Cardiovascular disease and diabetes: modifying risk factors other than glucose control.

Patients with type 2 diabetes have a significantly increased risk of developing cardiovascular disease. Atherosclerosis kills more diabetic patients than all other causes combined. Multiple risk factors tend to cluster in some patients in a syndrome termed insulin resistance syndrome or "Syndrome X." Increasing evidence has changed the recommended management of diabetes from simple glucose control to aggressive lipid management and control of the other components of the metabolic syndrome to prevent development of cardiovascular disease. One mechanism linking hyperglycemia and atherogenesis is nonenzymatic glycation of proteins. Hyperglycemia increases the linkage of glucose to proteins producing insoluble complexes, termed advanced glycation end products, that cause endothelial cell changes. Glycation of lipoproteins increases their atherogenic potential. It is not clear whether intensive glucose control in diabetic patients significantly lowers the rate of long-term macrovascular complications, and glucose control by itself may not be sufficient to prevent cardiovascular disease. Elevated triglyceride levels in diabetic patients are risk factors for cardiovascular disease. Though LDL-cholesterol levels are not necessarily elevated in type 2 diabetes, higher levels (or LDL phenotype B) are shown to be more atherogenic. The association between obesity and hypertension is well documented, and obesity can worsen other risk factors. Glycemic control may not always normalize lipid and lipoprotein levels, particularly in type 2 diabetes. Trials of intensive glycemic control have not shown a significant reduction in coronary events despite significant decreases in microvascular complications. Medical nutrition therapy and exercise remain the cornerstone for nonpharmacologic treatment with a goal of improved insulin sensitivity.