Tuesday, April 10, 2007

Will Bionic Beta Cells Be The Cure We're Waiting For?

When I was diagnosed with type 1 diabetes as a 7-year old kid in 1976, two of the popular television shows were The Six Million Dollar Man and The Bionic Woman. In fact, the Bionic Woman began life as her own television series right around the time I was diagnosed, so I hold a special affinity for Lindsay Wagner even if she's now pushing Sleep Number Beds. She still looks great!

In medicine, bionics means the replacement or enhancement of organs or other body parts by mechanical versions. Bionic implants differ from mere prostheses by mimicking the original function very closely, or even surpassing it.

This definition of bionics is best known to the general public in reference to the television series The Six Million Dollar Man and The Bionic Woman, in which the cyborg characters are referred to as the "bionic man" and "bionic woman". In the mid-1970s, when scientists in these popular TV series rebuilt a wounded, barely-living test pilot into the world's first bionic man, they made him "better, stronger, faster", but the field of medical bionics was the stuff of science fiction. Today, this field of science has progressed somewhat. For example, on the TV show Dancing with the Stars we have a contestant with a bionic leg -- maybe its just a prosthetic, but it certainly has not impeded her ability to dance!

As a kid, I was completely fascinated by the possibility of getting superhuman bionic parts (like a pancreas) to replace my own damaged goods. I reasoned that if The Six Million Dollar Man had super, bionic vision which enabled him to see as if he had built-in binoculars, and The Bionic Woman could hear footsteps from a mile away with her bionic ear, and both of them could run more than 60 mph and jump to the rooftops of 12-story buildings, what's not to like? Their bionic body parts were actually improvements upon the real things! In fact, I recall a scene from the Bionic Woman where Jaime Sommers hits a tennis ball so hard that it goes straight through her tennis racquet before skyrocketing into the outer reaches of space. She had super hearing, able to hear wispers from miles away, while Steve Austin had super vision able to see long distances. Plus, the bionic characters looked great.

For more than 30 years, I've been hearing about a so-called "artificial pancreas" (or perhaps better described as bionic beta cells, since the actual pancreas works just fine in people with type 1 diabetes, only the cell functions found in the Islets of Langerhans are compromised), but so far, this idea has remained the stuff of SciFi dreams rather than reality. However, these days, its starting to look like a real-life "artificial pancreas" could finally emerge in the next few years. After all, we finally have continuous blood glucose monitors, so the next logical progression is to close the loop. From what I am reading, however, it seems that what is more likely to emerge is a semi-closed loop system rather than a completely closed loop system. The difference being that unlike a completely closed loop system, patients would still have to input data about their meals into the device so that the computer algorithm doesn't get surprised by unpredictable rapid blood glucose changes caused by meals.

At the present time, the artificial pancreas is designed to deliver insulin, but forget about the other hormones like amylin or glucagon which are also part of a healthy metabolism. JDRF's Aaron Kowalski, who is managing the artificial pancreas project for JDRF was asked about glucagon and Symlin, and he acknowledged that they need to start looking at them. So far, they've made considerable progress with glucagon. In a recent announcement, JDRF noted that they are actually funding research into including glucagon (the necessary counterregulatory hormone that many type 1 patients have lost the ability to make) in its closed-loop system.

Apparently, researchers at Boston University have shown that glucagon can be used effectively in tandem with insulin in a closed-loop setting. In JDRF's studies using diabetic pigs, the insulin-glucagon combination rapidly increased glucose levels and helped maintain virtually normal-range levels without incidence of hypoglycemia! Perhaps the next phase will include Symlin, and maybe down the road, C-peptide, if we are lucky! Regardless, the trial results with glucagon were so encouraging that human tests could begin by the middle of 2007. No word on whether this might require yet another set of tubing and infusion set, but the way things are going, I would venture to guess it would. This raises an important issue the pharmaceutical industry is doing very little about, but really needs to consider.

When I was diagnosed in 1976, most insulin formulations could be mixed in the same syringe, but today, manufacturers caution against mixing any analogs (not that they've even bothered doing any extensive clinical trials to investigate this), and forget about other injectables like Symlin. More surprisingly, even analogs from the same manufacturer, including Novo Nordisk's Novolog and Levemir and Sanofi Aventis' Apidra and Lantus advise against mixing them in the same syringe. But the truth is that researchers at the Barbara Davis Diabetes Center in Colorado did do a small trial of mixing Lantus and Humalog and did not find a significant decline in blood glucose control. The real question is why are manufacturers not working to resolve the issue of mixing their insulins in a syringe or pump reservoir? I am well aware that the mechanism in analogs is accomplished by modifying the genetic structure of the insulin rather than via an additive such as zinc, but the pharmaceutical companies seem so busy pushing expensive analogs to enhance their bottom line, that they have lost sight of what patients need in terms of next generation treatments.

