Of all the possible complications of diabetes, the cardiac ones are the most lethal. Cardiovascular disease is in fact the number one cause of death in patients with type 2 diabetes. Researchers are using the term "cardiodiabetes" to describe the co-occurrence of diabetes and significant cardiovascular disease (CVD). At the American Diabetes Association annual sessions, held in June 2005, findings were presented, and a media teleconference was held on June 8. Professors Thomas Forst, MD, Jorge Plutzky, MD, and Mehmood Khan, MD, FACE, a senior vice president from Takeda Pharmaceuticals, were the presenters.
There is no absolute predictor of a "cardiovascular event" such as heart attack or stroke, nor is there any 100 percent accurate predictor of CVD, cardiovascular disease. It is a matter of playing the odds. An apparently fit individual of a given age, weight, and lifestyle has a given set of odds he/she will or will not experience CVD, and the odds go up with the presence of "risk factors." There are many risk factors.
We know that smoking is a risk factor, as are obesity and high-stress, sedentary lifestyle. Diabetes is a risk factor, of two to three times the lethality of the others, according to the presenters, who stated the presence of diabetes confers as much risk of a new cardiovascular event as does a history of previous heart attack. The number of different risk factors a given patient possesses will guide treatment. The more risk factors, the higher the risk of cardiac events, and the more aggressive the treatment.
Where does this risk come from? Data suggest the increased risk of CVD in type 2 diabetics shows up well before overt diabetes--and thus does not result from the elevated blood sugars that are diabetes' chief symptom. The researchers described various "metabolic derangements," subtle forms of abnormal metabolism that are precursors to impaired glucose tolerance (IGT) and thus to overt type 2 diabetes.
LDL Cholesterol ("bad" cholesterol) plays a prominent role in this "diabetic dislipidemia," and is considered strongly atherogenic, more a cause than a simple marker of increased risk. The variant known as VLDL, very low density lipoprotein, seems particularly dangerous--though it appears a rise in HDL, high density lipoprotein ("good") cholesterol may moderate its destructive action, even without a corresponding drop in LDL numbers.
The researchers introduced a new term, "TLC." Not far from its traditional meaning, it stands for "therapeutic lifestyle changes." In general, this means stopping smoking, losing weight, starting and maintaining a sensible exercise program, and cutting down on stress. For some individuals, TLC will include blood-pressure-lowering medications, and cholesterol-reducing drugs. The researchers note the generally-recommended maximum LDL cholesterol level is 100 mg/dL, but for diabetics, it should be no higher than 70 mg/dL.
That clinicians have been prescribing members of the drug class called statins to reduce and control cholesterol is not news. What is news is that the thiazoldinediones, the TZDs, Actos and Avandia, are showing some facility at doing the same thing. A diabetic taking one of these "glitazones" may not need a statin, the researchers suspect. They pointed out how up to 1/4 of their study population, who had been previously taking antihypertensives, could cease doing so once therapy was commenced with TZDs.
In another arm of the study, the researchers compared the TZD pioglitazone with the sulfonylurea glimiperide. Both were effective at lowering blood glucose--but while daily blood glucose test numbers, and the A1c improved with both, the insulin sensitizing TZD also yielded improvement in blood pressure and HDL cholesterol. Researchers suspected it might also provide nephropathy benefits, in a manner similar to ACE inhibitors (this needs further testing!), and they pointed out these benefits are independent of the blood glucose reduction that is Actos' primary purpose and benefit.
There are three thiazolidinediones: Rezulin (now banned), Avandia (rosiglitazone), and Actos (pioglitazone). In head-to-head studies, involving more than 800 patients with dislipidemia, the researchers reported, the pioglitazone lowered triglycerides--but the rosiglitazone apparently raised them. The pioglitazone also substantially raised the HDL ("good") cholesterol level.
Pioglitazone is not magic. Like Rezulin, it can sometimes restore fertility in pre/perimenopausal women. It has not been tested in patients with advanced heart failure. Use is contraindicated if the individual has significant liver failure.
Where might this all lead? The researchers suggested prompt TZD therapy, at the earliest stages of insulin resistance, could perhaps substantially reduce risk of vascular complications, and perhaps, at the same time, preserve pancreatic beta cells from autoimmune destruction. Given to women with gestational diabetes, TZDs appear to cut risk of developing type 2 diabetes.
There is far more work to do. It is always exciting to discover that a drug created to fill one purpose has other benefits as well. Our job is now to understand how and why.
If you or a friend would like to remember the Diabetes Action Network of the National Federation of the Blind in your will, you can do so by employing the following language:
"I give, devise, and bequeath unto the Diabetics Action Network of the National Federation of the Blind, 1800 Johnson Street, Baltimore, Maryland 21230, a District of Columbia nonprofit corporation, the sum of $_______________" (or "_______________ percent of my net estate" or "the following stocks and bonds:____________________") to be used for its worthy purposes on behalf of blind persons."