title: Apolipoprotein B-48 as a determinant of endothelial function in obese subjects with type 2 diabetes mellitus: effect of fenofibrate treatment.
abstract: OBJECTIVE
  Elevated triglyceride-rich lipoproteins may contribute to endothelial dysfunction in obese diabetic subjects. We investigated the association between plasma concentrations of chylomicron-related particles and endothelial function, and the corresponding responses to fenofibrate treatment.
  
  
  METHODS
  Plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol concentrations were measured in 28 obese subjects with T2DM. Flow-mediated endothelium-dependent dilation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) in the brachial artery during reactive hyperaemia were examined by high-resolution ultrasound technique.
  
  
  RESULTS
  In univariate analysis, plasma apoB-48 and RLP-cholesterol concentrations were inversely associated with brachial artery FMD (r = -0.425 and -0.423, respectively, P<0.05), but not with GTNMD. In regression models including BMI and HOMA score, plasma apoB-48 was an independent predictors (P<0.05) of brachial artery FMD (β coefficient = -0.384). Replacing HOMA-IR score with plasma triglyceride, adiponectin or CRP concentrations did not alter the findings. The subjects were then randomized to a 12-week treatment period of either 200mg micronized fenofibrate or matching placebo. Compared with the placebo group, fenofibrate treatment (200mg daily for 12 weeks) achieved significant increase in FMD (+34%) and reduction in plasma triglyceride (-42%), apoB-48 (-52%) and RLP-cholesterol (-51%) concentrations. The increase in FMD with fenofibrate was significantly associated with the corresponding decrease in plasma apoB-48 (r = -0.644, P<0.02) concentrations.
  
  
  CONCLUSIONS
  Our findings demonstrate an association between changes in lipid metabolism and improvement in endothelial function in patients with diabetic dyslipidaemia treated with fenofibrate that may involve the effect of apoB-48 on endothelium-dependent vasodilator function.
authors.affiliation: Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Dick C
authors.initials: DC
authors.lastname: Chan
authors.forename: Annette T Y
authors.initials: AT
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D053283:Apolipoprotein B-48 / Q000097:blood*; D053305:Apolipoprotein C-III / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D053298:Chylomicron Remnants / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage; D014904:Western Australia
chemical_list: D053283:Apolipoprotein B-48; D053305:Apolipoprotein C-III; D053298:Chylomicron Remnants; D000960:Hypolipidemic Agents; D014665:Vasodilator Agents; D002784:Cholesterol; D005996:Nitroglycerin; D011345:Fenofibrate