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Studies have found that diabetes is closely linked to cardiovascular disease (CVD). With this being the case, "the trend is to look more and more at the factors that cause cardiovascular problems," according to R. Keith Campbell, B.Pharm., CDE, MBA, professor of pharmacy at Washington State University College of Pharmacy.
The crux of the problem seems to be insulin resistance, which causes several other malfunctions, such as hyperinsulinemia, increased triglycerides, and lowered HDL cholesterol levels. Patients with insulin resistance may also have hyperglycemia and hypertension. It is important to note that the majority of people with insulin resistance do not develop Type 2 diabetes. According to the National Institutes of Health, about 40% of Americans have abnormal glucose levels but do not have diabetes.
The tendency for insulin resistance, hypertension, obesity, low HDL cholesterol, and elevated triglycerides to be present in patients concurrently has been the subject of many studies for nearly two decades. This group of risk factors is now referred to most commonly as metabolic syndrome. Although there has been some disagreement among experts as to what criteria constitute metabolic syndrome, most experts acknowledge the correlation between the risk factors and their propensity to develop into diabetes, CVD, or both.
Distinguishing cardiodiabetes from metabolic syndrome is important, according to Khan, because the outcomes in patients with both diabetes and CVD are worse than those of other patients. For about 50% of patients with diabetes, a fatal heart attack is the first sign that they have heart disease, said Khan. It is therefore critical to screen all diabetes patients for CVD.
The concept of cardiodiabetes is so new that treatment options have not been established. Pharmaceutical companies have recognized cardiodiabetes, however, and some of them have been investigating which single-drug regimens may attack several or all of the risk factors for metabolic syndrome and possibly prevent cardiodiabetes.
Sanofi-Aventis, for example, received an approvable letter from the Food & Drug Administration in February for rimonabant (Acomplia). Although the drug was originally targeted at obesity, study results indicate it may also improve several of the conditions involved in metabolic syndrome. Rimonabant treatment has decreased waist circumference, triglycerides, insulin resistance, and A1c. It has also raised HDL levels.
According to Khan, anytime patients lose weight intentionally, almost all will have lowered triglycerides, blood sugar, and so on. In his former position with the Mayo Clinic, Khan specialized in obesity and metabolism.
While it is true that any drug that produces even a modest weight loss can also improve metabolic risk factors, researchers are convinced that the benefits observed with rimonabant exceed those that would be expected from weight loss alone. "Weight loss, for the majority of patients, is transient," said Khan. Sanofi-Aventis is aware of this as well, and research into the long-term use of rimonabant is ongoing.
Insulin resistance is behind most or all of the risk factors included in metabolic syndrome, and it is one of the defining factors of Type 2 diabetes. Decreasing insulin resistance may, therefore, be a key treatment for both metabolic syndrome and cardiodiabetes. Both metformin and the thiazolidinediones (nicknamed glitazones or TZDs) treat insulin resistance by increasing tissue sensitivity to insulin.
Most diabetes patients die of CVD, Campbell said, and the TZDs can decrease the risk factors for CVD. The TZDs have several different cardioprotective effects, and he believes that with further investigation, one or more of the TZDs may eventually receive an indication in this area.
THE AUTHOR is a clinical writer based in the Seattle area.