You hear a lot of talk about how type 2 diabetics have lost so many beta cells, in other words so many of our beta cells have died, and this is held to be a central feature of type 2 diabetes actually.
So with this beta cell loss, where diabetics have been shown to have lost anywhere from 25% to 65% of beta cells, creates what is termed a relative insulin deficiency, meaning that our pancreases can no longer secrete the amounts it could, although this doesn't mean it can no longer secrete normal amounts.
So there's no question that we lose beta cells, and it's not just that our beta cells die, it's that too many die. So you hear about beta cell mass here, insofar as we have a reduced beta cell mass, and this takes into account the hypertrophy, or enlarging, of our beta cells, which is actually a compensatory mechanism when we lose too many.
So there are some who just see this reduced capacity as due to the loss of this beta cell mass, but we do know that aside from this there is a loss of function of beta cells here as well, in other words they aren't dead but aren't able to secrete as much insulin as they normally would.
So there is a sort of debate here between the relative effects of both of these conditions, death versus just illness of beta cells we could call it. If most or all of this is actually caused by a lack of beta cell mass, and we do know that this occurs in type 2 diabetics in significant amounts, then there is a lot less hope of fixing the problem or at least significantly improving it than there is if a lot of the problem is loss of functionality.
So for those who are interested, here is a very good discussion of this debate, and it does seek to take a balanced approach to the issue, which is why I selected it.
The article does approach this problem from the perspective of relative insulin deficiency rather than hyperinsulinemia, meaning that in spite of insulin levels being higher than normal, they see the problem as not enough insulin being secreted, but we'll leave that aside because that's not what we're after here, it is a relative insulin deficiency in spite of whether that's desirable or not.
I do want to point out though that this alleged deficiency is often not a just a matter of just looking at lack of insulin secretion, as through hepatic liver production we can exceed the capacity of the healthiest of pancreases, as at the higher levels of this extra glucose secretion, our bodies are simply not designed to cope with this much glucose in our blood.
Our pancreases as type 2 diabetics clearly have lost some insulin secretory function though, so what we need to do now is to look into why. As I've said, often we just assume that it's loss of beta mass, although we do have evidence that shows that it can't just be that, as beta cell function can be improved quite dramatically by various means, in a way that can't be explained by any changes in beta cell mass that may have resulted.
For instance, when we take a drug like a sulfonylurea, drugs that stimulate insulin secretion, they don't work by increasing beta cell mass, and we actually know how they work and that is by overcoming beta cell dysfunction. So more insulin is secreted because the beta cells work better. Incretin drugs do this as well, although incretin drugs also increase beta cell mass as well, although perhaps not in a desirable way.
It may be that our beta cells are functioning less efficiently due to their being downregulated by the body intentionally though, but what I want to look at is our looking to restore function, but with a view to not just do this artificially like drugs do, but instead to do this more naturally, or at least see if we can do so.
One of the most enlightening ways we've found to restore beta cell function is by way of bariatric surgery, and it's well known that this can cause dramatic changes in glycemic control, reversing diabetes in a matter of just days, but one of the things we see happening with this is a restoration of beta cell function in a way that cannot be explained by changes in mass.
We do know that this sort of surgery greatly restricts nutrient intake, although people aren't going to want to undergo this surgery just for diabetes management, but perhaps we can get similar effects from more natural nutrient restriction.
So this idea was tested, where subjects were placed on a very low calorie diet for several weeks, and beta cell function also improved very robustly. It's unclear whether this effect was due more to a reduction in calories or a reduction in dietary glucose sources, in other words carbohydrates, and to a lesser extent protein, but even fat may be involved here as well, and the effect of an intake more resembling fasting may be behind this.
What jumps out at me when I see something like this is that this may be similar to what we saw in the Newcastle study, which used very low calorie as well to improve glycemia, and one of the big mechanisms behind this appears to be its reduction in fatty liver and pancreas, and treating fatty pancreas would very likely improve beta cell function.
Intensive treatment with insulin therapy, both exogenous insulin and oral agents, both showed improved beta cell function, and the goal of this was to reduce blood sugar and it showed that doing that improves beta cell function, but that's not hard to imagine since high blood sugar negatively affects this, but the real interesting part is that this even happened with the oral meds, which many people think have a negative effect on this.
I don't think that the medication here was primary, it's very likely that the effects here were from tight blood sugar control, but this does leave us coming away with an appreciation of the importance of glycemic control on beta cell function, and since medication certainly isn't the only way to achieve good control, this can also provide insights on how we may able to further restore function apart from nutrient restriction.
Now how much beta cell function we actually need is another matter, but it's good to have a look at what does improve this, and we all want better functioning beta cells even though we may not want them needing to go full tilt all the time.
So it seems that it's easier to improve this than many would have thought, and our decreased beta cell output may have a whole lot less with beta cell death or loss of mass than we may have once thought, although it's certainly the case that there is a lot of redundancy here and we certainly don't want to just focus on this when we treat diabetes, although it certainly is one thing that bears looking at, especially when it comes to the loss of acute postprandial insulin secretion, the phase one response, which is something we really need help with.