Beta Cell #012: Every Advance Counts: Lessening the Burden of T1D Transcript

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Craig: This is Beta Cell, a show about people living with type 1 diabetes. I'm Craig Stubing.


Craig: This is the second episode of a four-part T1D looks like me series that Beta Cell is doing a partnership with JDRF for National Diabetes Awareness Month. Each Monday of November, we're exploring a new theme that focuses on some of the challenges that come along with type 1 diabetes. While here on Beta Cell we focus on type 1, there's actually a ton of overlap of new drugs and technologies between type 1 and type 2 diabetes.

With today being World diabetes day, we thought it would make sense to talk about this overlap. I discussed this with Dr. Aaron Kowalski the chief Mission officer for JDRF. Just one note before we get started. There isn't a ton of terminology in this episode you need to know, but there are three terms that I just want to emphasize for those who might not use them every day.

The first two are hypoglycemia and hyperglycemia. Hypoglycemia just means low blood sugar and hyperglycemia, as you might have guessed, means high blood sugar. When I was first diagnosed, the way I remembered this is when you eat a lot of sugar, you get really hyper. Hyperglycemia means high blood sugar. The third term is HBA1C or A1C for short. This is a blood test that tells you your average blood sugar for about the last three months.

This is the main test doctors use to tell how well our blood sugars are under control. I won't get into all the technical details, but basically people with diabetes want their A1C to be under 7, which is an average blood sugar of about 155 to avoid the long-term complications of high blood sugars. All right, now that that's out of the way, here's Aaron.

Aaron: Our mission is to cure type 1 diabetes as soon as humanly possible, but also appreciating that a cure is not going to happen tomorrow that we need to provide better options to treat the disease to keep people healthy, to minimize the burden of diabetes management until we get there. If we judge ourselves on the ultimate metric being people doing better, then we need not only research to happen, but regulatory approvals to happen, reimbursement to be in place, clinicians to prescribe new therapies and people with diabetes to have access to them so that they can benefit.

My job within JDRF is working across the spectrum, across what we call the development pipeline. To make sure that we are aligned and driving the mission as fast as humanly possible.

Craig: You have a personal stake in this because you have type 1.

Aaron: Yes. I was diagnosed as a 13-year-old back in 1984 and one of my brother Steve was diagnosed when he was three. He was actually diagnosed first in 1977 and we've been involved for now almost 40 years, which has almost unbelievable to say, but it certainly motivates me every day to push as hard as possible to make this disease go away.

Craig: When you're looking at new technology or new drugs, are you keeping in mind your own personal experience and what you think would help from sort of a type 1s perspective as opposed to maybe just a researcher who doesn't have the burden of living with it every day?

Aaron: I think it certainly adds a very, very important perspective. I have to say that there are a tremendous amount of amazing researchers who don't have a personal connection, but ultimately when you work in this field, you build many personal connections, the living with does influence how I think about things. I'll often see pitches for different ideas where I think even if that were wildly successful, it certainly wouldn't move the needle for me.

Now, I'm an “N of 1” as we would say, I'm one person perspective and that varies from person to person. My brother interestingly has had a much different experience with his diabetes than I have. I've been fortunate not to have bad hypoglycemia issues, whereas he has really bad hypoglycemia unawareness. That provides a different context, he has different issues than I do.

When I travel around I certainly meet so many people, whether it's infants versus somebody who's lived with diabetes for over 70 years, parents versus siblings, spouses. I think all of those experiences influence me, but I live with this day to day and face the same challenges that many people out there and realize the difficulties and that certainly plays into what I think could be meaningful for us.

Craig: This episode is going to go up on World Diabetes Day and we talk a lot about type 1 diabetes, but there's two types and we're going to look at how some of the research JDRF is doing and some of the drugs in the pipeline right now for type 2 can affect people with type 1. Maybe if you could just start by telling me through the difference between type 1 and type 2 and how their care is different.

Aaron: Type 1 is an autoimmune disease and in people with type 1 the immune system attacks the cells that make insulin. These are called beta cells in your pancreas, insulin is a very, very important hormone in human metabolism. In fact, in all animals. It essentially allows glucose into cells. If you think of your body just being made up of tons of cells and they need energy, insulin opens the doors to the cells to allow energy and in the form of glucose, so that's very, very important.

