title: Liver ATP synthesis is lower and relates to insulin sensitivity in patients with type 2 diabetes.
abstract: OBJECTIVE
  Steatosis associates with insulin resistance and may even predict type 2 diabetes and cardiovascular complications. Because muscular insulin resistance relates to myocellular fat deposition and disturbed energy metabolism, we hypothesized that reduced hepatic ATP turnover (fATP) underlies insulin resistance and elevated hepatocellular lipid (HCL) contents.
  
  
  METHODS
  We measured hepatic fATP using (31)P magnetic resonance spectroscopy in patients with type 2 diabetes and age- and body mass-matched controls. Peripheral (M and M/I) and hepatic (suppression of endogenous glucose production) insulin sensitivity were assessed with euglycemic-hyperinsulinemic clamps.
  
  
  RESULTS
  Diabetic individuals had 29% and 28% lower peripheral and hepatic insulin sensitivity as well as 42% reduced fATP than controls. After adjusting for HCL, fATP correlated positively with peripheral and hepatic insulin sensitivity but negatively with waist circumference, BMI, and fasting plasma glucose. Multiple regression analysis identified waist circumference as an independent predictor of fATP and inorganic phosphate (P(I)) concentrations, explaining 65% (P = 0.001) and 56% (P = 0.003) of the variations. Hepatocellular P(I) primarily determined the alterations in fATP.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes, insulin resistance relates to perturbed hepatic energy metabolism, which is at least partly accounted for by fat depots.
authors.affiliation: MR Center of Excellence, Medical University of Vienna, Vienna, Austria. michael.roden@ddz.uni-duesseldorf.de
authors.forename: Albrecht Ingo
authors.initials: AI
authors.lastname: Schmid
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.forename: Marek
authors.initials: M
authors.lastname: Chmelik
authors.forename: Martin
authors.initials: M
authors.lastname: Krssák
authors.forename: Ewald
authors.initials: E
authors.lastname: Moser
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism / Q000502:physiology; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010759:Phosphorus Isotopes
chemical_list: D001786:Blood Glucose; D010759:Phosphorus Isotopes; D000255:Adenosine Triphosphate