In 1923, Dr. Elliott Joslin said, “Insulin is a remedy primarily for the wise and not for the foolish, be they patients or doctors. Everyone knows it requires brains to live long with diabetes, but to use insulin successfully requires more than brains.”
Diabetes is a hard disease to understand for both patients and doctors. Too often, we boil it down to insulin, or the lack thereof, but there is so much more to it than that. Even if you are very careful with what you eat and are right on top of your insulin therapy, good A1C control can be difficult to maintain. That’s something that even medical professionals have a hard time understanding, partly because we’re just beginning to grasp all that goes into internal glucose control.
It can be hard for a general practitioner to keep up. Recently, during a lecture to physicians, I put the following multiple-choice question on the screen:
What is the hormone that is co-secreted from the beta cell in equal concentrations as insulin?
e) Islet Ghrelin
Don’t feel bad if you don’t know which to choose. In a room of some 50 physicians, none gave the correct answer of amylin.
As a hormone, amylin is a relativelynew kid on the block. It was discovered in 1987, and for the first few years afterwards no one knew quite what it did. I was excited to learn about this hormone because I thought it played a key role in stabilizing A1C levels, a goal which is hard to achieve with just insulin therapy alone. It turns out that it might be the Robin to insulin’s Batman in that it regulates excess glucagon in the bloodstream.
I have focused my career on understanding diabetes, with a special interest on the Islets of Langerhans, which make the hormones insulin, amylin, somatostatin, pancreatic polypeptide, glucagon, and ghrelin. Each of these Scrabble-busting hormones plays a role in regulating blood sugar, albeit not as lifesaving a role as insulin.
I was one of the researchers that took part in the Diabetes Control and Complications Trial (DCCT), which was the first randomized controlled trial among patients with T1. It was an object lesson in the value of scientific failure, as we learned the limits of insulin therapy. In that trial, we were unable to meet the endpoints of an A1C of less than 6.05% with insulin therapy alone. Had we known about amylin and how, like insulin, it is a missing hormone among people with T1, patients in the trial might have reached the goals of the study while experiencing lower rates of weight gain and hypoglycemia.
We have since learned that the synthetic form of amylin, known as pramlintide, reduces insulin requirements and helps with weight maintenance among people with T1 (this synthetic form of amylin is marketed as Symlin). As a researcher, I initiated several studies using glucose sensors to monitor amylin therapy. What I found is that amylin is a vital part of the delicate dance the body does to keep blood glucose levels in a healthy range. In my studies, patients on pramlintide reduced unregulated glucagon made in the pancreas, especially after meals. This is a good thing because that excess glucagon otherwise would be dumped into the liver, which in turn would elevate glucose levels, creating a vicious cycle. Pramlintide also reduced the wide swings in both high and low glucose levels, but this required a shift in traditional insulin therapy adjustment. Patients needed to reduce their premeal insulin by some 25% to avoid going low.
Diabetes is a tough disease to treat. It sometimes feels like the more we learn about it, the harder it can be to treat it well, as we are trying to mimic the marvelously complex processes of the human body. Our understanding of internal blood glucose control is evolving so fast that I can’t even expect a room full of doctors to keep up.
My hunch is that it will ultimately prove easier to regenerate whole new functional Islets of Langerhans from one’s own ductal tissue than to try to synthesize and regulate all the hormones that lead to good blood sugar levels in a functioning pancreas. That’s what we’re focused on at Perle Bioscience. It’s our belief that a multiple-choice fail on a question of hormones is one thing on the blackboard, but another in the bloodstream.
Stay tuned for more data on the ideas that we have scribbled on the blackboard and are turning into new therapies for diabetes.
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