title: Detrimental effects of high-fat diet loading on vascular endothelial function and therapeutic efficacy of ezetimibe and statins in patients with type 2 diabetes.
abstract: Several recent reports from large clinical trials have described the role of postprandial hyperlipidemia in the onset of atherosclerosis. In this pilot study, the effects of postprandial lipid abnormalities induced by high-fat diet loading on vascular endothelial function in type 2 diabetes were investigated and the effects of ezetimibe and statins on endothelial function were compared. In 20 patients in Study 1, peripheral arterial tonometry tests were performed before and 4h after loading to measure the reactive hyperemia index (RHI). In Study 2, the same patients were randomly allocated to ezetimibe or rosuvastatin. After 1 week of treatment, loading tests were conducted in the same manner. In Study 1, the RHI decreased from 1.86 to 1.60. There were no significant correlations between changes in RHI and the area under the curve (AUC) or coefficient of variation (CV) of each metabolic marker. In Study 2, ezetimibe treatment resulted in a significant improvement in RHI. The two drugs had comparable effects on changes in AUC. There were no significant correlations between changes in RHI and changes in AUC or changes in CV. When age, sex, drug, hemoglobin A1c, and changes in each lipid were evaluated as independent variables with RHI improvement as the dependent variable, drug differences were found to exert the greatest effect on RHI improvement using a stepwise procedure. The results of this study suggest that the progression of atherosclerosis is due to abnormalities in postprandial lipid metabolism and that ezetimibe can potentially inhibit the aggravation of vascular endothelial dysfunction after high-fat diet loading.
authors: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Akira
authors: A
authors: Kurozumi
authors: Yosuke
authors: Y
authors: Okada
authors: Hiroko
authors: H
authors: Mori
authors: Takuya
authors: T
authors: Kobayashi
authors: Daisaku
authors: D
authors: Masuda
authors: Shizuya
authors: S
authors: Yamashita
authors: Yoshiya
authors: Y
authors: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006940:Hyperemia / Q000503:physiopathology; D006949:Hyperlipidemias / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019518:Postprandial Period / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D004041:Dietary Fats; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe