2012-05-10

Chimeras: No Two Men Are An Islet

Islet cell transplantation is an experimental treatment for type 1 diabetes. It is not right for everyone.

Some type 1 diabetics are particularly prone to hypoglycemia and have great difficulty gaining any kind of control of their blood sugar. They frequently experience nocturnal hypoglycemia, which is life-threatening because they can enter a coma in their sleep and subsequently die, all without ever knowing anything was ever wrong, because they were asleep.

So, for some diabetics, islet cell transplantation offers a possible alternative to certain death.

However, this alternative as it currently stands is far from a pleasant one. Like all transplant recipients, islet cell recipients can often reject the transplanted cells. Their bodies attack and kill the new cells and the patient once again becomes type 1 diabetic. (From one perspective, they were never cured, because type 1 diabetics are people whose immune system's defaul state is one that attacks islet cells - whether or not they were transplanted. This is precisely what causes them to be diabetic in the first place.)

That fact in and of itself is is not any more unpleasant than simply being type 1 diabetic. The real problem with islet cell transplantation is the fact that recipients are placed on a permanent regimen of immuno-suppressant drugs. These are heavy-duty chemicals designed to keep the human immune system at bay (so that it won't attack the islet cells). They work exactly as advertised, but this means that the patient is also exposed to an enormously increased risk of infection.

So the patient gets a cold, but because their immune systems are being chemically suppressed, they cannot fight the virus effectively. Simple viruses quickly become major health threats. The patient could contract pneumonia, or worse, and that means they have another specter standing over their shoulder. To make matters worse, immuno-suppressants are highly carcinogenic.

For patients who face a real risk of dying from nocturnal hypoglycemia, though, this choice is a no brainer. If you get a cold, you have a fighting chance. If you go hypoglycemic in your sleep and don't know it, you're pretty much screwed.

Since a fighting chance is better than no chance at all, islet cell transplantation presents an attractive health option for some diabetics.

New Developments
A new study suggests a potential method for overcoming the need for hefty, ongoing immuno-suppressant therapy: mixed chimerism.

Here I should probably define what chimerism is. Chimerism is a genetic state in which two separate sets of DNA coexist within the same organism, each retaining its own distinct traits. Typically, the way this happens in nature is that two eggs are fertilized during conception, and they somehow manage to grow into a single organism. It is very rare in nature, but it does happen.

Plants can become chimeras through grafting. Humans can become chimeras through organ transplant.

So, basically what we are talking about is medically inducing chimerism in a transplant recipient so that the immune system stops attacking the alien cells. So far, this has only been done in mice.

I have mixed feelings about islet cell transplants. For one thing, the need for immuno-suppressants makes the clinical viability of the procedure limited to a highly unique population. But for the most part, I feel the procedure does not treat the disease, merely the symptoms. Type 1 diabetics are diabetics because their bodies kill their own beta cells. Implanting new beta cells does not really address the core problem, only a symptom of the problem.

Mixed chimerism offers at least a pathway toward overcoming the real problem. If the system becomes tolerant of the beta cells, diabetes can be reversed. But that's a big if.

Regardless, it is an important piece of diabetes research, and the researchers should be commended for their efforts.