Non-insulin-dependent diabetes mellitus and hypertriglyceridemia impair lipoprotein metabolism in chronic hemodialysis patients

Patients with diabetes mellitus undergoing chronic hemodialysis treatment h ave the worst outcome on dialysis due to an increased rate of cardiovascula r complications. Nearly all patients present with dyslipidemia. a prominent vascular risk factor, probably responsible for the high rate of vascular i njury. Since both uremia and diabetes predispose to hypertriglyceridemia, t he present study was conducted to investigate the influence of diabetes mel litus and/or hypertriglyceridemia on lipoprotein metabolism in hemodialysis patients. LDL was isolated and characterized from hyper- and normotriglyce ridemic diabetic and nondiabetic hemodialysis patients (n = 40; 10 in each group); also, LDL-receptor-dependent uptake and intracellular cholesterol m etabolism were studied in HepG2 cells. In addition, scavenger-receptor-medi ated uptake was examined in mouse peritoneal macrophages. LDL isolated from nondiabetic normotriglyceridemic hemodialysis patients exhibited impaired cellular uptake via the LDL receptor. Additionally, intracellular sterol sy nthesis was less inhibited and cholesterol esterification was reduced compa red with LDL from healthy control subjects. Reduction of catabolic capaciti es was more marked in hemodialysis patients who were either diabetic or hyp ertriglyceridemic and even more pronounced in patients presenting with a co mbination of both diabetes and hypertriglyceridemia. Hypertriglyceridemic a nd diabetic patients showed reduced lipase activity and increased LDL oxida tion. Furthermore, they accumulated a fraction of small, dense LDL, and LDL was predominantly taken up via the scavenger-receptor pathway in peritonea l macrophages, This study elucidates the distinct influence of diabetes and /or hypertriglyceridemia in hemodialysis patients on cellular LDL metabolis m via specific and nonspecific metabolic pathways. Furthermore, it undersco res the: cumulative impact of these pathologic entities on impairment of li poprotein metabolism and increase of cardiovascular risk.