AIMS/HYPOTHESIS: 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/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: 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/ INTERPRETATION: 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: Martin G Bischof; Elisabeth Bernroider; Martin Krssak; Michael Krebs; Harald Stingl; Peter Nowotny; Chunlin Yu; Gerald I Shulman; Werner Waldhäusl; Michael Roden Journal: Diabetes Date: 2002-01 Impact factor: 9.461
Authors: J H Hwang; G Perseghin; D L Rothman; G W Cline; I Magnusson; K F Petersen; G I Shulman Journal: J Clin Invest Date: 1995-02 Impact factor: 14.808
Authors: Kristen J Nadeau; Judith G Regensteiner; Timothy A Bauer; Mark S Brown; Jennifer L Dorosz; Amber Hull; Phil Zeitler; Boris Draznin; Jane E B Reusch Journal: J Clin Endocrinol Metab Date: 2009-11-13 Impact factor: 5.958
Authors: Marietta Stadler; Christian Anderwald; Giovanni Pacini; Stefan Zbýn; Miriam Promintzer-Schifferl; Martina Mandl; Martin Bischof; Stephan Gruber; Peter Nowotny; Anton Luger; Rudolf Prager; Michael Krebs Journal: Diabetes Date: 2009-10-15 Impact factor: 9.461