title: Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism.
abstract: OBJECTIVE
  To determine insulin sensitivity and skeletal muscle fatty acid (FA) handling at baseline and after a high-fat mixed meal in impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and normal glucose tolerance (NGT) subjects.
  
  
  METHODS
  In this multi-center study, insulin sensitivity and β-cell function were assessed (n=102), using a euglycemic-hyperinsulinemic and hyperglycemic clamp with additional arginine stimulation and a 75 g oral glucose tolerance test. Fasting and postprandial skeletal muscle FA handling was examined in a substudy using the forearm balance technique (n=35).
  
  
  METHODS
  A total of 102 subjects with IFG (n=48), IGT (n=12), IFG/IGT (n=26) and NGT (n=16).
  
  
  RESULTS
  IFG, IGT and IFG/IGT subjects had lower insulin sensitivity with no differences between groups, and lower impaired β-cell function compared with NGT controls. The early postprandial increase in triacylglycerol (TAG) concentration was higher (iAUC(0-2 h) IFG: 238.4±26.5, IGT: 234.0±41.0 and NGT: 82.6±13.8 μmol l(-1) min(-1), both P<0.05) and early TAG extraction was increased (AUC(0-2 h) IFG: 56.8±9.0, IGT: 52.2±12.0 and NGT: 3.8±15.4 nmol·100 ml(-1) min(-1), P<0.05 and P=0.057, respectively) in both IFG and IGT subjects.
  
  
  CONCLUSIONS
  IFG, IGT and IFG/IGT subjects have lower insulin sensitivity and impaired β-cell function compared with age- and BMI-matched NGT controls. The increased postprandial TAG response and higher muscle TAG extraction in both IFG and IGT compared with NGT may lead to ectopic fat accumulation in the skeletal muscle, thereby contributing to insulin resistance.
authors.affiliation: Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands. C.Moors@maastrichtuniversity.nl
authors.forename: C C M
authors.initials: CC
authors.lastname: Moors
authors.forename: N J
authors.initials: NJ
authors.lastname: van der Zijl
authors.forename: M
authors.initials: M
authors.lastname: Diamant
authors.forename: E E
authors.initials: EE
authors.lastname: Blaak
authors.forename: G H
authors.initials: GH
authors.lastname: Goossens
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D005215:Fasting; D005227:Fatty Acids; D005260:Female; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D019518:Postprandial Period; D011236:Prediabetic State / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids