.001).

A table comparing the average number of symptoms, frequency, severity, and individual symptom scores between people with diabetes with and without exocrine pancreatic insufficiency (EPI). People with EPI have more symptoms and higher frequency and severity than without EPI: regardless of diabetes.

Conclusion 

  • EPI has a high symptom burden, irrespective of diabetes.
  • High scores using the EPI/PEI-SS among people with diabetes can distinguish between EPI and other GI conditions.
  • The EPI/PEI-SS should be further studied as a possible screening method for EPI and assessed as a tool to aid people with EPI in tracking changes to EPI symptoms over time based on PERT titration.

What does this mean if you are a healthcare provider? What actionable information does this give you?

If you’re a healthcare provider, you should be aware that people with diabetes may be more likely to have EPI – rather than celiac or gastroparesis (source) – if they mention having GI symptoms. This means you should incorporate fecal elastase screening into your care plans to help further evaluate GI-related symptoms.

If you want to further improve your pre-test probability of the elastase testing, you can use the EPI/PEI-SS with your patients to assess the severity and frequency of their GI-related symptoms. I will explain the cutoff and AUC numbers we calculated, but first understand the caveat that these were calculated in the initial real-world study that included people with EPI who are already treating with PERT; thus these numbers might change a little when we repeat this study and evaluate it in people with untreated EPI. (However, I actually predict the mean score to go up in an undiagnosed population, because scores should go down with treatment.) But that different population study may change these exact cutoff and sensitivity specificity numbers, which is why I’m giving this caveat. That being said: the AUC was 0.85 which means a higher EPI/PEI-SS is pretty good for differentiating between EPI and not having EPI. (In the diabetes sub-population specifically, I calculated a suggested cutoff of 59 (out of 225) with a sensitivity of 0.81 and specificity of 0.75. This means we estimate that if people are bringing up GI symptoms to you and you have them take the EPI/PEI-SS and their score is greater than or equal to 59, you would expect that out of 100 people that 81 with EPI would be identified (and 75 of 100 people without EPI would also correctly be identified via scores lower than 59). That doesn’t mean that people with EPI can’t have a lower score; or that people with a higher score do have EPI; but it does mean that the chances of having fecal elastase <=200 ug/g is a lot more likely in those with higher EPI/PEI-SS scores.

In addition to the cutoff score, there is a notable difference in people with diabetes and EPI compared to people with diabetes without EPI in their top individual symptom scores (representing symptom burden based on frequency and severity). For example, the top 3 symptoms of those with EPI and diabetes include avoiding certain food/groups; urgent bowel movements; and avoiding eating large meals. People without EPI and diabetes also score “Avoid certain food/groups” as their top score, but the score is markedly different: the mean score of 8.94 for people with EPI as compared to 3.49 for people without EPI. In fact, the mean score on the lowest individual symptom is higher for people with EPI than the highest individual symptom score for people without EPI.

QR code for EPI/PEI-SS - takes you to https://bit.ly/EPI-PEI-SS-WebHow do you have people take the EPI/PEI-SS? You can pull this link up (https://bit.ly/EPI-PEI-SS-Web), give this link to them and ask them to take it on their phone, or save this QR code and give it to them to take later. The link (and the QR code) go to a free web-based version of the EPI/PEI-SS that will calculate the total EPI/PEI-SS score, and you can use it for shared decision making processes about whether this person would benefit from a fecal elastase test or other follow up screening for EPI. Note that the EPI/PEI-SS does not collect any identifiable information and is fully anonymous.

(Bonus: people who use this tool can opt to contribute their anonymized symptom and score data for an ongoing observational study.)

If you have feedback about whether the EPI/PEI-SS was helpful – or not – in your care of people with diabetes; or if you want to discuss collaborating on some prospective studies to evaluate EPI/PEI-SS in comparison to fecal elastase screening, please reach out anytime to Dana@OpenAPS.org. 

What does this mean if you are a patient (person with diabetes)? What actionable information does this give you?

If you don’t have GI symptoms that bother you, you don’t necessarily need to take action. (Just put a note in your brain that EPI is more likely than celiac or gastroparesis in people with diabetes so if you or a friend with diabetes have GI symptoms in the future, you can make sure you are assessed for EPI.) You can also choose to take the EPI/PEI-SS regardless, and also opt in to donate your data.

If you do have GI symptoms that are annoying, you may want to take the EPI/PEI-SS to help you evaluate the frequency and severity of your GI symptoms. You can take it for free and anonymously – no identifiable information is needed to access the tool. It will generate the EPI/PEI-SS score for you.

Based on the score, you may want to ask your doctor (which could be the doctor that treats your diabetes, or a primary/general care provider, or a gastroenterologist – whoever you seek routine care from or have an appointment from next) about your symptoms; share the EPI/PEI-SS score; and explain that you think you may warrant screening for EPI.

(You can also choose to contribute your anonymous symptom data to a research dataset, to help us improve the EPI/PEI-SS and help us figure out how to help improve screening and diagnosis and treatment of EPI. Remember, this tool will not ask you for any identifying information. This is 100% optional and you can opt out of doing so if you do not prefer to contribute to research, while still using the tool.)

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You can see a pre-print version of the diabetes sub-study here or pre-print of the general population data here.

If you’re looking for more personal experiences about living with EPI, check out DIYPS.org/EPI, and also for people with EPI looking to improve their dosing with pancreatic enzyme replacement therapy – you may want to check out PERT Pilot (a free iOS app to record enzyme dosing).

Researchers & clinicians, if you’re interested in collaborating on studies in EPI (in diabetes, or more broadly on EPI), whether specifically on EPI/PEI-SS or broader EPI topics, please reach out! My email is Dana@OpenAPS.org

New Systematic Review Showing General Population Prevalence of Exocrine Pancreatic Insufficiency Is Higher Than In Co-Conditions

by Dana Lewis

For those unfamiliar with academic/medical journal publishing, it is slow. Very slow. I did a systematic review on EPI prevalence and submitted it to a journal on May 5, 2023. It underwent peer review and a round of revisions and was accepted on July 13, 2023. (That part is actually relatively quick.) However, it sat, and sat, and sat, and sat, and sat. I was impatient and wrote a blog post last year about the basic premise of the review, which is that despite commonly repeated statements about the prevalence of EPI being so high in co-conditions that those conditions therefore are the highest drivers of EPI… this unlikely to be true because it is mathematically improbable.

And then this paper still sat several more months until it was published online ahead of print…today! Wahoo! You can read “An Updated Review of Exocrine Pancreatic Insufficiency Prevalence finds EPI to be More Common in General Population than Rates of Co-Conditions” in the Journal of Gastrointestinal and Liver Diseases ahead of print (scheduled for the March 2024 issue).

It’s open access (and I didn’t have to pay for it to be!), so click here to go read it and download your own PDF copy of the article there. (As a reminder, I also save a version of every article including those that are not open access at DIYPS.org/research, in case you’re looking for this in the future or want to read some of my other research.) If you don’t want to read the full article, here’s a summary below and key takeaways for providers and patients (aka people like me with EPI!).

