title: The atherogenic plasma remnant-like particle cholesterol concentration is increased in the fasting and postprandial state in active acromegalic patients.
abstract: BACKGROUND
  Premature atherosclerosis is a clinical feature in untreated acromegaly. Increased postprandial lipoprotein remnant levels are associated with premature atherosclerosis. In most studies, remnants have been measured indirectly using retinyl esters (RE) as a chylomicron core label. Remnants can also be directly quantified by immunoseparation using monoclonal antibodies to apolipoprotein (apo) AI and apo B100 to remove nonremnant lipoproteins. Cholesterol is quantified in the remaining apo E-rich remnant fraction (RLP-C).
  
  
  OBJECTIVE
  The aim of the present study was to investigate the role of postprandial lipaemia in patients with acromegaly to further define abnormalities leading to increased susceptibility for atherosclerosis.
  
  
  METHODS
  In a case-control study, the plasma postprandial lipoprotein remnant fraction (RLP-C and RE) were analysed in six patients with active acromegaly [two females, four males; aged 53 +/- 9 years; body mass index (BMI), 29 +/- 4 kg/m2] and in six normolipidaemic control subjects (matched for age, gender, BMI and apo E genotype). They underwent an oral vitamin A fat loading test.
  
  
  RESULTS
  Baseline plasma triglycerides (TG) were not significantly different in patients (1.75 +/- 0.71 mM) and controls (1.15 +/- 0.46 mM). Lipoprotein lipase activity was significantly lower in patients than in controls (108 +/- 21 vs. 141 +/- 19 U/l, respectively; P < 0.05). Baseline plasma apo E levels were higher in patients (60.8 +/- 7.9 mg/l) than in controls (48.3 +/- 5.9 mg/l; P < 0.05). No differences were found in the area under the postprandial TG curve (AUC-TG), the incremental AUC-TG (DeltaAUC-TG) and AUC-RE in the Sf < 1000 remnant fraction. However, fasting plasma RLP-C concentrations, isolated by immunoseparation, were increased in patients with active acromegaly (0.41 +/- 0.13 mM) compared to control subjects (0.20 +/- 0.07 mM; P < 0.05). Incremental postprandial RLP-C response (corrected for fasting values) was also significantly elevated in patients (2.14 +/- 1.19 mM/h/l) compared to controls (0.86 +/- 0.34 mM/h/l; P < 0.05). In both groups, the maximal RLP-C concentration was reached between 2 and 4 h.
  
  
  CONCLUSIONS
  In conclusion, the atherogenic postprandial remnants, represented by RLP-C, were significantly elevated at baseline and in the postprandial period, whereas the larger-sized remnants, represented by retinyl esters (Sf < 1000), were not different from controls. The disturbances in the postprandial RLP-C response increased the susceptibility for premature atherosclerosis as observed in patients with acromegaly.
authors.affiliation: Department of Internal Medicine, University Medical Center Utrecht (UMCU), 3508 GA Utrecht, The Netherlands. th.b.twickler@digd.azu.nl
authors.forename: T B
authors.initials: TB
authors.lastname: Twickler
authors.forename: G M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: P M
authors.initials: PM
authors.lastname: Zelissen
authors.forename: H P
authors.initials: HP
authors.lastname: Koppeschaar
authors.forename: D W
authors.initials: DW
authors.lastname: Erkelens
mesh_terms: D000172:Acromegaly / Q000097:blood* / Q000150:complications; D000328:Adult; D001053:Apolipoproteins / Q000097:blood*; D001161:Arteriosclerosis / Q000209:etiology; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats; D004198:Disease Susceptibility; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology*; D014280:Triglycerides / Q000097:blood*
chemical_list: D001053:Apolipoproteins; D004041:Dietary Fats; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol