Abstract | AIMS/HYPOTHESIS: METHODS: We performed a two-step (1.5 and 6 pmol min(-1) kg(-1)) 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<0.0001) 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 significantly shorter in the patients than in the control subjects (48+/-12 vs 63+/-13 min, p<0.04). Lipid oxidation was significantly 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.
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Authors | E Bugianesi, A Gastaldelli, E Vanni, R Gambino, M Cassader, S Baldi, V Ponti, G Pagano, E Ferrannini, M Rizzetto |
Journal | Diabetologia
(Diabetologia)
Vol. 48
Issue 4
Pg. 634-42
(Apr 2005)
ISSN: 0012-186X [Print] Germany |
PMID | 15747110
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Blood Glucose
- C-Peptide
- Enzymes
- Fatty Acids, Nonesterified
- Insulin
- Lipids
- Lipoproteins, LDL
- Glucose
- Glycerol
- 3-Hydroxybutyric Acid
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Topics |
- 3-Hydroxybutyric Acid
(blood, metabolism)
- Adipose Tissue
(metabolism)
- Adult
- Blood Glucose
(metabolism)
- Body Composition
- C-Peptide
(blood)
- Calorimetry, Indirect
- Enzymes
(blood)
- Fasting
(metabolism)
- Fatty Acids, Nonesterified
(metabolism)
- Fatty Liver
(metabolism, physiopathology)
- Glucose
(metabolism)
- Glucose Clamp Technique
- Glycerol
(blood, metabolism)
- Humans
- Insulin
(blood, metabolism)
- Insulin Resistance
- Lipid Metabolism
- Lipids
(blood)
- Lipoproteins, LDL
(metabolism)
- Liver
(metabolism, pathology)
- Male
- Middle Aged
- Oxidation-Reduction
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