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I read and systematically categorized 649 articles related to exocrine pancreatic insufficiency, which is known as EPI or PEI depending on where in the world you are. EPI occurs when the pancreas no longer produces enough enzymes to successfully digest food completely; when this occurs, pancreatic enzyme replacement therapy (PERT) is needed. This means swallowing enzyme pills every time you eat or drink something with fat or protein in it.

Like many of my other EPI-related research articles, this one found that EPI is underdiagnosed; undertreated; treatment costs are high; and prevalence is widely misunderstood, possibly leading to missing screening key populations.

  • Underdiagnosis – for a clearer picture and specific disease-related example of how EPI is likely underdiagnosed in a co-condition, check out my other systematic review specifically assessing EPI in diabetes. I show in that paper how EPI is likely many times more likely than gastroparesis and celiac disease, yet it’s less likely to be screened for.
  • Undertreated – another recent systematic review that I wrote after this paper (but was published sooner) is this systematic review on PERT dosing guidelines and dosing literature, showing how the overwhelming majority of people are not prescribed enough enzymes to meet their needs. Thus, symptoms persist and the literature continues to state that symptoms can’t be managed with PERT, which is not necessarily true: it just hasn’t been studied correctly with sufficient titration protocols.
  • PERT costs are high – I highlight that although PERT costs continue to rise each year, there are studies in different co-condition populations showing PERT treatment is cost-effective and in some cases reduces the overall cost of healthcare. It’s hard to believe when we look at the individual out of pocket costs related to PERT sometimes, but the data more broadly shows that PERT treatment in many populations is cost-effective.
  • Prevalence of EPI is misunderstood. This is the bulk of the paper and goes into a lot of detail showing how the general population estimates of EPI may be as high as 11-21%. In contrast, although prevalence of EPI is much higher within co-conditions, these conditions are such a small fraction of the general population that they therefore are also likely a small fraction of the EPI population.

As I wrote in the paper:

“The overall population prevalence of cystic fibrosis, pancreatitis, cancer, and pancreatic-related surgery combined totals <0.1%, and the lower end of the estimated overall population prevalence of EPI is approximately 10%, which suggests less than 1% of the overall incidence of EPI occurs in such rare co-conditions.

We can therefore conclude that 99% of EPI occurs in those without a rare co-condition.”

I also pointed out the mismatch of research prioritization and funding to date in EPI. 56-85% of the EPI-related research is focused on those representing less than ~1% of the overall population with EPI.

—

So what should you take away from this research?

If you are a healthcare provider:

Make sure you are screening people who present with gastrointestinal symptoms with a fecal elastase test to check for EPI. Weight loss and malnutrition does not always occur with EPI (which is a good thing, meaning it’s caught earlier) and similarly not everyone has diarrhea as their hallmark symptoms. Messy, smelly stools are often commonly described by people with EPI, among other symptoms such as excess gas and bloating,

Remember that conditions like diabetes have a high prevalence of EPI – it’s not just chronic pancreatitis or cystic fibrosis.

If you do have a patient that you are diagnosing or have diagnosed with EPI, make sure you are aware of the current dosing guidelines (see this systematic review) and 1) prescribe a reasonable minimal starting dose; 2) tell the patient when/how they can adjust their PERT on their own and when to call back for an updated prescription as they figure out what they need, and; 3) tell them they will likely need an updated prescription and you are ready to support them when they need to do so.

If you are a person living with EPI:

Most people with EPI are not taking enough enzymes to eliminate their symptoms. Dose timing matters (take it with/throughout meals), and the quantity of PERT matters.

If you’re still having symptoms, you may still need more enzymes.

Don’t compare what you are doing to what other people are taking: it’s not a moral failing to need a different amount of enzymes (or insulin, for that matter, or any other medication) than another person! It also likely varies by what we are eating, and we all eat differently.

If you’re still experiencing symptoms, you may need to experiment with a higher dose. If you still have symptoms or have new symptoms that start after taking PERT, you may need to try a different brand of PERT. Some people do well on one but not another, and there are different kinds you can try – ask your doctor.

—

How to cite this systematic review:

Lewis D. An Updated Review of Exocrine Pancreatic Insufficiency Prevalence finds EPI to be More Common in General Population than Rates of Co-Conditions. Journal of Gastrointestinal and Liver Diseases. 2024. DOI: 10.15403/jgld-5005

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For other posts related to EPI, see DIYPS.org/EPI for more of my personal experiences with EPI and other plain-language research summaries.

For other research articles, see DIYPS.org/research

A systematic review shows EPI prevalence is more common in the general population than in co-conditions

Systematic Review of PERT Research and Guidelines for Exocrine Pancreatic Insufficiency (EPI or PEI)

by Dana Lewis

New Systematic Review And Evaluation of Pancreatic Enzyme Replacement Therapy (PERT) Dosing Guidelines and Research for Exocrine Pancreatic Insufficiency (EPI or PEI)

I wrote a new paper evaluating the research behind pancreatic enzyme replacement therapy (aka, PERT) dosing for people with exocrine pancreatic insufficiency (known as EPI or PEI). I decided to do this research and write this paper because in my previous papers on EPI, I saw a lot of inconsistencies in when PERT was studied, how it was studied, and how that research was then used to develop guidelines.

(Big thanks to Julia Blanchette, Jordan Rieke, Claudia Lewis (no relation), Khaleal Almusaylim , and Anuhya Kanchibhatla for collaborating on this research and co-authoring the paper with me!)

You can find an author copy of the paper here, or see it on the journal website here. As a reminder, all my research papers have author copies and you can find them at DIYPS.org/research! I also have several other EPI-related articles.

A note on methods – this is a systematic review, meaning I used keywords to search multiple electronic databases to find articles about exocrine pancreatic insufficiency. I screened articles to make sure they were about EPI in humans and focused on English-language articles. We then reviewed the title and abstract of 2,530 remaining articles (!) that mentioned EPI, and excluded those that were not focused on EPI or a co-condition and unlikely to include guidelines or specific dose information related to EPI. That left 820 articles, which we then screened again looking for the full text and reviewing them for relevancy. I ended up reading 257 papers that we used for the basis of the research described below!

We found 7 key findings from this body of research:

  1. PERT Titration Protocols Aren’t Very Specific (or useful as typically written)“Most PERT dosing guidelines do not articulate a specific, defined dose range. Instead, PERT is commonly dosed with a general starting dose, such as 50,000 units of lipase per meal and 25,000 units of lipase per snack. If needed, guidelines then recommend increasing (i.e., titrating) the dosage by a factor of two to three (commonly described as increasing by 2x – 3x), and if symptoms persist, adding a proton pump inhibitor (PPI) before exploring other potential diagnoses. As a result, providers are prompted to focus primarily on the starting dose, rather than the full range of recommended doses.”

    I ended up crafting a table (Table 2) for the paper that shows how this dosing process can result in much bigger doses – such as 150,000 units of lipase per meal – to contrast  how prescriptions are often given at very low doses in comparison and often are not sufficient.

