Understanding the Difference Between Open Source and DIY in Diabetes

There’s been a lot of excitement (yay!) about the results of the CREATE trial being published in NEJM, followed by the presentation of the continuation results at EASD. This has generated a lot of blog posts, news articles, and discussion about what was studied and what the implications are.

One area that I’ve noticed is frequently misunderstood is how “open source” and “DIY” are different.

Open source means that the source code is openly available to view. There are different licenses with open source; most allow you to also take and reuse and modify the code however you like. Some “copy-left” licenses commercial entities to open-source any software they build using such code. Most companies can and do use open source code, too, although in healthcare most algorithms and other code related to FDA-regulated activity is proprietary. Most open source licenses allow free individual use.

For example, OpenAPS is open source. You can find the core code of the algorithm here, hosted on Github, and read every line of code. You can take it, copy it, use it as-is or modify it however you like, because the MIT license we put on the code says you can!

As an individual, you can choose to use the open source code to “DIY” (do-it-yourself) an automated insulin delivery system. You’re DIY-ing, meaning you’re building it yourself rather than buying it or a service from a company.

In other words, you can DIY with open source. But open source and DIY are not the same thing!

Open source can and is usually is used commercially in most industries. In healthcare and in diabetes specifically, there are only a few examples of this. For OpenAPS, as you can read in our plain language reference design, we wanted companies to use our code as well as individuals (who would DIY with it). There’s at least one commercial company now using ideas from the OpenAPS codebase and our safety design as a safety layer against their ML algorithm, to make sure that the insulin dosing decisions are checked against our safety design. How cool!

However, they’re a company, and they have wrapped up their combination of proprietary software and the open source software they have implemented, gotten a CE mark (European equivalent of FDA approval), and commercialized and sold their AID product to people with diabetes in Europe. So, those customers/users/people with diabetes are benefitting from open source, although they are not DIY-ing their AID.

Outside of healthcare, open source is used far more pervasively. Have you ever used Zoom? Zoom uses open source; you then use Zoom, although not in a DIY way. Same with Firefox, the browser. Ever heard of Adobe? They use open source. Facebook. Google. IBM. Intel. LinkedIn. Microsoft. Netflix. Oracle. Samsung. Twitter. Nearly every product or service you use is built with, depends on, or contains open source components. Often times open source is more commonly used by companies to then provide products to users – but not always.

So, to more easily understand how to talk about open source vs DIY:

  • The CREATE trial used a version of open source software and algorithm (the OpenAPS algorithm inside a modified version of the AndroidAPS application) in the study.
  • The study was NOT on “DIY” automated insulin delivery; the AID system was handed/provided to participants in the study. There was no DIY component in the study, although the same software is used both in the study and in the real world community by those who do DIY it. Instead, the point of the trial was to study the safety and efficacy of this version of open source AID.
  • Open source is not the same as DIY.
  • OpenAPS is open source and can be used by anyone – companies that want to commercialize, or individuals who want to DIY. For more information about our vision for this, check out the OpenAPS plain language reference design.
Venn diagram showing a small overlap between a bigger open source circle and a smaller DIY circle. An arrow points to the overlapping section, along with text of "OpenAPS". Below it text reads: "OpenAPS is open source and can be used DIY. DIY in diabetes often uses open source, but not always. Not all open source is used DIY."

Continuation Results On 48 Weeks of Use Of Open Source Automated Insulin Delivery From the CREATE Trial: Safety And Efficacy Data

In addition to the primary endpoint results from the CREATE trial, which you can read more about in detail here or as published in the New England Journal of Medicine, there was also a continuation phase study of the CREATE trial. This meant that all participants from the CREATE trial, including those who were randomized to the automated insulin delivery (AID) arm and those who were randomized to sensor-augmented insulin pump therapy (SAPT, which means just a pump and CGM, no algorithm), had the option to continue for another 24 weeks using the open source AID system.

These results were presented by Dr. Mercedes J. Burnside at #EASD2022, and I’ve summarized her presentation and the results below on behalf of the CREATE study team.

What is the “continuation phase”?

The CREATE trial was a multi-site, open-labeled, randomized, parallel-group, 24-week superiority trial evaluating the efficacy and safety of an open-source AID system using the OpenAPS algorithm in a modified version of AndroidAPS. Our study found that across children and adults, the percentage of time that the glucose level was in the target range of 3.9-10mmol/L [70-180mg/dL] was 14 percentage points higher among those who used the open-source AID system (95% confidence interval [CI], 9.2 to 18.8; P<0.001) compared to those who used sensor augmented pump therapy; a difference that corresponds to 3 hours 21 minutes more time spent in target range per day. The system did not contribute to any additional hypoglycemia. Glycemic improvements were evident within the first week and were maintained over the 24-week trial. This illustrates that all people with T1D, irrespective of their level of engagement with diabetes self-care and/or previous glycemic outcomes, stand to benefit from AID. This initial study concluded that open-source AID using the OpenAPS algorithm within a modified version of AndroidAPS, a widely used open-source AID solution, is efficacious and safe. These results were from the first 24-week phase when the two groups were randomized into SAPT and AID, accordingly.

The second 24-week phase is known as the “continuation phase” of the study.

There were 52 participants who were randomized into the SAPT group that chose to continue in the study and used AID for the 24 week continuation phase. We refer to those as the “SAPT-AID” group. There were 42 participants initially randomized into AID who continued to use AID for another 24 weeks (the AID-AID group).

One slight change to the continuation phase was that those in the SAPT-AID used a different insulin pump than the one used in the primary phase of the study (and 18/42 AID-AID participants also switched to this different pump during the continuation phase), but it was a similar Bluetooth-enabled pump that was interoperable with the AID system (app/algorithm) and CGM used in the primary outcome phase.

All 42 participants in AID-AID completed the continuation phase; 6 participants (out of 52) in the SAPT-AID group withdrew. One withdrew from infusion site issues; three with pump issues; and two who preferred SAPT.

What are the results from the continuation phase?

In the continuation phase, those in the SAPT-AID group saw a change in time in range (TIR) from 55±16% to 69±11% during the continuation phase when they used AID. In the SAPT-AID group, the percentage of participants who were able to achieve the target goals of TIR > 70% and time below range (TBR) <4% increased from 11% of participants during SAPT use to 49% during the 24 week AID use in the continuation phase. Like in the primary phase for AID-AID participants; the SAPT-AID participants saw the greatest treatment effect overnight with a TIR difference of 20.37% (95% CI, 17.68 to 23.07; p <0.001), and 9.21% during the day (95% CI, 7.44 to 10.98; p <0.001) during the continuation phase with open source AID.

Those in the AID-AID group, meaning those who continued for a second 24 week period using AID, saw similar TIR outcomes. Prior to AID use at the start of the study, TIR for that group was 61±14% and increased to 71±12% at the end of the primary outcome phase; after the next 6 months of the continuation phase, TIR was maintained at 70±12%. In this AID-AID group, the percentage of participants achieving target goals of TIR >70% and TBR <4% was 52% of participants in the first 6 months of AID use and 45% during the continuation phase. Similarly to the primary outcomes phase, in the continuation phase there was also no treatment effect by age interaction (p=0.39).

The TIR outcomes between both groups (SAPT-AID and AID-AID) were very similar after each group had used AID for 24 weeks (SAPT-AID group using AID for 24 weeks during the continuation phase and AID-AID using AID for 24 weeks during the initial RCT phase).. The adjusted difference in TIR between these groups was 1% (95% CI, -4 to 6; p=-0.67). There were no glycemic outcome differences between those using the two different study pumps (n=69, which was the SAPT-AID user group and 18 AID-AID participants who switched for continuation; and n=25, from the AID-AID group who elected to continue on the pump they used in the primary outcomes phase).

In the initial primary results (first 24 weeks of trial comparing the AID group to the SAPT group), there was a 14 percentage point difference between the groups. In the continuation phase, all used AID and the adjusted mean difference in TIR between AID and the initial SAPT results was a similar 12.10 percentage points (95% CI, p<0.001, SD 8.40).

Similar to the primary phase, there was no DKA or severe hypoglycemia. Long-term use (over 48 weeks, representing 69 person-years) did not detect any rare severe adverse events.

CREATE results from the full 48 weeks on open source AID with both SAPT (control) and AID (intervention) groups plotted on the graph.

Conclusion of the continuation study from the CREATE trial

In conclusion, the continuation study from the CREATE trial found that open-source AID using the OpenAPS algorithm within a modified version of AndroidAPS is efficacious and safe with various hardware (pumps), and demonstrates sustained glycaemic improvements without additional safety concerns.

Key points to takeaway:

  • Over 48 weeks total of the study (6 months or 24 weeks in the primary phase; 6 months/24 weeks in the continuation phase), there were 64 person-years of use of open source AID in the study, compared to 59 person-years of use of sensor-augmented pump therapy.
  • A variety of pump hardware options were used in the primary phase of the study among the SAPT group, due to hardware (pump) availability limitations. Different pumps were also used in the SAPT-AID group during the AID continuation phase, compared to the pumps available in the AID-AID group throughout both phases of trial. (Also, 18/42 of AID-AID participants chose to switch to the other pump type during the continuation phase).
  • The similar TIR results (14 percentage points difference in primary and 12 percentage points difference in continuation phase between AID and SAPT groups) shows durability of the open source AID and algorithm used, regardless of pump hardware.
  • The SAPT-AID group achieved similar TIR results at the end of their first 6 months of use of AID when compared to the AID-AID group at both their initial 6 months use and their total 12 months/48 weeks of use at the end of the continuation phase.
  • The safety data showed no DKA or severe hypoglycemia in either the primary phase or the continuation phases.
  • Glycemic improvements from this version of open source AID (the OpenAPS algorithm in a modified version of AndroidAPS) are not only immediate but also sustained, and do not increase safety concerns.
CREATE Trial Continuation Results were presented at #EASD2022 on 48 weeks of use of open source AID

Wondering about the “how” rather than the “why” of autoimmune conditions

I’ve been thinking a lot about stigma, per a previous post of mine, and how I generally react to, learn about, and figure out how to deal with new chronic diseases.

