A Miracle Technology for Type 1s: Can It Be Saved?
What if there were a technology that could make people with type 1 diabetes feel absolutely wonderful, completely healthy, better than they ever realized was possible? And what if it were about to disappear? Well, there is such a technology, and it is in serious jeopardy. It's called the implantable insulin pump, currently made by Medtronic. This is the story of four people who have been using this device for 20 years, and their desperate crusade to keep it from disappearing forever.
Chris Witkowski, age 58, is a lawyer who has had type 1 diabetes since the age of 14. Greg Peterson is a successful 61-year-old entrepreneur who was diagnosed with type 1 diabetes at the age of eight. Anne Nordyke, a technical supervisor who is 48 years old, got diabetes when she was 22. And Sheila Klaesius is a retired nurse, age 58, who got diabetes at the age of 19. The first three used subcutaneous insulin, by injections or pump, until about 20 years ago, when they entered the implantable pump clinical study being run by MiniMed. Sheila used injections until 2003, when she got her first implantable pump as part of a clinical trial being run by Medtronic.
Greg Peterson says, "Before I received my first implantable pump in 1992, I was the poster child for diabetes care. My control was superb, and I thought I was doing quite well. But the day after I had my implantable pump installed, it was as if I were a new person. It absolutely changed my life. As I said to a friend of mine, ‘Holy Toledo, I feel incredibly good. Is this what normal is?' The difference is not describable to a person who hasn't experienced it, unfortunately, but all of us will tell you this: It's a phenomenal difference."
The key difference between the implantable pump and typical forms of insulin delivery is that the implantable pump does not deliver insulin subcutaneously, or below the skin. Instead, it delivers insulin directly to the peritoneal cavity just like a normal pancreas. Greg says, "Subcutaneous insulin is life-saving, but it is also very, very abnormal. In the normal human, insulin is released from the pancreas and goes directly to the liver via the portal circulation. The liver, which is the primary organ for maintaining normoglycemia, extracts at least 50 percent of that insulin for itself. The peripheral circulation, on the other hand, normally has a lower level of insulin. It's called a positive portal-peripheral gradient of insulin."
"When you inject insulin subcutaneously, inject it intravenously, or inhale it, that positive portal-peripheral gradient is reversed. Now you have a higher concentration in the peripheral tissue than coming into the liver. This is nonphysiologic and abnormal, and it leads to a raft of problems. For one thing, it makes control more difficult. If you're controlling diabetes with sub-Q insulin, you can do one heck of a good job, as I've proved, but you just cannot do the job that you can do with intraperitoneal insulin. Sub-Q insulin just does not normalize the abnormal metabolic condition of diabetes very well. Something profound is going on metabolically in our bodies with the implantable technology."
"This is a technology that is phenomenally effective. I have over 500 research papers that address different aspects of the physiology of intraperitoneal (IP) insulin versus sub-Q, and the information is incontrovertible. It's just not well known. Part of the reason it's not well known is that early on in the developmental path of this pump, there were some serious technical problems. Short battery life, catheter obstruction, precipitation of the insulin, infection at the implantation site, and a very small supply of pumps: All those things got in the way of doing coherent large scale studies of the technology."
"But what we do have is a lot of information from animal studies, which are very indicative of the superiority of IP insulin, and we have a lot of individual human studies from researchers around the world who experimented with IP insulin when they had pumps to do it. The results are astounding: the changes in lipid patterns that should help prevent atherosclerosis, the decrease in the hyperinsulinemia that is common with sub-Q insulin, the amazing reduction in severe hypoglycemia. When you try to control diabetes well with sub-Q insulin, there is a disastrous rise in the incidence of severe hypoglycemia. This does not happen with IP insulin. I can go on and on. The thing that is astounding is that this is simply not known, and the reason is that the technology had those bumps. But it had those bumps because several aspects of the technology were just not adequate to the task. These pumps were first developed in the early 1980s, and very little development has been done in recent years. If they were to revisit it now, it would be a different story."
