Non-insulin-dependent diabetes mellitus and hypertriglyceridemia impair lipoprotein metabolism in chronic hemodialysis patients
| Autor: | Peter Schollmeyer, Matthias Nauck, Thomas Quaschning, Michael Schömig, Annette Krämer-Guth, Christoph Wanner, Markus Keller, Joachim Thiery |
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| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Time Factors medicine.medical_treatment Lipoproteins chemistry.chemical_compound Mice Renal Dialysis Diabetes mellitus Internal medicine medicine Tumor Cells Cultured Animals Humans Dialysis Aged Apolipoproteins B Hypertriglyceridemia business.industry Cholesterol General Medicine Lipase Middle Aged medicine.disease Lipids Uremia Lipoproteins LDL Sterols Endocrinology chemistry Diabetes Mellitus Type 2 Liver Nephrology LDL receptor lipids (amino acids peptides and proteins) Female Hemodialysis Cholesterol Esters business Oxidation-Reduction Dyslipidemia |
| Zdroj: | Journal of the American Society of Nephrology : JASN. 10(2) |
| ISSN: | 1046-6673 |
| Popis: | Patients with diabetes mellitus undergoing chronic hemodialysis treatment have the worst outcome on dialysis due to an increased rate of cardiovascular complications. Nearly all patients present with dyslipidemia, a prominent vascular risk factor, probably responsible for the high rate of vascular injury. Since both uremia and diabetes predispose to hypertriglyceridemia, the present study was conducted to investigate the influence of diabetes mellitus and/or hypertriglyceridemia on lipoprotein metabolism in hemodialysis patients. LDL was isolated and characterized from hyper- and normotriglyceridemic diabetic and nondiabetic hemodialysis patients (n = 40; 10 in each group); also, LDL-receptor-dependent uptake and intracellular cholesterol metabolism were studied in HepG2 cells. In addition, scavenger-receptor-mediated 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 synthesis was less inhibited and cholesterol esterification was reduced compared with LDL from healthy control subjects. Reduction of catabolic capacities was more marked in hemodialysis patients who were either diabetic or hypertriglyceridemic and even more pronounced in patients presenting with a combination of both diabetes and hypertriglyceridemia. Hypertriglyceridemic and diabetic patients showed reduced lipase activity and increased LDL oxidation. Furthermore, they accumulated a fraction of small, dense LDL, and LDL was predominantly taken up via the scavenger-receptor pathway in peritoneal macrophages. This study elucidates the distinct influence of diabetes and/or hypertriglyceridemia in hemodialysis patients on cellular LDL metabolism via specific and nonspecific metabolic pathways. Furthermore, it underscores the cumulative impact of these pathologic entities on impairment of lipoprotein metabolism and increase of cardiovascular risk. |
| Databáze: | OpenAIRE |
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