I’ve observed a pattern in my experiences. When I suspect an issue, I begin with research. I read medical literature to find out the basics of what is known. I read a high volume of material, over a range of years, to see what is known and the general “ground truth” about what has stayed consistent over the years and where things might have changed. This is true for looking into causal mechanisms as well as diagnosis and then more importantly to me, management/treatment.

A lot of times with autoimmune related diseases…the causal mechanism is unknown. There are correlations, there are known risk factors, but there’s not always a clear answer of why things happen.

I realize that I am lucky that my first “thing” (type 1 diabetes) was known to be an autoimmune condition, and that probably has framed my response to celiac disease (6 years later); exocrine pancreatic insufficiency (19+ years after diabetes); and now Graves’ disease (19+ years after diabetes). Why do I think that is lucky? Because when I’m diagnosed with an autoimmune condition, it’s not a surprise that it IS an autoimmune condition. When you have a nicely overactive immune system, it interferes with how your body is managing things. In type 1 diabetes, it eventually makes it so the beta cells in your pancreas no longer produce insulin. In celiac, it makes it so the body has an immune reaction to gluten, and the villi in your small intestine freak out at the microscopic, crumb-level presence of gluten (and if you keep eating gluten, can cause all sorts of damage). In exocrine pancreatic insufficiency, there is possibly either atrophy as a result of the pancreas not producing insulin or other immune-related responses – or similar theories related to EPI and celiac in terms of immune responses. It’s not clear ‘why’ or which mechanism (celiac, T1D, or autoimmune in general) caused my EPI, and not knowing that doesn’t bother me, because it’s clearly linked to autoimmune shenanigans. Now with Graves’ disease, I also know that low TSH and increased thyroid antibodies are causing subclinical hyperthyroidism symptoms (such as occasional minor tremor, increased resting HR, among others) and Graves’ ophthalmology symptoms as a result of the thyroid antibodies. The low TSH and increased thyroid antibodies are a result of my immune system deciding to poke at my thyroid.

All this to say…I typically wonder less about “why” I have gotten these things, in part because the “why” doesn’t change “what” to do; I simply keep gathering new data points that I have an overactive immune system that gives me autoimmune stuff to deal with.

I have contrasted this with a lot of posts I observe in some of the online EPI groups I am a part of. Many people get diagnosed with EPI as a result of ongoing GI issues, which may or may not be related to other conditions (like IBS, which is often a catch-all for GI issues). But there’s a lot of posts wondering “why” they’ve gotten it, seemingly out of the blue.

When I do my initial research/learning on a new autoimmune thing, as I mentioned I do look for causal mechanisms to see what is known or not known. But that’s primarily, I think, to rule out if there’s anything else “new” going on in my body that this mechanism would inform me about. But 3/3 times (following type 1 diabetes, where I first learned about autoimmune conditions), it’s primarily confirmed that I have autoimmune things due to a kick-ass overactive immune system.

What I’ve realized that I often focus on, and most others do not, is what comes AFTER diagnosis. It’s the management (or treatment) of, and living with, these conditions that I want to know more about.

And sadly, especially in the latest two experiences (exocrine pancreatic insufficiency and Graves’ disease), there is not enough known about management and optimization of dealing with these conditions.

I’ve previously documented and written quite a bit (see a summary of all my posts here) about EPI, including my frustrations about “titrating” or getting the dose right for the enzymes I need to take every single time I eat something. This is part of the “management” gap I find in research and medical knowledge. It seems like clinicians and researchers spend a lot of time on the “why” and the diagnosis/starting point of telling someone they have a condition. But there is way less research about “how” to live and optimally manage these things.

My fellow patients (people with lived experiences) are probably saying “yeah, duh, and that’s the power of social media and patient advocacy groups to share knowledge”. I agree. I say that a lot, too. But one of the reasons these online social media groups are so powerful in sharing knowledge is because of the black hole or vacuum or utter absence of research in this space.

And it’s frustrating! Social media can be super powerful because you can learn about many n=1 experiences. If you’re like me, you analyze the patterns to see what might be reproducible and what is worth experimenting in my own n=1. But often, this knowledge stays in the real world. It is not routinely funded, studied, operationalized, and translated in systematic ways back to healthcare providers. When patients are diagnosed, they’re often told the “what” and occasionally the “why” (if it exists), but left to sometimes fall through the cracks in the “how” of optimally managing the new condition.

(I know, I know. I’m working on that, in diabetes and EPI, and I know dozens of friends, both people with lived experiences and researchers who ARE working on this, from diabetes to brain tumors to Parkinson’s and Alzheimer’s and beyond. And while we are moving the needles here, and making a difference, I’m wanting to highlight the bigger issue to those who haven’t previously been exposed to the issues that cause the gaps we are trying to fill!)

In my newest case of Graves’ disease, it presented with subclinical hyperthyroidism. As I wrote here, that for me means the lower TSH and higher thyroid antibodies but in range T3 and T4. In discussion with my physician, we decided to try an antithyroid drug, to try to lower the antibody levels, because the antibody levels are what cause the related eye symptoms (and they’re quite bothersome). The other primary symptom I have is higher resting HR, which is also really annoying, so I’m also hoping it helps with that, too. But the game plan was to start taking this medication every day; and get follow-up labs in about 2 months, because it takes ~6 weeks to see the change in thyroid levels.

Let me tell you, that’s a long time. I get that the medication works not on stored thyroid levels; thus, it impacts the new production only, and that’s why it takes 6 weeks to see it in the labs because that’s how long it takes to cycle through the stored thyroid stuff in your body.

My hope was that within 2-3 weeks I would see a change in my resting HR levels. I wasn’t sure what else to expect, and whether I’d see any other changes.

But I did.

It was in the course of DAYS, not weeks. It was really surprising! I immediately started to see a change in my resting HR (across two different wearable devices; a ring and a watch). Within a week, my phone’s health flagged it as a “trend”, too, and pinpointed the day (which it didn’t know) that I had started the new medication based on the change in the trending HR values.

Additionally, some of my eye symptoms went away. Prior to commencing the new medication, I would wake up and my eyes would hurt. Lubricating them (with eye drops throughout the day and gel before bed) helped some, but didn’t really fix the problem. I also had pretty significant red, patchy spots around the outside corner of one of my eyes, and eyelid swelling that would push on my eyeball. 4 days into the new medication, I had my first morning where I woke up without my eyes hurting. The next day it returned, and then I had two days without eye pain. Then I had 3-4 days with the painful eyes. Then….now I’m going on 2 weeks without the eye pain?! Meanwhile, I’m also tracking the eye swelling. It went down to match the eye pain going away. But it comes back periodically. Recently, I commented to Scott that I was starting to observe the pattern that the red/patchy skin at the corner and under my right eye would appear; then the next day the swelling of and above the eyelid would return. After 1-2 days of swelling, it would disappear. Because I’ve been tracking various symptoms, I looked at my data the other day and saw that it’s almost a 6-7 day pattern.

Interesting!

Again, the eye stuff is a result of antibody levels. So now I am curious about the production of antibodies and their timeline, and how that differs from TSH and thyroid hormones, and how they’re impacted with this drug.

None of that is information that is easy to get, so I’m deep in the medical literature trying again to find out what is known, whether this type of pattern is known; if it’s common; or if this level of data, like my within-days impact to resting HR change is new information.

Most of the research, sadly, seems to be on pre-diagnosis or what happens if you diagnose someone but not give them medication in hyperthyroid. For example, I found this systematic review on HRV and hyperthyroid and got excited, expecting to learn things that I could use, but found they explicitly removed the 3 studies that involved treating hyperthyroidism and are only studying what happens when you don’t treat it.

Sigh.

This is the type of gap that is so frustrating, as a patient or person who’s living with this. It’s the gap I see in EPI, where little is known on optimal titration and people don’t get prescribed enough enzymes and aren’t taught how to match their dosing to what they are eating, the way we are taught in diabetes to match our insulin dosing to what we’re eating.

And it matters! I’m working on writing up data from a community survey of people with EPI, many of whom shared that they don’t feel like they have their enzyme dosing well matched to what they are eating, in some cases 5+ years after their diagnosis. That’s appalling, to me. Many people with EPI and other conditions like this fall through the cracks with their doctors because there’s no plan or discussion on what managing optimally looks like; what to change if it’s not optimal for a person; and what to do or who to talk to if they need help managing.

Thankfully in diabetes, most people are supported and taught that it’s not “just” a shot of insulin, but there are more variables that need tracking and managing in order to optimize wellbeing and glucose levels when living with diabetes. But it took decades to get there in diabetes, I think.

What would it be like if more chronic diseases, like EPI and Graves’ disease (or any other hyper/hypothyroid-related diseases), also had this type of understanding across the majority of healthcare providers who treated and supported managing these conditions?

How much better would and could people feel? How much more energy would they have to live their lives, work, play with their families and friends? How much more would they thrive, instead of just surviving?

That’s what I wonder.

