HIGH PREVALENCE OF SMALL LDL PARTICLES IN NON-INSULIN-DEPENDENT DIABETIC-PATIENTS WITH NEPHROPATHY

To determine whether small-sized low density lipoprotein (LDL) is asso ciated with a high incidence of coronary heart disease in diabetic nep hropathy, we measured the LDL particle size in non-insulin-dependent d iabetes mellitus (NIDDM) patients with various degrees of albuminuria (n = 95) and age-, weight-matched non-diabetic control subjects (n = 3 1). The diabetic subjects were divided into three groups, normoalbumin uric, microalbuminuric and macroalbuminuric NIDDM, based on the amount of albuminuria. The average diameter of LDL particles was determined by non-denaturing polyacrylamide gradient (2-16%) gel electrophoresis. The plasma lipid and lipoprotein concentrations were comparable betwe en the non-diabetic controls and normoalbuminuric NIDDM, whereas the p lasma triglyceride, very-low-density lipoprotein (VLDL) or LDL concent ration was significantly increased in diabetic nephropathy. The mean L DL particle size was significantly smaller in microalbuminuric NIDDM c ompared with the controls or normoalbuminuric NIDDM, and the LDL size was further decreased in macroalbuminuric NIDDM. The incidence of smal l LDL (diameter < 255 Angstrom) was remarkably increased in microalbum inuric (58%) and macroalbuminuric NIDDM (67%) compared to the control (13%) and normoalbuminuric NIDDM (27%). Corresponding to the decreased LDL size, the cholesterol content of the LDL was significantly deplet ed in NIDDM with nephropathy. The high prevalence of small LDL in diab etic nephropathy was also observed even when hypertriglyceridemic or h ypertensive subjects were excluded from each group. The increment in t riglyceride-rich lipoprotein (d ( 1.006) after oral fat-loading was in creased, and postheparin lipoprotein lipase activity was decreased sig nificantly in diabetic nephropathy. These abnormalities were significa ntly associated with LDL particle size. Multivariate regression analys is revealed that the amount of albuminuria was closely associated with the average LDL particle size, and this association was independent o f the plasma triglyceride level. Neither insulin resistance nor glycem ic control was directly associated with LDL particle diameter. The pre sent study indicates that LDL particles become smaller in diabetic nep hropathy, and this may be associated primarily with abnormal triglycer ide metabolism. However, in addition to hypertriglyceridemia, other me tabolic abnormalities caused by diabetic nephropathy may also be invol ved in the pathogenesis of small LDL particles.