When you lose the ability to make insulin, you lose the ability for the cells to open those doors and glucose builds up in the blood, before the invention of insulin, every single person with type 1 diabetes died and that was in the early 1920s, and that invention obviously was a massive step forward for people with diabetes, it saved many, many lives myself included and won a Nobel Prize.

Type 2 diabetes is a little bit different. It's a different disease, but with kind of the same net result. Type 2 diabetes people still make insulin, but the body doesn't use the insulin properly. If you think of insulin is a key to opening the door, no keys in type 1, the doors don't open and type 2s the keys aren't working well or the door is rusty and it won't open properly.

Two different diseases, same net result, high blood sugar. High blood sugar is the thing that's really bad here. High blood sugar causes the long-term complications of diabetes, like blindness and kidney disease and nerve damage and that's really really bad.

Craig: I take insulin. I'm on a pump and I've been taking insulin for as long as I've had type 1, and it works. I can keep my blood sugar and range so why isn't insulin enough? Why does JDRF feel like they should fund research into other drugs?

Aaron: I think for everybody with diabetes out there who's on insulin, it's pretty obvious that it is not a cure for diabetes, despite the life-saving advance in the early 1920s. What we realized very quickly is that dosing insulin through your skin? You mentioned you're taking you're wearing a pump as do my brother and I. Many other people do shots insulin injections, all of these mean that your dosing insulin through your skin.

What we know is that the dosing of insulin through your skin is not as effective as through the bloodstream like your pancreas does it and what this all adds up to is that it's a balancing act. We know that high blood sugar causes diabetes complications, so many people I guess if you don't know the disease would say, "Well, just take more insulin. It's pretty straightforward."

The challenge with that is insulin, many people don't appreciate, is one of the most dangerous drugs that's regulated by the FDA because if you give too much insulin at the wrong time, it can cause the other side of the equation which is low blood sugar or what we call hypoglycemia. Unlike diabetes complications like eye disease that take decades to form, low blood sugar can happen on the scale of minutes, and low blood sugar can be life-threatening.

You can be cognizant and talking one minute and then unconscious a few minutes later, and go into a seizure a few minutes after that and unfortunately, sometimes people die from low blood sugar. The fear of hypoglycemia is the balance point that makes managing diabetes with insulin so very difficult, and what we know from data in the United States is less than one in three adults with type 1 diabetes achieve recommended glucose levels, which means that there are at increased risk of the long-term complications of diabetes, and even worse only one in five children do.

Insulin saved people's lives and it saves anybody would type 1 if they stop taking insulin they'll die, but we know that it's not a cure and that's why JDRF is driving so hard. We want people to have better.

Craig: Maybe we can speak broadly at first on what do these different drugs do?

Aaron: We can go through a number of different drugs that are becoming interesting in type 1 that have been used in type 2 and probably what's going to happen as vice versa as well. I'll actually start with insulin because it's an interesting story. When you look at the evolution of insulin, this is a big focus of ours at JDRF, my brother and I started on cow and pig insulin.

We've seen a tremendous advances in insulin, going to human insulin through the advent of recombinant DNA technology to what we call insulin analogs, which are modified insulins to have much better properties. They make our glucose levels better with lower risk of hypoglycemia, or low blood sugar, and JDRF we're even focused on what we call glucose responsive insulins, which would only react in your body when needed, meaning if the glucose levels went up, it would be freed up to work, but if the glucose levels were normal, it would be inactive.

The other area on insulin is we're looking at faster-acting insulins. We just had the approval of the first hybrid closed loop, and one of the reasons that you still need to dose around mealtime with these first-generation artificial pancreas systems is the insulin doesn't work fast enough. In type 1 where we're moving, which is really interesting are a couple of new classes of drugs.

These drugs work in different ways. I'll start with the SGLT2 inhibitors, which are really interesting, and I've been very popular in type 2 diabetes, these drugs cause you to pee out extra levels of glucose. In fact, the term diabetes mellitus, which is kind of the blanket term for diabetes, comes from the ancient origins meaning sieve and honey-like and the idea they're back in again of ancient Egyptian times, is they realize that these people who are wasting away from this disease that they called diabetes mellitus, were peeing out sugar. They saw ants attracted to the urine.