Wondering "how" rather than "why" of autimmune conditions, by @DanaMLewis from DIYPS.org

New Research on Glycemic Variability Assessment In Exocrine Pancreatic Insufficiency (EPI) and Type 1 Diabetes

I am very excited to share that a new article I wrote was just published, looking at glycemic variability in data from before and after pancreatic enzyme replacement therapy (PERT) was started in someone with type 1 diabetes with newly discovered exocrine pancreatic insufficiency (EPI or PEI).

If you’re not aware of exocrine pancreatic insufficiency, it occurs when the pancreas no longer produces the amount of enzymes necessary to fully digest food. If that occurs, people need supplementary enzymes, known as pancreatic enzyme replacement therapy (PERT), to help them digest their food. (You can read more about EPI here, and I have also written other posts about EPI that you can find at DIYPS.org/EPI.)

But, like MANY medications, when someone with type 1 diabetes or other types of insulin-requiring diabetes starts taking them, there is little to no guidance about whether these medications will change their insulin sensitivity or otherwise impact their blood glucose levels. No guidance, because there are no studies! In part, this may be because of the limited tools available at the time these medications were tested and approved for their current usage. Also this is likely in part because people with diabetes make up a small fraction of the study participants that most of these medications are tested on. If there are any specific studies on the medications in people with diabetes, these studies likely were done before CGM, so little data is available that is actionable.

As a result, the opportunity came up to review someone’s data who happened to have blood glucose data from a continuous glucose monitor (CGM) as well as a log of what was eaten (carbohydrate entries) prior to commencing pancreatic enzyme replacement therapy. The tracking continued after commencing PERT and was expanded to also include fat and protein entries. As a result, there was a useful dataset to compare the impacts of pancreatic enzyme replacement therapy on blood glucose outcomes and specifically, looking at glycemic variability changes!

(You can read an author copy here of the full paper and also see the supplementary material here, and the DOI for the paper is https://doi.org/10.1177/19322968221108414 . Otherwise, below is my summary of what we did and the results!)

In addition to the above background, it’s worth noting that Type 1 diabetes is known to be associated with EPI. In upwards of 40% of people with Type 1 diabetes, elastase levels are lowered, which in other cases is correlated with EPI. However, in T1D, there is some confusion as to whether this is always the case or not. Based on recent discussions with endocrinologists who treat patients with T1D and EPI (and have patients with lowered elastase that they think don’t have EPI), I don’t think there have been enough studies looking at the right things to assess whether people with T1D and lowered elastase levels would benefit from PERT and thus have EPI. More on this in the future!

Because we now have technology such as AID (automated insulin delivery) and CGM, it’s possible to evaluate things beyond simple metrics of “average blood sugar” or “A1c” in response to taking new medications. In this paper, we looked at some basic metrics like average blood sugar and percent time in range (TIR), but we also did quite a few calculations of variables that tell us more about the level of variability in glucose levels, especially in the time frames after meals.

Methods

This person had tracked carb entries through an open source AID system, and so carb entries and BG data were available from before they started PERT. We call this “pre-PERT”, and selected 4 weeks worth of data to exclude major holidays (as diet is known to vary quite a bit during those times). We then compared this to “post-PERT”, the first 4 weeks after the person started PERT. The post-PERT data not only included BGs and carb entries, but also had fat and protein entries as well as PERT data. Each time frame included 13,975 BG data points.

We used a series of open source tools to get the data (Nightscout -> Nightscout Data Transfer Tool -> Open Humans) and process the data (my favorite Unzip-Zip-CSVify-OpenHumans-data.sh script).

All of our code for this paper is open source, too! Check it out here. We analyzed time in range, TIR 70-180, time out of range, TOR >180, time below range, TBR <70 and <54, the number of hyperglycemic excursions >180. We also calculated total daily dose of insulin, average carbohydrate intake, and average carbohydrate entries per day. Then we calculated a series of variability related metrics such as Low Blood Glucose Index (LBGI), High Blood Glucose Index (HBGI), Coefficient of Variation (CV), Standard Deviation (SD), and J_index (which stresses both the importance of the mean level and variability of glycemic levels).

Results

This person already had an above-goal TIR. Standard of care goal for TIR is >70%; before PERT they had 92.12% TIR and after PERT it was 93.70%. Remember, this person is using an open source AID! TBR <54 did not change significantly, TBR <70 decreased slightly, and TOR >180 also decreased slightly.

More noticeably, the total number of unique excursions above 180 dropped from 40 (in the 4 weeks without PERT) to 26 (in 4 weeks when using PERT).

The paper itself has a few more details about average fat, protein, and carb intake and any changes. Total daily insulin was relatively similar, carb intake decreased slightly post-PERT but was trending back upward by the end of the 4 weeks. This is likely an artifact of being careful to adjust to PERT and dose effectively for PERT. The number of meals decreased but the average carb entry per meal increased, too.

What I find really interesting is the assessment we did on variability, overall and looking at specific meal times. The breakfast meal was identical during both time periods, and this is where you can really SEE visible changes pre- and post-PERT. Figure 2 (displayed below), shows the difference in the rate of change frequency. There’s less of the higher rate of changes (red) post-PERT than there is from pre-PERT (blue).

Figure 2 from GV analysis on EPI, showing lower frequency of high rate of change post-PERT

Similarly, figure 3 from the paper shows all glucose data pre- and post-PERT, and you can see the fewer excursions >180 (blue dotted line) in the post-PERT glucose data.

Figure 3 from GV analysis paper on EPI showing lower number of excursions above 180 mg/dL

Table 1 in the paper has all the raw data, and Figure 1 plots the most relevant graphs side by side so you can see pre- and post-PERT before and after after all meals on the left, versus pre and post-PERT before and after breakfast only. Look at TOR >180 and the reduction in post-breakfast levels after PERT! Similarly, HBGI post-PERT after-breakfast is noticeably different than HBGI pre-PERT after-breakfast.

Here’s a look at the HBGI for breakfast only, I’ve highlighted in purple the comparison after breakfast for pre- and post-PERT:

High Blood Glucose Index (HBGI) pre- and post-PERT for breakfast only, showing reduction in post-PERT after breakfast

Discussion

This is a paper looking at n=1 data, but it’s not really about the n=1 here. (See the awesome limitation section for more detail, where I point out it’s n=1, it’s not a clinical study, the person has ‘moderate’ EPI, there wasn’t fat/protein data from pre-PERT, it may not be representative of all people with diabetes with EPI or EPI in general.)

What this paper is about is illustrating the types of analyses that are possible, if only we would capture and analyze the data. There are gaping holes in the scientific knowledge base: unanswered and even unasked questions about what happens to blood glucose with various medications, and this data can help answer them! This data shows minimal changes to TIR but visible and significant changes to post-meal glycemic variability (especially after breakfast!). Someone who had a lower TIR or wasn’t using an open source AID may have more obvious changes in TIR following PERT commencement.

This paper shows several ways we can more easily detect efficacy of new-onset medications, whether it is enzymes for PERT or other commonly used medications for people with diabetes.

For example, we could do a similar study with metformin, looking at early changes in glycemic variability in people newly prescribed metformin. Wouldn’t it be great, as a person with diabetes, to be able to more quickly resolve the uncertainty of “is this even working?!” and not have to suffer through potential side effects for 3-6 months or longer waiting for an A1c lab test to verify whether the metformin is having the intended effects?

Specifically with regards to EPI, it can be hard for some people to tell if PERT “is working”, because they’re asymptomatic, they are relying on lab data for changes in fat soluble vitamin levels (which may take time to change following PERT commencement), etc. It can also be hard to get the dosing “right”, and there is little guidance around titrating in general, and no studies have looked at titration based on macronutrient intake, which is something else that I’m working on. So, having a method such as these types of GV analysis even for a person without diabetes who has newly discovered EPI might be beneficial: GV changes could be an earlier indicator of PERT efficacy and serve as encouragement for individuals with EPI to continue PERT titration and arrive at optimal dosing.

Conclusion

As I wrote in the paper:

It is possible to use glycemic variability to assess changes in glycemic outcomes in response to new-onset medications, such as pancreatic enzyme replacement therapy (PERT) in people with exocrine pancreatic insufficiency (EPI) and insulin-requiring diabetes. More studies should use AID and CGM data to assess changes in glycemic outcomes and variability to add to the knowledge base of how medications affect glucose levels for people with diabetes. Specifically, this n=1 data analysis demonstrates that glycemic variability can be useful for assessing post-PERT response in someone with suspected or newly diagnosed EPI and provide additional data points regarding the efficacy of PERT titration over time.

I’m super excited to continue this work and use all available datasets to help answer more questions about PERT titration and efficacy, changes to glycemic variability, and anything else we can learn. For this study, I collaborated with the phenomenal Arsalan Shahid, who serves as technology solutions lead at CeADAR (Ireland’s Centre for Applied AI at University College Dublin), who helped make this study and paper possible. We’re looking for additional collaborators, though, so feel free to reach out if you are interested in working on similar efforts or any other research studies related to EPI!

Findings from the world’s first RCT on open source AID (the CREATE trial) presented at #ADA2022

September 7, 2022 UPDATEI’m thrilled to share that the paper with the primary outcomes from the CREATE trial is now published. You can find it on the journal site here, or view an author copy here. You can also see a Twitter thread here, if you are interested in sharing the study with your networks.

Example citation:

Burnside, M; Lewis, D; Crocket, H; et al. Open-Source Automated Insulin Delivery in Type 1 Diabetes. N Engl J Med 2022;387:869-81. DOI:10.1056/NEJMoa2203913


(You can also see a previous Twitter thread here summarizing the study results, if you are interested in sharing the study with your networks.)

