title: Five-year follow-up of waist circumference, insulin and ALT levels in familial combined hyperlipidaemia.
abstract: BACKGROUND
  Familial combined hyperlipidemia (FCHL), an entity with many features of the metabolic syndrome, is characterized by changes in cholesterol and triglyceride phenotype over time. This study was conducted to investigate the relation of alanineaminotransferase (ALT) levels, used as a surrogate for the amount of hepatic fat, with the switch in triglyceride phenotype and the increased susceptibility to develop hypertriglyceridemia in FCHL.
  
  
  METHODS
  Body mass index, waist circumference, plasma triglycerides, insulin and ALT levels were measured in 145 FCHL family members and 54 spouses at baseline and after a five-year follow-up.
  
  
  RESULTS
  A switch from normotriglyceridemia to hypertriglyceridemia or vice versa, as observed in 22 of 145 FCHL family members, was associated with changes in plasma ALT levels (p=0.001), but not with insulin levels or waist circumference. In five-year follow-up, an intra-individual relation was observed between waist circumference and both plasma triglycerides, insulin and ALT levels. For each waist circumference FCHLpatients, but not their normolipidemic relatives, exhibited higher triglyceride and insulin levels than spouses (p<0.001). Remarkably, both FCHL patients and the normolipidemic relatives showed higher ALT levels for each waist circumference as compared to spouses(p<0.001 for FCHL patients, p=0.035 for normolipidemic relatives).
  
  
  CONCLUSIONS
  The present study shows that the longitudinal relation abdominal obesity-ALT is more specific for all FCHL family members, i.e. patients and their normolipidemic relatives, than the relation abdominal obesity-triglycerides. Additionally,the association of ALT with the switch in triglyceride phenotype suggests a central role of the liver in the pathogenesis of FCHL.
authors.affiliation: Department of Medicine, University Hospital Maastricht, University of Maastricht, Maastricht, The Netherlands. martijn.brouwers@intmed.unimaas.nl
authors.forename: Martijn C G J
authors.initials: MC
authors.lastname: Brouwers
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.forename: Vicky M M-J
authors.initials: VM
authors.lastname: Vermeulen
authors.forename: Josephine M J P
authors.initials: JM
authors.lastname: van Lin
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: Tjerk W A
authors.initials: TW
authors.lastname: de Bruin
mesh_terms: D050154:Adiposity; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000704:Analysis of Variance; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000201:enzymology; D007328:Insulin / Q000097:blood*; D016014:Linear Models; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; D014280:Triglycerides; D000410:Alanine Transaminase