Tuesday, July 31, 2007

Diabetes Drugs On The Hot Seat

Even if you don't have diabetes, you may find this post useful. One in three of us is walking around with a condition (insulin resistance) that is setting the stage for diabetes later.

Drugs can extend lives. Drugs can improve the quality of a life. Drugs can also make people feel miserable and carve out a nice chunk of their income. Sometimes, drugs can shorten lives. When it comes to pharmaceutical drugs, the longer you can hold off taking them, the better.

Enter the diabetes drugs Avandia (rosiglitazone) and Actos (pioglitazone). I've been following this class of drugs since the demise of one of their sisters, Rezulin (troglitazone) in 2000. Likewise with these, it's best to delay the time when you are hard-pressed to fill a prescription. That can be accomplished with lifestyle changes. (I feel this way about statin drugs too.) But there's a certain something about these new diabetes drugs that warrants this post.

Preserve The Beta

By the time people are diagnosed with type 2 diabetes, they may have lost up to half of their beta-cell function. (Beta cells are found in the pancreas. They make insulin. We can't live without insulin.) This loss is often unrecoverable, and progressive. No amount of exercise, healthful diet, or drug therapy (until recently) seems to halt it, let alone reverse it, once it has reached a certain point.

This loss of beta-cell function is depicted by the dotted line in the graph below. Notice that no type of drug, including injections of insulin, changed the downward slope of that line.

Catch Insulin Resistance Before It Progresses to Diabetes

Some beta-cell function can be recovered if lifestyle changes such as weight loss are instituted early.1

This is why I harp about getting your blood sugar tested - long before you notice symptoms. No matter what your age, if you are overweight and relatively inactive (or if you are a healthy weight but you smoke2), there's a good chance your cells are becoming insulin resistant. To compensate for this resistance, those precious beta cells pump out more insulin. After a while, they lose the ability to respond. Once that happens, you won't be able to avoid taking drugs - for the rest of your life.

Get your blood sugar tested. If it's over 100 mg/dl after an overnight fast, you are insulin resistant. If it's over 126 mg/dl, you may very well have type 2 diabetes.3, 4 (See my post "Are You Insulin Resistant? Get Pricked" for a photo of what blood sugar testing entails.)

The Promise Of TZDs

Many diabetes drugs until recently worked either by inducing the pancreatic beta cells to pump out more insulin (you can see this might reduce beta-cell function even faster) or by reducing glucose output from the liver (e.g. metformin). Avandia and Actos are different. They belong to a new class of drugs called thiazolidinediones (I still have difficulty pronouncing that word) or TZDs which act upon cells to decrease their insulin resistance. Bingo. Beta cell function (somewhat) preserved.

TZDs do many other things, some beneficial, some not so good. One undesirable side effect is fluid retention or edema. Recently, in June, the New England Journal of Medicine published what has become a controversial study that linked Avandia to an increased risk of heart attack. That spurred an FDA safety alert. Thus, Avandia's hot seat.

How To Avoid Filling A TZD Prescription

The very best thing you can do to avoid taking diabetes drugs is to avoid insulin resistance. You can do that by maintaining a healthy weight, remaining active, not smoking, and eating a diet that does not put incessant demands on your insulin-producing cells. Sugar and starches, especially highly processed carbohydrates (of the type at the bottom of this post), consumed with abandon, put demands on your insulin-producing cells.
1 Diet-Induced Weight Loss Is Associated with an Improvement in ß-Cell Function in Older Men
2 A few studies that link smoking to insulin resistance:
Smoking Induces Insulin Resistance - A Potential Link with the Insulin Resistance Syndrome
Insulin Resistance and Cigarette Smoking
The Insulin Resistance Syndrome in Smokers is Related to Smoking Habits
3 The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
4 The single number cutoff point (100 mg/dl) exists in an imaginary world, but is useful for diagnostic purposes. In reality, ideal blood glucose exists within a range. That range differs among people. It can also vary within a person at different life stages and different physiological conditions. However, wellness or good health is partially defined by homeostasis, that is, the maintenance of limits for optimum functioning. Thus, the blood glucose range within a healthy person should be small.

A fasting blood glucose value of 100 mg/dl to 125 mg/dl is considered, diagnostically, as Impaired Fasting Glucose (IFG) and is derived from a test of plasma (syringe to a vein), not capillary (finger stick) blood. Fortunately, newer meters are plasma-calibrated so these two numbers should coincide. If a meter is not calibrated, its result may be 10% to 15% lower than a result from a venous test. For example, if your finger stick test result from a non-plasma-calibrated meter is 100 mg/dl, this may equate to a venous result of 110 to 115 mg/dl, which still falls well within the range for IFG.


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