TLDR: The CREATE Trial was a multi-site, open-labeled, randomized, parallel-group, 24-week superiority trial evaluating the efficacy and safety of an open-source AID system using the OpenAPS algorithm in a modified version of AndroidAPS. Our study found that across children and adults, the percentage of time that the glucose level was in the target range of 3.9-10mmol/L [70-180mg/dL] was 14 percentage points higher among those who used the open-source AID system (95% confidence interval [CI], 9.2 to 18.8; P<0.001) compared to those who used sensor augmented pump therapy; a difference that corresponds to 3 hours 21 minutes more time spent in target range per day. The system did not contribute to any additional hypoglycemia. Glycemic improvements were evident within the first week and were maintained over the 24-week trial. This illustrates that all people with T1D, irrespective of their level of engagement with diabetes self-care and/or previous glycemic outcomes, stand to benefit from AID. This study concluded that open-source AID using the OpenAPS algorithm within a modified version of AndroidAPS, a widely used open-source AID solution, is efficacious and safe.

The backstory on this study

We developed the first open source AID in late 2014 and shared it with the world as OpenAPS in February 2015. It went from n=1 to (n=1)*2 and up from there. Over time, there were requests for data to help answer the question “how do you know it works (for anybody else)?”. This led to the first survey in the OpenAPS community (published here), followed by additional retrospective studies such as this one analyzing data donated by the community,  prospective studies, and even an in silico study of the algorithm. Thousands of users chose open source AID, first because there was no commercial AID, and later because open source AID such as the OpenAPS algorithm was more advanced or had interoperability features or other benefits such as quality of life improvements that they could not find in commercial AID (or because they were still restricted from being able to access or afford commercial AID options). The pile of evidence kept growing, and each study has shown safety and efficacy matching or surpassing commercial AID systems (such as in this study), yet still, there was always the “but there’s no RCT showing safety!” response.

After Martin de Bock saw me present about OpenAPS and open source AID at ADA Scientific Sessions in 2018, we literally spent an evening at the dinner table drawing the OpenAPS algorithm on a napkin at the table to illustrate how OpenAPS works in fine grained detail (as much as one can do on napkin drawings!) and dreamed up the idea of an RCT in New Zealand to study the open source AID system so many were using. We sought and were granted funding by New Zealand’s Health Research Council, published our protocol, and commenced the study.

This is my high level summary of the study and some significant aspects of it.

Study Design:

This study was a 24-week, multi-centre randomized controlled trial in children (7–15 years) and adults (16–70 years) with type 1 diabetes comparing open-source AID (using the OpenAPS algorithm within a version of AndroidAPS implemented in a smartphone with the DANA-i™ insulin pump and Dexcom G6® CGM), to sensor augmented pump therapy. The primary outcome was change in the percent of time in target sensor glucose range (3.9-10mmol/L [70-180mg/dL]) from run-in to the last two weeks of the randomized controlled trial.

  • This is a LONG study, designed to look for rare adverse events.
  • This study used the OpenAPS algorithm within a modified version of AndroidAPS, meaning the learning objectives were adapted for the purpose of the study. Participants spent at least 72 hours in “predictive low glucose suspend mode” (known as PLGM), which corrects for hypoglycemia but not hyperglycemia, before proceeding to the next stage of closed loop which also then corrected for hyperglycemia.
  • The full feature set of OpenAPS and AndroidAPS, including “supermicroboluses” (SMB) were able to be used by participants throughout the study.

Results:

Ninety-seven participants (48 children and 49 adults) were randomized.

Among adults, mean time in range (±SD) at study end was 74.5±11.9% using AID (Δ+ 9.6±11.8% from run-in; P<0.001) with 68% achieving a time in range of >70%.

Among children, mean time in range at study end was 67.5±11.5% (Δ+ 9.9±14.9% from run-in; P<0.001) with 50% achieving a time in range of >70%.

Mean time in range at study end for the control arm was 56.5±14.2% and 52.5±17.5% for adults and children respectively, with no improvement from run-in. No severe hypoglycemic or DKA events occurred in either arm. Two participants (one adult and one child) withdrew from AID due to frustrations with hardware issues.

  • The pump used in the study initially had an issue with the battery, and there were lots of pumps that needed refurbishment at the start of the study.
  • Aside from these pump issues, and standard pump site/cannula issues throughout the study (that are not unique to AID), there were no adverse events reported related to the algorithm or automated insulin delivery.
  • Only two participants withdrew from AID, due to frustration with pump hardware.
  • No severe hypoglycemia or DKA events occurred in either study arm!
  • In fact, use of open source AID improved time in range without causing additional hypoglycemia, which has long been a concern of critics of open source (and all types of) AID.
  • Time spent in ‘level 1’ and ‘level 2’ hyperglycemia was significantly lower in the AID group as well compared to the control group.

In the primary analysis, the mean (±SD) percentage of time that the glucose level was in the target range (3.9 – 10mmol/L [70-180mg/dL]) increased from 61.2±12.3% during run-in to 71.2±12.1% during the final 2-weeks of the trial in the AID group and decreased from 57.7±14.3% to 54±16% in the control group, with a mean adjusted difference (AID minus control at end of study) of 14.0 percentage points (95% confidence interval [CI], 9.2 to 18.8; P<0.001). No age interaction was detected, which suggests that adults and children benefited from AID similarly.

  • The CREATE study found that across children and adults, the percentage of time that the glucose level was in the target range of 3.9-10mmol/L [70-180mg/dL] was 14.0 percentage points higher among those who used the open-source AID system compared to those who used sensor augmented pump therapy.
  • This difference reflects 3 hours 21 minutes more time spent in target range per day!
  • For children AID users, they spent 3 hours 1 minute more time in target range daily (95% CI, 1h 22m to 4h 41m).
  • For adult AID users, they spent 3 hours 41 minutes more time in target range daily (95% CI, 2h 4m to 5h 18m).
  • Glycemic improvements were evident within the first week and were maintained over the 24-week trial. Meaning: things got better quickly and stayed so through the entire 24-week time period of the trial!
  • AID was most effective at night.
Difference between control and AID arms overall, and during day and night separately, of TIR for overall, adults, and kids

One thing I think is worth making note of is that one criticism of previous studies with open source AID is regarding the self-selection effect. There is the theory that people do better with open source AID because of self-selection and self-motivation. However, the CREATE study recruited a diverse cohort of participants, and the study findings (as described above) match all previous reports of safety and efficacy outcomes from previous studies. The CREATE study also found that the greatest improvements in TIR were seen in participants with lowest TIR at baseline. This means one major finding of the CREATE study is that all people with T1D, irrespective of their level of engagement with diabetes self-care and/or previous glycemic outcomes, stand to benefit from AID.

This therefore means there should be NO gatekeeping by healthcare providers or the healthcare system to restrict AID technology from people with insulin-requiring diabetes, regardless of their outcomes or experiences with previous diabetes treatment modalities.

There is also no age effect observed in the trail, meaning that the results of the CREATE Trial demonstrated that open-source AID is safe and effective in children and adults with type 1 diabetes. If someone wants to use open source AID, they would likely benefit, regardless of age or past diabetes experiences. If they don’t want to use open source AID or commercial AID…they don’t have to! But the choice should 100% be theirs.

In summary:

  • The CREATE trial was the first RCT to look at open source AID, after years of interest in such a study to complement the dozens of other studies evaluating open source AID.
  • The conclusion of the CREATE trial is that open-source AID using the OpenAPS algorithm within a version of AndroidAPS, a widely used open-source AID solution, appears safe and effective.
  • The CREATE trial found that across children and adults, the percentage of time that the glucose level was in the target range of 3.9-10mmol/L [70-180mg/dL] was 14.0 percentage points higher among those who used the open-source AID system compared to those who used sensor augmented pump therapy; a difference that reflects 3 hours 21 minutes more time spent in target range per day.
  • The study recruited a diverse cohort, yet still produced glycemic outcomes consistent with existing open-source AID literature, and that compare favorably to commercially available AID systems. Therefore, the CREATE Trial indicates that a range of people with type 1 diabetes might benefit from open-source AID solutions.

Huge thanks to each and every participant and their families for their contributions to this study! And ditto, big thanks to the amazing, multidisciplinary CREATE study team for their work on this study.


September 7, 2022 UPDATE – I’m thrilled to share that the paper with the primary outcomes from the CREATE trial is now published. You can find it on the journal site here, or like all of the research I contribute to, access an author copy on my research paper.

Example citation:

Burnside, M; Lewis, D; Crocket, H; et al. Open-Source Automated Insulin Delivery in Type 1 Diabetes. N Engl J Med 2022;387:869-81. DOI:10.1056/NE/Moa2203913

Note that the continuation phase study results are slated to be presented this fall at another conference!

Findings from the RCT on open source AID, the CREATE Trial, presented at #ADA2022

AID (APS) book now available in French!

Thanks to the dedicated efforts of Olivier Legendre and Dr. Mihaela Muresan, my book “Automated Insulin Delivery: How artificial pancreas “closed loop” systems can aid you in living with diabetes” (available on Amazon in Kindle, paperback, and hardcover formats, or free to read online and download at ArtificialPancreasBook.com) is now available in French!

The French version is also available for free download as a PDF at ArtificialPancreasBook.com or in Kindle (FR), paperback (FR), and hardcover (FR) formats!

 

French version of the AID book is now available, also in hardcover, paperback, and Kindle formats on Amazon

Merci au Dr. Mihaela Muresan et Olivier Legendre pour la traduction de l’intégralité de ce livre !

(Thank you to Dr. Mihaela Muresan and Olivier Legendre for translating this entire book!)

An example of the challenges of (constantly) titrating pancreatic enzyme replacement therapy (PERT)

As someone new to EPI who is also new to figuring out how to optimally dose my pancreatic enzyme replacement therapy (PERT), I’m constantly balancing the cost of PERT from prescription enzymes against the cost of over the counter enzymes.