    This is a similar version of the table that I had developed for a previous blog post talking about the ranges of PERT dosing:
    Examples of PERT starting doses of 25,000, 40,000, and 50,000 (plus half that for snacks) and what the dose would be if increased according to guidelines to 2x and 3x, plus the sum of the total daily dose needed at those levels.
    Most guidelines, and the underlying studies, do not do a good job describing what doses people actually took in the studies. This may influence then providers’ understanding of how much PERT is needed.

  1. People are not taking enough PERTLike I found in my own previous research, there have been numerous studies showing that people are not getting prescribed enough PERT. This is both based on people reporting ongoing symptoms and reduced quality of life, but also studies that show a huge gap between the doses recommended to start with in guidelines and the fact that >90% of the time, providers don’t prescribe anywhere near this dose (and therefore are not prescribing enough PERT).
  2. Comparing different PERT studies is challengingWhen PERT studies are done, they are typically for safety and efficacy at a specific dose. Very few studies record what dosing people take when they are allowed to take the amount that they need to effectively reduce symptoms.

    As a result, we don’t know how much PERT people need (on average) in order to reduce symptoms.

  3. PERT Dosing Studies and Guidelines Only Focus on Fat (and we need to talk about protein)If you’ve read my previous blog posts about ratios and PERT dosing, you’ll notice I talk about protein dosing. For some people with EPI, protein dosing makes a huge difference in symptom outcomes.

    However, PERT is described based on units of lipase (for fat digestion) and primarily studied for fat, which means that doctors often prescribe it and only talk about changing PERT doses for different sized meals based on fat.

    This is a huge area of need for future studies to determine what role protein malabsorption plays for people with EPI. I suspect, based on personal experience and talking to others in the EPI community about when they have symptoms, this influences a lot of PERT dosing efficacy in real life.

  4. PERT Dosing Guidelines Are Very Different Around The World – But Should They Be?There are dozens of PERT dosing guidelines by condition, and in different parts of the world. They don’t always agree!

    My hypothesis is that this is not because of a true varying need geographically for PERT dosing (meaning your PERT dosing needs aren’t likely different if you live in South America or Europe), but because of the selection of studies used to determine the guidelines. And because most studies have only looked at basic, minimal doses for safety/efficacy, they haven’t studied how much people need to eliminate symptoms. There’s also no data on what people eat in these studies, so the ‘regional’ differences perceived may be a result of different composition of foods, but we have no evidence for this because the studies are poorly described and/or the studies don’t actually record this.

  5. PERT Dosing Guidelines Are Different By Co-Condition The majority of the studies on EPI and PERT dosing are in chronic pancreatitis (CP). As I’ve written previously, this is likely a small fraction of the number of people with EPI. But because this body of research on CP and EPI is so big, it has a very loud voice in determining what the guidelines say about PERT dosing. (Cystic fibrosis (CF) is the second-most studied and also plays the second-biggest role in influencing guidelines).

    If you want to dig in to the differences between conditions, note that the guidelines are influenced by the volume of studies, and so many conditions (such as diabetes) have very few guidelines and very few studies, so most of the ‘guidance’ on dosing is extrapolated from CF and/or chronic pancreatitis. It’s therefore very possible that people with EPI need more dosing or different dosing than is studied in those co-conditions – but we don’t know more because it hasn’t been studied!

    (I have a lot of details in the paper about what has been studied, and you can look at Table 4 for a summary of some of the less-studied conditions or check out the appendix for a narrative description of all of the co-conditions and their bodies of research.)

  6. PERT Dosing Is Determined By Clinicians And They’re Not Following The GuidelinesMost doctors and clinicians are not following PERT guidelines. This means that many people are prescribed a too-low dose of PERT according to the guidelines. This could be because providers are unaware of the guidelines; or don’t agree with the guidelines; or have not seen evidence showing clear effects of PERT on symptom resolution (in part because this hasn’t been studied!).

    More work needs to be done to understand why patients with EPI are under-prescribed and under-dosed when prescribed, and understanding barriers for clinicians may be a key factor to study moving forward.

So, what next?

Here’s what I want to see studied next for EPI, based on the findings in this paper:

  1. All PERT studies should clearly document the titration protocol in a way that can be understood and reproduced.
  2. PERT studies should record what dose people take throughout or at the end of the trial.
  3. PERT should be studied for symptom resolution. (PS – take the anonymous EPI symptom survey if you haven’t already!) This should be done outside of conditions such as chronic pancreatitis, because there is pain associated with CP that is confounding the results of EPI symptoms. And, CP is a tiny fraction of EPI and should not therefore be used to determine whether PERT is effective at resolving EPI-related symptoms.
  4. We need more awareness of the prevalence of EPI and for clinicians to screen for EPI. When elastase results are low (e.g. less than or equal to 200-ish), providers should initiate a trial of PERT and aid people in increasing their doses to the point that symptoms resolve. We need to study the barriers/factors determining why providers are not screening for EPI and why they are not prescribing PERT.
  5. We need more tools to help doctors and patients increase PERT dosing to achieve symptom resolution.
  6. We need studies on the effect of protein in the diet of people with EPI and PERT dosing to improve protein digestion.

If clinicians are reading this, here is your call to action:

  • Screen for EPI using a fecal elastase test. This includes anyone presenting with GI symptoms, not just in people that you suspect have chronic pancreatitis. You’re probably missing a not-insignificant number of people coming to you with EPI. For example, a previous systematic review shows EPI is likely much more common in people with diabetes than celiac or gastroparesis!
  • If fecal elastase results are around or below 200, prescribe PERT. Yes, even if they’re close to 200 – PERT can help for those with EPI who have symptoms!

    This study was published after our systematic review, so I wasn’t able to cite it in the paper, but includes evidence that PERT also can help reduce symptoms when elastase is 200-500. Don’t get too hung up on the elastase result, it’s not very precise but that doesn’t mean you shouldn’t prescribe a trial of PERT. 
  • Prescribe PERT at a minimum of 40,000-50,000 units PER MEAL and tell patients specifically to increase dosing as needed, such as when they’re eating larger meals. Many people need much larger doses (evidence here). Give guidance on how to adjust based on meals. If you want tools, consider things like PERT Pilot or other calculators to aid in matching dosing to food intake. This matches the recent AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency (EPI) by Whitcomb et al which emphasizes that “PERT treats the meal, not the pancreas” meaning that PERT should match food intake.The level of elastase does NOT determine the dosing need, and the size of your prescriptions shouldn’t be influenced by the elastase result.

    All EPI needs PERT, and PERT needs should be driven by the individual’s symptoms and the dose it takes to reduce or eliminate their symptoms.

