Dana Lewis

The multivariable equation that is running with type 1 diabetes, celiac disease, and exocrine pancreatic insufficiency

by Dana Lewis

I’ve written in the past about running with type 1 diabetes. I’ve tried running fasted, which works well in one sense because I have no extra insulin on board. I’ve modified my strategy further to run 2 or more hours after breakfast, so I have fuel but don’t have (much) IOB. But as I’ve extended my forays deeper into longer distance ultrarunning, and as I learned I have exocrine pancreatic insufficiency (EPI), running is getting a little more complicated.

For past thoughts on T1D running, here’s my post on running fasted and thinking about IOB. I also wrote more here last year about marathon and 50k ultramarathon training and how I use small doses of carbs to “correct” for dipping blood sugars. Last year, my body didn’t seem to need or want much additional fuel, so I didn’t force it. Part of that was likely a symptom of my undiscovered EPI. Now, however, that I am taking enzymes for pancreatic enzyme replacement therapy so I can digest what I eat, I have more energy (because my body is actually using what I eat), but I also get hungry and seem to need more fuel while running. But everything I eat needs enzymes to help me digest it, even things that I eat while ultrarunning.

So…it’s complicated to run with type 1 diabetes and micromanage insulin and carbs to manage blood glucose levels; and I’m limited in my fuel choices because I have celiac disease; and now I have to also carry, titrate, and dose enzymes for any fuel that I eat on the run as well.

Oh, and like insulin, the timing of enzymes matters. But there are no studies on enzyme digestion and how that changes during exercise, let along endurance activities like ultrarunning. So I am running in the dark, so to speak, trying to figure out things myself as I go along.

Here is more detail about what I’m doing and why I’m constantly running multivariable equations in my head while training for a 50k, 50 mile, and maybe even 100 mile run later this year:

First and foremost, managing blood sugar levels comes first.

I wear a CGM, so I can see how my blood sugar (BG) is changing during the run. I have a pump, so I can make any changes to insulin dosing. I also have an open source AID system (OpenAPS), so before running I set a higher target which tells the system not to give me as much insulin as it would otherwise. (It also does an awesome job with post-run insulin sensitivity changes! But that’s another post.) As I’ve previously written about, reducing insulin on board (IOB) when I know I’ll be running is the important first step, so I don’t have to start taking carbs and treating a low at the start of my run. Usually, my open source AID and I (by giving it a temporary target) do a good job getting me to my run start without much IOB, and ideally somewhere around 120-130 mg/dL.

From that level area, I can see rises and dips in BGs and dose accordingly. I carry easily dissolving small mint-like candies that are a few carbs (3-4g), or Airhead minis (8g of carbs), and with any dip below 120 or recurring drop that’s not coming up after 15 minutes since my last carb, I take more. These are pretty much straight sugar, and my body seems to do ok with absorbing carbs without enzymes, as long as there is no fat or protein involved.

However, with ultrarunning it’s generally considered to be ideal to proactively be consuming fuel to balance out the energy that you’re burning. Again, this is where I’m less experienced because for the last years, my body never wanted fuel and I did ok. However, now I seem to need fuel, so I’m working on figuring this out because food typically has some fat and protein, and I have to dose enzymes for it.

I carry a baggy with some single-enzyme (lipase) pills and some multi-enzyme (lipase for fat, amylase for carbs, and protease for protein) pills. I carry carefully measured single-serving snacks that I know the fat and protein quantity of. For each snack, I might need 1-2 enzyme pills of various sorts.

Timing matters: I can’t take enzymes and then snack slowly for 30 minutes. To eat slowly, I would need to take enzymes every 10-15 minutes to match the speed of eating so it will ultimately be there to help the food digest.

But, more carbs/food at once has an effect on how I feel while running and also to my BGs. I’ve tried to find things I love to eat running and can eat within 5 minutes – even while running 30 seconds and walking 60 seconds repeatedly – that are also less than 1-2 enzyme pills worth of fat and protein and aren’t too many carbs at once. These may be 15-20g carb snacks which means a bigger impact to my BG levels, and I may need to even do a small bolus (give insulin) for what I am eating. The challenge again is that food can hit BGs in about 15 minutes but it takes ~45 minutes for insulin activity to peak. And, during exercise, I’m more sensitive to insulin than I normally am. There’s no magical calculation to know how much “more” sensitive I am in the midst of a run, so I have to guess and thread the needle between not giving too much insulin that would cause a low BG but giving enough so I don’t spike above 180 mg/dL, which is what makes me feel icky while running.

Preferably, and very personally, I’d like to float up and down between 120-140 mg/dL or 130-150 mg/dL, which is higher than BGs usually hang out for me without exercise (remember: open source AID!), but is high enough that I have buffer against a low, so if I suddenly dip and I haven’t looked at my BGs in 15 minutes, I can usually still carb up and prevent an annoying low. (Lows matter even more on runs because they slow me down physically, which is usually not what I’m going for.)