I’ve personally calculated that one pill of my current dose of PERT covers about 30-4o grams of fat, and 30 grams of protein.

Meals with more than 30 grams of protein get 2 PERT pills, but meals with more than 40 or so grams of fat could be covered by 1 PERT pill and some OTC lipase.

But not all meals come with nutrition information, which makes titrating PERT at every single meal a challenge.

And, now that I’ve realized I’m likely not sensitive to all FODMAPs after all (hooray, although I may still have some slight sensitivity to massive amounts of onion or garlic), I’ve been able to eat a lot more takeout food from restaurants, both enthralling my taste buds and challenging my brain trying to estimate how much fat and protein there is in what I am choosing to eat.

I’ve been keeping careful notes of what I’m eating along with my fat and protein estimates and the results following each meal. Then, if I want to repeat or alter a similar meal, I can use my data and results to guesstimate my next PERT dosing.

For example, we have a local taco place that has done a really good job to enable online ordering with gluten-free and celiac tags in the order, so you can order digitally without having to talk to humans at the store. A few weeks ago, I ordered 3 tacos and some queso dip. It was delicious. I estimated it was more than 30g of protein, so I took 2 PERT with it.

However, while I didn’t have post-meal immediate symptoms, my next-day results were slightly off, and I made a note that I probably needed a little more lipase the next time I had that quantity of tacos.

Yesterday, I ordered 3 tacos again but decided to try a small “street corn” appetizer instead of queso. Corn is less fat and protein than queso, but I figured there was still >30g of protein from tacos like from before, so I took 2 PERT. This time, due to my notes, I added a few lipase to cover additional fat.

I had no immediate post-meal symptoms and felt great! However, today indicated that I did not have enough enzymes, and I’m suspecting that it’s because I swapped one of my taco types. Last time, I had a shrimp taco, but this time I tried a lamb taco for my third taco type. Even with the reduced fat and protein going from queso to corn, the increase in fat and/or protein (likely the protein, given my extra lipase) from shrimp to lamb meant that my meal was not optimally dosed.A gif showing three tacos and queso plus 2 PERT got ok results, but next time I swapped queso for corn and added lipase and still got it wrong, likely due to increased fat and protein in lamb instead of shrimp in one of the tacos.

 

Next time, I need to pay closer attention to what kind of tacos I eat as well as whether I get queso or not. If I did the same meal (three tacos, one of which is lamb, and corn), I’d probably experiment with 3 PERT to cover the suspected increased protein that I was missing with the 2 PERT + extra lipase. If I went back to a shrimp taco and queso, I’d probably re-try 2 PERT + extra lipase again.

PERT dosing, like insulin dosing, involves a lot of experimentation and some art, and some science, to try to get it right (or better) every time.

(PS, if you didn’t see them, I have other posts about EPI at DIYPS.org/EPI)

A Do-It-Yourself Protocol for Over-The-Counter Enzymes for Suspected Exocrine Pancreatic Insufficiency (EPI) Before Gaining Access to Pancreatic Enzyme Replacement Therapy (PERT)

A humorous side note – the title of this blog, DIYPS, stands for “do-it-yourself pancreas system”, the name I gave my first automated insulin delivery (AID) system, back in 2013. An AID system doesn’t fully replicate all functions of the pancreas, so we evolved from describing it as an artificial pancreas system (APS) to automated insulin delivery (AID). But now that I have exocrine pancreatic insufficiency and am doing quite a bit of DIY around titration of enzymes….the name of this blog feels more appropriate than ever.

After I started writing about exocrine pancreatic insufficiency, I’ve gotten a lot of questions from friends and connections who think they might have EPI. (And they are likely not wrong – there are estimates that as many as 40% of people with type 1 diabetes have lowered elastase levels. Alone, that doesn’t indicate EPI, but if symptomatic and you’ve already ruled out celiac and gastroparesis, it should be (in my opinion) high on the list of things to test for. Ditto for other types of diabetes and anyone with celiac disease.) Some people, though, may have delays in getting doctor’s appointments, and/or clinicians who aren’t (yet) willing to order the elastase or other EPI-related tests without testing for other things first.

This post is for that group of folks, and anyone stumbling across this post who has seen their test results for their fecal elastase testing indicating they have “moderate pancreatic insufficiency” or “severe pancreatic insufficiency” and are wondering what they can do while they wait for their doctor’s appointment.

It’s also for people with EPI who are struggling to afford their pancreatic enzyme replacement therapy (PERT) or are limiting the number or size of meals they eat as a result of the cost of PERT.

A bit of background on why I did the math about OTC enzyme cost and why I had tested them myself

Due to the holidays in December 2021 I had a lag between getting my test results (over Christmas) and then confirming that my doctor would write a prescription for PERT, and then a delay in getting it filled by the pharmacy since they had to order it. One of the things I did during that time was read up a lot about PERT and also look to see if there were any other kinds of enzymes that would be useful to take if my doctor didn’t want to prescribe me PERT. I found out that PERT contains THREE types of enzymes, and together they’re known as pancrelipase. Pancrelipase contains lipase (helps digest fat), protease (helps digest protein), and amylase (helps digest starches and other complex carbohydrates). It’s typically made from ground up pig pancreas, which is one of the reasons that PERT costs so much. Amylase from non-pancreatic sources is not widely available for human consumption, but there are some other ways to make protease and lipase. And it turns out that these standalone enzyme versions, often produced by microbes, are available to buy over the counter.

While waiting for my test to be ordered, I went ahead and ordered a standalone lipase product that is over the counter (OTC). In part, that was because some of the reviews for lipase talked about having EPI and how they were only sensitive to lipase, and so this was a viable and cheaper alternative for them rather than taking PERT with all 3 enzymes, since they didn’t need that. Based on my experience with FODMAPs and trying an enzyme powder to target fructans (which did help me some), it seemed like trying small doses of lipase would help if I did have EPI, and likely wouldn’t hurt even if I did not have EPI.

And it helped. It didn’t reduce all my symptoms, but even minor doses (3000 units of lipase) made a noticeable difference in my symptoms and I got a sense for what meals were more fat and protein-laden than others.

As a result, when my test results came in and I was on the borderline for moderate EPI, I agreed with my HCP that since it likely wouldn’t hurt to take PERT (other than the cost), and it would be obvious if it helped, that I should try PERT.

So having done the tests with OTC (over the counter) lipase was helpful for deciding to take PERT and advocating for my prescription.

And it turns out, wow yes, I do have EPI and do definitely need PERT (more about my first two weeks on PERT here).

And as I wrote here, because I had the OTC lipase sitting around, even after I finally had access to PERT, I eventually titrated my dosing and calculated separate ratios for lipase:fat and protease:protein, so I can decide for every meal or snack whether I need one full PERT (all three enzymes), two PERT, a PERT plus some lipase (and how much), or just a standalone OTC lipase. The cost differs greatly between those options: one PERT might be $9 and a standalone lipase pill around $0.26. You can’t break apart a PERT (e.g. take only half), so adding a few lipase is a cost-effective approach if you don’t need more protease or amylase and the OTC lipase works for you.

Some of the reasons to explore over the counter enzymes with exocrine pancreatic insufficiency or a suspected case of EPI

One interesting thing about one of the main tests (fecal elastase) used to assess EPI is that it is NOT impacted by taking enzymes. Someone who is started on pancreatic enzyme replacement therapy (PERT) can still have an elastase test without stopping taking PERT. So if someone had an inconclusive result or was borderline and started taking PERT, but their doctor wanted to re-test again, the use of PERT would not affect the test. The same goes for other types of enzymes.

I’ve realized that the following groups of people might want to investigate various OTC enzyme options:

  • Someone who has been diagnosed with EPI, but has done careful testing with meals of various sizes (low fat & high protein, high fat & low protein, etc.) to determine that they really only need lipase, may benefit from cheaper lipase-only OTC options.
  • Someone who has a test result for EPI but doesn’t yet have an appointment with their doctor or a prescription for PERT could start taking some OTC enzymes for quicker symptom relief, even if they ultimately want to use PERT for all their enzyme needs once they get their prescription filled.
  • Someone diagnosed with EPI who cannot afford the ideal dose of PERT that they need for their meals and snacks, may want to calculate the out of pocket costs for OTC lipase (not covered by insurance) vs the cost of PERT with or without insurance.
  • Someone who can’t get tested for EPI, but suspects they have EPI, might want to also explore OTC lipase and/or OTC multiple enzyme products.

However, not everyone with EPI will want OTC enzymes. Some people may have great insurance coverage, so their PERT costs them less than $9 a pill. OTC enzymes are not covered by insurance, but I’d still do the math and assess what your standard cost is per pill, because it may surprise you how cheap add-on OTC lipase is vs. your insurance deductible or copay to take additional PERT for larger meals. The other reason some people may not want to take OTC enzymes is the pill burden: OTC doses tend to be smaller, so you usually need to take more pills to cover the same meal as a single, larger PERT.

Picking what enzymes (in general, or specific brands) work for you

I often see a variety of OTC enzyme products recommended in peer groups on social media for EPI. There are no studies that I can find assessing the efficacy of these OTC brands (meaning, how good they are). I would be very cautious when trying different single or multiple enzyme products and keep a careful log of your symptoms from before enzymes as well as symptoms at every meal that you take enzymes, and your bathroom results afterward. This can help you assess OTC enzymes as well as PERT if you get access to it. By having a good log of your symptoms, you can tell if you’re taking enough enzymes (OTC or PERT) or if you’re developing new symptoms (which could be a side effect of whatever brand/type you are taking).

