LDL subclasses in IDDM patients: relation to diabetic nephropathy

Abstract

SummaryTo 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 gg/min, median and range], in 46 microalbuminuric btg/min] and in 33 proteinuric [AER 422 (233-1756)btg/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 L DL particles than non-diabetic control subjects (260 A vs 254 A, p < 0.05). LDL particle diameter was inversely correlated with serum triglycerides in all groups (p < 0.05 for normoalbuminuric andp < 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. [Diabetologia (1994) 37: 681q588] Key words IDDM, diabetic nephropathy, microalbuminuria, proteinuria, lipid metabolism, small dense LDL Cardiovascular disease is the major cause of excess morbidity and mortality among IDDM patients [1][2][3][4]. In particular the patients with diabetic nephropathy are at high risk of cardiovascular disease and have a relative Abbreviations: AER, urinary album excretion rate; CETR cholesteryl ester transfer protein; IDDM, insulin-dependent diabetes mellitus; CHD, coronary heart disease; ApoB, apolipoprotein B. mortality 30-times higher than patients without nephropathy [5,6]. Recently, microalbuminuria per se has been recognized as a risk marker for CHD mortality in both NIDDM and non-diabetic populations [7][8]. In IDDM patients microalbuminuria predicts the development of clinical proteinuria but so far the impact of microalbuminuria on CHD mortality in IDDM has been evaluated only in small groups [9]. The link between dyslipidaemias and diabetic nephropathy is commonly recognized, and lipid abnormalities may contribute to the excess CHD risk although the quantitative and differential impact of the several risk factors present in these...

Increased small dense LDL and intermediate-density lipoprotein with albuminuria in type 1 diabetes.

“…The present study demonstrated higher levels of dense LDL with albuminuria, which would be expected if HL plays an important physiologic role in the formation of small dense LDL. The findings of this study differ from those of Lahdenperä et al (35), who found no significant differences in LDL density distribution among the three levels of albuminuria in subjects with diabetes. However, serum triglyceride was higher at higher levels of albuminuria in this study, and this study also controls for known sex-related effects on LDL density (36) and particle size (37).…”

Risk factors for renal failure: The WHO multinational study of vascular disease in diabetes

“…However, the WHO Multinational Study is large enough and of sufficiently long duration to detect associations that might have gone undetected in studies with less power and there are several biologically plausible mechanisms by which triglycerides could be truly predictive of renal disease. Raised triglycerides are associated with increased formation of small dense low density lipoproteins [39,40] which in turn have increased susceptibility to oxidation and which could initiate endothelial damage and thus renal disease. Alternatively it is possible that the association between triglycerides and renal failure could have arisen because higher triglycerides are associated with higher concentrations of non-esterified fatty acids (NEFA).…”

Lipid Disorders in Type 1 Diabetes

“…In patients with type 1 diabetes, LDLs are often enriched in triglycerides and increased number of small dense LDL particles is observed (Guy et al, 2009;Lahdenperä et al, 1994;James & Pometta, 1990;Skyrme-Jones et al, 2000). In a study performed in 2657 patients with type 1 diabetes, it has been shown that dense LDL increased with HbA1c with buoyant LDL shifting toward dense LDL for HbA1c values above 8% (Albers et al, 2008).…”