It doesn’t always work that way. Sometimes I undershoot the insulin because I’ve miscalculated my effort running, and my BG drifts high and I have to decide whether or not to correct further. Other times, I overshoot (or have increased my run effort and didn’t take that into consideration) and cause BG to dip or dive toward low. Then I have to carb up but hopefully not so much that I cause a high.

My priority list therefore is: manage BGs, take in fuel, try not to over or undershoot on insulin for the fuel or overshoot carb corrections for drifting BGs, plus remember to take enzymes for the fuel and dose the right amount, plus stay on top of my electrolytes. Oh, and keep run-walking.

And along the way, I am also trying to document and learn whether the absorption of enzymes changes during different intensities or lengths of exercise; whether these over the counter enzymes are reliably measured enough for small snacks, and whether my personal ratios for fat and protein are any different during exercise the way my sensitivity to insulin changes during exercise.

It’s a lot of work. Plus, the pre-work that goes in to finding, measuring, and preparing foods that I think I want to eat during the run!

My current short list of single-serving snacks that I can tolerate while doing long runs includes: 8 gluten free peanut butter pretzel nuggets; 1 serving of chili cheese Fritos; 6 gluten free yogurt covered pretzels; and 1 gluten free stroopwaffle. Each of those is 15-20g of carb, 1-2 enzyme pills, and some of them have a bit of sodium. (I’m also fairly sensitive to sodium so I take electrolyte pills every 30-45 minutes while racing, but I’ve realized the extra fueling with a bit of sodium makes it so I don’t have to take the electrolyte pills every 30 minutes like I used to.)

When I build up to my longer (50 mile or maybe 100 mile ultras, if I get there!) runs, I’m also going to need additional “real food” options, as I doubt I will be able to or want to eat stroopwaffle and Fritos for as long as the run will take. This is just a theoretical list, but it includes tomato soup (sodium and warm liquid!), instant mashed potatoes (soft and not much chewing involved), grits and oatmeal (not together, but same reason as mashed potatoes). These all luckily also happen to be lower in fat and protein, which means easier to digest (in theory), and I am less likely to have better error margins against getting the enzyme dosing wrong given the small amounts of fat and protein.

What it comes down to is that running with type 1 diabetes is a giant constant personal science experiment. Celiac makes it more work, but also removes some of the variables by limiting what I can to eat: as at races I can’t eat out of any open bowl or package due to cross contamination concerns, and reading packages takes time, so it’s way safer to just eat what I bring myself. Having EPI on top of that means mastering the art of digesting food with pancreatic enzyme replacement therapy, which is its own special form of science experiment.

There’s a lot of variables, a lot of science, and a lot of learning going on every time I go for a run. Doesn’t it sound fun?!

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(PS – If you’re someone with EPI who has some experience with endurance activity and changes to dosing enzymes..or find that it doesn’t change anything…please reach out! I’d love to chat and take my knowledge base from n=1 to n=2!)

Multivariable Equations: Running with Type 1 diabetes, celiac disease, and Exocrine Pancreatic Insufficiency

Peer pressure during and “after” the COVID-19 pandemic, why it’s similar to living with celiac disease or food allergies, and a reminder that we usually have choices

by Dana Lewis

Imagine that you are invited to go out to eat with a group of friends, or with colleagues at a conference.

Your mind races.

You start to think through the venue and if it’s safe for you to go. What the experience will be like at the venue. What the short-term risks are over the next few days. What the long-term risks are for you and your health, because what you choose to do will potentially influence your health for years to come.

Maybe you shouldn’t, or don’t want to go.

Given the venue, you realize that you can make choices for yourself to make it safer for you, regardless of what anyone else does. You can choose to go, but you can also do things differently than everyone else. But there’s a cost. There’s a short term cost of being the “different” one at the table.

So what do you choose? Do you cave to social pressure, and “just do what everyone else is doing”, because you think the risk of short term costs isn’t a big deal, and you don’t worry about the long-term costs to your health? Or do you decide to do something different, either not going, or doing something different at the venue than everyone else? Or do you decide to suggest an alternative?

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For those of us who are reading this in 2022 or beyond, we may read the above scenario and think primarily about COVID-19 risk factors and mitigations.

But for those of us living with celiac disease (or food allergies or other significant dietary restrictions), the above scenario is one we lived with even prior to 2019 and COVID.

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Here’s how this scenario could read specifically for COVID-19, with COVID-specifics bolded:

Imagine that you are invited to go out to eat with a group of friends, or with colleagues at a conference.

Your mind races.

You start to think through the venue and if it’s safe for you to go. What will the experience be like at the venue: Is it indoor or outdoor? What is the ventilation like? Is everyone in your group vaccinated and boosted? What the short-term risks are over the next few days: If you get COVID-19, how will that impact your schedule/life/childcare etc? How at risk are you for hospitalization with COVID-19? What the long-term risks are for you and your health, because what you choose to do will potentially influence your health for years to come: Are you concerned about “long COVID” or associated conditions? What are the risks that a COVID infection would make your personal health situation worse?

