Thiazolidinediones, mercifully abbreviated as TZDs, is a class of medication designed to increase insulin sensitivity in diabetic patients. On the face, there is no medication that shows more promise in treating diabetes, provided that one is confused about what really goes wrong here.
Isn’t diabetes a disease characterized by high blood sugar caused by insulin resistance? Many think that it’s also caused by insulin deficiency but that’s certainly not the case when we bother to measure serum insulin levels, and in spite of our beta cells being downregulated, there’s too much in our blood, and that is in no sense a deficiency.
So the problem is insulin resistance then, right? If only our cells could take in this extra glucose, our blood sugar would go down, and it’s because we have been desensitized to insulin that it doesn’t, since there’s both too much insulin and too much glucose in our blood.
So a class of meds come along that fixes this to a large degree, is this not a Godsend? TZDs don’t just improve insulin sensitivity, a lot, they also improve several hormonal profiles that are out of whack with diabetes. They reduce the need for insulin. They lower excessive leptin levels and improve leptin sensitivity. They improve the expression of PPAR gamma and adiponectin, both low in diabetics. They of course lower blood sugar. This sure looks like a dream.
With that all said, while all anti diabetic medications have certain dangers inherent in them, TZDs are actually in a class by themselves, and it’s not even side effects that are the concern, it’s the medication doing what it is supposed to, overriding the native insulin resistance that type 2 diabetics have. That’s very dangerous indeed if we understand what really goes on here.
There’s a rather simple explanation for the dangers of TZDs, and it’s that it increases cellular uptake of nutrients well beyond their capacity. With type 2 diabetes, we already exceed this capacity, that’s why we have insulin resistance, to protect the cells from even more damage.
Why is it that non diabetics can metabolize all the glucose and all the fat in their blood and be fine, but we can’t, and in fact it’s dangerous for us to do so? Well there’s two reasons why not.
The first reason and the biggest reason by far is that there is simply a lot more glucose and fat being put into our blood versus the amount a non diabetic has. Imagine a diabetic and a non diabetic eating a meal. In a fasting state, the liver will secrete a certain amount of glucose into our blood to maintain normal blood sugar, to keep it from going too low.
In a diabetic, we get this as well, but a lot more extra glucose than is needed to keep our blood sugar normal, enough to keep it high all the time basically.
So now both people eat the meal. In the non diabetic, this extra glucose is no longer needed, so production shuts down, and will resume again after the glucose in the meal is metabolized and it is needed again to keep our blood sugar from dropping too low.
Guess what happens with the diabetic? This extra glucose production doesn’t shut down, it actually increases. So you have the meal plus all this extra glucose from the liver, the kidneys, and elsewhere being added.
Since insulin levels are high in diabetics, this causes too much fat to be in our blood as well, and the damage to cells that diabetes causes is from both too much glucose, glucotoxicity, and too much fat, lipotoxicity. The body seeks to limit the damage from these excess nutrients in our blood and becomes resistant to being overloaded with them.
This causes high blood sugar and high levels of fat in our blood but at least all this stuff isn’t all going into our cells or we’d really be screwed. Take a TZD though and that will all change.
The second issue is that, from excess exposure to glucose and fat over time, the mitochondria of our cells become damaged and lose their capacity to metabolize these nutrients. So we can tolerate less than the average person, and they want to give us even more than the average person gets, a horrible idea actually.
Since TZDs overwhelm insulin resistance, now the natural defenses of the cells are broken down, and they get flooded with even more toxic levels of glucose and fat. We check our blood sugar, we see it’s lower, wow great job, this medication sure is working!
As a result of all of this, all sorts of things go wrong here, and a lot of conditions are due to cellular toxicity, cancer for instance. We get cancerous cells all the time, and they love glucose, and now we’ve created a 24 hour all you can eat buffet. So it’s no surprise that this class of med has been shown to cause cancer.
This cellular toxicity also plays a role in a number of other conditions that are also very serious and even lethal, like liver failure and heart attacks. These are also increased by these medications.
For the most part, when the body downregulates something, like PPAR gamma, it does know what it is doing, and it’s doing so to look to balance out other issues that may be going on, like for instance all these excess nutrients in our blood. When you have an excess of something, like excess glucose, the body recognizes this and looks to compensate at least somewhat.
So it’s often a bad idea to look to treat what we could call intermediary processes such as insulin resistance, and what we should be looking to do is address the cause of the insulin resistance, not override it. That’s actually pretty stupid, but thinking the pathology of diabetes is solely defined by hyperglycemia is even more stupid, but that’s how conventional medicine sees these things.
The problems we see with TZDs should well illustrate the problems we can get into when we look to address downstream effects while ignoring the causes. The danger with these drugs is great enough that some have been banned due to their killing too many people, and of course the lawsuits have really piled up as well, the only thing that pharmaceutical companies understand, since everything is measured in dollars and cents to them.
You can still get a prescription for this stuff, although it’s supposed to only be used as a last resort, when everything else has been tried, although this is often ignored. This class of med isn’t good as any resort, but this is what happens when we just look at blood sugar as the only marker here, to hell with the fact that this really fattens people up, and it sure does that, as you might expect with anything that accelerates fat storage this much.
The takeaway here though is that we need to be using our heads here and not just say, well someone has too much glucose in their blood, let’s just look to get more if it into our cells, and just do that and ignore everything else, what’s causing it to go so high in the first place, because that’s a very dumb and dangerous approach.