Wednesday, March 9, 2011

Outsmarting Smart Insulin?

I tuned into yesterday's JDRF Advocacy webcast with Dr. Aaron Kowalski to find out some more about what's going on with the Artificial Pancreas Project. (If you didn't have a chance to tune in, the recorded version can be found here.)

Not drawn to scale.
Also, not drawn by me.
I'm a fan of Dr. Kowalski. He's a smart and engaging presenter with the perfect storm of expertise and experience - because he is a scientist AND a person living with type 1. (He also appears to be an avid Diet Coke drinker - bonus points.) Who better to have on our side?

Listening to, as well as participating in, these webcasts helps me as someone without an extensive science background understand my own disease a bit better (and reassures me that I'm pronouncing words like "interstitial" correctly). It also gives me (what feels like) an insider's look at what JDRF is working on, and what they need volunteers (like myself) to do to help. These webcasts help put a face and voice to a huge organization. It endears them to me, frankly. Seeing that kind of transparency and accessibility is refreshing.

Though much of what was discussed were topics I'm already fairly familiar with - clinical trials for the AP, smart insulin, etc. - it did get me thinking about a few things. And so, as I'm want to do, here's my (short) feedback about what was discussed.

  • The idea of an AP that incorporates a CGM, insulin pump, and glucagon pump seems to make the most sense to me. However, that brings up some real-world concerns in my mind, like "Aren't I going to run out of skin real estate with that many sites to rotate around?" And if I'm worried about that problem as a fully-grown adult, it is sure to be even more of an issue for small children.
  • As someone who tends to see their BG plummet during certain types of exercise, the idea of "smart insulin" concerns me. If you're not familiar with the concept of what "smart insulin" is, take a look here. Essentially, it's an insulin that could both detect and respond to elevated glucose levels. So here's my concern: there are times when I want my blood sugar to be elevated. Like before I walk that marathon in May. Exercise + Insulin On Board usually = Big Trouble. Which would mean that Exercise + Insulin That Dispenses Itself Without Knowledge That I Don't Need It = Yikers. I'd need a way to outsmart the "smart" insulin.
  • Dr. Kowalski touched on that concern that many of us have - that CGMs can sometimes be inconsistent and inaccurate, and it's hard to trust that having one hooked up to an insulin pump would be a good thing. He made a great point that I hadn't really thought of before: because these monitors do not test blood, they can't be expected to exactly match blood testing results. Just think - what if, instead of blood glucose monitors, we had been using interstitial fluid glucose monitors this whole time, and then they came up with Continuous BLOOD Glucose monitors? Then we'd think that blood testing was "way off". It's not realistic to think of the two technologies in apple-to-apple terms. When I see the Dexcom being accurate most of the time, I start to think that it should be that way all of the time - when, really, it's supposed to be there just for trending information. I keep forgetting that.

***Disclosure: As in the past, JDRF has not asked me to blog about their webcasts. They did ask for any follow-up questions and thoughts viewers might have had via Twitter, but I didn't think I could fit all of this into 140 characters.  :)


  1. Thanks Kim,

    I wanted to tune in too, but was busy and couldn't get away from it, so unfortunately I missed it. I'm glad that you caught it and shared this with us.

    Sounds like I missed a great session!

  2. Maybe they are putting the cart before the horse with regards to the AP, though if they allow you to turn the AP function off for a period of time, I would be more thrilled with it. How much more sensible and useful would a NON INVASIVE cgms be? Because, frankly, many kids don't want to wear two sites, let alone THREE, if you need to dispense glucose. How about a noninvasive or implantable cgms where we can respond to the trends ourselves? Three sites? Thanks, but no thanks, we are not up to it. And, having Type 1 at an early age, you are right. We would run out of real estate pretty darn quick. What then?

  3. I thought they were working on a way to test blood sugar like the pulse oximeter? Dang it.

  4. I really enjoyed the webcast and agree whole-heartedly with your opening sentiments. It was an hour very well spent and I look forward to the next one.

  5. Thank you for the update and your thoughts. I don't feel like I missed out anymore. :)

  6. Thanks for this post! I had also wanted to tune in but alas, that work thing... ;) I agree with your comments and feedback as well.

  7. Thanks for the recap! I needed the cliff notes version today :)

  8. Thanks, Kim. I didn't attend as I had meetings at work. I agree that Aaron Kowalski is an engaging speaker, I have attended several in-person events where he spoke and also attended online "chats" (the in-person events were better by virtue of his personality).

    Still, I'm not sure I understand your concern about SmartInsulin. If SmartInsulin passes through human clinical trials successfully, your concerns might be misplaced. In essence, a SmartInsulin molecule would be encapsulated in a polymer (e.g. a shell of sorts) that would only open to enable the insulin molecule to be released into the bloodstream when blood glucose levels are elevated. If they are within range or low, the insulin on board would do absolutely nothing, at least that's what the idea is. If that were true, then why would you need have your BG's elevated to handle exercise?

