The Heart Of Diabetes Part 7

insulin and glucagon









We're looking at a video by diabetes pioneer Dr. Roger Unger, and this is part 7 of the discussion.  So we left off by looking at the paracrine levels of insulin in the pancreas, the levels that the alpha cells are exposed to with natural insulin secretion, which Dr. Unger points out are at a concentration of 2000 units.

We're looking at type 1 diabetics here with no insulin secretion or extremely low levels and to replace this paracrine insulin level, we'd have to use 2000 units, which he says would produce severe hypoglycemia, I would say that anything even close to this amount would produce fatal hypoglycemia.

However, if you set the levels at what is normally found in the periphery, 5 units, then this isn't going to really do much to control excess glucagon production, given that it normally requires 2000 units at the pancreatic level to do this.  So you can see that this isn't really a solution, and we can't even come close to replicating natural insulin by way of injecting it because of the way the body naturally proportions insulin in various organs in order to achieve proper glycemic control.

I do want to point out here that people may say, well if less than 2000 units and a lot less in fact can produce hypoglycemia, why are we so worried about suppressing glucagon?  Well no one is saying that we need that much for control, but what happens here is that the dosing that we're forced to use does not replicate the body's natural insulin secretion at all.

Sure, we can keep people alive with this but it doesn't do a very good job and not even close to what natural insulin does, so at the very least we need to be less glib about how well this works and less confident that we've slayed the dragon, we've just slowed it down, and we need to look harder at ways to further glucose management in type 1's, aside from things like looking at stem cells and such.

Dr. Unger indeed suggests that we look at alternative approaches, and the first thing he wants to do is to look to eliminate hypoglycemia, which I think is a very good idea since there is a lot less margin for error on the hypoglycemic side.  A small mistake on that side is dangerous, where a small mistake erring on the side of it being too high isn't anywhere near as significant.

To do this though, we need to start by measuring the insulin levels of patients and use that as a tool for dosing.  What a concept though, prescribing exogenous insulin and actually checking to see if there is too much.  No one bothers with such things though, and to be fair this is far less practical than giving a patient a glucometer and getting them to monitor their blood sugar, but this is way too important to just turn our heads away from, as we do.

So in the hypoglycemic state, Dr. Unger states that insulin levels are 20 times higher than normal, but even without testing we can surmise that they are much higher than they should be just from the hypoglycemia occuring.  This is a result of an overdose, pure and simple, and we need to pay a whole lot more attention to preventing an overdose of the medications we provide patients.

The big problem here is that we use blood sugar to dose insulin, and this is the case with type 2's as well, and this is an even bigger problem with type 2's by the way, because our condition is the opposite of type 1's, we don't tend to have insulin deficiency, we have insulin excess.  So we have too much already and they aren't checking nor do they care anyway, here's some more because you need it to lower blood sugar.

I do want to mention that dietary restriction does play a big role in reducing the insulin requirements of type 1's, Dr. Bernstein's law of small numbers if you are familiar with his book, which reminds me, I have to do some articles on that at some point, although that will be a big project for sure as he's got lots to say and I have lots to say in response as well.

So Dr. Unger suggests that we first look to remove the hypoglycemic risk in type 1 patients by reducing the insulin dosage enough, which is going to be a healthy reduction indeed.  However, when we do that, glucagon is less suppressed, resulting in a lot of hyperglycemic episodes.

So he suggests we look at that separately, and if we are able to reduce glucagon secretion to normal levels without having to increase insulin levels to way beyond normal, we can actually achieve normal blood sugar with type 1 patients and achieve this goal very well.

We have done this successfully as far back as 1978, using glucagon suppressors, and have used them to achieve normoglycemia.  The amount of insulin used is reduced very dramatically with this protocol, only a small fraction of what is normally used, because with the glucagon suppressor being used, we no longer require supranormal amounts of insulin in the blood stream to suppress glucagon.

So this is something that deserves a lot more focus than it gets, and to be honest I'm not that comfortable with turning this over to pharmaceutical companies, and to my knowledge, none of their attempts at a patentable agent have even come close to meeting their lax safety standards.

With type 1's, as well, we require a much more targeted approach than we would with type 2's, where even a slight reduction in glucagon could be helpful, but with type 1's, we are leaving their control pretty much entirely in the hands of injected insulin, where type 1's secrete plenty of their own and what we'd be looking to do is to improve the natural processes already available to us, meaning that the amount of insulin we secrete is plenty to suppress glucagon very nicely if not for the pathologies involved, the main one of course being lack of insulin sensitivity of the alpha cells themselves.

For type 1's though, we can at least say that this all may hold some promise for improving their treatment should we be able to come up with some effective ways to reduce glucagon secretion apart from using injected insulin to do that, which may include some natural approaches as well, and while type 1 is outside the scope of this site, a lot of the things that we'll be talking about as far as managing excess glucagon would apply to type 1's as well.

So Dr. Unger moves on to the myths surrounding type 2 diabetes, which we will start discussing in part 8.

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