Maybe you shouldn’t, or don’t want to go.

Given the venue, you realize that you can make choices for yourself to make it safer for you, regardless of what anyone else does. You can choose to go, but you can also do things differently than everyone else. But there’s a cost. There’s a short term cost of being the “different” one at the table. You could go, but wear an N95 mask and only take off your mask to quickly eat or drink. Or you could go and mask, but not eat. Or you could bring a CO2 meter to evaluate the ventilation, and use that to decide.

So what do you choose? Do you cave to social pressure, and “just do what everyone else is doing”, because you think the risk of short term costs isn’t a big deal, and you don’t worry about the long-term costs to your health? Or do you decide to do something different, either not going, or doing something different (e.g. N95 masking, and/or not eating) at the venue than everyone else? Or do you decide to suggest an alternative, such as picking an outdoor venue instead of indoors, or choosing an activity that doesn’t involve close proximity and eating or drinking, such as a walk?

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Now consider how this scenario could read specifically for someone with celiac disease (or food allergies or food restrictions), with those specifics bolded (in a pre-pandemic life):

Imagine that you are invited to go out to eat with a group of friends, or with colleagues at a conference.

Your mind races.

You start to think through the venue and if it’s safe for you to go. What will the experience be like at the venue: Do they have a gluten free menu? Do they indicate that they have cross-contamination practices in place for making the food gluten free? Does the menu even have food that is worth eating? What the short-term risks are over the next few days: If you get glutened and are someone who is symptomatic, how will the minutes, hours, and days following of not feeling well influence your schedule/life/childcare etc? What will you not be able to do because you won’t feel well enough? What the long-term risks are for you and your health, because what you choose to do will potentially influence your health for years to come: Some people with celiac disease aren’t symptomatic, but are causing damage even if they don’t feel it in the minutes/hours/days following. Eating gluten causes the immune system to attack the body, increasing the risk for cancer and other complications.

Maybe you shouldn’t, or don’t want to go.

Given the venue, you realize that you can make choices for yourself to make it safer for you, regardless of what anyone else does. You can choose to go, but you can also do things differently than everyone else. But there’s a cost. There’s a short term cost of being the “different” one at the table. You could go, but not eat if there’s not food worth eating or if you determine (in advance or at the restaurant) that they doesn’t have safe practices for preventing cross-contamination. You could go, but bring your own food and do your own thing.

So what do you choose? Do you cave to social pressure, and “just do what everyone else is doing”, because you think the risk of short term costs isn’t a big deal, and you don’t worry about the long-term costs to your health? Or do you decide to do something different, either not going, or doing something different (e.g. not eating, or bringing your own food) at the venue than everyone else? Or do you decide to suggest an alternative, such as recommending a different venue that has safer gluten free options, or choosing an activity that doesn’t involve eating, such as a walk?

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In both a COVID-19 scenario and a scenario for someone with food allergies, food restrictions, or celiac disease, my point is that you have choices. While other people’s choices can affect you, your choices are the ones that matter most.

With celiac disease, which I’ve had for more than 13 years, I’ve personally chosen many times to not eat at places that weren’t safe for me.

I would eat a meal or snack before I go or while I’m there, or I bring food from elsewhere. Sometimes I’ve felt really awkward, but it was safer and the right choice for me to make. Sometimes it’s because I couldn’t change the venue, and the venue’s safe food was dry lettuce and dry chicken, and it just wasn’t worth eating. (Ever turned your nose up at airplane food? Same idea.) Sometimes I would bring my own food, and it’s gotten a lot easier to use a delivery service to get food from a safer (and often tastier) place. Or sometimes I couldn’t change the venue and there were supposedly safe options, but then the waiter did something that indicated it was likely not safe for me (e.g. saying “oh, just take the bread off your plate, no big deal”). That’s pretty much an automatic “do not eat here, it’s not safe” red flag being waved in my face.

It’s not fun to not get to eat or not get to do what everyone else around you is doing. I get it. Trust me, I do.

But do you know what is even LESS fun than feeling awkward? Getting glutened. Within minutes, feeling your chest tighten and getting abdominal cramps (that are like getting a “stitch in your side”, but all the way across your abdomen, and unrelenting for 30 minutes) that make you think you should go to the ER. Days of fatigue, brain fog and sore abdominal muscles. Knowing that you’ve increased the chances of tears in your small intestines and increased the risk of various types of cancers. All because of a speck of a crumb that found its way into your food.

So I make awkward choices. Sometimes I face teasing, and occasionally outright bullying, although thankfully that has been rare. And I’ve survived these choices.

