Abnormal lipoprotein metabolism in diabetic nephropathy

Abstract

It is well known that patients with diabetes have a high incidence of cardiovascular disease (CVD), and the incidence of CVD becomes substantially elevated with development of diabetic nephropathy. The mechanisms for dyslipidemia in diabetic nephropathy are multifactorial and complex. Long-term hyperglycemia causes generalized vascular endothelial damage, which reduces functional lipoprotein lipase, leading to increased triglyceride (TG) levels and decreased high-density lipoprotein cholesterol (HDL-C). In overt-diabetic nephropathy, hypoproteinemia markedly increases low-density lipoprotein cholesterol (LDL-C), and renal failure specifically increases remnant lipoproteins and decreases HDL-C and LDL-C. Overt diabetic nephropathy exhibits remarkable postprandial hypertriglyceridemia with hyper-apolipoprotein (apo) B48, a marker of chylomicron and its remnants. Apo CIII is a key inhibitor of lipolysis and particle uptake of TG-rich lipoproteins, which is specifically increased in advanced chronic kidney disease, irrespective of the presence of diabetes. LDL size becomes smaller with advanced stages of diabetic nephropathy, whereas LDL size is not reduced in hemodialysis patients (HD). HD patients have marked lower levels of HDL3-C than controls. HD patients also have substantially low apo AI and high serum amyloid A (SAA) levels, suggesting the replacement of apo AI by SAA is stimulated in HDL particles.