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Here’s how to cite this paper:

Lewis DM, Rieke, JG, Almusaylim, K, Kanchibhatla, A, Blanchette, JE, Lewis, C. Exocrine Pancreatic Insufficiency Dosing Guidelines For Pancreatic Enzyme Replacement Therapy Vary Widely Across Disease Types. Digestive Diseases and Sciences. 2023. https://doi.org/10.1007/s10620-023-08184-w

Accepted, Rejected, and Conflict of Interest in Gastroenterology (And Why This Is A Symptom Of A Bigger Problem)

by Dana Lewis

Recently, someone published a new clinical practice update on exocrine pancreatic insufficiency (known as EPI or PEI) in the journal called Gastroenterology, from the American Gastroenterology Association (AGA). Those of you who’ve read any of my blog posts in the last year know how much I’ve been working to raise awareness of EPI, which is very under-researched and under-treated clinically despite the prevalence rates in the general population and key sub-populations such as PWD. So when there was a new clinical practice update and another publication on EPI in general, I was jazzed and set out to read it immediately. Then frowned. Because, like so many articles about EPI, it’s not *quite* right about many things and it perpetuates a lot of the existing problems in the literature. So I did what I could, which was to check out the journal requirements for writing a letter to the editor (LTE) in response to this article and drafting and submitting a LTE article about it. To my delight, on October 17, 2023, I got an email indicating that my LTE was accepted.

You can find my LTE as a pre-print here.

See below why this pre-print version is important, and why you should read it, plus what it reminds us about what journal articles can or cannot tell us in healthcare.

Here’s an image of my acceptance email. I’ll call out a key part of the email:

A print of the acceptance email I received on October 17, 2023, indicating my letter would be sent to authors of the original articles for a chance to choose to respond (or not). Then my LTE would be published.

Letters to the Editor are sent to the authors of the original articles discussed in the letter so that they might have a chance to respond. Letters are not sent to the original article authors until the window of submission for letters responding to that article is closed (the last day of the issue month in which the article is published). Should the authors choose to respond to your letter, their response will appear alongside your letter in the journal.

Given the timeline described, I knew I wouldn’t hear more from the journal until the end of November. The article went online ahead of print in September, meaning likely officially published in October, so the letters wouldn’t be sent to authors until the end of October.

And then I did indeed hear back from the journal. On December 4, 2023, I got the following email:

A print of the email I received saying the LTE was now rejected
TLDR: just kidding, the committee – members of which published the article you’re responding to – and the editors have decided not to publish your article. 

I was surprised – and confused. The committee members, or at least 3 of them, wrote the article. They should have a chance to decide whether or not to write a response letter, which is standard. But telling the editors not to publish my LTE? That seems odd and in contrast to the initial acceptance email. What was going on?

I decided to write back and ask. “Hi (name redacted), this is very surprising. Could you please provide more detail on the decision making process for rescinding the already accepted LTE?”

The response?

Another email explaining that possible commercial affiliations influenced their choice to reject the article after accpeting it originally
“In terms of this decision, possible commercial affiliations, as well as other judgments of priority and relevance among other submissions, dampened enthusiasm for this particular manuscript. Ultimately, it was not judged to be competitive for acceptance in the journal. “

Huh? I don’t have any commercial affiliations. So I asked again, “Can you clarify what commercial affiliations were perceived? I have none (nor any financial conflict of interest; nor any funding related to my time spent on the article) and I wonder if there was a misunderstanding when reviewing this letter to the editor.”

The response was “There were concerns with the affiliation with OpenAPS; with the use of the term “guidelines,” which are distinct from this Clinical Practice Update; and with the overall focus being more fit for a cystic fibrosis or research audience rather than a GI audience.”

A final email saying the concern with my affiliation of OpenAPS, which is not a commercial organization nor related to the field of gastroenterology and EPI

Aha, I thought, there WAS a misunderstanding. (And the latter makes no sense in the context of my LTE – the point of it is that most research and clinical literature is a too-narrow focus, cystic fibrosis as one example – the very point is that a broad gastroenterology audience should pay attention to EPI).

I wrote back and explained how I, as a patient/independent researcher, struggle to submit articles to manuscript systems without a Ringgold-verified organization. (You can also listen to me describe the problem in a podcast, here, and I also talked about it in a peer-reviewed journal article about citizen science and health-related journal publishing here). So I use OpenAPS as an “affiliation” even though OpenAPS isn’t an organization. Let alone a commercial organization. I have no financial conflict of interest related to OpenAPS, and zero financial conflict of interest or commercial or any type of funding in gastroenterology at all, related to EPI or not. I actually go to such extremes to describe even perceived conflicts of interest, even non-financial ones, as you can see this in my disclosure statement publicly available from the New England Journal of Medicine here on our CREATE trial article (scroll to Supplemental Information and click on Disclosure Forms) where I articulate that I have no financial conflicts of interest but acknowledge openly that I created the algorithm used in the study. Yet, there’s no commercial or financial conflict of interest.

A screenshot from the publicly available disclosure form on NEJM's site, where I am so careful to indicate possible conflicts of interest that are not commercial or financial, such as the fact that I developed the algorithm that was used in that study. Again, that's a diabetes study and a diabetes example, the paper we are discussing here is on exocrine pancreatic insufficiency (EPI) and gastroenterology, which is unrelated. I have no COI in gastroenterology.

I sent this information back to the journal, explaining this, and asking if the editors would reconsider the situation, given that the authors (committee members?) have misconstrued my affiliation, and given that the LTE was originally accepted.

Sadly, there was no change. They are still declining to publish this article. And there is no change in my level of disappointment.

Interestingly, here is the article in which my LTE is in reply to, and the conflict of interest statement by the authors (committee members?) who possibly raised a flag about supposed concern about my (this is not true) commercial affiliation:

The conflict of interest statement for authors from the article "AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency 2023"

The authors disclose the following: David C. Whitcomb: consultant for AbbVie, Nestlé, Regeneron; cofounder, consultant, board member, chief scientific officer, and equity holder for Ariel Precision Medicine. Anna M. Buchner: consultant for Olympus Corporation of America. Chris E. Forsmark: grant support from AbbVie; consultant for Nestlé; chair, National Pancreas Foundation Board of Directors.

As a side note, one of the companies with consulting and/or grant funding to two of the three authors is the biggest manufacturer of pancreatic enzyme replacement therapy (PERT), which is the treatment for EPI. I don’t think this conflict of interest makes these clinicians ineligible to write their article; nor do I think commercial interests should preclude anyone from publishing – but in my case, it is irrelevant, because I have none. But, it does seem weird given the stated COI for my (actually not a) COI then to be a reason to reject a LTE, of all things.

Here’s the point, though.

It’s not really about the fact that I had an accepted article rejected (although that is weird, to say the least…).

The point is that the presence of information in medical and research journals does not mean that they are correct. (See this post describing the incorrect facts presented about prevalence of EPI, for example.)

And similarly, the lack of presence of material in medical and research journals does not mean that something is not true or is not fact! 

There is a lot of gatekeeping in scientific and medical research. You can see it illustrated here in this accepted-rejected dance because of supposed COI (when there are zero commercial ties, let alone COI) and alluded to in terms of the priority of what gets published.

I see this often.

There is good research that goes unpublished because editors decide not to prioritize it (aka do not allow it to get published). There are many such factors in play affecting what gets published.

There are also systemic barriers.

