"If you add back pancreas, you simply end up becoming hyperinsulinemic and, while that will work for awhile, it doesn't get at the core of the problem. "
That's pretty much what we do now with sulfonylureas and other insulin secretagogues, not to mention insulin therapy.
Agreed. That's why diabetes treatment sucks so badly (yes, better than nothing). The PPAR agonists seem promising, in theory. In practice they don't seem quite so awesome. I'm still hopeful; GWAS has offered us some new targets that should be exploited in the near future.
The PPAR agonists stimulate adipogenesis - one of their main effects is to make you fatter so that you have a dumping ground for excess sugars. This doesn't seem like a very good idea, and I'm not surprise that it turns out that they suck (kill people).
Well, yeah, insulin sensing leads to adipogenesis. Since the PPAR agonists increase insulin sensitivity, you're going to become fatter if you continue overeating. This sort of brings us back to the root cause of most DM (overeating). And while some of the PPAR agonists kill people, it does not seem to be a class effect; pioglitazone looks OK. (CHF is a class effect of the thiazoladinediones, but it's a more balanced tradeoff with diabetes.)
That's pretty much what we do now with sulfonylureas and other insulin secretagogues, not to mention insulin therapy.