I’ve gotten better over time, researching venues and making recommendations about safe places for me to eat. 99% of the time, people have zero problem going to the places I recommend. They want me to be safe and happy, they don’t really care what they eat, they’d rather have my (happy) company than to go someplace without me. (And if your  friends/colleagues/family members don’t care that much about you…maybe this will give you some food for thought.) I can’t always find safe GF options, so I also plan ahead and pack tasty snacks or food options, eat in advance, or plan to eat afterward.

And when that’s not possible, I make the choice to do the “awkward” but safe thing for me.

So in a COVID-19 or similar pandemic, I want you to know that you have choices. I’ve read a few stories from folks online who have shared regrets that they felt “peer pressure” to go eat at a conference, inside, because that’s what their friends or colleagues were doing. And they got COVID-19. Which doesn’t sound fun in the short run (being sick, getting stuck in foreign countries or strange cities, having to disrupt the lives of everyone around you, struggling to not infect your loved ones, being stuck without child care), nor the long run (risks of long COVID, or risks of additional conditions that can occur following COVID).

If you need ideas, here are some you can consider:

  • Pick an outside venue.
  • Get takeout food and go eat outside somewhere.
  • If you are inside, ensure good ventilation (sit by windows, open the windows). If you’re unsure the ventilation is good enough, you can bring a CO2 meter* to measure just how stale the air is. If you have a choice, sit somewhere quieter and further away from others, so you don’t have to yell in each other’s faces to be heard.
  • If the ventilation isn’t great, or you’re in a loud and/or crowded venue talking face to face with people who haven’t recently tested, you might want to stay masked except for when you are eating or drinking. Then put your mask back on. Limit the time you are exposed to the indoor air that everyone else’s been breathing.
  • If you are inside a poorly ventilated, loud, and/or crowded space, or otherwise consider the risks to be too high for your comfort, you can leave your N95 mask on the whole time – you don’t have to eat just because everyone else is eating unmasked!

I get it. It’s hard, it’s awkward, and peer pressure is real. But you do have choices you can make, and it gets easier when you think about your choices in advance and mitigate or decide how you’ll handle such a situation.

I hope this has given you food for thought about what choices you could make if you’re worried about such situations, and know that there are many others out there making similar choices, whether it’s because of COVID-19 or because of things like celiac disease, food allergies, or other dietary restrictions for health reasons.

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Note: this is the CO2 monitor we bought (amazon affiliate link). It’s pricey, but we’ve definitely put it to use on planes and at meetings and feel like it is a worthwhile tool.

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

by Dana Lewis

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 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

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(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.

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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.

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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.

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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.

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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

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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

Reflecting on 4 months with Exocrine Pancreatic Insufficiency (EPI) and Experiences with Pancreatic Enzyme Replacement Therapy (PERT)

by Dana Lewis

Exocrine Pancreatic Insufficiency (EPI or PEI) is an invisible disease – you don’t see or hear much of it and there’s not a lot of information for patients online, nor information written by people with EPI. (That’s in part why I’ve been documenting my experiences with EPI – more at DIYPS.org/EPI if you want to see the other EPI-related posts that I’ve written, including about PERT Pilot, the first iOS app for Exocrine Pancreatic Insufficiency! It’s an iOS app that allows you to record as many meals as you want, the PERT dosing and outcomes, to help you visualize and review more of your PERT dosing data!).

I’ve now spent more than 4 months with (known) EPI and taking pancreatic enzyme replacement therapy (PERT), and I’m sharing what I’ve found so far that’s worked for me. I also wanted to share an update on my experiences and what I wish I had known at the start that I know now.

Mainly, it gets better. It gets easier.

4 months on PERT for EPI

“It” being how I felt and now feel, and the process of figuring out how much enzymes to take, and the process of working more math into the choices of what, when, and how I was eating. It’s a lot of work, but it has gotten easier. And I feel a lot better. I now have multi-week streaks where I have perfect dosing for everything that I eat and dose for, and it’s rare to not get it right.

The early weeks were not this great: I definitely felt better than before, but not “back to normal”.

Now, I feel “back to normal” like I think I did 2-3 years ago before symptoms became noticeable. When I don’t manage to dose perfectly, the symptoms are way more minimal than previously, in part due to the fact that I’ve had so many days of feeling great and in part due to the fact that the margin of error is a lot smaller since I’ve figured out a good ratio of lipase:fat and protease:protein that works well and reliably for me.

This has confirmed for me that titrating doses of enzyme does matter. I documented everything I was eating (including listing out the amount of fat and protein) and the amount/level of enzymes I was taking. Over time, I was able to see a general threshold above/below which dosing usually worked or didn’t work, and then test slightly smaller amounts of fat and/or protein to get to an amount that reliably “worked” with that size of enzyme dose. From there, it was simple math to divide the thousand units of lipase in that size of enzyme dose by the grams of fat or protein to identify the ratio of fat:lipase or protein:protease that I needed. This has helped me get the right dose of enzymes for every meal. It has also enabled me to then choose between the more expensive and higher-dose prescription enzyme pills I have, or choose a combination of prescription and smaller-dose single or multi-enzyme over the counter pills. This ends up giving me more flexibility in the cost of enzymes it takes to cover the food I want to eat (or snack, or treat, or whatever) as well as more precision with dosing the right level of enzyme instead of 1x, 2x, 3x (etc.) a single dose size prescription pill.

