Remarkable increase of apolipoprotein B48 level in diabetic patients with end-stage renal disease

Abstract

Apolipoprotein (apo) B48 is a structural protein of chylomicrons. Fasting serum levels of apoB48 suggest the presence of small number of remnant chylomicron particles which are thought to be an atherogenic lipoprotein. In view of the high incidence of coronary heart disease (CHD) in patients with diabetic nephropathy, we decided to measure the plasma apoB48 level in type 2 diabetics with diabetic nephropathy at various stages to ascertain how apoB48 relates to the progression of diabetic nephropathy. Patients with type 2 diabetes ( n = 105) were stratified into four groups: normo-albuminuria, micro-albuminuria, overt-proteinuria, and patients with end-stage renal disease (ESRD) receiving hemodialysis. Age-matched-diabetic hypertensive patients ( n = 24) and non-diabetic ESRD patients on hemodialysis ( n = 47) were also enrolled. Plasma triglyceride (TG) levels rose as diabetic nephropathy progressed to overt-proteinuria. No further elevation in TG was observed in diabetic ESRD, however, and the TG levels were normal in non-diabetic ESRD. A similar pattern was observed for remnant-like particle-cholesterol (RLP-C). In contrast to the changes observed for TG and RLP-C, the levels of apoB48 increased steadily as the diabetic nephropathy progressed (control, 3.7; normo, 5.7; micro, 6.9; overt, 10.6 mg/l, respectively). ApoB48 peaked in the diabetic ESRD (19 mg/l) and was also markedly elevated in non-diabetic ESRD (10.1 mg/l). The apoB48/TG and apoB48/total-apoB ratios were substantially elevated in both diabetic and non-diabetic ESRD. These results are the first to demonstrate remarkable elevations of plasma apoB48 in patients with both diabetic and non-diabetic ESRD. The remarkably high level of apoB48 in diabetic ESRD seems to be attributable to dyslipidemia induced by both diabetic nephropathy and ESRD.