Fatty liver and insulin resistance in children with hypobetalipoproteinemia: the importance of aetiology.
OBJECTIVE
Hepatic steatosis is strongly associated with insulin resistance, but causative mechanisms that link these conditions are still largely unknown. Nowadays, it is difficult to establish whether fatty liver is the cause of insulin resistance or instead the complex metabolic derangements of insulin resistance determine hepatic steatosis and its progression to fibrosis. In patients with familial hypobetalipoproteinemia (FHBL), hepatic steatosis is because of the genetically determined defective form of apolipoprotein B, independently of metabolic derangements. Therefore patients with FHBL represent a good in vivo model to evaluate the relationships between fatty liver and insulin sensitivity.


METHODS
We evaluated insulin resistance through HOMA-IR in 60 children with echografic and histological features of steatosis; 30 of whom had nonalcoholic fatty liver disease (NAFLD) and 30 had FHBL.


RESULTS
All patients had histological features of hepatic steatosis. Patients with FHBL were hypolipidemic, as expected. No significant differences between two groups were observed in liver function tests. IRI and HOMA-IR were statistically higher in NAFLD subjects compared to the FHBL group.


CONCLUSIONS
In our study, we demonstrated that in children with FHBL, hepatic steatosis is dissociated from insulin resistance. This finding suggests that fat accumulation per se may be not a sufficient causal factor leading to insulin resistance, and that other mediators may be involved in the development of alteration in glucose metabolism and metabolic syndrome in patients with NAFLD.
Hepato-Metabolic Department, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy. claudia.dellacorte@opbg.net
Claudia
C
Della Corte
Danilo
D
Fintini
Ugo
U
Giordano
Marco
M
Cappa
Claudia
C
Brufani
Fabio
F
Majo
Chiara
C
Mennini
Valerio
V
Nobili
D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D005215:Fasting / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000150:complications / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D006801:Humans; D052476:Hypobetalipoproteinemia, Familial, Apolipoprotein B / Q000097:blood / Q000150:complications / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008111:Liver Function Tests; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000378:metabolism; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease; D012307:Risk Factors
D001786:Blood Glucose; D007328:Insulin; D008055:Lipids