The implantable pump is a small, battery-powered device that looks a lot like a metal hockey puck. It is stitched into a pocket of tissue directly under the skin and has a catheter that pokes through the peritoneal wall to deliver a constant stream of insulin directly into the body cavity. It's like having a titanium pancreas that provides a basal amount of insulin 24/7. At mealtimes, patients just punch a few buttons on a hand-held communicator, instructing the pump to deliver a bolus of insulin. Four times a year, patients must return to the hospital for a 15-minute process during which the pump is refilled with a highly concentrated form of special insulin. At this time, the refills are available only in Europe. Because they believe so strongly in the benefits of the implantable pump, Anne, Chris, Greg, and Sheila travel to France every three months for a refill, at significant financial and personal cost.
The era of implantable insulin pumps began in 1980, when in one short year, several research groups implanted the first pumps in human subjects. In 1986, the first MiniMed implantable insulin pump was implanted in a patient by Dr. Christopher Saudek. In 1995, MiniMed received CE mark approval, the EU's equivalent of FDA approval, which meant that it could market the implantable pump throughout Europe. In 2000, it received CE mark approval for its next generation implantable pump, the Model 2007-A, which had an improved memory and a longer battery life. In 2001, Medtronic acquired MiniMed. In 2007, Medtronic discontinued its clinical trial of the pump in the US.
The supply of pumps available for implantation in Europe is currently severely limited. To all outward appearances, Medtronic is showing little enthusiasm for preserving this technology, and the future of the implantable pump may be in serious jeopardy. Medtronic attributes the limited number of pumps available for implantation in Europe to "supplier changes for part of the mechanism and also the requirement to change the formulation of insulin." Despite their profession of "clear commitment to ensure continuation of the current technology for the many patients who are benefiting from this therapy," they also say that "the future of the new implantable pump technology is currently not defined."
"Throughout those early years, there were a lot of technical problems because miniaturizing the circuitry was not as possible as it is now. Battery life was nowhere near sufficient. They knew little about how to do the implantation procedures and post-surgery follow-up care to prevent infection, and catheter technology was very crude. Most importantly, there was only one insulin back in those days, a very special insulin that could tolerate body temperature and constant movement, as is the environment for the implantable pump."
When that insulin had to be altered due to environmental concerns related to its manufacturing, the pumps began to plug up. It took a few years to solve that problem, but Sanofi-Aventis has since developed a replacement version that works very well, and they are now in studies with a human version of that insulin. Greg says, "Over the 20-year span that I've had this pump, all the technical problems have reached the very cusp of being solved. The French, particularly in the hands of Professor Eric Renard, have been very good at figuring all these problems out, so the technology is on the verge of just exploding if it gets the right moves."
"When Medtronic decided to cancel the technology in the US, they did so, I imagine, for business reasons. But I believe there is a very strong business case to be made for the implantable pump. If you're looking at it purely from the standpoint of the risk return ratio, you can see why some businesses might shy away from it. But what amazing technology was ever developed without somebody saying, ‘Well, that's worth it, let's take the risk and do it.'"
"We're already at the point where it's possible to develop algorithms and control systems that can make an artificial pancreas a reality. But we're trying to do this with both hands tied behind our backs, by using a subcutaneous delivery route. We've squeezed everything we can out of sub-Q insulin already. There are dozens of different formulations for time of onset, duration and speed of onset. Amazing work has been done with sub-Q insulin, but it is fundamentally limited."
"In the 1990s, the DCCT finally gave us the proof we needed that tight control is crucially important to preventing long-term complications. Yet here we are 20 years later, and how many type 1 diabetics are superbly well controlled on sub-Q insulin? It's just not possible. A few rare individuals can control type 1 diabetes extremely well with sub-Q insulin, but it's only because we're obsessive-compulsive about it. Most people don't have that capability, and so they can't do it. Even if they can do it, they end up with severe hypoglycemic problems. And they still have this abnormal physiological situation going on in their bodies, where they're not getting the benefits that they would have if insulin were delivered directly to the liver."
"I don't want to be jaded and say that the problem is that wealthy companies don't want to endanger their revenue from their current insulins, pumps, and so on. That may or may not be the case. What I do believe is that companies are not fully aware of just how profoundly important and invaluable this technology is."
"I was perfectly controlled on sub-Q insulin if you use the standard of blood glucose alone. I ran ultra-marathons, I built my own company and I traveled all over the world. I figured, I've got this thing nailed. I thought I was feeling good and doing great. And then I got IP insulin, and it was like giving sight to a blind person. I know that there are champions of external pumps, but those people don't know what they're missing. They could not possibly know. They're doing the best they can and fighting the good fight, and they think they're okay, but they don't know what they're missing. Massive amounts of research data show how superior IP insulin is at a basic metabolic, biological level."
