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(plus or minus)7 years, BMI 23(plus or minus)3 kg/m2, HbA1c 8.7(plus or minus)1.4%) and 19 healthy matched individuals were studied by (1) euglycaemic-hyperinsulinaemic clamp combined with [6,6-2H 2]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(plus or minus)1.3 ml kg-1 min-1) in comparison with normal subjects (6.0(plus or minus)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(plus or minus)30 vs 92(plus or minus)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(plus or minus)0.7% and 2.2(plus or minus)1.0% respectively; p<0.03), the latter in association with a reduced respiratory quotient (0.74(plus or minus)0.05 vs 0.84(plus or minus)0.06; p=0.01) and increased fasting lipid oxidation (1.5(plus or minus)0.5 vs 0.8(plus or minus)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. (copyright) Springer-Verlag 2005.
Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes / G. Perseghin, G. Lattuada, F. De Cobelli, A. Esposito, F. Costantino, T. Canu, P. Scifo, F. De Taddeo, P. Maffi, A. Secchi, A. Del Maschio, L. Luzi. - In: DIABETOLOGIA. - ISSN 0012-186X. - 48:12(2005 Dec), pp. 2615-2621.
Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes
G. PerseghinPrimo
;L. LuziUltimo
2005
Abstract
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(plus or minus)7 years, BMI 23(plus or minus)3 kg/m2, HbA1c 8.7(plus or minus)1.4%) and 19 healthy matched individuals were studied by (1) euglycaemic-hyperinsulinaemic clamp combined with [6,6-2H 2]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(plus or minus)1.3 ml kg-1 min-1) in comparison with normal subjects (6.0(plus or minus)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(plus or minus)30 vs 92(plus or minus)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(plus or minus)0.7% and 2.2(plus or minus)1.0% respectively; p<0.03), the latter in association with a reduced respiratory quotient (0.74(plus or minus)0.05 vs 0.84(plus or minus)0.06; p=0.01) and increased fasting lipid oxidation (1.5(plus or minus)0.5 vs 0.8(plus or minus)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. (copyright) Springer-Verlag 2005.Pubblicazioni consigliate
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