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- Title
Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms.
- Authors
Bugianesi, E.; Gastaldelli, A.; Vanni, E.; Gambino, R.; Cassader, M.; Baldi, S.; Ponti, V.; Pagano, G.; Ferrannini, E.; Rizzetto, M.
- Abstract
Aims/Hypothesis: Non-alcoholic fatty liver dis- ease (NAFLD) has been associated with the metabolic syndrome. However, it is not clear whether insulin resistance is an independent feature of NAFLD, and it remains to be determined which of the in vivo actions of insulin are im- paired in this condition. Methods: We performed a two- step (1.5 and 6 pmol min1 kg1) euglycaemic insulin clamp coupled with tracer infusion ([6,6-2H2]glucose and [2H5] glycerol) and indirect calorimetry in 12 non-obese, normolipidaemic, normotensive, non-diabetic patients with biopsy-proven NAFLD and six control subjects. Results: In NAFLD patients, endogenous glucose production (basal and during the clamp) was normal; however, peripheral glucose disposal was markedly decreased (by 30% and 45% at the low and high insulin doses, respectively, p<O.0001) at higher plasma insulin levels (p=0.05), due to impaired glucose oxidation (p=0.003) and glycogen synthesis (p<0.001). Compared with control subjects, glycerol appearance and lipid oxidation were significantly increased in NAFLD patients in the basal state, and were suppressed by insulin to a lesser extent (p<0.05-0.001). The lag phase of the in vitro copper-catalysed peroxidation of LDL particles was signif- icantly shorter in the patients than in the control subjects (48±12 vs 63±13 mm, p43.04). Lipid oxidation was signif- icantly related to endogenous glucose production, glucose disposal, the degree of hepatic steatosis, and LDL oxidisability. Conclusions/interpretation: Insulin resistance appears to be an intrinsic defect in NAFLD, with the metabolic pattern observed indicating that adipose tissue is an important site.
- Subjects
FATTY liver; INSULIN resistance; GLUCOSE; BLOOD plasma; ADIPOSE tissues; GLYCOGEN synthesis
- Publication
Diabetologia, 2005, Vol 48, Issue 4, p634
- ISSN
0012-186X
- Publication type
Article
- DOI
10.1007/s00125-005-1682-x