"This is a situation where there needs to be a groundswell of interest and demand created. Unless something dramatic occurs, this technology is going to blink out and disappear. I'm 61 years old. I can go back on sub-Q insulin and make it work, but there are millions of people who deserve this technology, and I'm sitting here watching it die."
With the implantable pump, I feel normal. I don't feel like I have diabetes, and it's because of getting a direct insulin flow that goes into the peritoneal cavity and then right to the liver. To really appreciate this phenomenon, you have to be a diabetic who's been on subcutaneous delivery, and then you switch to the internal pump. I came back and I said, "I feel like a new man. This feels totally different. I feel normal again."
I would much rather have the implantable pump and test manually than have a sub-Q delivery with a continuous loop because you're just not getting the benefit of that delivery into the peritoneal cavity. I wouldn't touch sub-Q with a ten-foot pole when I've got this. Even though I'm of limited means and it's a sacrifice, my family fully supports my going to France to get the insulin refills every three months.
The feeling you get using the peritoneal delivery is just so much better. When people are on sub-Q and their blood sugars are under control, they get used to how they feel and they think that it's normal. But when you switch from the sub-Q to IP, it's a totally different feeling.
The quality of life is so much better, it's just unbelievable. I can even go a day or two without eating anything, and my sugars stay 85, 90 or 95 all the time. It's just like being a person without diabetes. You don't have those swings, those high highs and low lows, that really reduce your productivity, decrease your ability to work and think properly, and increase the risk of complications.
When I got the implantable pump, it was fantastic. For me, it was a feeling of independence, freedom. I felt really healthy, even a little bit euphoric. The change is just so striking: You feel better as soon as you wake up from the surgery, and as the days go by, you just feel better and better. It's so hard to quantify a quality of life, but I can remember telling my friend one day after I got my pump, "You know what, even if I die because something goes wrong with this pump, it will have been worth it." I felt that much better.
All four of us have to go to France four times a year for insulin refills, and it's just a chore, about 30 hours of traveling for a 15-minute procedure. But all I need to do is think, "Are you ready to give it up?" and the answer is always "Nope." We're all very down to earth, smart people, not people who do this on a whim. There's just something very different about it.
When I talk to people who have come off of the implantable pump because Medtronic discontinued the program here in America, they are really suffering. But when Medtronic tried to terminate the program in France, the French doctors stood up to the company and told them (I'm paraphrasing) "No!" because this technology has helped far too many people lead a better life with diabetes.
When I was on subcutaneous insulin, I had three severe insulin reactions where I actually passed out. With the implantable pump, you feel more confidence because you have fewer and fewer lows. You can begin to really bring your blood glucose into much tighter control without that constant fear of hypoglycemia.
This is my fourth pump. The only time I was off of it for any extended period was when they had to change the insulin formulation, and it took about two years for them to get the new insulin going. Eventually you adjust to sub-Q, but then you go back on the implantable pump, and you feel great again! You didn't think you felt badly when you were off of it, but when you get back on it, you get that feeling of "This is good."
It really does get down to quality of life. Physiologically, you're getting insulin the way you're supposed to get insulin. Neither Greg nor I has any complications at all from diabetes. I've had diabetes for 26 years, and he's had it for 50, and when we go to our doctors, they're amazed that we don't have any complications. I have to attribute a lot of that to the implantable pump.
There's very little information out there about this technology. I don't think it ever got out what a great product this is. All people ever saw was the other pumps that failed in this same arena. But if people out there who have diabetes, or who have children with diabetes, could see what this technology would mean for them, I just can't imagine that they wouldn't choose it.
I was one of the last ones to get the implantable pump. I got my first one in January of 2003 as part of a clinical trial being run by Medtronic. When I started the study, as hard as I tried, my A1Cs were 9% to 10%, but shortly thereafter I was down to 7%.
We were notified in 2007 that they were stopping the study and wanted to explant all the pumps. At the time I had some health problems unrelated to diabetes, so they were kind enough to let me keep it for another year or so past when everybody else had theirs taken out.