These new drugs amazingly facilitate this happening. In your kidneys, normally above a certain level, you actually pee out glucose. These new drugs lower that level, so when your blood sugar's high, you actually just pee it out, you urinate out the extra glucose. This has been beneficial in type 2 diabetes to lower A1C levels, to help people lose a little weight, to use a little less insulin.

They are in FDA tests in type 1, but there are people who are using them already off label. Now there can be risks associated with this. For example, one of the things that's been reported in the scientific literature is a phenomenon called euglycemic DKA. That's a fancy term for DKA diabetic ketoacidosis at a normal blood sugar level. That can be a big problem.

What's been happening, it seems, is in type 1 people who've been prescribed with these drugs is they've been lowering and lowering their insulin doses and potentially lowering them too much. What many people don't appreciate is that high blood sugar doesn't cause ketoacidosis, lack of insulin causes ketoacidosis, so in the case of SGLT2 inhibitors, you're not getting the high blood sugar levels because you're peeing out the sugar.

However, your body doesn't have enough insulin to allow glucose into the cells or enough glucose, so what it starts doing and what the cause of diabetic ketoacidosis is it's breaking down fat and protein as the source of energy, and that causes ketones as a byproduct. I run marathons and I've had this happen where I turned my pump down too low, I ran, I finished with a normal blood sugar level, but I was ketotic.

For many people, that just doesn't add up. If you're not thinking about it, you're like, "Well, I shouldn't be ketotic because my blood sugar's normal," but I didn't have enough insulin on board. Because I was running and not eating, my blood sugar was normal. Here, you're peeing out the sugar. Now that can be very dangerous, as you know, diabetic ketoacidosisis a very dangerous, life threatening complication that can kill people.

Certainly, in these tests, the FDA has already put out warnings that ketones need to be monitored. People need to be aware, if you have type 1 diabetes, you still need insulin, and if you're sick, you need to monitor for ketones. All of that said, I think these drugs still will be helpful, and I think probably approved for type 1 people. Because if you do monitor your ketones, they have a powerful additional effect with a very low risk of hypoglycemia, and could be another great tool for people.

Craig: When JDRF is deciding what drug research to fund, or what trials to fund, drugs that are already out there, are you just looking at type 2 things and sort of thinking maybe this could work? Or are you getting information from doctors who have maybe used stuff off label or maybe a combination of the two?

Aaron: It comes from all angles. We are fortunate here at JDRF that we have a team of over 20 scientists who are in constant search of where is the next best pathway to help people with type 1 diabetes as we drive to a cure or better treatments. Then the other thing we always do is, is it working? Sometimes research doesn't work and we stopped that research and we move elsewhere.

I remember when smart insulin or glucose-responsive insulin came around, it kind of came out of left field. It was a small company that had spun out of MIT. They were looking to develop a drug for type 1 and type 2 diabetes that would help people, would be transformational. We saw that, we evaluated it and we said, "Wow, this is amazing. We should support this. If it works, it could change everything." We're always on the lookout on all corners of the globe for those ideas, and on a daily basis are hearing new ideas.

Craig: You mentioned that does the insulin through skin isn't very effective. Could you talk a little bit about Afrezza?

Aaron: Yes, people who don't have diabetes, their pancreas make insulin, a big burst of insulin before the fork even hits their mouth. As soon as a person sees food. Your brain is literally hardwired to your pancreas. Meaning there are neurons that run from your brain to your pancreas and send signals to start the making of insulin before you even eat, people with type 1, that process is delayed.

When we grew up and we took human regular insulin or back in the day regular insulin in MPH, we were told to dose 45 minutes before eating. Now you can dose closer to meals, but still, if you don't dose until after you eat, you're going to have high blood sugar if you eat carbs, what can we do? We need faster-acting insulin and you bring up, Afrezza is probably the fastest acting insulin.

This is an inhaled powdered form of insulin, got approval about a year and a half ago. That is absorbed through your lungs and gets into your bloodstream much faster. I can speak from personal experience using this drug and I found it pretty amazing. You take it after you eat. The dosing is very strange, it takes some getting used to because it only comes in two dosing increments four and eight-units, or I guess maybe they just released a 12-unit increment as well.

You take this big bolus, or it's kind of a different bolus than you're used to maybe. You inhale it through your lungs, I did it. I happen to do it with a pump, so I use the pump for my Bazell and the Afrezza for the bolus. I found it pretty amazing because it knocked down that post-meal spike very quickly. In fact, many times I didn't even get a post meal spike.