There are multiple brands and sizes of PERT, too, and it’s possible that a filler product or how the PERT is made by one brand doesn’t work well for you. If that’s the case, you can try another brand of PERT.

The same goes for OTC enzymes: it is very possible some types of pills may be made with ingredients that could bother you and cause symptoms themselves. You should definitely be very cautious if you go this route and explore small doses and ensure no side effects (no new symptoms) before increasing any doses.

When I search for lipase, it’s easy to find standalone lipase (here is an example, as an Amazon affiliate link). When I search for protease, it’s more common to find products that are multiple enzymes (e.g. lipase AND protease AND other random things that are “good for digestion”). Personally, I’m very wary of anything OTC that’s described as “digestive enzymes” and prefer to stick to products that only have the ingredients I’m looking for.

A pro-con list for over the counter (OTC) enzymes for EPI. Pros include: lower cost overall and per pill; that you can take smaller quantities of individual enzymes; and you can buy them without a prescription. Cons include: it's not covered by insurance so cost is out of pocket; you have to take more pills with smaller amounts of enzymes; it's not regulatory approved so othere are no studies on efficacy; and providers may not be able to advise for titration.
In diabetes, we often say “your diabetes may vary” (YDMV), indicating that different people can have different experiences.

In EPI, it’s no different – “your digestion may vary” and it’s important to test and record and find what works for you, and to find a balance of reducing or eliminating symptoms with enzymes in a cost-effective way that you can afford.

(PS, if you didn’t see them, I have other posts about EPI at DIYPS.org/EPI)

Cost calculations of Pancreatic Enzyme Replacement Therapy (PERT) for Exocrine Pancreatic Insufficiency (EPI) and alternative over the counter enzyme products

I previously wrote about my experience figuring out that I have exocrine pancreatic insufficiency (known as EPI or PEI), and also a little bit about starting on pancreatic enzyme replacement therapy (PERT). I talked briefly about the method I was using to figure out the right amount of PERT for me, but I realize that there’s a lot more detail I could provide about how to titrate enzymes in general, and not just PERT.

Some background first, though. When I write about PERT (pancreatic enzyme replacement therapy), I am talking about the FDA-approved class of drugs (called “pancrelipase”) that contain THREE types of enzymes, which the FDA calls “pancreatic enzyme products” or PEPs. Pancrelipase contains lipase (helps digest fat), protease (helps digest protein), and amylase (helps digest starches and other complex carbohydrates). As of 2010, all pancrelipase products that are marketed for EPI must be FDA approved.

Any time I refer (here or in other blog posts) to other enzyme products (either single enzyme or multi-enzyme), I’m referring to over the counter products that are not FDA approved.

Why does FDA approval matter for PEPs? FDA approval is essentially a rubber stamp saying you can trust the FDA to have validated that the companies making these products are making them as they describe them, meaning if they say they have 25,000 units of lipase, they actually have 25,000 units of lipase in them. (And protease and amylase). FDA-approved PEPs used in PERT are made from ground up pig pancreas (really), which is why they’re expensive. There is no generic PEP or PERT. (FDA also has a nice page here explaining the importance of understanding what is and is not an approved PEP/PERT product, and it also explains the brands that are currently approved and the differences between them.) This matters because when you talk about the cost people will probably suggest a “generic” of PERT, but there isn’t one.

However, there are non-FDA-approved over the counter enzyme products. They do exist, but because they have not been vetted by the FDA, I (and you!) should be wary about trusting them when they say they contain X units of lipase or any other enzyme product. Additionally, there are no studies (that I can find) comparing the efficacy between over the counter enzymes (single or multi-enzyme products) and FDA-approved PERT. (If you have found such a study, please leave a comment!)

So does that mean you can’t take them? No, I’m not saying that. What I am saying is you should only try other products with enzymes if you are willing to carefully test and vet FOR YOURSELF whether they work FOR YOU or not. (P.S. – did I mention I’m not a doctor? This is not medical advice; for medical advice, talk with your doctor. Although, doctors may not be aware of the over the counter enzyme options either, and this post might be worth sharing with them as well).

Three goals for optimally titrating enzymes for exocrine pancreatic insufficiency

I have three goals for getting my PERT dose titrated well.

  • First, get enough enzymes (through PERT) to reduce all symptoms.
  • Second, test and assess my lipase:fat and protease:protein ratios so I can figure out how to optimally dose enzymes for new meals of different amounts of fat and protein.
  • Third, optimize for reducing cost with enzymes, through a combination of supplementing PERT with standalone lipase and/or using lipase for fat-only snacks.

Here’s an example of how you might consider vetting over the counter enzyme products, and using them to supplement your FDA-approved (and hopefully insurance-covered) PERT:

As I mentioned earlier, I titrated and found out that my current dose of PERT covers about 30-40 grams of fat and 30 grams of protein. Some individuals only need support in digesting fat (e.g., need only lipase), but I have found that my body also needs support in digesting protein. (However, I don’t appear to need much amylase for carbohydrates.) Therefore I am tracking what amount of fat and protein I am eating with every meal. A 25,000 (lipase) dose of my PERT also contains enough protease to cover 30 grams of protein. Sometimes, I eat higher (>30-40g) fat meals that mean I need more lipase. So I would need two pills of the current dose of PERT, because 25,000 only covers ~30-40g of fat (FOR ME).

But – what if there was another way to get additional lipase without needing a full second pill of PERT, if I don’t need the additional support for more protein for this meal?

Enter over the counter enzyme options. In this example, a single enzyme option for lipase. Here is an example (Amazon affiliate link) to a standalone, single enzyme lipase product that is available as an over the counter product.

I personally have experimented with using standalone over the counter lipase to supplement my PERT dose, for the reason described above (needing more lipase but not necessarily needing more protease or amylase). The reason I would choose standalone lipase has to do with cost.

PERT, being ground up pig pancreas, is expensive. There is no generic for PERT! However, there have been methods to develop lipase from microbes as well as other sources beyond animals. Thus, it is possible to have a standalone source of lipase that is a lot cheaper than PERT. How much cheaper? Well, the bottle linked above when I calculated this was $23.50 for 90 pills. One pill each contains roughly 3,150 units of lipase (again, caveat from above about trusting the amount in over the counter products). That means each pill ($23.50/90 pills) is $0.26 USD, and each 1,000 units of lipase is roughly $0.08.

This math is then helpful to compare the cost of PERT. Depending on the size of prescription PERT, you might see a prescription anywhere from 3,000 to 25,000 to 36,000 units (depending on the brand, they have different amounts, but they are all measured based on units of lipase). Using GoodRx, you can generally compare retail prices of medications, such as this search for 24,000 PERT of one brand (90 capsules) or this search for 25,000 PERT of a different brand (also 90 capsules). Both of them are in the ballpark (for 90 capsules each) of $700-900, so let’s use $800 for 90 capsules for simple math. The per-pill price is $8.89 ($800/90 pills). The per-1,000 unit of lipase cost depends on whether you are using the 24,000 PERT ($8.89/24) or 25,000 PERT ($8.89/25) option, but those are roughly $0.37 and $0.36 per 1000 units of lipase.

So if you were to consume a meal that was ~10g of fat above your current PERT dose, and you didn’t need additional protein support, it would be cheaper to add on additional lipase (at $0.08 per 1000 units of lipase) as a standalone enzyme product instead of an additional PERT (which is, per our estimates, ~$0.36 per 1000 units of lipase). You don’t get to break apart a PERT (It can’t be cut in half, for example), so the per-pill cost is the better comparison. Adding a 3000-ish unit lipase onto your meal to cover an additional 10g of fat costs $0.26, and a second PERT is $8.89.

Therefore, a meal that needs 28,000 lipase is cheaper as 1 PERT and 1 extra standalone lipase rather than 2 PERT.

This of course assumes you have tested the standalone lipase and found that it works for you. I personally have done so and found that standalone lipase of the brand I chose works for this purpose (there are many brands and sizes: again, test what works for you), so I can titrate my meals as PERT+lipase, or even take 1-2 lipase (depending on the fat content) for a snack that’s mainly fat. However, again, a caveat that I personally am sensitive to protein and am tracking everything that I’m eating, so I know my personal math very well. Typical PERT dosing and recommendations is to take “2 or more” for meals or “1-2 for snacks”, but that completely ignores how much fat and protein is in the meals, and might be significantly undertreatment or overtreatment for you.

Why does undertreatment matter? Well, you get symptoms. Those are no fun.

Why does overtreatment matter? Well, you can get constipation. (I haven’t had it, but it also doesn’t sound like fun). At the extreme end of the scale, there is also a risk of fibrosing colonopathy if you take more than certain units per kg of body weight for a long time. (If you’re concerned about this issue and haven’t discussed it with your doctor, do so – they should be able to tell you where the risk threshold is based on your personal body weight if you don’t want to calculate it yourself).
A gif showing a square moving along a spectrum from "too little" to "too much enzyme". Too little enzyme and you have symptoms, not enough and you reduce but don't eliminate symptoms. Enough enzymes and you eliminate symptoms. Too much risks constipation.

My approach was making sure my meals were covered first with prescription PERT, then evaluating additional standalone products that I could use to supplement or replace PERT depending on what I was eating, so I could prioritize reducing symptoms and then for improving the cost required to achieve that.

There are other standalone enzyme products, including products containing multiple enzymes. If you join one of the Facebook groups for EPI, you’ll see people recommencing various names of enzymes for over the counter products. But again, you really should test things and see if they work for you. Read all the ingredients on any product you’re taking. A lot of times you can search for lipase and you’ll get a multiple-enzyme product. And that product may have additional ingredients or fillers that don’t sit well with you. You may even find that one brand of prescription PERT might not work for you, whereas another one does.