In addition to feeling a lot better simply by having better GI-related outcomes and massive reduction in symptoms 95% of the time, my energy levels are way up. I’m also training to run an ultramarathon again this year, and the way I feel during training this year (with enzymes) compared to last year is startling. Even though I have another year’s worth of experience running that I didn’t have last year, the way I feel during and after runs is likely more attributable to the fact that I’m now digesting what I’m eating.

Additionally, the diversity of food that I’m choosing to eat is increasing constantly. I started conservatively, in part due to trying to figure out if I still had any FODMAP-related sensitivity, and also to make it easier to get the math “right” to figure out my optimal dose. As I got confident with my ratios and dosing PERT, I began eating a wider selection of foods, and finally have eaten my way back to eating actual onions (!) in the form of gluten free onion rings. They were delicious, and gave me zero problems. So I’m now confident the FODMAP-perceived sensitivities was really the increasing sensitivity to fat and protein as my elastase levels were dropping. It’s wonderful to not be as restricted in my food options. (I still have celiac disease and eat 100% gluten free and can’t have any cross-contamination, but after almost a year of not eating onion or garlic in any form including “natural flavors” of foods… “just” eating gluten free feels amazingly plentiful in options now.)

And because I’ve eaten more and a greater selection of foods, the thought of eating food doesn’t scare me anymore. I don’t cringe at the thought of actually eating, like I used to. I know it’s a matter of estimating or counting the fat and protein and dosing for it. If in doubt, I try to round up the number of pills I’m taking to provide a buffer. Unlike insulin, taking a little too much enzyme doesn’t hurt (other than the cost). But also like insulin (after almost 20 years), I am no longer counting the cost of every dose in my head with every meal. That definitely took over 3 months, because before then I was swallowing a PERT pill and knowing each and every one costs $9. Ugh. So that’s an improvement, even though I’m still aware of the cost, it’s not quite as bothersome to me on an every-instance basis.

Things aren’t perfect, though, despite it being a lot better. I still get overwhelmed sometimes by the amount of work to decide what I want to eat and how I’m going to estimate what is in it to try to figure out how much PERT to dose.

Some of the strategies I’ve identified that help reduce being overwhelmed include:

  • Asking for help when I can. I ask Scott (my husband) when he’s standing in the kitchen to glance at a label of a food and tell me the counts (grams of fat and protein per serving), so I can decide if I want to build a meal with that item in it. I also sometimes ask him to help me portion out individual servings of foods, such as taking a larger bag of chips and telling him the serving size that I want and asking him to weigh them out.
  • Separate the work of preparing (and counting) food from the process of deciding what to eat. (I hate using a scale and weighing things out, but it’s been really helpful to pre-portion snacks and other items). Having the pre-portioned and pre-counted amounts helps me then more easily incorporate them on the fly, because I’ve already done the counting work of figuring out what’s in them. (I either make a note on my phone in a spreadsheet or write with a marker on the baggie what the counts are.) Separating the work in advance from the decision of what to eat when it’s time to eat helps me cut down on the decision fatigue that occurs a lot for me.
  • Buying individual portions and “snack size” items of things I regularly eat. When I can find them, and thankfully I can afford to, I try to buy individual sizes of things that are pre-packaged and have the nutrition label for that serving size. It’s less work to portion it out and figure out the counts for it, so while it’s sometimes more expensive it saves me time and makes me more likely to incorporate it into my food choices.
  • Asking for help estimating what’s in mystery food (e.g. unlabeled/uncounted food items). I’ve got almost 20 years experience of estimating carb counts, but only a few months attempts of trying to estimate fat and protein counts. Sometimes I ask Scott to pitch in an estimate. Sometimes we try to look up an equivalent item (e.g., if assessing a local gluten free hamburger we got as takeout food, we’ll look up online what a few other chain restaurant hamburgers would be, and use that to triangulate). Sometimes he’ll weigh it on the scale and we’ll eyeball proportions of fat and protein in the meat versus the vegetables or rice. I’m already getting better at guesstimating, so like carb counting I imagine this will continue to get easier over time.

Managing decision fatigue is now the biggest hassle for me. I have developed a nice routine for taking counts and converting that to the right PERT doses, but I still get frustrated with having to think about what I’m eating and how I’m going to dose for it sometimes. This may be somewhat influenced by the fact that I’m running a lot and trying to eat a slightly higher level of protein than I would naturally be picking out in my diet. So having to pay attention to everything to count it for dosing and overall trying to achieve a general higher baseline of protein sometimes gets annoying (although obviously the increased need for protein is a choice, whereas EPI and dosing in general is not!).

