Interview with inventor and anesthesiologist Jeffrey Joseph, DO about devices for monitoring & treating diabetes and safely delivering insulin.
David Klonoff:
Welcome to Diabetes Technology Report. This is a podcast devoted to Diabetes Technology, hosted by me, Dr David Klonoff and Dr David Kerr, and he will introduce our guest today.
David Kerr:
Okay, well, welcome everyone. David Kerr here. It gives me enormous pleasure to welcome to the conversation today Dr Jeff Josepha, longtime friend, supporter, collaborator, inventor, associate with diabetes technologies. Jeff, we know you extremely well at the society. Maybe there's a few listeners out there who are less familiar, so can you just give us a little thumbnail sketch of who you are, where you are and what you've been doing?
Jeffrey Joseph:
Thank you, David and David, for the invitation to speak. My name is Dr Jeffrey Joseph. I'm classically trained as a cardiac anesthesiologist. I've been at Thomas Jefferson University since the mid-80s taking care of patients. I've also been involved in diabetes technology. Way back in the late 80s early 90s, I had this idea of connecting an insulin pump and a glucose sensor for automated insulin delivery. I put together an idea of a sensor that used optics to measure glucose and I presented that to NIH and they liked the idea. However, it did not get funded. They said you need to have more resources to do this type of work. So, naively, I put together a business plan and tried to get a company started, and that became Animas Corporation. We developed a glucose sensor initially and then an insulin pump. I'm pretty much self-taught on insulin delivery as well as connecting an insulin pump to a glucose sensor. Way back then people were not really sure of whether that technology was safe and effective. It's good to see after many years that it's now become a standard of care.
David Kerr:
Jeff, that's just fantastic. You're really an inventor and an innovator. So what are you up to now, what's kind of on your plate at the moment?
Jeffrey Joseph:
Well, a second company that I helped co-found is Capillary Biomedical. Capillary initially was founded again around a glucose sensor, but we quickly identified the need for more effective insulin delivery and, talking to many people with diabetes and the funding sources, Not only did they want a infusion set and insulin delivery system that functioned for more than three to four to five days, but they wanted one that gave more consistent or precise insulin absorption from day to day and dose to dose. So we founded the company Capillary Biomedical that last year was acquired by tandem diabetes And basically we did an iterative process over about an eight-year period where we came up with an infusion set that actually did solve many of the problems of conventional infusion sets, with the understanding that when you put something under the skin it acts as a foreign body and it develops inflammation. So we did everything we could to identify the failure modes and to engineer around those failure modes, And that technology is currently in clinical trials to get FDA approval.
David Klonoff:
Jeff, what were the features in your capillary biomedical infusion system that would give it a longer duration than previous setups?
Jeffrey Joseph:
Well, we initially tested the commercial infusion sets, both the steel and the teflon, both straight and angled. Initially it was easy to identify that there was an inflammatory process that developed around the cannula due to the insertion, tissue damage and the insulin. Its excipients and fibrils also were pro-inflammatory. So basically we took something that was rather traumatic to the tissue and we made a cannula that is soft and flexible. I like to call it limp spaghetti. But yet if you did that type of cannula it would kink and have difficulty to get through the skin. So we developed a novel, a trocar or needle to get it through the skin. It was wire reinforced so it eliminated kinking. And then we came up with the idea of multiple holes like a sprinkler needle, and we demonstrated that one. That redundancy allowed the device to work for an animal model beyond 7 to 14 days. But more importantly, it spread the insulin into a greater surface area. So we got rapid and more consistent absorption of the insulin. So we hope that what we learned in our laboratory studies pans out in the human trials.
David Klonoff:
Jeff, do you think we'll ever see a continuous glucose monitor and an insulin infusion set on the same catheter so that a person only has a single device in their skin?
Jeffrey Joseph:
The answer is it's possible, but when you deliver your bolus of insulin into the local area, you get a dilution around the sensor. So for a brief period of time it may affect sensor performance, but, more importantly, that inflammatory process may affect sensor function. So the answer is we and others are working on that type of technology. However, it's difficult because when you think of the sensor, it's almost like a human hair. It's very small, thin, flexible and the inflammatory process is minimal around the sensor, whereas an infusion set is much larger and causes, because of the insulin itself and the foreign body causes, a more significant inflammatory process. So it's difficult to put them into one device.
David Kerr:
So, Jeff, this is an amazing science. I'm not sure if people with diabetes and most clinicians are aware of the complexities of what goes on as a device enters the skin. You think that's a fair thing to say that there's also a need for people like us to better understand some of the limitations of this technology?
Jeffrey Joseph:
That is correct and once we identified the failure modes of why insulin absorption is so variable, we are working on technology to minimize that inflammatory process around the cannula. So soft and flexible was the first step. However, we're doing work where we're having coatings on the cannula that are anti-inflammatory, The steroids, local anesthetic things that minimize the inflammatory process around the cannula In the. yes, we want to get longer duration of wear, but ideally you would like to have consistent absorption from dose to dose and day to day. that would greatly improve glucose control.
David Kerr:
Yeah, I think for people with diabetes that's a must have. That consistency is just something that's a real challenge now. So, going forward and looking forward over the next few years where do you see the next frontier is for the work that you're involved in and what you're thinking about?
Jeffrey Joseph:
Well, the current closed loop systems or automated insulin delivery are really exciting because they actually work and they actually give people improvement in glucose control without an increase in hypoglycemia, which is totally amazing because just five to ten years ago we were doing studies in a very controlled environment and now we know they're safe and effective.
Jeffrey Joseph:
But there's still some room to improve our technology, especially around meals, and basically we would love to have a system where the insulin mimics the PK and PD or the actions of insulin in a person that's non-diabetic. So you need rapid onset and rapid offset to avoid hypoglycemia during the meal and hypoglycemia after the meal. We're currently working with an industry collaborator on peritoneal insulin delivery And I chaired a workshop a few years ago with JDRF and NIH on peritoneal insulin delivery. And yes, the technology is a little more challenging because it's a little more invasive. It's a permanent catheter, but delivering insulin into the portal vein has significant advantages because it goes to the liver first and it regulates both insulin or both glucose uptake, glucose release and people that have had implantable insulin pumps swear by them and it almost eliminates the glucose variability in hypoglycemia. So I'd love to see that type of research and technology advance in the future.
David Klonoff:
Jeff, is there any other area where you'd like to see more funding directed to improve the technology for folks with diabetes?
Jeffrey Joseph:
Putting a device through the skin into the subcutaneous fatty tissue always it's a foreign body you're damaging tissue. Both the sensors and the infusion sets do cause tissue damage And in certain people matter of fact, in most people it heals with a little scar tissue. So if you start using these technologies at a young age, you start to lose infusion sites and the insulin isn't absorbed as well if you're putting your sensor or your insulin infusion set into an area of scar tissue. So a lot of effort into how do you minimize that foreign body, that inflammatory process, not only for the set that you're currently wearing, but to avoid scar formation over months to years.
David Klonoff:
Jeff, thank you for speaking with us today. This completes the Diabetes Technology Report podcast and we'll see you next time. Thank you, bye.