FAQ: How has thinking changed about the relative roles of insulin resistance and secretion in the pathophysiology of T2DM?

Frequently asked questions for the primary care community, excerpted from a conversation between a leading primary care physician and a world-renowned beta cell researcher. (1:28)


Dr. Leahy: The average provider ten years ago knew insulin resistance was important in the disease and that has not changed.  This is clearly a disease of insulin resistance and the reason that it’s expanding around the world is because worldwide people are westernizing and getting happier and fatter and moving away from working on farms and working in offices and gaining weight and eating terrible things and all of that’s related to worsening insulin sensitivity.

The change that occurred ten years ago was a simple understanding of a lot of beta cell researchers that for people who get Type II diabetes can’t compensate to the kind of metabolic stresses that are out there and are worsening and, in fact, these studies when they’re really carefully done and when they’re sort of clever trying to move earlier in time to study people before diabetes, before pre-diabetes and when people are still normally glucose tolerant who will eventually go on to get this disease, there’s already demonstrated defects in beta cell function and probably a reduction in beta cell mass.

Researchers these days consider this really kind of a two-hit disease.  You have to have some kind of compromised beta cells at the earliest stages of the disease and if you don’t face metabolic stresses maybe you’ll be fine your whole life.  But as these metabolic stresses or other issues come along, your beta cells can’t compensate and then the slippery slope starts that gets us to the clinical disease that our primary care doctors deal with.