In general, I’ve not found it hard to remember to take my enzymes. I’ve developed habits around figuring out my counts, converting that to what number and type of pills I’m taking, and I get those out to take with my first bite and/or throughout my meal, depending on the number. One thing that has helped with this is getting smaller pill cases (like these – they’re purple! They also come in white or multicolor) that I visually don’t hate and can put both the prescription and over the counter pills in. I have 2-3 of these filled and ready to go at any given time, which makes it easy to grab one when I head out for the day, or to have sitting in different spots on my kitchen island/counter so I have the visual reminder in addition to my traditional “prescription” bottle.

The other aspect aside from decision fatigue is the stress of uncertainty around food. I took a trip recently and it was very stressful being out of my routine at home for the first time since we realized I had EPI. I had to take a lot of enzymes with me, take extras in case something happened to them, pack snacks, figure out food in advance but also be ready to figure out food on the fly. This included guessing what was in airplane (gluten free) food. On the first flight, I gave Scott my dry airplane chicken because it didn’t look good or even worth the PERT, and ate snacks from my bag instead. On the flight home, the chicken had a sauce (woohoo) and came with cheesy potatoes, so I rounded up my dose guess and things were fine. In between on the trip, I also erred on the side of caution and rounded up my doses.That meant I took a little more than usual, but I had already factored that into the amount of enzymes I had packed for the trip. So that went fine. But the uncertainty in what I’d be eating for several days was stressful and hard. To help work around that, I had picked a hotel near a gluten free bakery and near a gluten free restaurant that I knew from a previous trip, so that at least I could reduce the uncertainty of “is there anything celiac-safe (gluten free) that I can eat” (which used to be my sole concern when traveling) and limit myself only to the uncertainty of “what do I dose for this?” every time I ate. That helped. So I’ll probably continue to use the pre-planning skills I learned from living with celiac because the uncertainty at every meal for EPI is a lot, especially when jet-lagged, and so everything I can do to pre-estimate or pre-plan and make sure I have access to food pays off.

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(As I mentioned at the start of this post, you can find my previous posts about EPI at DIYPS.org/EPI. And I’m working on a number of research initiatives related to EPI and improving methods for helping people titrate doses of PERT. If you’re interested in collaborating on research related to EPI, please reach out any time!

You also may want to check out PERT Pilot, the first iOS app for Exocrine Pancreatic Insufficiency! It’s an iOS app that allows you to record as many meals as you want, the PERT dosing and outcomes, to help you visualize and review more of your PERT dosing data!)

AID (APS) book now available in French!

by Dana Lewis

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!)

Why it feels harder to dose pancreatic enzyme replacement therapy (PERT) than insulin

by Dana Lewis

In 2002 when I was diagnosed with Type 1 diabetes, I struggled with being handed a vial of insulin and told vaguely to eat X amount of food and take Y amount of insulin. There was no ability to eat more and adjust the dose accordingly. It was frustrating. The only tool I had was a huge (imagine three iPhone 13 or equivalently large smartphones sitting on top of each other) blood glucose meter that took a lot of blood and a long time (a minute or more) to return a single blood glucose data point. The feedback loop wasn’t very useful, even when I tested my blood sugar manually 10-14 times per day.

Thankfully, in the last two decades, diabetes tools have evolved. Meters got smaller, faster, and take less blood. There has also been the devlopment of continuous glucose monitors (CGM) which I can wear and get near real-time readings of glucose data and can see what’s happened in the past. And, paired with an algorithm that also knows about the history of any insulin dosing on my insulin pump, and it can automatically adjust my insulin delivery in real time to predict, prevent, and reduce hypo- and hyperglycemia. (AID is awesome and if you haven’t heard about it, there’s a 4-minute free animated video here that explains it.) Diabetes no longer is quite the headache it was twenty – or even ten – years ago.

But realizing that I have exocrine pancreatic insufficiency (known as EPI or PEI) and learning how to take pancreatic enzyme replacement therapy (known as PERT) is a similar headache to diabetes in 2002.

With insulin, taking too much can cause hypoglycemia (low blood sugar). Taking too little can cause hyperglycemia (high blood sugar). Yet, with diabetes, you can measure blood glucose and see the response to insulin within a minutes-to-hours time frame. You can also use an insulin pump and an automated insulin delivery system to titrate and adjust insulin in real time.

However, for EPI, you need to take enzymes (that your pancreas doesn’t produce enough of) to help you digest your food. Your pancreas makes three types of enzymes: lipase, to help fat digest; protease, to help protein digest; and amylase, to help starches and carbohydrates digest. These are taken by mouth as a pill that you swallow. Together in one pill, it’s called “pancrelipase”, and it’s for pancreatic enzyme replacement therapy (PERT). (I’m personally bad about using pancrelilpase/PERT interchangeably, because PERT is faster to say and type, but it is possible to use standalone enzymes in PERT).