I was very unhappy about having to lose the pump. When Ann and Greg got in touch with me, they said I might be able to get it refilled in France, so I started doing that in November of 2008. For the three months before I could get the refill, I had to use an external pump, and I absolutely hated it. It is so much more obvious, and the tape always irritated my skin and ripped it off. I don't sleep soundly, so the catheter always got in my way. And it just wasn't as good as the implantable pump in the way it delivered the insulin and how I reacted to it.
The implantable pump is much more predictable than the external pump. It's more comforting to have it. I feel better, I feel safer, I feel more in control of what I'm doing and I'm feeling all around physically better. With the implantable pump, I managed to make it through some really serious surgeries. When I get sick, it's much easier to manage.
In August, I got a new pump implanted by Dr. Renard in France. I guess that tells you how much I like it, because that was very, very expensive. It's an enormous financial drain to go to France, but it's worth it. I won't give it up. It's less obtrusive and just so much easier. I feel more comfortable both not eating and eating, and it's just a whole lot more flexible.
I have great hopes that maybe Medtronic will realize what they have. I think there are a lot of people who would really benefit from it if they just knew about it.
Comments of Dr. Eric Renard, University Hospital of Montpellier, France:
The experiences and feelings reported by Greg, Chris, Anne, and Sheila clearly illustrate the benefits of being treated by an implantable pump using intraperitoneal insulin delivery. My colleagues and I hear the same testimonies from the 380 or so of our French patients who are using this technology to control their diabetes, some of them since 1990 when the first MiniMed implantable pumps became available. As underscored by the patients, the reliability and reproducibility of insulin absorption, as well as the quicker action of insulin thanks to its first distribution to the liver, demonstrate the superiority of intraperitoneal insulin infusion when compared to subcutaneous infusion.
Intraperitoneal insulin allows patients to reach near-normal glucose levels without increasing the risk of hypoglycemia, especially in its severe form. Most diabetic patients report that they fear unexpected glucose swings more than persistent hyperglycemia. This badly tolerated glucose variability is solved by avoiding the non-reproducible insulin absorption that occurs when insulin is delivered under the skin, a place where physiological insulin is not expected in large amounts.
For patients with visible reactions at their subcutaneous insulin injection or infusion sites (for example, lipodystrophy), bypassing the skin obstacle by intraperitoneal infusion is vital. Getting a reliable effect of insulin is, however, a benefit for all diabetic patients because they can safely tune their insulin delivery according to their changing needs related to their various activities and food intakes. It allows for reaching glycated hemoglobin levels close to 6%, similar to non-diabetic persons, with a minimized risk of mild hypoglycemia.
I have examples among my female patients who succeeded in giving birth to several babies thanks to the glucose control they reached with an implantable insulin pump. Without it, any pregnancy would have been an unachievable dream. Other highly benefited patients are those who have lost awareness of hypoglycemia, resulting in recurrent hypoglycemic coma. The lower level of insulinemia when insulin is delivered through the peritoneum minimizes the occurrence of hypoglycemia, restores the awareness of glucose lowering, and revives the physiological glucagon response to low blood glucose levels.
Recent trials that we have led using implantable pumps connected to glucose sensors to create a new model of the artificial pancreas have clearly shown the usefulness of this technology to reach the "holy grail" for all diabetic patients treated by insulin.
All these accumulated arguments support our efforts in France, Sweden, Belgium, and the Netherlands to keep this therapy available for our patients who cannot be safely treated by subcutaneous insulin. Our national health insurance systems reimburse this therapy because it dramatically reduces the time spent in the hospital by these difficult cases.
Due to the multiple benefits in terms of glucose control and quality of life offered by this technology, we cannot understand how it might be endangered. Instead, it should be considered a reference for the treatment of diabetes by insulin. It is even more incredible to realize that these implantable devices are made in the US but are not approved there to treat diabetes. Consequently, the American patients who recognize its benefits must come to us several times per year at their own expense to get them! It is hard to believe that this therapy would not be profitable to its manufacturer if promoted on a large scale in America. Let's hope the rationale will ultimately prevail for a better, "closer to normal" life for many diabetic patients. We in Europe will never, never give in!
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Medtronic Responds to A "Miracle Technology for Type 1s"
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