  • Many journals require fees (called article processing charges or “APC”s) if your article is accepted for publication. If you don’t have funding, that means you can’t publish there unless you want to pay $2500 (or more) out of pocket. Some journals even have submission fees of hundreds of dollars, just to submit! (At least APCs are usually only levied if your article is accepted, but you won’t submit to these journals if you know you can’t pay the APC). That means the few journals in your field that don’t require APCs or fees are harder to get published in, because many more articles are submitted (thus, influencing the “prioritization” problem at the editor level) to the “free” journals.
  • Journals often require, as previously described, your organization to be part of a verified list (maintained by a third party org) in order for your article to be moved through the queue once submitted. Instead of n/a, I started listing “OpenAPS” as my affiliation and proactively writing to admin teams to let them know that my affiliation won’t be Ringgold-verified, explaining that it’s not an org/I’m not at any institution, and then my article can (usually) get moved through the queue ok. But as I wrote in this peer-reviewed article with a lot of other details about barriers to publishing citizen science and other patient-driven work, it’s one of many barriers involved in the publication process. It’s a little hard, every journal and submission system is a little different, and it’s a lot harder for us than it is for people who have staff/support to help them get articles published in journals.

I’ve seen grant funders say no to funding researchers who haven’t published yet; but editors also won’t prioritize them to publish on a topic in a field where they haven’t been funded yet or aren’t well known. Or they aren’t at a prestigious organization. Or they don’t have the “right” credentials. (Ahem, ahem, ahem). It can be a vicious cycle for even traditional (aka day job) researchers and clinicians. Now imagine that for people who are not inside those systems of academia or medical organizations.

Yet, think about where much of knowledge is captured, created, translated, studied – it’s not solely in these organizations.

Thus, the mismatch. What’s in journals isn’t always right, and the process of peer review can’t catch everything. It’s not a perfect system. But what I want you to take away, if you didn’t already have this context, is an understanding that what’s NOT in a journal is not because the information is not fact or does not exist. It may have not been studied yet; or it may have been blocked from publication by the systemic forces in play.

As I said at the end of my LTE:

“It is also critical to update the knowledge base of EPI beyond the sub-populations of cystic fibrosis and chronic pancreatitis that are currently over-represented in the EPI-related literature. Building upon this updated research base will enable future guidelines, including those like the AGA Clinical Practice Update on EPI, to be clearer, more evidence-based, and truly patient-centric ensuring that every individual living with exocrine pancreatic insufficiency receives optimal care. “

PS – want to read my LTE that was accepted then rejected, meaning it won’t be present in the journal? Here it is on a preprint server with a DOI, which means it’s still easily citable! Here’s an example citation:

Lewis, D. Navigating Ambiguities in Exocrine Pancreatic Insufficiency. OSF Preprints. 2023. DOI: 10.31219/osf.io/xcnf6

New Survey For Everyone (Including You – Yes, You!) To Help Us Learn More About Exocrine Pancreatic Insufficiency

by Dana Lewis

If you’ve ever wanted to help with some of my research, this is for you. Yes, you! I am asking people in the general public to take a survey (https://bit.ly/GI-Symptom-Survey-All) and share their experiences.

Why?

Many people have stomach or digestion problems occasionally. For some people, these symptoms happen more often. In some cases, the symptoms are related to exocrine pancreatic insufficiency (known as EPI or PEI). But to date, there have been few studies looking at the frequency of symptoms – or the level of their self-rated severity – in people with EPI or what symptoms may distinguish EPI from other GI-related conditions.

That’s where this survey comes in! We want to compare the experiences of people with EPI to people without EPI (like you!).

Will you help by taking this survey?

Your anonymous participation in this survey will help us understand the unique experiences individuals have with GI symptoms, including those with conditions like exocrine pancreatic insufficiency (EPI). In particular, data contributed by people without EPI will help us understand how the EPI experience is different (or not).

A note on privacy:

  • The survey is completely anonymous; no identifying information will be collected.
  • You can stop the survey at any point.

Who designed this survey:

Dana Lewis, an independent researcher, developed the survey and will manage the survey data. This survey design and the choice to run this survey is not influenced by funding from or affiliations with any organizations.

What happens to the data collected in this survey:

The aggregated data will be analyzed for patterns and shared through blog posts and academic publications. No individual data will be shared. This will help fill some of the documented gaps in the EPI-related medical knowledge and may influence the design of targeted research studies in the future.

Have Questions?
Feel free to reach out to Dana+GISymptomSurvey@OpenAPS.org.

How else can you help?
Remember, ANYONE can take this survey. So, feel free to share the link with your family and friends – they can take it, too!

Here’s a link to the survey that you can share (after taking it yourself, of course!): https://bit.ly/GI-Symptom-Survey-All

You (yes you!) can help us learn about exocrine pancreatic insufficiency by taking the survey linked on this page.

New Research Shows Most People With Exocrine Pancreatic Insufficiency (EPI) Are Not Taking Enough Enzymes

by Dana Lewis

Last year when I was diagnosed with exocrine pancreatic insufficiency (known as EPI or PEI), I quickly noticed that many people in the online social media community I joined didn’t seem to have their pancreatic enzyme replacement therapy (PERT) working effectively for them.

Possibly because I have been counting carbohydrates and dosing insulin using a ratio of insulin to carbohydrates for ~20+ years (for type 1 diabetes), it came intuitively to me to try to develop ratios of the amount of enzymes compared to the amount of macronutrients I was consuming, For me, it worked really well (and you can read more about my methods for titrating enzymes and/or check out PERT Pilot if you have an iOS phone, which helps automating the dosing calculations based on logging what you eat).

However, I was surprised at how many people still seemed to share online that their PERT wasn’t working or that they still had symptoms. It made me curious: were these folks all newly diagnosed? How long does it take for most people to titrate their enzymes (e.g. arrive at an ideal dose or dosing strategy)? There seemed to be a mismatch between what I was seeing in real life in these communities versus what was in the medical literature about typical dosing of enzymes and expected outcomes for this community.

And so, I set out to do a survey to learn more. I sought permission from the administrators of the Facebook group, designed the survey, got the administrators’ feedback and incorporated it, had a few people trial the survey, and then shared it in the Facebook group and on Twitter.

I ended up closing the survey after 3 weeks and 111 responses, although I wish I had left it open to collect more data. I was so excited to analyze the data and get it published!

…but I forgot how long and silly the traditional medical literature publishing process is. I just now got this article published, almost a year later! Sigh. Anyway, this post is to share what we learned from the EPI Community survey and what I think people – both people with EPI and clinicians – should do based on this information.

(PS – the full research paper is available here and is open access and free to read anytime! Big thanks to Dr. Arsalan Shahid for collaborating with me on writing up the results and getting this published.

Below is a plain language summary that I wrote for those who don’t want to read the full paper.)

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Understanding who took the EPI Community survey

First things first, it’s helpful to understand who ended up taking the survey to help us understand the results.

111 people with EPI filled out the survey. Most (93%) were female, and most happened to be in North America. So, this survey won’t necessarily represent the entire EPI community, based on the small sample size and the demographic makeup. (That being said, I found a previous EPI study on a smaller sample size with a majority of male participants where the findings matched pretty similarly, so I don’t think gender played a large role in the results).

But I was interested to see that the ages ended up being pretty balanced: the largest group was between 55 and 64 years (27%) followed by 65-74 (23%); 45-54 (21%); 34-44 (16%); 25-34 (6%); 75+ (5%); and 18-24 (2%). Also, the duration of how long people had EPI was also fairly distributed: diagnosed within 0-6 months (27%);  1-2 years (25%); 5+ years and 3-5 years (both 18%); or 6 months – 1 year (12%). This was all coincidental, as I did not do any particular recruitment based on age groups or length of EPI.

