title: Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery.
abstract: OBJECTIVE
  Disturbances in substrate source metabolism and, more particularly, in fatty acid metabolism, play an important role in the aetiology and progression of type 2 diabetes. However, data on substrate source utilisation in type 2 diabetes are inconclusive.
  
  
  METHODS
  [U-(13)C]palmitate and [6,6-(2)H(2)]glucose tracers were used to assess plasma NEFA and glucose oxidation rates and to estimate the use of muscle- and/or lipoprotein-derived triacylglycerol and muscle glycogen. Subjects were ten male patients who had a long-term (7 +/- 1 years) diagnosis of type 2 diabetes and were overweight, and ten matched healthy, male control subjects. Muscle biopsy samples were collected before and after exercise to assess muscle fibre type-specific intramyocellular lipid and glycogen content.
  
  
  RESULTS
  At rest and during exercise, the diabetes patients had greater values than the controls for palmitate rate of appearance (Ra) (rest, 2.46 +/- 0.18 and 1.85 +/- 0.20 respectively; exercise, 3.71 +/- 0.36 and 2.84 +/- 0.20 micromol kg(-1) min(-1)) and rate of disappearance (Rd) (rest, 2.45 +/- 0.18 and 1.83 +/- 0.20; exercise, 3.64 +/- 0.35 and 2.80 +/- 0.20 micromol kg(-1) min(-1) respectively). This was accompanied by significantly higher fat oxidation rates at rest and during recovery in the diabetes patients (rest, 0.11 +/- 0.01 in diabetes patients and 0.09 +/- 0.01 in controls; recovery, 0.13 +/- 0.01 and 0.11 +/- 0.01 g/min respectively), despite significantly greater plasma glucose Ra, Rd and circulating plasma glucose concentrations. Furthermore, exercise significantly lowered plasma glucose concentrations in the diabetes patients, as a result of increased blood glucose disposal.
  
  
  CONCLUSIONS
  This study demonstrates that substrate source utilisation in long-term-diagnosed type 2 diabetes patients, in whom compensatory hyperinsulinaemia is no longer present, shifts towards an increase in whole-body fat oxidation rate and is accompanied by disturbances in fat and carbohydrate handling.
authors.affiliation: Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands. H.Boon@HB.unimaas.nl
authors.forename: H
authors.initials: H
authors.lastname: Boon
authors.forename: E E
authors.initials: EE
authors.lastname: Blaak
authors.forename: W H M
authors.initials: WH
authors.lastname: Saris
authors.forename: H A
authors.initials: HA
authors.lastname: Keizer
authors.forename: A J M
authors.initials: AJ
authors.lastname: Wagenmakers
authors.forename: L J C
authors.initials: LJ
authors.lastname: van Loon
mesh_terms: D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004734:Energy Metabolism / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000097:blood; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D012146:Rest / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D006003:Glycogen; D005990:Glycerol