title: Substrate metabolism during basal and hyperinsulinemic conditions in adolescents and young-adults with Barth syndrome.
abstract: BACKGROUND
  Barth syndrome (BTHS) is a rare X-linked disorder that is characterized by mitochondrial abnormalities, infantile or childhood onset of cardioskeletal myopathy, and high mortality rates. It is currently unknown if BTHS related mitochondrial dysfunction results in substrate metabolism abnormalities and thereby contributes to cardioskeletal myopathy in patients with BTHS.
  
  
  METHODS
  Adolescents and young adults with BTHS (n = 5, 20 ± 4 yrs) and age and activity matched healthy controls (n = 5, 18 ± 4 yrs) underwent an hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracers for measurement of lipolysis, fatty acid oxidation, glucose disposal, and whole-body proteolysis rates; dual energy x-ray absorptiometry for measurement of body composition and 2-D and strain echocardiography for measurement of left ventricular function.
  
  
  RESULTS
  Participants with BTHS had lower fat-free mass (FFM) (BTHS: 31.4 ± 6.9 vs.
  
  
  METHODS
  46.7 ± 5.3 kg, p < 0.005), lower systolic function (strain, BTHS: -15.2 ± 2.4 vs.
  
  
  METHODS
  -19.0 ± 2.4 %, p < 0.05), greater insulin-stimulated glucose disposal rate per kg FFM (BTHS: 96.5 ± 16.3 vs.
  
  
  METHODS
  67.4 ± 17.6 μmol/kgFFM/min, p < 0.05), lower basal (BTHS: 4.6 ± 2.7 vs.
  
  
  METHODS
  11.9 ± 4.4 μmol/kgFM/min, p < 0.05) and hyperinsulinemic (BTHS: 1.6 ± 0.4 vs.
  
  
  METHODS
  3.6 ± 1.6 μmol/kgFM/min, p < 0.05) lipolytic rate per kg fat mass (FM), and a trend towards higher basal leucine rate of appearance per kg FFM (BTHS: 271.4 ± 69.3 vs.
  
  
  METHODS
  193.1 ± 28.7 μmol/kgFFM/hr, p = 0.07) compared to controls. Higher basal leucine rate of appearance per kg FFM (i.e. whole-body proteolytic rate) tended to be associated with lower left ventricular systolic strain (r = -0.57, p = 0.09).
  
  
  CONCLUSIONS
  Whole-body fatty acid, glucose and amino acid metabolism kinetics when expressed per unit of body composition are altered and appear to be related to cardioskeletal myopathy in humans with BTHS. Further studies examining myocardial substrate metabolism and whole-body substrate metabolism during increased energy demands (e.g., exercise) and their relationships to skeletal and cardiac function are recommended.
authors.affiliation: Program in Physical Therapy & Department of Medicine, Washington University School of Medicine, Box 8502, St Louis, MO 63108, USA. tcade@wustl.edu
authors.forename: W Todd
authors.initials: WT
authors.lastname: Cade
authors.forename: Carolyn T
authors.initials: CT
authors.lastname: Spencer
authors.forename: Dominic N
authors.initials: DN
authors.lastname: Reeds
authors.forename: Alan D
authors.initials: AD
authors.lastname: Waggoner
authors.forename: Robert
authors.initials: R
authors.lastname: O'Connor
authors.forename: Melissa
authors.initials: M
authors.lastname: Maisenbacher
authors.forename: Jan R
authors.initials: JR
authors.lastname: Crowley
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Byrne
authors.forename: Linda R
authors.initials: LR
authors.lastname: Peterson
mesh_terms: D000293:Adolescent; D000328:Adult; D056889:Barth Syndrome / Q000097:blood / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D004452:Echocardiography / Q000379:methods; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D008066:Lipolysis / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D007930:Leucine; D005947:Glucose