I was also interested and a little surprised to look at the list of other conditions that people have. 68% of people mentioned at least one other condition. Remember, we had 111 participants – and 26 of them (35%) mentioned having diabetes of any type. The next most common was celiac (10 people), followed by chronic pancreatitis (8 people) and acute pancreatitis (4 people).

This is compelling additional evidence supporting my recent systematic review that shows a higher prevalence of EPI among people with diabetes, and also adds to my argument that chronic pancreatitis and cystic fibrosis are likely NOT the biggest co-conditions associated with EPI. No, this study is not necessarily a representative sample of EPI, but this is more evidence added to these arguments. People with diabetes, celiac, and other conditions presenting with GI symptoms should be screened for EPI.

Understanding the Elastase in the EPI Community

The most common diagnosis test for EPI is the fecal elastase test. Most participants in this survey (all but 15 people) had their elastase tested, although not everyone shared the number or remembered what it was. 76 people shared their elastase results, so the sub-analyses related to elastase are based on this group rather than the overall survey participant number (111).

Of those who reported their elastase, the average was 92 (with a standard deviation of 57).

Remember that the diagnostic criteria for EPI say that anything <200 is considered to be EPI, with 100-200 being “mild/moderate” and <100 being “severe”, although the categorization technically doesn’t change anything including how much enzymes are given to people. (That being said, though, it shows that the majority of people surveyed do have severe EPI, which helps counter potential pushback on this survey that people with only slightly lowered elastase don’t have EPI. Many of us with elastase in the mild/moderate category, myself included, show clear response to symptoms on PERT no matter what the elastase number says, but there seems to be some resistance in the clinical community to prescribing PERT when elastase is 100-200.)

I ended up reviewing the elastase data by age group and also by duration of EPI (meaning how long people have had EPI). A statistical test showed that as age increases, elastase levels tend to decrease. That wasn’t surprising to me as many studies that I have read also show that older adults are more likely to have lowered elastase. I also ran a statistical test that showed that people who have had EPI for longer are more likely to have reported lowered elastase levels, again matching previous studies.

If you look at Table 1 in the paper, you can see the breakdown of enzyme dosing for meals and snacks for each of the duration sub-groups. I chose 0-6 months, 6 months to 1 year, 1 to 2 years, 3-5 years, and 5+ years as the duration groups to ask people about. In the elastase column you can clearly see that elastase lowers over the duration groups, too. You can also see the varied enzyme dosing (with standard deviations) by groups, too. Interestingly, the 0-6 month group takes the highest average enzyme dose, followed by the 5+ year group, with lower amounts in the other groups. This I haven’t seen reported in the literature as I haven’t found any other studies evaluating enzyme dosing in the real world nor any breakdowns by duration of EPI, so this would be interesting to repeat in a study that better controls for variables of age and duration of EPI.

We did not observe a statistical correlation between enzymes taken for meals or snacks and elastase levels. That didn’t surprise me personally because the enzyme dosing guidelines are not different based on elastase levels (e.g. people with elastase <100 or between 100-200 are given the same dose).

What Enzymes Are People Taking, And What About the Cost of PERT?

I had hypothesized that maybe some people adjust their meals in order to reduce enzyme cost, because PERT can be expensive.

Most people (100, which is 90% of participants) do take enzymes, and 87% are taking prescription enzymes. The results of what people take prescription-wise in terms of brand is likely influenced by the order in which the prescription options entered the US market, given that most participants are in North America. 5 people reported taking OTC enzymes only (see my comments about over the counter or OTC enzymes here), and 7 people take a combination of prescription and OTC. The biggest reason people reported taking OTCs or a mix was that the enzyme prescription was not written so that they had enough to cover a full month (which means they are not getting enough prescription enzymes from their doctor, and their prescription should be increased). 7 people also indicated that lack of insurance coverage for prescription enzymes was an issue and that even OTC enzymes were expensive for them. Otherwise, for those taking prescription enzymes, 40% have insurance and said the cost was reasonable for them; 32% find the cost of prescription enzymes expensive even with insurance.

Based on my curiosity, I had asked people how often cost played a role in choosing what to eat and/or how much enzymes to take, 32% of people said ‘yes often”, 20% said sometimes, and 40% said they do not change what they eat in order to change the amount of enzymes they’re taking.

Again, this is primarily in North America where PERT can be very expensive, so the results in other geographic regions with different health plans and coverage options for PERT would likely be very different to those questions about cost and modifying food and PERT intake!

People With EPI Are Not Taking Enough Enzymes

Here’s where I was most surprised by the data:

I knew anecdotally that  many people with EPI weren’t taking enough enzymes, but this survey showed that only 1 in 5 people believe that they are always taking enough enzymes! Another 1 in 5 people said they are usually not taking enough, and the remaining 3 of 5 people think they take enough most of the time but not always.

Additionally, the data from this survey shows that the longer duration of EPI was correlated with taking less enzymes per meal. It’s possible that people were taking enough but their elastase production lowered further over time, and they did not (or were not able to due to lack of healthcare provider support for updating prescriptions) update their dosing over time, which I think would be another interesting area for future studies.

On average, individuals who reported their elastase levels were taking 64,303 (SD: ±39,980) units of lipase per meal (minimum 0; maximum 180,000). There were 14 participants who reported taking less than or equal to 30,000 units of lipase per meal; 7 participants reported taking between 30,000 and 40,000 units of lipase per meal; 6 participants who reported between 40-50,000 units of lipase per meal and 44 participants who reported taking >=50,000 units of lipase per meal. What do these numbers mean? Well, most dosing guidelines recommend a starting dose of 40-50,000 units of lipase per meal, so this means that the majority of people are taking at least the recommended starting dose (or higher), whereas about a third are taking well under even the recommended starting dose (more from me here in this blog about starting dose and the ranges people should increase to).

It probably will surprise a lot of clinicians to see that the average intake was around 64,000 units of lipase (with a large standard deviation, which means there was a lot of variance in dose sizes). It’s surprising because this is above the typical starting dose yet the majority of this population, as described above, is still experiencing symptoms and still not always taking enough enzymes to manage these symptoms

It’s also worth noting that most people said they still have not arrived at the ideal enzyme dosing: 42% said they still weren’t there yet. For those who thought they did have the ideal enzyme dosage, it took anywhere from a few weeks (16%) to a few months (20%); more than 6 months (10%), more than a year (10%) or even up to a few years (3%).

In summary:


People with EPI are not taking enough enzymes; are not arriving at an ideal dose quickly; and it is absolutely worth it for any clinician who sees someone with EPI – even someone who has been diagnosed by another clinician or had EPI for a long time – to check to see whether their prescription is meeting their needs and/or whether they need support in increasing their dose to resolve symptoms!

