High prevalence of small dense LDL in diabetic nephropathy is not directly associated with kidney damage: a possible role of postprandial lipemia.

To determine whether high prevalence of small dense low-density lipoprotein (LDL) in non-insulin-dependent diabetes (NIDDM) with nephropathy is directly associated with kidney damage, we measured LDL particle size by non-denaturing 2-16% gradient polyacrylamide gel electrophoresis in non-diabetic patients with primary renal disease and compared the results to particle size in NIDDM patients with diabetic nephropathy. The average LDL particle diameter was significantly smaller in patients with diabetic nephropathy (245+/-3 A mean +/- SEM) compared to the controls (263+/-1 A), diabetics without nephropathy (257+/-2 A), patients with primary renal disease (254+/-2 A) or non-diabetic patients treated with hemodialysis (HD) (260+/-1 A). The incidence of small LDL (mean diameter is < or =255 A) was remarkably increased in diabetic nephropathy (67%) compared to diabetes without nephropathy (27%), patients with renal disease (24%), HD patients (15%) and controls (10%). LDL size in patients with primary renal disease was significantly smaller than those in controls. However, because there was an excellent correlation between LDL size and plasma triglyceride (TG) levels, when hypertriglyceridemic subjects (TG >1.7 mM) were excluded, no difference of LDL size was observed between the renal disease group (260+/-2 A) and the control group (264+/-1 A). On the other hand, even when hypertriglyceridemic subjects were excluded, LDL size was still smaller in diabetic nephropathy (250+/-4 A). We performed an oral fat load test in normotriglyceridemic subjects (fasting TG <1.7 mM) of control, diabetes with and without nephropathy and primary renal disease. The TG responses in plasma and TG-rich-lipoprotein (TRL) (d <1.006) after the oral fat load were significantly greater in NIDDMs with nephropathy compared to controls or NIDDMs without nephropathy, while such a marked postprandial lipemia was not observed in patients with primary renal disease. In these fasting normotriglyceridemic subjects, LDL size was significantly inversely correlated with postprandial TG responses, which is totally independent from fasting TG levels. These results suggest that high prevalence of small dense LDL in NIDDM patients with nephropathy is not directly associated with kidney damage. Postprandial lipemia may play an important role in reducing LDL particle size in these patients.