The challenge with Afrezza has really been, it's been hard to access. It took me some fighting to get insurance coverage. You have to take a pulmonary function tests, so if you have lung issues, certainly if you're a smoker, it's counter indicated, but I found it a very helpful tool. I think it's going to be very interesting in these hybrid closed-loop systems and it really highlighted to me that if we had faster acting insulins, diabetes would be easier to manage.

Craig: It's like those problems you did in high school, the two trains coming in a different direction, what's going to arrive first? You eat something and you know that's starting to break down in your system. Maybe you have 15, 30 minutes, odepending on what you eat before that starts getting absorbed. Your insulin is coming from the other direction.

You have to know how long that takes to absorb as well, based on what other factors are doing, whether you're active, whether you're not, what time of day it is, if it's in the morning, the night. I can see how getting insulin faster and maybe even more reliably, would make a big difference. I even notice with my insulin pump, where on my body, that infusion site is could change dramatically my absorption and my control for those next three days.

Aaron: Yes, it's an incredibly good point. It shows the- you asked the question about why is it so hard if we have insulin, and there's so many variables that impact how insulin is absorbed, the type of food you eat, the exercises, sleep, the tissue, that makes it very, very challenging. The more we can do to reduce that variability will be ahead. You bring up infusion sets, I have a new infusion set that JDRF co-funded with the Helmsley trust that just launched last week that is intended to make the infusion of insulin more reliable.

I bought my first set, and it's been fantastic. That's a variable that I hope will be less variable with this new set. So far, so good. So far, so very good. That's a bit. Every one of these bits adds up. One of the things that people don't appreciate, is that even people who wear a continuous glucose monitor, who test six to eight times a day and wear an insulin pump, still spend over 50% of the day on average. These are big studies with blood sugar that's high. It's unbelievable to me, over 12 hours a day. We need less variability.

Craig: You mentioned briefly the partial closed-loop artificial pancreas system that just got pushed through with a lot of help from JDRF. Could you talk a little bit about JDRF's work in partnership with the FDA, on getting new drugs and technologies approved, and how that relationship somewhat based on this most recent example, will help future drugs and technologies move through faster to get to people.

Aaron: That project was an amazing journey highlighting that a number of areas can be helped through patient efficacy and research. We funded over $100 million in research in this area. That was needed to show that you could do this safely. When we started, there were lots of questions about could you really dose insulin with a CGM reading, that wasn't always reliable.

Many people used to say, "There's no way that I would ever let my CGM dose my insulin", we've shown it's possible. It is very possible. In fact, it is much better than what we do as individuals with diabetes. We worked with FDA. The FDA, as you point out is a critical component of this. We need safe and effective systems. I used to get the question a lot from folks with diabetes, why does FDA so slow here?

Why is it that Europe approves stuff so much faster? I used to say that, "Well, good things get approved faster in Europe, but bad things do as well." Of course, we don't want systems that will hurt people. In the work we did with FDA was really focused on what's the best balance point for people with diabetes. Meaning, how much risk are you willing to take to move forward from where we are today?

FDA had their perspective, but people with diabetes, FDA wanted to hear our perspective as well. As an independent entity that's not for profit and representing people with diabetes, we're able to go in and have a discussion with them and say, "You know what, I think you can be more aggressive here." I remember one of the questions that we debated was a system that reduced your hypoglycemia, but caused your A1C to go up approvable?

Envision a system that you put it on, and it eliminates your risk for lows, but your A1C gets worse. Maybe it goes from 7 to 7.3. At first, the FDA thought that that might not be an approvable product, because they were worried that well, it's costing you your A1C and A1C is the most important metric. I remember going in and talking to them and I said, "Listen, if my brother doesn't end up in the hospital because of severe hypoglycemia, and his A1C goes up a tiny bit, that is a huge win for him, a huge win for my family, and a huge win for his doctor and his clinical team."

Then again, even beyond the FDA, it's the payers. What if your A1C doesn't change, but again, you reduce your risk of hypo. Is that something that a payer should pay for? Diabetes is more than just A1C. It's hypoglycemia. It's sleep, it's poking yourself, it's worry, it's waking up overnight with your child or your spouse, there are a variety of outcomes and the perspective of people with type 1 is super important.

