How are type 2 diabetes and coronary artery disease rel...

How are type 2 diabetes and coronary artery disease related?

How are type 2 diabetes and coronary artery disease related?
MUSC

Type 2 diabetes is a major risk factor for CAD and CAD is the major cause of morbidity and mortality in people with type 2 diabetes. In other words, diabetics are more likely to develop CAD than nondiabetics. These two diseases also share a number of risk factors, notably obesity and physical inactivity and metabolic characteristics, notably dyslipidemia. What are the processes that link these diseases and what interventions are likely to be the most beneficial in preventing or delaying the changes that lead to fatal cardiac events in diabetic patients?

A major component of diabetics' increased risk of CAD is the atherosclerotic process. Although the pathophysiology of atherosclerosis is not fully understood, the process involves changes in the vascular endothelium, the accumulation of fatty plaques, restrictions in blood flow, and vascular and other tissue damage and can result in fatal cardiac events. Atherosclerosis occurs earlier, has an accelerated course, and is more extensive in diabetics compared with the general population. There are probably several factors that contribute to this. Type 2 diabetes is associated with abnormalities in lipoprotein metabolism and an increased propensity for oxidative damage; the hyperglycemia of diabetics, in itself, may accelerate vascular damage; and diabetes is a hypercoagulable state attributable to enhanced coagulation and decreased fibrinolysis, as well as platelet hyperaggregability and endothelial dysfunction (Calles-Escandon et al. 1999).

The Insulin Resistance Atherosclerosis Study reported finding considerably greater intima-media thickness in the common and internal carotid arteries among patients with established diabetes compared with nondiabetic subjects (Wagenknecht et al. 1998). Diabetic patients without previous myocardial infarctions (MI) and nondiabetic patients with a previous MI have been found to have equally high risks of MI. Diabetic patients also have a high mortality rate from a first MI (Miettenen et al. 1998). These observations suggest that diabetics without obvious coronary artery disease may still have extensive atherosclerosis that, if untreated, could lead to serious cardiovascular complications. Some have suggested that this provides a rationale for assessing and treating cardiovascular risk factors in diabetic patients with the same aggressive approaches recommended for nondiabetic patients with a prior MI (Haffner 1999).

Diabetes treatment protocols (diet, exercise, pharmacological agents, and insulin) concentrate on controlling glycemia which leads to CAD. However, glycemia is not as strongly associated with macrovascular disease as it is with microvascular disease. Macrovascular disease appears to result from dyslipidemia in the diabetic patient. The form of dyslipidemia most frequently observed in diabetics is characterized by increased triglyceride levels and decreased high density lipoprotein (HDL) cholesterol levels. Diabetics also tend to have a higher level of smaller, denser low density lipoprotein LDL subclass pattern B than nondiabetics due to increases in hepatic triglyceride lipase.

Several studies have provided evidence of the link between diabetic dyslipidemia and CAD. A study by Laasko et al. (1993) found that diabetic patients who had coronary artery disease events during a 7-year follow-up period had higher levels of total triglycerides, very low density lipoprotein (VLDL) triglycerides, and VLDL cholesterol, and lower levels of HDL and HDL2 cholesterol than diabetic patients who did not have such events. Other studies have found that both high levels of apolipoprotein B (apoB) and small, dense LDL among patients with high apoB levels also predict coronary artery disease.

Lamarche et al. (1998) compared three non-traditional risk factors for (fasting insulin level, apoB level, and small, dense LDL particle level) with traditional cardiovascular risk factors (elevated LDL level, elevated triglyceride level, and low HDL level) in terms of the risk of ischemic heart disease. They found that the risk was significantly increased in men with small, dense LDL particles and elevated fasting plasma insulin and apoB compared with men who had normal levels of two of these three risk factors.