If there is any doubt, I would call attention to a January 2006 interview with Jesper Brandgaard, the chief financial officer of Novo Nordisk, who told CNBC/Dow Jones Business Video "We are taking our portfolio from being generic product, human insulin, onto a patent-protected insulin analogue. We are about to convert the market from human insulin onto insulin analogue. If we look at it globally, we have more than 40% of the market now converting to analogue. So we are actually in a different situation from most other companies. We are taking our portfolio from being generic product, human insulin, onto a patent-protected insulin analogue. So we are actually getting our portfolio on-patent, not off-patent."

Back to the bionic thing. I wish I could say that I'm as thrilled about the prospect of a "bionic pancreas" today as I was 30 years ago, but the way it looks, I doubt I'll be among the first in line to get one. First, there's the issue of all those damn infusion sets and sensors and their accompanying wires and tubes, largely meant to fuel the multi-billion diabetes industry, not make patients feel better about themselves. Who the hell wants to wear all of that shit? Jaime Sommers was an incredible hottie, but if she wore an artificial pancreas, she'd look more like a transistor radio than a supermodel! With the artificial pancreas in its current generation, we'll get multiple tubes, wires and end up looking like dogs with several different leashes still attached. And I won't even discuss the permanent damage to patients' subcutaneous tissue, an issue that manufacturers are claiming doesn't exist in spite of evidence that some doctors like Dr. Bernstein argue is a very real issue.

But the main reason for my reservations about an artificial pancreas is that unlike the bionic parts that Steve Austin and Jaime Sommers had, the early bionic pancreas is, well ... not exactly a huge improvement upon the real thing, and in some ways, is worse than current treatments for reasons I've already noted. There is little doubt it will be expensive, and the manufacturers (such as DexCom and Metronic Minimed) have done very little to get their continuous monitors covered by insurers. Instead, they are leaving most of the work up to nonprofit organizations like JDRF. Aside from the cost, these things will still be subject to mechanical failure. Then there's the issue about the algorithm used -- no matter how many clinical trials the finished product undergoes, they always seem to work differently for me (and not as predicted), which has been my experience with every insulin analog ever created. As a result, I harbor a tremendous terror that it will deliver too much insulin and someday kill me given my issues with hypoglycemia-associated autonomic failure (which incidentally, never corrected itself as I was promised).

Oh, and did I mention the issue of all those unattractive tubes and wires, which is a big negative that seems to be an afterthought? If not, its worth repeating. My cat would probably love all those tubes and wires, but I won't. But in order to keep feeding the diabetes industry with ever more profits, there needs to be infusion sets which must be replaced every few days, as well as a new sensor that also needs to be replaced fairly regularly. Somehow, the whole bionic thing just doesn't look as appealing as it did in 1976. In the television depictions, the bionic characters were "better, stronger, and faster" than ever before, but patients with diabetes will probably not be any of these things. As Amy Tenderich recently wrote, they need to take design more seriously before I will even consider it.

3 comments:

Jeff said...

I'm a long term (31 year) T1 who is considering pumping. I notice you call yourself former-pumper. Have you written a blog describing why you stopped pumping - if so could you give a link to it? (I find lots of positive stuff on pumping on the web, but not much negative - I'de like to hear both sides of the story).

I am also a bit more hopeful about the moves towards an open-loop sensor/pump than you are in your article, but perhaps that is in part because I have no first-hand experience with pumping.

Anyway its an interesting article (and yes Lindsay Wagner was definitely hot),
Thanks
Jeff

Scott said...

I tried pumping and went back to shots. Although that happened before I began blogging (so there aren't any posts related to the decision) I will say that I already had great control before pumping. As a result, the pump did not deliver any noteworthy improvement, and I found changing infusion sets every 3 days to be a royal pain. Finally, I hated being tethered to that machine, and decided that the extra work and expense was simply not worth it for me. Many people find pumps to be liberating, but I would just caution you that you should consider it as a viable treatment option, not the next best thing to a cure.

It was worth trying, but don't let the expectations become greater than the actual potential or you'll be disappointed.

Lindsey said...

Scott,

So...maybe I was named after Lindsay Wagner for a reason! Type 1 bionic woman! Love it! She was my dad's fave!