The mission is people doing better. How we get there is not just researches, these downstream issues downstream being regulatory reimbursement and clinical adoption. I'm really proud of the artificial pancreas, the AP project here, has really provided a template to show that this can be successful and patient efficacy can really move the needle.

Craig: On that note, the research JDRF is putting into drugs and technologies for type 1 that can be used for people with type 2 and vice versa, can help alleviate some of those things besides just A1C.

Aaron: Hypoglycemia and A1C are metrics that we always are going to use because A1C is the furnace linked to our predictability of complications and hypoglycemia is just so incredibly obvious that it's such a barrier to take glucose control. I think these other outcomes are so important as well. JDRF, and the Helmsley Trust have launched a major initiative on this front to look at the outcomes and the cost on society of days out of work, days out of school, lost productivity because of lost sleep, for example. That these outcomes actually are very, very meaningful to people.

I have given a number of talks, and I've asked for people, how often is your sleep interrupted because of your diabetes? For many people, it's almost every night. I woke up last night myself because of hypoglycemia. My loved ones who don't have diabetes, that's not in their repertoire. It's not an issue, but it costs me sleep and that's not something that I want to have to deal with.

What if we could eliminate that, but we don't change other outcomes? Is that something that's meaningful, and I think most people with diabetes would say, "Of course." If we don't value that outcome, through FDA approval or through reimbursement with payers, then people won't have access. Our Health Policy Initiative, this is again with the Helmsley Trust and JDRF and we're partnering with a number of other organizations, ADA, ACE, AADE, Diatribe, Endocrine Society and many others.

We need to highlight the diabetes is more than just A1C and value those improvements in those outcomes because we have a lot of exciting stuff in the pipeline, but we can't get them approved or accessible to people then it's a Pyrrhic victory. What's next after artificial pancreas or where's artificial pancreas headed, and it kind of gets into a big initiative that we have here at JDRF that's focused on miniaturization.

I am so incredibly excited about, for example, I don't know if you've seen the Google Dexcom partnership focused on the miniaturization of CGM, the Dexcom CGM. They intend to deliver to the market a CGM that's less expensive than finger sticking in the size of a penny that's flexible and disposable. I think when we look at diabetes, and where we're headed, of course, we want to walk away and have a cure.

In the meantime, the artificial pancreas systems will improve glucose levels and that's going to be fantastic. Many people don't want to wear a pump or a sensor. What if we could miniaturize these and make the burden as little as possible? I think there's going to be a tech revolution that's going to take us beyond glucose control and minimize all this stuff we're wearing and I think that's going to be so incredible.

Craig: That's really exciting. It's really exciting for me, knowing how hard it can be with a pump and a CGM to find the position to sleep at night.

Aaron: I met a doctor from the UK and he told me the story of a young patient of his who he diagnosed with type 1 about eight months ago. When the little boy came to his first appointment to get his A1C, he sobbed when he got his finger poked, and the father apologized. He said, "Oh, I'm sorry, he's never poked his fingers like this before."

This little boy was put on the Abbott Libre, which is available in Europe, hopefully available soon here in the United States, which is a two-week continuous sensor with zero fingers sticking. I think the future of diabetes, having grown up from the point where my brother's diagnosed when we did urine testing, to the amazing revolution of blood sugar testing, to now here's a boy who is diagnosed with type 1 Diabetes and will never poke his fingers.

That just blew my mind. I think this technological revolution is going to change the way we manage diabetes and it's so incredibly exciting, especially for somebody who's been doing this a long time. I'm really proud of the JDRF that we've worked hard in this area because it's going to be a whole new world for people with type 1 until we get to a cure.


Craig: Beta Cell's produced, recorded and edited by me, Craig Stubing, and our theme music is by Purple Glitter. Aaron tweets regularly at the handle @aaronjkowalski. For more information about how your voice can help secure legislative support for research, influence sound policy making and improve the quality of life for all those affected by type 1 diabetes, visit or text @ ACT to JDRF1.

Be sure to subscribe to Beta Cell on iTunes, Stitcher, Google Play Music or the NPR one app to get the next two episodes of this T1D looks like me series delivered automatically to you. You can find Beta Cell on Twitter, Facebook and Instagram at @betacellpodcast.

I'm Craig Stubing and this is Beta Cell.