Hepatic insulin resistance in NAFLD: relationship with markers of atherosclerosis and metabolic syndrome components.
OBJECTIVE
Fat accumulation in the liver and in the muscle results in hepatic and muscle insulin resistance and has been associated with increased cardiovascular risk. It is unclear whether the individual role of hepatic and muscle insulin resistance in the onset of dyslipidaemia is observed in nonalcoholic fatty liver disease (NAFLD) patients and whether this association is mediated through traditional risk factors. The aim of this study was to assess hepatic and muscle insulin resistance in NAFLD and its relationship with carotid artery intima-media thickness (IMT) and the apoB/apoAI ratio as markers of atherosclerosis.


METHODS
We studied 132 patients with a non-invasive diagnosis of NAFLD stratified into two groups according to the severity of steatosis at ultrasound scan. In all subjects, we measured hepatic insulin resistance (H-IR) and muscle insulin sensitivity index (MISI) by oral glucose tolerance test as proposed by DeFronzo, IMT, apoB/apoAI and the components of the metabolic syndrome (MS) as defined by ATP III.


RESULTS
H-IR was significantly higher in moderate/severe steatosis than in the mild steatosis group (p < 0.0001). By contrast, MISI did not differ between the two groups. There was a significant correlation between H-IR, MISI and all of the components of MS. H-IR was significantly correlated with carotid IMT (r = 0.35; p < 0.0001) and the apoB/apoAI ratio (r = 0.43; p < 0.0001). Otherwise, a significant correlation was observed only between MISI and apoB/apoAI ratio. Multivariate analysis revealed that H-IR is related to early markers of atherosclerosis independent of MS components.


CONCLUSIONS
In our study population, NAFLD was positively associated with carotid IMT, and this association is independent of MS components, but strictly related to H-IR that might contribute to the development of atherosclerosis through an impairment of the lipid profile in terms of the apoB/apoAI ratio. By contrast, no significant relation was observed between MISI and carotid IMT.
Department of Clinical and Molecular Biomedicine, Garibaldi Hospital, University of Catania, Via Palermo, 636, 95122, Catania, Italy.
Graziella
G
Privitera
Department of Clinical and Molecular Biomedicine, Garibaldi Hospital, University of Catania, Via Palermo, 636, 95122, Catania, Italy.
Luisa
L
Spadaro
Department of Clinical and Molecular Biomedicine, Garibaldi Hospital, University of Catania, Via Palermo, 636, 95122, Catania, Italy.
Corradina
C
Alagona
Department of Clinical and Molecular Biomedicine, Garibaldi Hospital, University of Catania, Via Palermo, 636, 95122, Catania, Italy.
Salvatore
S
Calanna
Department of Clinical and Molecular Biomedicine, Garibaldi Hospital, University of Catania, Via Palermo, 636, 95122, Catania, Italy.
Salvatore
S
Piro
Department of Clinical and Molecular Biomedicine, Garibaldi Hospital, University of Catania, Via Palermo, 636, 95122, Catania, Italy.
Agata Maria
AM
Rabuazzo
Department of Clinical and Molecular Biomedicine, Garibaldi Hospital, University of Catania, Via Palermo, 636, 95122, Catania, Italy. fpurrell@unict.it.
Francesco
F
Purrello
D000293:Adolescent; D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000453:epidemiology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000453:epidemiology
C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D015415:Biomarkers
Cardiovascular risk; Carotid artery intima-media thickness; Hepatic insulin resistance; Nonalcoholic fatty liver disease; apoB/apoAI ratio