Diabetic dyslipidemia and atherosclerosis: Evidence from clinical trials

Abstract

Diabetes is a highly prevalent disease in the United States and is increasing in both incidence and prevalence. Atherosclerotic vascular disease is a major cause of morbidity and mortality in diabetic patients. Type 2 diabetes is characterized by insulin resistance and frequently co-exists with a variety of cardiovascular risk factors, including hypertension, obesity, dyslipidemia, and physical inactivity. Hygienic measures such as weight loss and exercise should form the basis of therapeutic interventions in the prevention and treatment of type 2 diabetes. The role of dyslipidemia as a causal factor in vascular disease associated with diabetes was previously downplayed because total cholesterol was frequently normal or minimally elevated. However, diabetic dyslipidemia is characterized by elevated triglycerides, low high-density lipoprotein, and small, dense low-density lipoprotein, the combination of which has been termed the “lipid triad.” The role of lipid modification as a means to decrease cardiovascular risk in type 2 diabetes has recently been clarified by a number of clinical trials. Subgroup analysis in early studies implied the potential for benefit of lipid modification in diabetes. The results of these early studies prompted the design of large-scale intervention trials that employed statin and fibric acid derivatives in diabetes patients. The preponderance of data from the statin trials implicates significant clinical benefit in cardiovascular risk reduction. The fibric acid derivatives have theoretic advantages in diabetic dyslipidemia. However, the robust bulk of clinical data obtained from prospective statin studies is lacking for the fibric acid derivatives, and the results of the major trials are equivocal.