Because they are pills that you have to swallow when you eat, it’s hard to dose. Taking too little means you may have GI-related symptoms in the hours following the meal and feeling bad until the next day or so. Taking too much is expensive, although unlike insulin it’s rare to take “too much” and cause bad side effects (although possible at super high doses). There’s also the “pill burden”, because swallowing a bunch of pills is annoying and sometimes hard, both physically to swallow and to remember to take them throughout your meal.

You also can’t take more hours later if you forgot to take them or realize you didn’t dose enough for that meal. If you underdosed, you underdosed and just get to experience the symptoms that come with it. Sometimes, it’s not clear why you are having symptoms. Because there are three enzymes being replaced, it’s possible that the dosing was off for any one of the three enzymes. But again, there’s no measurement or feedback loop, or a sign that appears saying “you underdosed protease, take more next time”. The best you can do is try different sized meals over time with different doses of PERT, trying to reverse engineer your lipase:fat and protease:protein and amylase:carb ratios and continuously update them as you have new data.

It’s a lot of work, the feedback loop is slow, getting it “wrong” is painful physically and psychologically, and there are no vacations from it. Everything I eat, now that I have EPI, needs enzymes, and given the fact that I have automated insulin delivery to help manage insulin dosing, I am finding PERT to be a lot harder and more annoying (currently).

A comparison of dosing insulin and dosing enzymes. Insulin can cause hypo- or hyperlgycemia but there are tools (CGM and BG meters) and a feedback loop in diabetes. With enzymes, there is no fast feedback loop and underdosing is common. There is no ability to correct an underdose and there are multiple variables that can influence the outcome.

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There’s no happy ending to this post, but this is one of the reasons why I am so interested in partnering with researchers to do research on EPI. There are a LOT of improvements that can be made, ranging from improving titration guidance of PERT to testing the efficacy of different over the counter enzymes to finding new technology that might begin to provide a feedback loop into EPI (either for short-term assessment or longer-term use for those who prefer it). If you’re someone interested in this type of research, please don’t hesitate to reach out (Dana@OpenAPS.org).

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(PS, if you didn’t see them, I have other posts about EPI at DIYPS.org/EPI – including one about PS –  PERT Pilot, the first iOS app for Exocrine Pancreatic Insufficiency! It’s an iOS app that allows you to record as many meals as you want, the PERT dosing and outcomes, to help you visualize and review more of your PERT dosing data! It’s one of the things I decided to build to help address the challenges I know those of us with EPI face every day.)

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

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Feeling hunger for the first time in two years after discovering Exocrine Pancreatic Insufficiency (EPI or PEI)

by Dana Lewis

Now that I’ve been taking pancreatic enzyme replacement therapy (PERT) for a month and a half for my newly discovered exocrine pancreatic insufficiency (EPI), I’ve not only discovered that the GI symptoms I had are gone, but I’ve also gained something back: the sensation of hunger.

For two years, I’ve struggled to eat. I found a breakfast that I could eat that was higher fiber (albeit nontypical American breakfast food) and kept me full for hours. So many hours that I didn’t feel like eating at lunchtime.

Essentially, I would eat breakfast and maybe one other meal, and occasionally a snack. Far from three meals. I learned quickly that eating just because other people were eating made things worse (worse symptom severity, plus gave me more symptoms), so I studiously avoided eating just because that’s what I had done in the past or that’s what other people were doing.

Figuring out I had EPI and starting to dose PERT was a relief. I could tell from symptom reduction that it was working. And within a week or so, I started to feel hunger multiple times a day! Now I’m more regularly eating three small meals a day, and sometimes more (especially on after long runs). My meals are more likely to be a little bit smaller due to how I’m titrating my PERT dosing, so that plus my activity levels plus actually digesting my food when I eat it means that I’m eating more often now than I have over the last few years.

The only downside is that my brain is VERY unfamiliar with the sensation of hunger, and despite knowing I will not starve or even be hungry for very long, there seems to be a switch after three minutes where I go from recognizing hunger and starting to think about doing something to having already passed the point of no return where my number one priority becomes eating.

The timeline of my body becoming hungry (0 minutes), my brain recognizing hunger (1 minute), thinking about eating (2 minutes), deciding to eat (3 minuntes), and then a flip switching and I go from wanting to NEEDING to eat as soon as possible.

I’m guessing this is what toddlers feel like, and I have a lot more empathy for their hanger now after experiencing this! And like toddlers, hopefully my brain re-learns how to deal with and moderate the feelings of hunger soon.

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

How I calculate fat and protein for pancreatic enzyme replacement therapy (PERT) dosing in homecooked meals

by Dana Lewis

As I’ve been re-adding food items to my diet now that I know I have exocrine pancreatic insufficiency (EPI), I’ve been eating a lot of packaged foods with nutrition labels that are quick and easy to read. I’ve done a few meals that are takeout from a restaurant, and certainly the ones from chain restaurants with nutrition labels online are the easiest to enable me to optimally dose my PERT. (But not all restaurants, including my new favorite local taco place, have them and so I also do quite a bit of guesswork and experimenting.)