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Recommended Takeaways From This Study

 

Patients (aka, people living with EPI):

  • If you are still experiencing symptoms, you may need to take more enzymes. The starting doses should be around 40-50,000 and it’s common for many people to need even larger doses. Based on this study, some people take up to 180,000 units per meal!
  • Talk to your doctor if you need your script adjusted, and remember PERT pills come in different sizes so you may be able to get a higher pill size (which holds more enzymes) so you have to take fewer pills per meal.
  • If your doctor seems resistant to adjusting your prescription, I have citations in this blog post that you can share listing out the various guidelines that point to 40-50,000 units of lipase being the starting dose with guidelines to increase up to 2-3x as needed based on the individual’s symptoms – share those guidelines/citations with your clinician if needed.
  • Over time, it is possible you will need to change your enzyme dosing as your body changes.

 

Doctors who treat people living with EPI

  • Other studies show that the majority of people with EPI are undertreated, even when compared to the baseline level of starting doses. This survey shows most people need more than the ‘starting dose’, so don’t be surprised and also proactively talk with patients about increasing enzyme doses and how to do so, and be prepared to update prescriptions for PERT over time.
  • Treat people with mild/moderate EPI (fecal elastase results 100-200, and not just those <100). The symptom burden of EPI is pretty significant even in those of us with mild/moderate EPI. Yes, PERT can be expensive, but let patients make the choice to treat/manage and don’t make the choice for them by refusing to prescribe PERT for elastase <200.
  • If symptoms aren’t resolved on the initial dose given, follow the guidelines for increasing the doses 2-3x from the starting 40-50,000 dose before considering adding a PPI or investigating other causes after that. But, dropping PERT after a short trail of a dose of <40,000 is not an approved nor evidence-based approach to treating EPI. Dose according to the starting guidelines and follow up or explain to your patients how to follow up on their own in order to increase their prescription as needed. Think of PERT similarly to insulin, where dosing is also self-managed by patients at every meal.
  • Speaking of insulin and diabetes: EPI occurs in more people than you think, and people with diabetes and celiac and other conditions need to be screened for EPI. Chronic pancreatitis is not the leading cause of EPI.

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The paper described in this blog post can be accessed here for free – it’s open access!

You can cite it as:

Lewis DM, Shahid A. Survey on Pancreatic Enzyme Replacement Therapy Dosing Experiences of Adults with Exocrine Pancreatic Insufficiency. Healthcare 2023, 11,2316. https://doi.org/10.3390/healthcare11162316

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Want to read more about EPI? Check out DIYPS.org/EPI for other posts I have written about my personal experiences with EPI and PERT, plus links to my other EPI-related research papers (with more on the way!)

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You can also contribute to another research study – take this anonymous survey to share your experiences with EPI-related symptoms!

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A blue square with white text that says "New Research: Most people with EPI (PEI) are not taking enough enzymes", a blog post by Dana M. Lewis

You’d Be Surprised: Common Causes of Exocrine Pancreatic Insufficiency

by Dana Lewis

Academic and medical literature often is like the game of “telephone”. You can find something commonly cited throughout the literature, but if you dig deep, you can watch the key points change throughout the literature going from a solid, evidence-backed statement to a weaker, more vague statement that is not factually correct but is widely propagated as “fact” as people cite and re-cite the new incorrect statements.

The most obvious one I have seen, after reading hundreds of papers on exocrine pancreatic insufficiency (known as EPI or PEI), is that “chronic pancreatitis is the most common cause of exocrine pancreatic insufficiency”. It’s stated here (“Although chronic pancreatitis is the most common cause of EPI“) and here (“The most frequent causes [of exocrine pancreatic insufficiency] are chronic pancreatitis in adults“) and here (“Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI“) and here (“Numerous conditions account for the etiology of EPI, with the most common being diseases of the pancreatic parenchyma including chronic pancreatitis, cystic fibrosis, and a history of extensive necrotizing acute pancreatitis“) and… you get the picture. I find this statement all over the place.

But guess what? This is not true.

First off, no one has done a study on the overall population of EPI and the breakdown of the most common co-conditions.

Secondly, I did research for my latest article on exocrine pancreatic insufficiency in Type 1 diabetes and Type 2 diabetes and was looking to contextualize the size of the populations. For example, I know overall that diabetes has a ~10% population prevalence, and this review found that there is a median prevalence of EPI of 33% in T1D and 29% in T2D. To put that in absolute numbers, this means that out of 100 people, it’s likely that 3 people have both diabetes and EPI.

How does this compare to the other “most common” causes of EPI?

First, let’s look at the prevalence of EPI in these other conditions:

  • In people with cystic fibrosis, 80-90% of people are estimated to also have EPI
  • In people with chronic pancreatitis, anywhere from 30-90% of people are estimated to also have EPI
  • In people with pancreatic cancer, anywhere from 20-60% of people are estimated to also have EPI

Now let’s look at how common these conditions are in the general population:

  • People with cystic fibrosis are estimated to be 0.04% of the general population.
    • This is 4 in every 10,000 people
  • People with chronic pancreatitis combined with all other types of pancreatitis are also estimated to be 0.04% of the general population, so another 4 out of 10,000.
  • People with pancreatic cancer are estimated to be 0.005% of the general population, or 1 in 20,000.

What happens if you add all of these up: cystic fibrosis, 0.04%, plus all types of pancreatitis, 0.04%, and pancreatic cancer, 0.005%? You get 0.085%, which is less than 1 in 1000 people.

This is quite a bit less than the 10% prevalence of diabetes (1 in 10 people!), or even the 3 in 100 people (3%) with both diabetes and EPI.

Let’s also look at the estimates for EPI prevalence in the general population:

  • General population prevalence of EPI is estimated to be 10-20%, and if we use 10%, that means that 1 in 10 people may have EPI.

Here’s a visual to illustrate the relative size of the populations of people with cystic fibrosis, chronic pancreatitis (visualized as all types of pancreatitis), and pancreatic cancer, relative to the sizes of the general population and the relative amount of people estimated to have EPI:

Gif showing the relative sizes of populations of people with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and the % of those with EPI, contextualized against the prevalence of these in the general population and those with EPI. It's a small number of people because these conditions aren't common, therefore these conditions are not the most common cause of EPI!

What you should take away from this:

  • Yes, EPI is common within conditions such as cystic fibrosis, chronic pancreatitis (and other forms of pancreatitis), and pancreatic cancer
  • However, these conditions are not common: even combined, they add up to less than 1 in 1000!
  • Therefore, it is incorrect to conclude that any of these conditions, individually or even combined, are the most common causes of EPI.

You could say, as I do in this paper, that EPI is likely more common in people with diabetes than all of these conditions combined. You’ll notice that I don’t go so far as to say it’s the MOST common, because I haven’t seen studies to support such a statement, and as I started the post by pointing out, no one has done studies looking at huge populations of EPI and the breakdown of co-conditions at a population level; instead, studies tend to focus on the population of a co-condition and prevalence of EPI within, which is a very different thing than that co-condition’s EPI population as a percentage of the overall population of people with EPI. However, there are some great studies (and I have another systematic review accepted and forthcoming on this topic!) that support the overall prevalence estimates in the general population being in the ballpark of 10+%, so there might be other ‘more common’ causes of EPI that we are currently unaware of, or it may be that most cases of EPI are uncorrelated with any particular co-condition.