My suggestions include:

  • Carefully test any product, whether it’s PERT or over the counter enzymes. Keep a good log of your post-meal symptoms and next-day symptoms (e.g. bathroom results) and try different meals with different amounts of fat and protein.
  • If you have symptoms regularly with a certain amount of enzymes, it could be either that this particular brand (over the counter or even prescription PERT) does not work well for you, OR that you are not taking enough enzymes to cover your needs.
  • If in doubt, talk with your doctor. They may/not have opinions on over the counter products, especially if they haven’t had other patients reporting back what is working for them or not, since there are no studies on those particular brands (and of course, they’re not FDA approved). But with approved PERT, they should be able to give you some more input on how to increase your dose or change your prescription to adjust. Having the data on how much fat and protein you’re eating and what results you’ve been getting could help you (and them) get to a more optimal dose more quickly.

(PS, if you didn’t see them, I have other posts about EPI at DIYPS.org/EPI)

What You Should Know About Exocrine Pancreatic Insufficiency (EPI) or Pancreatic Exocrine Insufficiency (PEI)

I have a new part-time job as a pancreas, but this time, I don’t have any robot parts I can make to help.

This is a joke, because I have had type 1 diabetes for 19+ years and 7 years ago I helped make the world’s first open-source artificial pancreas, also known as an automated insulin delivery system, that we jokingly call my “robot parts” and takes care of 90+% of the work of living with type 1 diabetes. PS if you’re looking for more information, there’s a book for that, or a free 3 minute animated video explaining automated insulin delivery. 

The TL;DR of this post is that I have discovered I have a mild or moderate exocrine pancreatic insufficiency, known as EPI (or PEI, pancreatic exocrine insufficiency, depending on which order and acronym you like). There’s a treatment called pancreatic enzyme replacement therapy (PERT) which I have been trying.

It took a long time for me to get diagnosed (almost 2 years), so this post walks through my history and testing process with my gastroenterologist (GI doctor) and the importance of knowing your own body and advocating for yourself when something is wrong or not quite right.

Background

About six years after I was diagnosed with type 1 diabetes, I was doing a summer internship in Washington, D.C. (away from home) and started getting chest tightness and frequent abdominal pain. Sometimes it felt like my abdominal muscles were “knitting” into each other. Because I had type 1 diabetes, I had heard at one point that about 10% of people with type 1 also develop celiac disease. So, thankfully, it was as simple as calling my endocrinologist and scheduling testing, and getting an endoscopy and biopsy to confirm I had celiac disease. It took about 2 months, and the timing was mostly that long due to getting back to Alabama after my internship and the testing schedule of the hospital. This is relevant detail, because I later read that it takes an average of 7 years for most people to get diagnosed with celiac disease. That has been floating around in my brain now for over a decade, this awareness that GI stuff is notoriously hard to diagnose when you’re not lucky enough to have a clear idea, like I did, of an associated condition.

So, with type 1 diabetes and celiac disease, I use automated insulin delivery to get great outcomes for my diabetes and a 100% very careful gluten-free diet to manage my celiac disease, and have not had any GI problems ever since I went gluten-free.

Until January/February 2020, when I took an antibiotic (necessary for an infection I had) and started to get very minor GI side effects on day 5 of the 7-day antibiotic course. Because this antibiotic came with a huge warning about C. diff, and I really didn’t want C. diff, I discontinued the antibiotic. My infection healed successfully, but the disruption to my GI system continued. It wasn’t C. diff and didn’t match any of the C. diff symptoms, but I really lost my appetite for a month and didn’t want to eat, so I lost 10 pounds in February 2020. On the one hand, I could afford to lose the weight, but it wasn’t healthy because all I could bring myself to eat was one yogurt a day. I eventually decided to try eating some pecans to add fiber to my diet, and that fiber and change in diet helped me get back to eating more in March 2020, although I generally was eating pecans and dried cranberries (to increase my fiber intake) for breakfast and wasn’t hungry until late afternoon or early evening for another meal. So, since my body didn’t seem to want anything else, I essentially was eating two meals a day. My GI symptoms were better: not back to how they were before February 2020, but seemed manageable.

However, in July 2020, one night I woke up with incredibly painful stabbing abdominal pain and thought I would need to go to the ER. Thankfully, it resolved enough within minutes for me to go back to sleep, but that was scary. I decided to schedule an appointment with my gastroenterologist. I took in a record of my symptoms and timing and explained what was most worrisome to me (sudden stabbing pains after I ate or overnight, not seemingly associated with one particular type of food; changes in bathroom habits, like steatorrhea, but not as severe as diarrhea). He made a list of suspected things and we began testing: we checked for C. diff (nope), parasites (nope), bloodwork for inflammation (nope, so no Crohn’s or IBS or IBD), my celiac markers to make sure I wasn’t being accidentally glutened (nope: 100% gluten-free as proven by the blood work), H. pylori (nope), and did a CT scan to check for structural abnormalities (all good, again no signs of inflammation or any obvious issues).

Because all of this happened during the global COVID-19 pandemic, I was cautious about scheduling any in-person tests such as the CT scan or the last test on my list, a colonoscopy and endoscopy. I have a double family history of colon cancer, so although it was extremely unlikely, given everything else on the list was coming back as negative, it needed to be done. I waited until I was fully vaccinated (e.g. 2 weeks after 2 shots completed) to have my colonoscopy and endoscopy scheduled. The endoscopy was to check for celiac-related damage in my small intestine since I hadn’t had an endoscopy since my diagnosis with celiac over a decade ago. Thankfully, there’s no damage from celiac (I wasn’t expecting there to be any damage, but is a nice confirmation of my 100% very careful gluten free diet!), and the colonoscopy also came back clear.

Which was good, but also bad, because…SOMETHING was causing all of my symptoms and we still didn’t know what that was. The last thing on my doctor’s list was potentially small intestine bacterial overgrowth (SIBO), but the testing is notoriously non-specific, and he left it up to me as to whether I decided to treat it or not. Having run out of things to test, I decided to do a two-week course of an antibiotic to target the bacteria. It helped for about two weeks, and then my symptoms came back with a vengeance. However, I had realized in spring 2021 (after about 9 months of feeling bad) that sometimes the stabbing abdominal pain happened when I ate things with obvious onion or garlic ingredients, so January-July 2021 I had avoided onion and garlic and saw a tiny bit of improvement (but nowhere near my old normal). Because of my research on onion and garlic intolerances, and then additional research looking into GI things, I realized that the low FODMAP diet which is typically prescribed for IBS/IBD (which I don’t have) could be something I could try without a lot of risk: if it helped, that would be an improvement, regardless of whatever I actually had.

So in August 2021, as noted in this blog post, I began the low FODMAP diet first starting with a careful elimination phase followed by testing and adding foods back into my diet. It helped, but over time I’ve realized that I still get symptoms (such as extreme quantities of gas, abdominal discomfort and distention, changed bathroom habits) even when I’m eating low FODMAP. It’s possible low FODMAP itself helped by avoiding certain types of food, but it’s also possible that it was helping because I was being so careful about the portions and timing of when I was eating, to avoid “stacking” FODMAPs.

One other thing I had tried, as I realized my onion and garlic intolerance was likely tied to being “fructans”, and that I had discovered I was sensitive to fructans in other foods, was an enzyme powder called Fodzyme. (I have no affiliation with this company, FYI). The powder works to target the FODMAPs in food to help neutralize them so they don’t cause symptoms. It worked for me on the foods I had experimented with, and it allowed me to eat food that had onion powder or garlic powder listed as a minor ingredient (I started small and cautious and am working my way up in testing other foods and different quantities). I longingly wished that there were other enzymes I could take to help improve digestion, because Fodzyme seemed to not only reduce the symptoms I had after I ate, but also seemed to improve my digestion overall (e.g. improved stool formation). I did some research but “digestive enzymes” are generally looked down upon and there’s no good medical research, so I chalked it up to snake oil and didn’t do anything about it.

Until, oddly enough, in November 2021 I noticed a friend’s social media post talking about their dog being diagnosed with exocrine pancreatic insufficiency (EPI). It made me go look up EPI in humans to see if it was a thing, because their experience sounded a lot like mine. Turns out, EPI is a thing, and it’s very common in humans who have cystic fibrosis; pancreas-related surgeries or pancreatic cancer; and there is also a known correlation with people with type 1 diabetes or with celiac disease.

Oh hey, that’s me (celiac and type 1 diabetes).

I did more research and found that various studies estimate 40% of people with type 1 diabetes have low levels of pancreatic elastase, which is a proxy for determining if you have insufficient enzymes being produced by your pancreas to help you digest your food. The causal mechanism is unclear, so they don’t know whether it’s just a ‘complication’ and side effect of diabetes and the pancreas no longer producing insulin, or if there is something else going on.

Given the ties to diabetes and celiac, I reached out to my GI doctor again in December 2021 and asked if I should get my pancreatic elastase levels tested to check for exocrine pancreatic insufficiency (EPI), given that my symptoms matching the textbook definition and my risk factors of diabetes and celiac. He said sure, sent in the lab request, and I got the lab work done. My results are on the borderline of ‘moderate’ insufficiency, and given my very obvious and long-standing symptoms, and given my GI doc said there would be no harm from trying, I start taking pancreatic enzyme replacement therapy (called PERT). Basically, this means I swallow a pill that contains enzymes with the first bite of food that I eat, and the enzymes help me better digest the food I am eating.