I’m now at the point where I can eat some onion and garlic and other FODMAPs again (yay!), so a lot of the homecooked meals I used to love to make – especially crockpot meals – are back on my list to try. This week I decided to try taco soup, a longtime favorite that involves cans of black beans, corn, dark red kidney beans, light red kidney beans, cooked ground beef, tomato paste, and ranch and taco seasonings.

One of the reasons I waited to cook large meals until this point in my EPI discovery experience was to save my energy for figuring out the fat and protein per portion size.

I’ve been creating a tab in my PERT enzyme tracking spreadsheet that’s labeled “ingredients”, and I’ve been listing commonly used ingredients (e.g. an egg, 1/4 cup of cheddar cheese, 1/4 cup of parmesan, 1 cup of milk) that I often add to my food and repeatedly need to add to my nutrient totals. I listed out all the ingredients for my taco soup recipe (see above), looked up the fat and protein and logged those, then added them all up for what one giant crockpot full of taco soup would be. That’s 44 grams of fat and 177 grams of protein.

(Side note – I found that Impossible ground beef tastes the same as ground beef and ends up being lower fat and protein. I was going to use it anyway, but that makes it easier to dose PERT by slightly reducing the fat and protein quantities.)

Then, after I cooked it (truly, set it and forget it), I scooped out a cup at a time to estimate the number of cups. For my current crockpot, it was about 12 cups.

So to figure out the taco soup individual serving size, I take 44 and 177 and divide each by 12, so it’s about 4 grams of fat and 15 grams of protein per cup of soup. I usually eat 2 cups at a time, so multiply by two to get the total of what I’m needing to dose PERT for, which is 8 grams of fat and 30 grams of protein. That’s *just* at my 1-PERT limit (at my current dosing)  for protein and well under my 1-PERT limit for fat (also about 30 grams), so I was able to cover 2 cups of soup with 1 PERT pill.

However, were I to add 1/4 cup of cheddar cheese, as I sometimes do, I’d need to add on additional enzymes to cover the protein. (It’s frustrating that I’m this sensitive to protein, enzyme-wise!)

This is also what I’ll do with potato soup (another crockpot favorite) and any other recipes that I make. Like diabetes tasks, I’ve found that splitting up the work whenever possible makes a difference, so I’ll list out the ingredients and look up the data and determine the total recipe counts separately from when I cook it, and from when I measure out how many servings there are and arrive at the final serving math.
An overview of the process of adding up fat and protein for all ingredients in a recipe; cooking and counting out the number of portions, then dividing the fat and protein totals by the number of portions (I use cups) to determine how many grams of each per serving and determine how much PERT to dose.

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

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

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

by Dana Lewis

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.

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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.

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(PS, if you didn’t see them, I have other posts about EPI at DIYPS.org/EPI, including one about PERT Pilot, the first iOS app for Exocrine Pancreatic Insufficiency! It’s an iOS app that allows you to record as many meals as you want, the PERT dosing and outcomes, to help you visualize and review more of your PERT dosing data!

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

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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)

by Dana Lewis

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” with additional ingredients and prefer to stick to products that only have the ingredients I’m looking for (lipase, protease, and amylase only).

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.

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The amount of enzyme also matters

The amount of enzyme you take matters, which is probably the second place that people trip up and make mistakes when trialing over the counter (OTC) enzymes. For example, the starting dose recommended for people with EPI is 40,000-50,000 units of lipase. Some of the most common OTC pills have 4-6,000 units of lipase: that means taking 10 OR MORE PILLS per meal in order to get the starting dose. Could you do that? Absolutely. (10 x $0.26 means that is around $2.60 cost, which may still be cheaper than the prescription pills.) However, the burden of consuming that many pills is pretty high in the long run. But you might be ok with that in the short run. There are other OTC options like this one (which I do use myself) that has around ~17,000 units of lipase. They are more expensive per pill, but you have to take fewer (e.g. 3-4 pills per meal) to match the starting dose.

For a lot more info on dosing, read this post about the starting dose and how most people end up needing MORE enzyme than this amount. Then read this post about how to figure out how much enzymes you may need to adjust to the food you’re eating and end up with an optimal dose. (You can also use PERT Pilot to help you with that).

That’s an advanced step, though, so if you’re just getting started I would focus on getting the minimum starting dose (equivalent to 40-50,000 units of lipase per meal) and see how that goes, then titrate (increase) from there.

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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.

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(PS, if you didn’t see them, I have other posts about EPI at DIYPS.org/EPI – including one about PERT Pilot, the first iOS app for Exocrine Pancreatic Insufficiency! It’s an iOS app that allows you to record as many meals as you want, the PERT dosing and outcomes, to help you visualize and review more of your PERT dosing data!)

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

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