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(Need a citation? This logic is found in the introduction paragraph of a systematic review found here, of which the DOI is 10.1089/dia.2023.0157. You can also access a full author copy of it and my other papers here.)

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You can also contribute to a research study and help us learn more about EPI/PEI – take this anonymous survey to share your experiences with EPI-related symptoms!

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New Systematic Review of Exocrine Pancreatic Insufficiency (EPI) In Type 1 Diabetes and Type 2 Diabetes – Focusing on Prevalence and Treatment

by Dana Lewis

I’m thrilled that the research I did evaluating the prevalence and treatment of EPI in both Type 1 diabetes and Type 2 diabetes (also presented as a poster at #ADA2023 – read a summary of the poster here) has now been published as a full systematic review in Diabetes Technology and Therapeutics.

Here is a pre-edited submitted version of my article that you can access if you don’t have journal access; and as a reminder, copies of ALL of my research articles are available on this page: DIYPS.org/research!

And if you don’t want to read the full paper, this is what I think you should take away from it as a person with diabetes or as a healthcare provider:

    1. What is EPI? 

      Exocrine pancreatic insufficiency (known as EPI in some places, and PEI or PI in other places) occurs when the pancreas no longer produces enough enzymes to digest food. People with EPI take pancreatic enzyme replacement therapy (PERT) whenever they eat (or drink anything with fat/protein).

    2. If I have diabetes, or treat people with diabetes, why should I be reading the rest of this about EPI?EPI often occurs in people with cystic fibrosis, pancreatitis, and pancreatic cancer. However, since these diseases are rare (think <0.1% of the general population even when these groups are added up all together), the total number of people with EPI from these causes is quite low. On the other hand, EPI is also common in people with diabetes, but this is less well-studied and understood. The research on other co-conditions is more frequent and often people confuse the prevalence WITHIN those groups with the % of those conditions occurring overall in the EPI community.This paper reviews every paper that includes data on EPI and people with type 1 diabetes or type 2 diabetes to help us better understand what % of people with diabetes are likely to face EPI in their lifetime.
    3. How many people with type 1 diabetes or type 2 diabetes (or diabetes overall) get EPI?TLDR of the paper: EPI prevalence in diabetes varies widely, reported between 5.4% and 77% when the type of diabetes isn’t specified. For Type 1 diabetes, the median EPI prevalence is 33% (range 14-77.5%), and for Type 2 diabetes, the median is 29% (range 16.8-49.2%). In contrast, in non-diabetes control groups, the EPI prevalence ranges from 4.4% to 18% (median 13%). The differences in ranges might be due to geographic variability and different exclusion criteria across studies.Diabetes itself is prevalent in about 10% of the general population. As such, I hypothesize that people with diabetes likely constitute one of the largest sub-groups of individuals with EPI, in contrast to what I described above might be more commonly assumed.
    4. Is pancreatic enzyme replacement therapy (PERT) safe for people with diabetes? 

      Yes. There have been safety and efficacy studies in people with diabetes with EPI, and PERT is effective just like in any other group of people with EPI.

    5. What is the effect of pancreatic enzyme replacement therapy (PERT) on glucose levels in people with diabetes?
      PERT itself does not affect glucose levels, but PERT *d0es* impact the digestion of food, which then changes glucose levels! So, most PERT labels warn to watch for hypoglycemia or hyperglycemia but the medicine itself doesn’t directly cause changes in glucose levels. You can read a previous study I did here using CGM data to show the effect of PERT actually causing improved glucose after meals in someone with Type 1 diabetes. But, in the systematic review, I found only 4 articles that even made note of glucose levels, and only 1 (the paper I linked above) actually included CGM data. Most of the studies are old, so there are no definitive conclusions on whether hypoglycemia or hyperglycemia is more common when a person with diabetes and EPI starts taking PERT. Instead, it’s likely very individual depending on what they’re eating, insulin dosing patterns before, and whether they’re taking enough PERT to match what they’re eating.TLDR here: more studies are needed because there’s no clear single directional effect on glucose levels from PERT in people with diabetes.Note: based on the n=1 study above, and subsequent conversations with other people with diabetes, I hypothesize that high variability and non-optimal post-meal glucose outcomes may be an early ‘symptom’ of EPI in people with diabetes. I’m hoping to eventually generate some studies to evaluate whether we could use this type of data as an input to help increase screening of EPI in people with diabetes.
    6. How common is EPI (PEI / PI) compared to celiac and gastroparesis in Type 1 diabetes and Type 2 diabetes? 

      As a person with (in my case, Type 1) diabetes, I feel like I hear celiac and gastroparesis talked about often in the diabetes community. I had NEVER heard of EPI prior to realizing I had it. Yet, EPI prevalence in Type 1 and Type 2 diabetes is much higher than that of celiac or gastroparesis!The prevalence of EPI is much higher in T1 and T2 than the prevalence of celiac and gastroparesis.Celiac disease is more common in people with diabetes (~5%) than in the general public (0.5-1%). Gastroparesis, when gastric emptying is delayed, is also more common in people with diabetes (5% in PWD).However, the  prevalence of EPI is 14-77.5% (median 33%) in Type 1 diabetes and 16.8-49.2% (median 29%) in Type 2 diabetes (and 5.4-77% prevalence when type of diabetes was not specified). This again is higher than general population prevalence of EPI.

      This data emphasizes that endocrinologists and other diabetes care providers should be more prone to initiate screening (using the non-invasive fecal elastase test) for individuals presenting with gastrointestinal symptoms, as the rates of EPI in diabetes are much higher in both Type 1 and Type 2 diabetes than the rates of celiac and gastroparesis.

    7. What should I do if I think I have EPI?
      Record your symptoms and talk to your doctor and ask for a fecal elastase (FE-1) screening test for EPI. It’s non-invasive. If your results are less than or equal to 200 (μg/g), this means you have EPI and should start on PERT. If you or your doctor feel that your sample may have influenced the results of your test, you can always re-do the test. But if you’re dealing with diarrhea, going on PERT may resolve or improve the diarrhea and improve the quality of the sample for the next test result. PERT doesn’t influence the test result, so you can start PERT and re-run the test any time.Symptoms of EPI can vary. Some people experience diarrhea, while others experience constipation. Steatorrhea or smelly, messy stools that stick to the side of the toilet are also common EPI symptoms, as is bloating, abdominal pain, and generally not feeling well after you eat.

      If you’ve been diagnosed with EPI, you may also want to check out some of my other posts (DIYPS.org/EPI) about my personal experiences with EPI and also this post about the amount of enzymes needed by most people with EPI. You may also want to check out PERT Pilot, a free iOS app, for recording and evaluating your PERT dosing.

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If you want to read the full article, you can find copies of all of my research articles at DIYPS.org/research

If you’d like to cite this specific article in your future research, here’s an example citation:

Lewis, D. A Systematic Review of Exocrine Pancreatic Insufficiency Prevalence and Treatment in Type 1 and Type 2 Diabetes. Diabetes Technology & Therapeutics. http://doi.org/10.1089/dia.2023.0157