LDL subclasses in IDDM patients: relation to diabetic nephropathy

Summary To answer the question whether the elevation of LDL-cholesterol in IDDM patients with incipient and established diabetic nephropathy is accompanied by changes in LDL size or composition, we studied distribution of LDL particles in 57 normoalbuminuric [AER 7 (1–19) g/min, median and range], in 46 microalbuminuric [AER 50 (20–192) g/min] and in 33 proteinuric [AER 422 (233–1756) g/min] IDDM patients as well as in 49 non-diabetic control subjects with normoalbuminuria. The three diabetic groups were matched for duration of diabetes and glycaemic control. The mean particle diameter of the major LDL peak was determined by nondenaturing gradient gel electrophoresis. Composition and density distribution of LDL were determined in the subgroups of each patient group by density gradient ultracentrifugation. Normoalbuminuric IDDM patients had larger LDL particles than non-diabetic control subjects (260 Å vs 254 Å, p<0.05). LDL particle diameter was inversely correlated with serum triglycerides in all groups (p<0.05 for normoalbuminuric and p<0.001 for other groups). Triglyceride content of LDL was higher in three IDDM groups compared to control group (p<0.05). The elevation of LDL mass in microalbuminuric and proteinuric IDDM groups compared to normoalbuminuric IDDM group (p<0.05 for both) was mainly due to the increment of light LDL (density 1.0212–1.0343 g/ml). There were no significant changes in the density distribution or composition of LDL between the three diabetic groups. In conclusion the increase of LDL mass without major compositional changes suggests that the elevation of LDL in incipient and established diabetic nephropathy is primarily due to the increased number of LDL particles. The prevalence of atherogenic small dense LDL particles in IDDM patients with microalbuminuria and proteinuria is closely dependent on plasma triglyceride concentration.Abbreviations AER urinary album excretion rate - CETP cholesteryl ester transfer protein - IDDM insulin-dependent diabetes mellitus - CHD coronary heart disease - ApoB apolipoprotein B