Tuesday, February 12, 2008

Diabetes Discussed: Part 3

Thus PalMD and I continue our cross-blogging endeavor to explain what researchers have figured out about diabetes in light of recent proclamations from the mouthpiece of science that type II diabetics may not benefit from dropping blood glucose levels to their minimum levels as much as previously thought.

Treatment of diabetes is multifaceted. As Pal pointed out, insulin is the mainstay of therapy, especially for type I diabetes. In type I, insulin is the only reasonable therapy; right now, nothing else works. They don't make insulin. They need insulin. Simple enough.

Insulin was the first protein drug product developed and widely used--it was originally derived from pigs or cows. Nowadays, we get our insulin from E. coli that have been genetically "reprogrammed" to produce human insulin through bioengineering. And we also have a huge variety of insulin products that are essentially just modifications made to the basic insulin design. Some insulins act more rapidly (like Humalog or Novolog) whereas others are intended to last up to 24 hours to provide an insulin "baseline" (like Lantus or Levemir). Insulin dosing may initially be based on weight, but after that, dosages are recalculated based on trial and error. It is difficult to predict precisely what quantity of insulin will produce the desired result, and there are several different rules and protocols for optimizing insulin dose. In short, insulin doses must be individualized to the patient, requiring a lot of careful monitoring by both the health care provider and the patient (with a home blood glucose monitor).

Treatment of type II diabetes is way, way more complicated.

Because type II diabetics can create insulin, but their cells are less responsive to its effects, the initial treatment of choice is usually metformin. Metformin is amazing. It's the only drug in its pharmaceutical "family" on the market, and nearly every type II diabetic is on it. It works by increasing the sensitivity of cells to insulin and by decreasing the amount of glucose the liver makes--it's that gluconeogenesis process again--which results in an overall decrease in blood sugar. It even causes some patients to lose weight, which is excellent; losing weight generally decreases the severity of type II diabetes.

Pal covered metformin and the other "oral hypoglycemics" already--sulfonylureas, like glipizide, force the pancreas to spit out more insulin. And thiazolidinediones (TZDs for short; that word is quite a mouthful) have multiple body effects, including increasing insulin sensitivity, but by a different mechanism than metformin--which means that they can be combined, and sometimes this produces better results.

I would like to stress at this point that if you or a loved one have diabetes, while this series may be thought-provoking and raise interesting questions, that you should discuss the matter with your primary care physician when it comes to individual treatment recommendations--not here. I'm not a licensed medical practitioner*, just a student of pharmacy with a flair for words and a desire to share his knowledge with the world. And even if I were licensed, reading some article written by an anonymous blogger is not an appropriate substitute for face-to-face medical advice.

With that out of the way. What does recent research tell us? Past research tells us that blood glucose is important. But new research says other things might be just as important--maybe more.

Heart disease is a number one killer of patients with type II diabetes. Kidney failure is more common in type I. They're both considered to be manifestations of the same disease. But they're clearly different in several ways. Pal mentioned ketoacidosis--that's common in type I, but incredibly rare in type II. What explains these differences?

If I wanted to indulge my inner conspiracy theorist I'd blame the drugs used to treat type II diabetes, which is kind of like the absurd claims made by tinfoil-hatwearing HIV denialists that AZT causes AIDS.

Much more likely is the difference in co-morbidities ("other diseases/conditions the same patient has") for both type I and type II patients. Type II patients are typically obese, or at least overweight. The Framingham heart study has demonstrated that being overweight (as defined by medical science, not People magazine) is a risk factor for cardiovascular disease. So is having wonky cholesterol levels--and those are pretty common for type II diabetics, too.

This study is kind of interesting. Essentially, cholesterol deposited on beta-cells--the part of the pancreas that secretes insulin--can induce beta-cell failure. Cholesterol essentially "clogs the pipes." Even more interesting is the fact that this whole problem may be tied to a gene that codes for a protein called ABCA1. ABCA1 is essentially the "conductor" responsible for regulating lipid transport in and out of beta-cells. People whose genes incorrectly code for the ABCA1 transmembrane protein may be more susceptible to lipid-based damage to the pancreas. It is entirely possible that controlling lipids is at least as important as controlling blood sugar in type II diabetes, which means that dietary modifications, exercise, and cholesterol-lowering drug therapy may all play an even greater role in achieving good treatment outcomes than previously thought. This is exciting research!

That study's too neat to just be a throwaway link. I might come back to it later.

I think the point of recent research basically demonstrates that we can't just treat blood sugar. It doesn't mean we're completely mean about how we're treating diabetes. It just gives us a new direction to focus our research. Diabetes may be conceptualized as a problem with glucose metabolism, but that isn't the end of the story. Physicians, pharmacists, and patients have to work together to design treatment regimens that address cholesterol and sugar, among other factors.

*Well, I have a pharmacy intern's license. Which permits me to practice pharmacy, compound medications, and counsel patients under the guidance of a licensed pharmacist. But it's essentially a learner's permit. And you shouldn't be using the internet as your sole source of health advice anyway. It's not a good resource. In pharmacy, we call using a drug by itself that shouldn't be used alone "inappropriate monotherapy." Getting all your medical information online is the same. Go talk to your doctor!

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