Risk for atherosclerosis is greatly increased in people who have type 2 diabetes (T2D). Because of this, the emerging epidemic of adolescent T2D holds ominous implications for premature cardiovascular disease (CVD). High density lipoprotein cholesterol (HDL-C) represents the body’s natural defense against CVD but its levels are depressed in individuals with T2D. Recent studies indicate HDL exists as distinct subspecies raising the possibility that certain species may be more cardioprotective than others. However, little is known regarding the role of HDL subspecies in T2D, especially in the adolescent population. Thus we sought to evaluate HDL subspecies and determine whether certain subspecies are associated with protection against the development of early atherosclerosis as measured by carotid intima medial thickness (IMT). Healthy controls and youth with T2D were recruited. Whole plasma was analyzed by high-resolution gel filtration chromatography to resolve HDL sized particles and lipids in each fraction were quantitated by colorimetric assay. T-tests were used to evaluate group differences and linear regression models were constructed to determine independent predictors of carotid IMT. Youth with T2D had higher BMI, total cholesterol and lower HDL-C compared to healthy controls, p<0.05. The groups did not differ in LDL-C, triglycerides or BP. Phospholipid distributions of HDL subspecies were found to be shifted in participants with T2D compared to controls (p<0.05). There was a significant inverse correlation between carotid IMT and the phospholipid content of larger HDL subfractions 22-24 (p<0.05) in youth with T2D. Linear models demonstrate HDL fraction 22 was the only independent predictor of carotid IMT while HDL-C, LDL-C, total -C and triglycerides were not significant. These data suggest an altered HDL particle subclass distribution may better predict protection against early atherosclerosis. Thus analyzing the HDL subspecies may be a more powerful approach to assessing cardiovascular risk than the currently accepted standard of HDL-C.
HIGH-DENSITY LIPOPROTEIN FUNCTION IN PATIENTS WITH TYPE 2 DIABETES: DIFFERENCES BETWEEN THE ACUTE AND CHRONIC PHASES OF CORONARY ARTERY DISEASE
