On the subject of type 2 diabetes my understanding is the process is you develop insulin resistance. At first your pancreas makes more insulin but soon you are so resistant the pancreas can’t keep up and blood sugar rises.
So you go on oral meds to raise insulin levels, increase insulin sensitivity, etc.
But eventually that stops working too and you switch to insulin.
So does anyone ever reach a point where even insulin itself stops working for getting Glucose into the cells? If so what do they do then?
Can you just keep increasing the dosage of insulin until you are on huge doses, or is insulin like oral meds where after a point it alone can’t get enough Glucose into your cells?
In typical Type 2 Diabetes, you develop insulin resistance partly from genetics and partly from being overweight so that fat clogs up the insulin receptors on your cells. You can get Type 2 Diabetes without being overweight, but this is the most common way that people get it, at least in the U.S.
It’s not necessarily so much that your insulin resistance increases. Once you get to the point where fat is clogging up the insulin receptors on your cells, what happens is that the cells in your pancreas are overworked and start to die off. These cells do not regenerate, so when they are dead, they are gone forever. When enough cells die off that your body can no longer regulate your blood sugar, then your blood sugar level rises.
Of course, if you continue to gain weight, then your insulin resistance will also continue to increase, but once you reach the point where your pancreas is stressed, you don’t necessarily need to keep increasing your insulin resistance to develop diabetes. The stress on the pancreas alone can cause the cells to die off.
If you catch it early enough, you can often be “cured” of diabetes by losing enough weight so that the fat no longer clogs up your insulin receptors. I put “cured” in quotes because the damage to your pancreas is permanent. You don’t really get better, you just reduce your insulin resistance to the point where your damaged pancreas can properly regulate your blood sugar.
I personally am currently in this state. My pancreas is permanently damaged, but my blood sugar is currently under control. I just have to watch what I eat. So there isn’t necessarily a constant progression of the disease.
If you don’t get your blood sugar under control and the disease does progress, you can progress to the point where even with insulin you can have poor control over your blood sugar. In this case, other medications can be prescribed to help you get your blood sugar under control. I don’t know what these medications are off the top of my head (maybe one of our medical dopers can add that), but I know they exist.
Reducing stress and exercising also help.
I thought newer research found a near starvation diet could bring your pancreas ability to produce insulin back online.
The concept of insulin resistance can be tricky. Although most people with type II diabetes are insulin resistant, they are clearly not resistant to the effects of insulin to build up fat. As you know, the prototypical person with T2D is obese. This illustrates that a key disturbance in T2D is resistance to the effects of insulin on muscle (muscle being a major consumer of glucose).
Some people have no fat tissue (or very little of it) and even though they may have all the insulin in the world, they are resistant to it insofar as the insulin has no fat tissue on which to act and thus has lost a major ‘sink’ to deposit nutrients.
Getting back to your question whether someone can be “totally resistant” to insulin, there are, in fact, some syndromes where people are pretty much totally resistant to insulin. For example, people can very rarely develop antibodies to insulin which neutralize its effect. Likewise, people can become truly allergic to insulin (which is problematic if they require insulin treatment!).
There are also two related syndromes where, either by virtue of having nonfunctional insulin receptors or antibodies blocking the binding site for insulin at the receptor, people are almost ‘totally’ insulin resistant. If their pancreases remain healthy, they (try to) compensate by putting out huge amounts of insulin. Then, something very interesting may occur. When insulin levels are an order of magnitude or two higher than normal, the high concentration of insulin can begin to act on other receptors - receptors whose usual ligand shares structural similarity (homology) with insulin. In fact, many of the body’s growth factors very much resemble insulin (i.e. have high homology with insulin) so it is not surprising that the receptors for those growth factors are capable of responding to insulin if the insulin levels are high enough.
One example of the ability of high levels of insulin to act on other protein-hormones’ receptors occurs in the Polycystic Ovarian Syndrome. In this condition, insulin resistance leads to compensatory high levels of insulin which act on growth factor receptors in the ovaries causing them to produce androgens (male hormones) and thus leads to the development of things like excess facial hair, or even male pattern baldness. Reducing the insulin level in women so affected (say, with weight loss or treatment with the drug metformin) leads to reduction in their male hormone levels and thence a reduction in their hirsutism (excess male pattern hair growth).