Abnormal Composition of High Density Lipoproteins in Non-insulin-dependent Diabetics

Abstract

Atherosclerosis is the major cause of morbidity and mortality among non-insulin-dependent diabetics (NIDDM). High density lipoprotein (HDL) cholesterol levels are reportedly low in NIDDM patients, which may add to their risk of atherosclerosis. Changes in the amount and composition of HDL and the relationship of HDL cholesterol to other lipid and protein components of HDL were investigated in a well-characterized NIDDM population not receiving either insulin or oral hypoglycemic agents. Also, the levels of the lipid and protein components of HDL in the NIDDM group were compared within each sex to those in a control group of comparable age. In the NIDDM group, total triglyceride was inversely related to HDL cholesterol (P < 0.05) and positively related to HDL triglyceride (P < 0.001). There was no relationship between total triglyceride and apoprotein A-I (the major protein component of HDL). If adjustment was made for factors that may affect HDL cholesterol levels and for apoprotein A-I (which adjusts for varying numbers of HDL particles), a highly significant inverse correlation between HDL cholesterol and HDL triglycerides emerged (r = −0.71, P < 0.001), suggesting that elevated plasma triglyceride levels decreases the amount of cholesterol associated with each HDL particle rather than reducing the actual number of particles, possibly by replacing esterified cholesterol with triglyceride in the lipid core. When the NIDDM group was compared with the control group, diabetic males had lower HDL cholesterol than did controls (P < 0.01) and a trend in the same direction was noted for females. Total triglycerides were higher than control levels in diabetic men (P < 0.05) and showed a trend in the same direction in diabetic females. Concomitantly, HDL triglycerides were higher than controls in diabetic males (P < 0.01) and diabetic females (P < 0.05). However, adjustment for either total triglycerides or HDL triglycerides only partially reduced the differences in HDL cholesterol between diabetics and controls, indicating that additional factors are involved in the low HDL cholesterol levels seen in NIDDM populations. Apoprotein A-I levels were not lower in diabetic males and were actually somewhat higher in diabetic females, again suggesting a reduction of cholesterol for each HDL particle rather than a smaller number of HDL particles in these diabetics. The apoprotein A-I/ A-II ratio was higher in diabetic women than in controls (P < 0.05) and showed a trend in the same direction in diabetic men, suggesting a relative shift from the HDL3 to the HDL2 density range in the NIDDM group. Thus abnormal HDL composition is characteristic of untreated NIDDM. Their low HDL cholesterol is only in part related to increased plasma triglyceride levels.