And guess what? For me, it works and definitely has helped reduce symptoms after I’m eating and with next-day bathroom habits. So I consider myself to have mild or moderate exocrine pancreatic insufficiency (EPI).

(Also, while I was waiting on my test results to come back, I found that there is a lipase-only version of digestive enzymes available to purchase online, so I got some lipase and began taking it. It involves some titration to figure out how much I needed, but I saw some improvement already from low doses of lipase, so that also led me to want to try PERT, which contains all 3 types of enzymes your pancreas normally naturally produces, even though my elastase levels were on the borderline of ‘moderate’ insufficiency. Not everyone with lower levels of elastase has insufficiency in enzymes, but my symptoms and response to lipase and PERT point to the fact that I personally do have some insufficiency.)

More about my experiences with exocrine pancreatic insufficiency

Unfortunately, there is no cure for exocrine pancreatic insufficiency. Like Type 1 diabetes, it requires lifelong treatment. So, I will be taking insulin and now PERT likely for the rest of my life. Lazy pancreas! (Also, it’s possible I will need to increase my PERT dose over time if my insufficiency increases.)

Why treat EPI? Well, beyond managing very annoying symptoms that impact quality of life, if left untreated it’s associated with increased mortality (e.g. dying earlier than you would otherwise) due to malnutrition (because you’re not properly absorbing the nutrients in the food you’re eating) and bone density problems.

Oddly enough, there seem to be two versions of the name (and therefore two acronyms) for the same thing: EPI and PEI, meaning exocrine pancreatic insufficiency or pancreatic exocrine insufficiency. I haven’t found a good explanation for why there are two names and if there are any differences. Luckily, my research into the medical literature shows they both pop up in search results pretty consistently, so it’s not like you end up missing a big body of literature if you use one search term or the other.

Interestingly, I learned 90% of people with cystic fibrosis may need PERT, and thankfully my friend with CF didn’t mind me reaching out to ask her if she had ever taken PERT or had any tips to give me from her knowledge of the CF community. That was nice that it turns out I do know some other people with EPI/PEI, even though they don’t usually talk about it because it seems to go hand in hand with CF. Some of the best resources of basic information about EPI/PEI are written either by CF foundations or by pancreatic cancer-related organizations, because those are the two biggest associated conditions that also link to EPI/PEI. There are also other conditions like diabetes and celiac with strong correlations, but these communities don’t seem to talk about it or have resources focused on it. (As with low FODMAP resources where everything is written for IBS/IBD, you can extrapolate and ignore everything that’s IBS/IBD specific. Don’t be afraid to read EPI/PEI information from communities that aren’t your primary community!)

Sadly, like so many GI conditions (remember in the intro I referenced 7 years average diagnosis time with celiac), it seems ridiculously hard to get to a diagnosis of EPI. I essentially self-diagnosed myself (and confirmed the diagnosis in partnership with my GI doc who agreed to run the tests). I am still very surprised that it never came up on his list of possible conditions despite having symptoms that are textbook EPI and having diabetes and celiac, which are known correlations. Apparently, this is common: I read one study that says even people with super high-risk factors (e.g. pancreas surgery, pancreatic cancer) aren’t necessarily screened, either! So it’s not just me falling through the cracks, and this is something the gastroenterology world needs to be better about. It’s also common for patients to bring this up to their doctors vs their doctors suggesting it as a potential diagnosis – this study found 24% of people brought up EPI, like I did, to their doctors.

Also, unfortunately, I had a few people (including family members) suggest to me in the last two years that my symptoms are psychosomatic, or stress-related. They’re clearly, as proven by lab work, not psychosomatic or stress-related but are a result of my exocrine pancreatic functions failing. Please, don’t ever suggest someone dealing with GI issues is experiencing symptoms due to stress – this is the kind of comment you should keep to yourself. (The last time someone mentioned this to me was months ago, and it still bothers me to think about it.)

Advocate for yourself

One of the very important things I learned early on when living with type 1 diabetes was the importance of knowing my own body, and advocating for myself. This unfortunately was a hard lesson learned, because I had general practice (GP or primary care / PCP) doctors who would refuse to treat me because I had diabetes because they were concerned about prescribing something that would mess up my blood sugars. They’d completely ignore the point that whatever infection I had would cause MORE disruption to my blood sugars by having me be sick and suffer longer, than I would have disruption to my blood sugar levels from a prescription. Sigh. So for the last almost two decades, I have had to go into every health encounter prepared to advocate for myself and make sure I get the medical expertise for whatever I’m there for, and not the less experienced take on diabetes (assuming I wasn’t there for diabetes, which I usually wasn’t).

This has translated into how I approached finding solutions for my GI symptoms. Per my history described above, I had increasing but minor GI symptoms from February-July 2020. Having new, stabbing pains in my abdomen led me to the gastroenterologist for a long list of testing for various things, but I had to continue to push for the next round of testing and schedule and manage everything to proceed through the list we had discussed at my appointment. Later, after we ran through the list, I had to try things like low FODMAP for myself, and then do additional research and identify the test for EPI as a likely next step to try.

I felt a little like the ‘boiling frog’ analogy, where my symptoms gradually worsened over time, but they weren’t startling bad (except for the points in time when I had stabbing abdominal pain). Or the two times, almost one year apart (Oct 2020 and Dec 2021) where I had what I considered bad “flares” of something where I got really hot and feeling really ill all of a sudden, but it wasn’t COVID-19 and it wasn’t anything specific causing it, there were no obvious food triggers, and the only thing I could do was lay down for 2-3 hours and rest before I started to feel better. Those were probably correlated with “overdoing it” with physical activity, but I’ve also run a marathon and a 50k ultramarathon in the last year and didn’t have problems on those days, so there’s not a certain threshold of activity that appears to cause that. Thankfully, that has only happened two times.

Other than those scenarios, it wasn’t like breaking my ankle where there was a clear “everything was fine and now something is broken”, but it was more like “I have had not-good-digestion and various increasing GI symptoms that don’t fit any clear problem or diagnosis on our shortlist of the 5 likely things it might be. It’s not excruciating but it is increasingly impacting my quality of life, and twisting myself into a pretzel with an evolving pattern of dietary modifications is not solving it”. It took me continuing to advocate for myself and not accepting suffering for the rest of my life (hopefully!) with these symptoms to get to an answer, which for me, so far, seems to be moderate exocrine pancreatic insufficiency.

What it’s like to start taking pancreatic enzyme replacement therapy (PERT)

PERT is typically measured by the units/amount of lipase it contains, even though it contains all 3 types of enzymes. (Some of the Medicare documents in different states actually are really helpful for comparing the size of dosing across the different brands of PERT. That also helped me look up the various brands in my insurance plan to see whether there would be a price difference between two of the most common brands.) Depending on symptoms and your level of insufficiency, like insulin, it requires some titration to figure out the right doses. I’ve been attempting to track generally the amount of fat that I’m eating to try to get a sense of my “ratio” of fat to lipase needed, although the research shows there is likely not a linear correlation between grams of fat and units of lipase needed. Another way to think about it is at what level of grams of fat in your meal do you need more than your current dose. For example, one pill of PERT at my current dose seems to work up to around 70 or so grams of fat per meal, as long as it doesn’t have more than 50% protein. Meals containing much more fat (120 g or so) definitely require more, as do meals with either a higher quantity of protein or a closer ratio of 1:1 fat to protein.

Different people have different needs with regard to whether they need enzyme support “just” for fat, or also for protein and carbs. I appear to at least need some support for carbs as well as protein, but am still establishing at what levels I need which dosing of which enzymes.

Personally, I am tracking to see whether my symptoms are reduced or eliminated in the hours following my meals (gas, abdominal discomfort, a sick feeling after eating) as well as the next day (bloating/abdominal distension, bathroom habits such as reduced steatorrhea), and overall whether I have any more of those really bad “flares”. My initial tests of taking PERT show improvements after my meals (I don’t feel sick after I eat anymore!) and often the next day.

After the first few days of trying food that was low FODMAP but giving me minor symptoms before PERT, I’ve also felt confident enough to try meals that I’ve avoided eating for over a year, such as a gluten free burger from one of our nearby local favorites! Even though it’s been well over a year since I’ve had it last, I immediately could tell a difference in how I felt eating it, due to taking PERT with it. There was no wave of fatigue before I was halfway through the burger, and no gas or feeling sick to my stomach after eating. I had clearly forgotten what it was like to not feel miserable after eating and to actually enjoy eating food! So far, PERT has been exceeding my expectations (although those were rather low).

It makes it slightly less annoying, then, to think about the price of PERT. Roughly, one month of PERT at the dosage I’m currently on costs the same as 3 vials of insulin in the US (in the ballpark of $800). Like insulin, PERT is necessary and worthwhile (and thankfully I do have health insurance).

Pancreases are great when they work…and expensive to replace!

A play on the spiderman meme of two spiderman's pointing at each other, indicating similar things. Labeled "exocrine pancreatic functions" and "endocrine pancreatic functions", indicating both of mine are not working as they should be.

TLDR: I have a new thing, exocrine pancreatic insufficiency, to deal with. Thankfully, there’s a treatment (PERT) that I can use to reduce symptoms and hopefully limit the potential impacts on morbidity long term. If you have diabetes or celiac and you have unexplained GI symptoms over time, you might want to do some research into EPI and discuss it with your gastroenterologist.

Also…for any endocrinologist reading this…or any other healthcare providers…if you have patients with diabetes and suspected GI issues, please consider EPI as a possible diagnosis once you’ve ruled out celiac disease and other likely suspects. Given the high rates of lowered elastase in all types of diabetes, it’s worth screening for EPI in patients with otherwise-unexplained steatorrhea or similar symptoms.