title: Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes.
abstract: OBJECTIVE
  Insulin resistance may be associated with ectopic fat accumulation potentially determined by reduced lipid oxidation. In patients with type 1 diabetes peripheral insulin resistance is associated with higher intramyocellular lipid content. We assessed whether these patients are also characterised by intrahepatic fat accumulation and abnormal fat oxidation.
  
  
  METHODS
  Nineteen patients with type 1 diabetes (6 women, 13 men, age 35+/-7 years, BMI 23+/-3 kg/m2), HbA1c 8.7+/-1.4%) and 19 healthy matched individuals were studied by (1) euglycaemic-hyperinsulinaemic clamp combined with [6,6-2H2]glucose infusion to assess whole-body glucose metabolism; (2) indirect calorimetry to assess glucose and lipid oxidation; and (3) localised 1H-magnetic resonance spectroscopy of the liver to assess intrahepatic fat content.
  
  
  RESULTS
  Patients with type 1 diabetes showed a reduced insulin-stimulated metabolic clearance rate of glucose (4.3+/-1.3 ml kg(-1) min(-1)) in comparison with normal subjects (6.0+/-1.6 ml kg(-1) min(-1); p<0.001). Endogenous glucose production was higher in diabetic patients (p=0.001) and its suppression was impaired during insulin administration (66+/-30 vs 92+/-8%; p=0.047) in comparison with normal subjects. Plasma glucagon concentrations were not different between groups. The estimated hepatic insulin concentration was lower in diabetic patients than in normal subjects (p<0.05), as was the intrahepatic fat content (1.5+/-0.7% and 2.2+/-1.0% respectively; p<0.03), the latter in association with a reduced respiratory quotient (0.74+/-0.05 vs 0.84+/-0.06; p=0.01) and increased fasting lipid oxidation (1.5+/-0.5 vs 0.8+/-0.4 mg kg(-1) min(-1); p<0.01).
  
  
  CONCLUSIONS
  In patients with type 1 diabetes, insulin resistance was not associated with increased intrahepatic fat accumulation. In fact, diabetic patients had reduced intrahepatic fat content, which was associated with increased fasting lipid oxidation. The unbalanced hepatic glucagon and insulin concentrations affecting patients with type 1 diabetes may be involved in this abnormality of intrahepatic lipid metabolism.
authors.affiliation: Internal Medicine Section of Nutrition/Metabolism, via Olgettina 60, 20132, Milan, Italy. perseghin.gianluca@hsr.it
authors.forename: G
authors.initials: G
authors.lastname: Perseghin
authors.forename: G
authors.initials: G
authors.lastname: Lattuada
authors.forename: F
authors.initials: F
authors.lastname: De Cobelli
authors.forename: A
authors.initials: A
authors.lastname: Esposito
authors.forename: F
authors.initials: F
authors.lastname: Costantino
authors.forename: T
authors.initials: T
authors.lastname: Canu
authors.forename: P
authors.initials: P
authors.lastname: Scifo
authors.forename: F
authors.initials: F
authors.lastname: De Taddeo
authors.forename: P
authors.initials: P
authors.lastname: Maffi
authors.forename: A
authors.initials: A
authors.lastname: Secchi
authors.forename: A
authors.initials: A
authors.lastname: Del Maschio
authors.forename: L
authors.initials: L
authors.lastname: Luzi
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis*; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D005934:Glucagon