    As for the AP, there are concerns about the accuracy of the CGMS devices which Aaron has addressed in the past. He seems to fault the FDA for this, and there may be a grain of truth to that. But they seem to be handling these issues as best as possible under the circumstances -- everything except the cost. Many of us STILL cannot get coverage for CGMS devices, so the idea of an artificial pancreas seems like a bit like a joke to some of us. But he does say that the devices are only useful if people have access to them. I just don't buy the notion that JDRF needs to fund the studies to get coverage for them. Lean on the companies that will sell these devices a bit harder IMHO.

  9. Hey Scott! Thanks for the comment! :)

    While doing aerobic exercise, my blood sugar will plummet unless 1. I eat some carbs and protein ahead of time (sans bolus), and 2. I turn off my basal rate for about an hour beforehand. My concern with Smart Insulin then becomes two-fold: it will "bolus" me automatically for what I eat, and there's no way to "turn off" the insulin delivery beforehand. Does that make sense? I probably didn't explain it very well the first time (and maybe not this time, either...).

    You're right that CGM cost and accessibility is still a big issue for many. I'm frustrated for everyone who doesn't have one - it's a life-saving device we should all have access to.

  10. With smart insulin, you may not need to "eat" before exercise. Right now you do because once the insulin is on board there is no way to "stop" it.

    The radical departure from traditional insulins is that it is self-regulating; only becoming active in the presense of elevated glucose levels.

    so, if you don't eat your insulin is "smart" enough not to work

    It is very similar to your comments about measuring blood glucose vs interstitial glucose. We are so used to using blood values that it will take re-training and new habits to sucessfully utilize interstitial levels.

    We will also need re-training and new habits with smart insulin. Heck, in theory it could eliminate pumps and MDI; just one shot a day of the smart insulin and you are good to go

  11. Hello Third Scott! :)

    My understanding is - and maybe this is where my logic is flawed - that Smart Insulin would, in addition to compensating for food with a "bolus", administer itself in small doses several times over an hour, much as an insulin pump would provide basal insulin. The problem is my above example is that I wouldn't be able to tell that Smart Insulin to back the heck off for an hour - so that "basal" does would still be active in my system while exercising.

    I guess I can't wrap my head around the idea of something that can only lower my BG, but do nothing to forsee what activity may be ahead, and have no capability to RAISE my BG when it's "wrong".

    Admittedly, I'm a scaredy cat when it comes to this stuff.

  12. Ah, I think I see what the issue may be. You are considering smart insulin as only a bolus insulin.

    Think of it terms of it being a bolus AND a basal insulin.

    As your sugars rise without the presense of insulin, the smart insulin would sense that and react to it. That is why I said that if it pans out, MDI and pumps could very well be a thing of the past.

    Now if they could just add a little "smart glucagon" to the mix...

  13. Smart insulin... I feel stupider just thinking about it. Maybe I'll get some of that smartness by osmosis. However, I digress. This is about... never mind. I forgot.

  14. Nope; I'm considering it as both. :)

    Smart glucagon! Yes! I would be sold, if that were part of it.

    Thanks for the patience/explanations, all. I am learning!

  15. ok, one last tidbit then I'll shut up... once the smart insulin is released to cover glucose the cells of the body will consume the smart insulin to metabolize the glucose. Once the glocose level is normal, there is no more IOB since it has been already utilized

  16. I've been a big fan of the Smart Insulin concept and been following them just as Scott S. has for quite a few years now. As diabetics we have no protection against both highs and low as we all know. The concept and likely reality of Smart Insulin is that it will start to release once sugars start elevating but at what level that happens has not been discussed in any detail though if you watch the online video Dr Zion did a few years ago it shows nearly indentical to a real pancreas. The tricky part is how in gods name can they get it to stop at specific level and just shut off? This is their claims in the large animal trials but until it gets tested in humans in real life situations its possible there could be problems with it. My guess is its gonna work but will it be 100% foolproof? We'll have to wait and see

  17. From what I've read, the target BG for Smartinsulin is 5.5 mmol/L or 100 mg/dL. Above that figure it goes to work, below that figure it stops. Allegedly.

    The big killer for Smartinsulin will be if any substances are found to interact and cause insulin to be dumped into the bloodstream when not needed. That could be deadly.

