Thursday, November 11, 2010

Insulin Sensitivity, or The Therapeutic Index

Last spring I was (I think erroneously) told that I had a very low vitamin D level and that I needed to supplement. My doctor suggested 50,000 IU per week. When I started reading about how safe it was to take vitamin D supplements, I learned about a concept called the therapeutic index. Basically what the therapeutic index of something is, is how much you have to take for it to be dangerous, divided by the amount that's the most healthy to take.
The example that was given that made it clear was water. If xe drinks and drinks and drinks water, the average person can get dangerously sick from about 40 cups of water in a day. The healthiest amount of water for the average person to drink (or eat in food) is 8 cups per day. So the therapeutic index of water is 40 divided by 8 or 5.
The therapeutic index for vitamin D is about 10- you have to take a lot more vitamin D than you need in order to get sick. Despite that, I ended up taking an amount of vitamin D that was dangerous for me... so much for doctor internet.

But something about this that got me thinking was imagining the therapeutic index for insulin. Insulin is pretty tricky to dose. Two times your correct dose of insulin will almost definitely make you sick, so the therapeutic index of insulin is definitely less than two. I can't find anyplace online where an actual value for the therapeutic index of insulin is stated, and actually it would be pretty meaningless, because the therapeutic index of a drug is computed for an average person and frankly, average people don't take insulin.

But let's look at the insulin needs of a type 1 diabetic with little to no counter regulatory ability to deal with hypoglycemia.
Let's say the person's blood sugar is 200. Xe would like to get down to 140 or less. Getting down to 60 or less is what we'll consider toxic. Now, if the person uses an insulin sensitivity factor of 60, they assume that 1 unit will lower them to 140, two units would lower them to 80, and two and a third units would lower them to 60, making the therapeutic index two and a third- not too low, actually.
Now, let's assume this same person wants to eat 100 carbs, has a blood glucose of 200, and has a carb ratio of 1:12. They should take 9 1/2 units of insulin. It would still take only one and third extra units to make xem hypoglycemic. Now the difference between the best dose- 9 1/2 units -and the dangerous dose 10 5/6 units - is pretty small, and the therapeutic index is now 1.14; pretty low.

There are two other problems with calculating the therapeutic index of insulin.

One is how much insulin sensitivity varies from person to person. As you may have noticed, most medications don't come in a very wide variety of doses. One dose may not quite fit all... but close enough. And you can probably guess the right dose with a simple weight chart.
Insulin's not that easy. Two people who both weigh 150 lb can have wildly different insulin needs. One person weighing 150 lb can have wildly different insulin needs simply depending on how active xe is, or especially if she's a woman, on the time of the month.
Type 1 and type 2 diabetes are sometimes distinguished by a tendency for the type 1 diabetic to have fairly normal insulin needs- normal still being a wide range- and type 2 diabetics to have fairly high insulin needs. But simply classifying people as insulin resistant and insulin sensitive, which is often what happens when doctors are doing the classifying, ignores the reality that everybody gets a little more insulin sensitive and a little more insulin resistant sometimes.

Another problem is that insulin itself changes insulin sensitivity. When your blood sugar goes high, your body doesn't use insulin as efficiently and when your blood sugar is lower, the insulin works more. That is, once insulin starts working... it really works. And once it isn't... it's not.
The idea that a person has a fixed insulin sensitivity is just that: an idea. A useful one. But the reality is more likely that the person has an insulin sensitivity of, say, 55 when xyr blood sugar is 300. An insulin sensitivity of 61 when xyr blood sugar is 200; an insulin sensitivity of 66 when xyr blood sugar is 100. An insulin sensitivity of 70 when xyr blood sugar is 60.

So it takes more insulin to get down from 200 to 150 than it does to get down from 100 to 50.

In 2004-2005 insulin was the second most common drug sending seniors in the United States to the hospital, responsible for 1 in 7 visits to the hospital caused by taking a medication (1 in 4 of these was from hypoglycemia that caused loss of consciousness).

EDIT: When I first posted this, I had the ISFs in the wrong order, which just goes to show that diabetes math is tricky.

1 comment:

Wendy said...

THANK YOU SO MUCH for these wonderful informative posts!

ISF is one of those things that have boggled my brain...well...I guess all of this jazz has, to be honest :)