title: Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency.
abstract: OBJECTIVE
  Several studies have investigated the lipoprotein phenotype in heterozygous carriers of a defective lipoprotein lipase allele. We studied whether heterozygosity for lipoprotein lipase deficiency also affects glucose metabolism beyond its effect on plasma lipids.
  
  
  METHODS
  To address this question 85 heterozygous carriers of either a missense mutation (Gly188Glu) or a splice site mutation (C-->A in position -3 at the acceptor splice site of intron 6) in the LPL gene which both result in a catalytically inactive product were compared with 108 unaffected subjects from the same families.
  
  
  RESULTS
  Carriers for one of these mutations had higher fasting insulin levels but only a trend towards increased fasting blood glucose concentrations could be detected. HOMA index values were significantly higher in carriers than in non-carriers. Furthermore, in carriers, a significantly higher BMI and a trend towards higher systolic and diastolic blood pressure were observed. Carriers also had significantly higher fasting triglycerides, lower HDL cholesterol, and lipoprotein lipase particles of smaller size, confirming previous reports. Among carriers, subjects with one rare allele of the SstI polymorphism in the apo CIII gene had significantly higher plasma triglyceride levels than those with two common SstI alleles. This difference could not be observed in non-carriers of a mutant lipoprotein-lipase allele. The mean intima media thickness of the carotid arteries was slightly, but not significantly higher in carriers when compared with non-carriers.
  
  
  CONCLUSIONS
  This study shows that carrier status of one defective lipoprotein-lipase allele is associated with impaired insulin sensitivity, an atherogenic lipoprotein profile and other characteristics of the metabolic syndrome, which are risk factors for atherosclerotic vascular disease. A higher incidence of atherosclerotic vascular disease, however, could not be firmly established in carriers of this study population.
authors.affiliation: First Department of Internal Medicine, St. Johanns Spital, Salzburg, Austria. b.hoelzl@lks.at
authors.forename: B
authors.initials: B
authors.lastname: Hölzl
authors.forename: B
authors.initials: B
authors.lastname: Iglseder
authors.forename: A
authors.initials: A
authors.lastname: Sandhofer
authors.forename: L
authors.initials: L
authors.lastname: Malaimare
authors.forename: J
authors.initials: J
authors.lastname: Lang
authors.forename: B
authors.initials: B
authors.lastname: Paulweber
authors.forename: F
authors.initials: F
authors.lastname: Sandhofer
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D017398:Alternative Splicing; D019943:Amino Acid Substitution; D001786:Blood Glucose / Q000378:metabolism; D018660:Blood Pressure Monitoring, Ambulatory; D015992:Body Mass Index; D006580:Genetic Carrier Screening; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics; D007438:Introns; D008071:Lipoprotein Lipase / Q000235:genetics*; D020125:Mutation, Missense; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D008071:Lipoprotein Lipase