High prevalence of small dense LDL in diabetic nephropathy is not directlyassociated 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 direct ly associated with kidney damage, we measured LDL particle size by non-dena turing 2-16% gradient polyacrylamide gel electrophoresis in non-diabetic pa tients with primary renal disease and compared the results to particle size in NIDDM patients with diabetic nephropathy. The average LDL particle diam eter was significantly smaller in patients with diabetic nephropathy (245 /- 3 Angstrom mean +/- SEM) compared to the controls (263 +/- 1 Angstrom), diabetics without nephropathy (257 +/- 2 Angstrom), patients with primary r enal disease (254 +/- 2 Angstrom) or non-diabetic patients treated with hem odialysis (HD) (260 +/- 1 Angstrom). The incidence of small LDL (mean diame ter is less than or equal to 255 Angstrom) was remarkably increased in diab etic nephropathy (67%) compared to diabetes without nephropathy (27%), pati ents with renal disease (24%), HD patients (15%,) and controls (10%). LDL s ize in patients with primary renal disease was significantly smaller than t hose in controls. However, because there was an excellent correlation betwe en LDL size and plasma triglyceride (TG) levels, when hypertriglyceridemic subjects (TG > 1.7 mM) were excluded, no difference of LDL size was observe d between the renal disease group (260 +/- 2 Angstrom) and the control grou p (264 +/- 1 Angstrom). On the other hand, even when hypertriglyceridemic s ubjects were excluded, LDL size was still smaller in diabetic nephropathy ( 250 +/- 4 Angstrom). We performed an oral fat load test in normotriglycerid emic subjects (fasting TG < 1.7 mM) of control, diabetes with and without n ephropathy and primary renal disease. The TG responses in plasma and TG-ric h-lipoprotein (TRL) (d < 1.006) after the oral fat load were significantly greater in NIDDMs with nephropathy compared to controls or NIDDMs without n ephropathy, while such a marked postprandial lipemia was not observed in pa tients with primary renal disease. In these fasting normotriglyceridemic su bjects, LDL size was significantly inversely correlated with postprandial T G responses, which is totally independent from fasting TG levels. These res ults suggest that high prevalence of small dense LDL in NIDDM patients with nephropathy is not directly associated with kidney damage. Postprandial li pemia may play an important role in reducing LDL particle size in these pat ients. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.