Nephrology Dialysis Transplantation, Vol 13, Issue 11 2833-2841, Copyright © 1998 by Oxford University Press
P Attman, C Knight-Gibson, M Tavella, O Samuelsson and P Alaupovic
Background: Diabetic nephropathy (DN) is a common
cause of chronic renal failure (CRF). Patients with DN have abnormal
lipoprotein metabolism that can be influenced by both the impairment of
renal function and the metabolic control of diabetes. The aim of the study
was to explore the specific composition lipoprotein abnormalities in
patients with insulin-dependent DN in comparison with diabetic patients
without nephropathy and non-diabetic CRF patients.
Methods: The lipid and apolipoprotein (apo)
composition of major lipoprotein density classes were determined in 20
patients with insulin-dependent diabetes mellitus and nephropathy and
compared with that in seven diabetic patients without nephropathy, 20
patients with non-diabetic CRF, and nine healthy control subjects.
Lipoproteins isolated by preparative ultracentrifugation were
very-low-density lipoproteins (VLDL), intermediate-density lipoproteins
(IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL).
Results: Patients with DN had a plasma lipid and
apolipoprotein profile characteristic of renal dyslipoproteinaemia with
increased concentrations of triglycerides and cholesterol, reduced levels
of apoA-I and apoA-II and increased levels of apoB, apoC-II, apoC-III and
apoE. These changes were more pronounced in diabetic than in non-diabetic
patients with comparable degrees of renal failure. All density classes were
characterized by abnormal concentration and composition of some lipid and
apo-lipoprotein constituents. DN patients had a more than four-fold
increase of VLDL mass, a three-fold increase of IDL mass, and a significant
reduction of HDL mass compared to control subjects. They also had
significantly higher concentrations of apoB, apoC-peptides and apoE
particularly in VLDL and IDL, and to some extent in LDL. In HDL, DN
patients had lower cholesterol, apoA-I, apoA-II and apoC-II levels than
controls. The major compositional change in DN patients was a significant
increase in the relative content of apoC-peptides in IDL and LDL. The
lipoprotein abnormalities were more pronounced in patients with high HbA1c
values. In addition, lower GFR and increased proteinuria were associated
with higher concentrations of triglycerides and apoC peptides in VLDL, IDL,
and LDL in DN patients. Conclusions: The results
indicate that patients with DN share the characteristic features of
dyslipidaemia of CRF with accumulation of intact or partially delipidized
apoB-containing lipoproteins enriched in apoC-peptides and apoE, which are
present not only in VLDL and IDL but also in LDL density range. The
alterations are more marked in DN than in non-diabetic CRF patients
reflecting the additional impact of metabolic control. Increased levels of
these lipoproteins may represent risk factors for the accelerated
development of atherosclerotic vascular disease in these patients.
Key words: apolipoproteins; lipids; lipoproteins;
insulin-dependent diabetes mellitus; renal failure
ORIGINAL ARTICLES
The compositional abnormalities of lipoproteins in diabetic renal failure
Department of Nephrology, Sahlgrenska University Hospital, University of Goteborg, Goteborg, Sweden; Lipid and Lipoprotein Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA; Corresponding author at: Department of Nephrology, Sahlgrenska University Hospital, S-41345 Goteborg, Sweden
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