  18. Personally I feel better below 100. I know were splitting hairs here but for me anyway my ideal level is around 90. I am overly sensitive to the glucose fluctuations and levels and mentally disturbed most of my existence. A little too high or a little too low is a huge difference in my well being. As far as Smart Insulin goes I don't think it should take but a good solid two years if even that of human trials in real life situations to know if there is any possible way to trigger a release of that stuff below the threshold level. Lets put this way the stuff we have now is deadly. I've come close to death a few times from lows in the past several months. I'm really hoping and praying for either a Faustman/Exsulin or Curedm breakthrough and getting my own insulin production back. The Smart Insulin if works as suggested would be a huge life altering welcome as well. The AP not so much. I'd pass.

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  20. I did not watch the video yet, and while I have not researched this very thoroughly, I do have 2 cents. I am no chemist or scientist, but it roughly sounds like we are going to have to rethink how we PREPARE for exercise and eating with smart insulin.

    It sounds to me like smart insulin will sit directly around our blood cells until the instant it is needed. The main component in the smart insulin mix is a sort of cover that shields our blood cells from insulin absorption as long as the blood cells are in the target BG range.

    Lets say the target BG range is 100-115. If your BG is 140 (although, according to how this works it never would be) the smart insulin mix would allow absorption of insulin until the moment it was in range. The moment your BG is in range, the shield would go back up and stop your blood cells from absorbing further insulin. Thus, your BG could not get lower (due to insulin) because absorption of insulin has been shut down.

    Without putting words in other people’s mouths, I think the main concern focused by Kim and some others is that exercise alone will lower your BG if it is vigorous enough. If you are in range, and you have zero basal/bolus insulin in your system and you go out and run, ride, ski or whatever hard enough, you will probably get low. But on the other hand, nobody should expect to exercise without replenishing the body of the nutrients that it needs. I think the CGM along with smart insulin will have to be key. While exercising you’ll keep an eye on the CGM and if a low approaches then it’s time to eat/drink a few carbs. Because there is no absorption of insulin allowed while in range, it’s possible that the carbs will work even faster than they do with our current technology. With current technology when we have low BG’s, we still have insulin on board doing its job, thus the carbs don’t work as fast as they could.

    I am very excited about this technology. Insulin will be stored in our blood stream, not in a vial or reservoir. It will be absorbed instantly as needed instead of being pushed manually, hoping the next few hours that you pushed the correct amount. No more infusion sets, multiple bulky items to carry or batteries to change, just a per diem of smart insulin and a CGM.

    Ok, this was more like 3 or 4 cents!

  21. I think one of the most stressful things about living with diabetes is reality of the structured time frame you under. Go out to a dinner see a 250 blood sugar, wait at least an hour before it comes down before eating or taking a shot and getting a call and not being able to do anything till you stuff food down your mouth. Its a horrible way to have to live. Still the worst part is feeling ill often from the swings. I suffer with great anxiety and depression for it. As I said I pray everyday for a regeneration of my own insulin production however if none of those potential treatments pan out Smart Insulin if it works as suggested will be the next best alternative at least until a possible true cure is found. FWIW there is another company out in Texas that is working on their version of a glucose responsive insulin as well. The study is being done by Dr Ananth Annapragada. They are a little behind Smart Cells but the technology is apparently feasible. Why anyone would love to see an expensive AP become available is strange to me. We deserve far better then that after years of suffering. Just my 2 cents

  22. Theoretically, it shouldn't be possible for Smartinsulin to cause hypo, regardless of exercise. If the action of the insulin can be suspended directly in the bloodstream, it won't be physically possible for BG to drop beyond the predetermined level. Any type 1 diabetic will know that, given the absence of sufficient insulin, no amount of exercise will lower blood sugar.

  23. I am optimistic about Smart Insulin. I hope it works as advertised. It seems like maybe a similar technology could be used for "smart glucogon" -- which would release only when glucose is low. This could be mixed in with Smart Insulin and would add maybe avoid problems with low glucose during exercise and such.

  24. You might visit JDRF New England's Blog with a presentation and video speech from SmartCells' Todd Zion. See

  25. Very hopeful re Smart Insulin even if Smart can only handle the basal aspect. That way you would know all highs lows are a result of bolus insulin only and much easier to then trouble-shoot. It would be wonderful if Smart insulin could also handle the heavier carb load from meals, but I am not sure if it can. If it can't the concern re insulin on board and exercise is valid. Since the alpha cells are not functioning correctly, there is no protection if Smart insulin should work too aggressively, especially after a carb heavy meal. Will have to wait and see after future animal and human studies. I would settle for an insulin that could handle the basal patterns without risk of hypoglycemia. Anything would be an improvement.

  26. Dr Zion gave a talk in Syracuse last April. He said the animal trials were completed successfully and human trials were beginning in Belgium. I checked international trials and couldn't find anything. I have a kindergartener's knowledge of computers and perhaps someone can find this info.