Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease.
BACKGROUND
To address the hypothesis that liver steatosis causes systemic insulin resistance, we sought to determine the liver histological feature that most strongly contributes to insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD).


METHODS
Liver biopsy specimens were obtained from 131 patients with clinically suspected NAFLD. The stage, grade of nonalcoholic steatohepatitis (NASH), and level of steatosis were scored and analyzed in relation to the homeostasis model assessment of insulin resistance (HOMA-IR) and the metabolic clearance rate (MCR), measured using the glucose clamp method.


RESULTS
In the univariate analysis, the degree of hepatic steatosis (r = 0.458, P < 0.001), stage (r = 0.360, P < 0.001), and grade (r = 0.349, P < 0.01) of NASH were significantly correlated with the HOMA-IR. Multiple regression analysis adjusting for age, sex, body mass index, and each histological score showed that steatosis was significantly and independently associated with HOMA-IR (coefficient = 1.42, P < 0.001), but not with the stage (coefficient = 0.33, P = 0.307) or grade (coefficient = 0.67, P = 0.134) of NASH. Similar independent relationships were observed between steatosis and MCR, but the relationship was weaker (coefficient = -0.98, P = 0.076).


CONCLUSIONS
Steatosis of the liver, but not the stage or the grade of NASH, is associated with insulin resistance in patients with NAFLD.
Sakurai
Masaru
M
Department of Disease Control and Homeostacis, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
Takamura
Toshinari
T
Ota
Tsuguhito
T
Ando
Hitoshi
H
Akahori
Hiroshi
H
Kaji
Kyosuke
K
Sasaki
Motoko
M
Nakanuma
Yasuni
Y
Miura
Katsuyuki
K
Kaneko
Shuichi
S
D000328:Adult; D000410:Alanine Transaminase / Q000032:analysis; D001219:Aspartate Aminotransferases / Q000032:analysis; D015992:Body Mass Index; D005234:Fatty Liver / Q000473:pathology*; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000473:pathology*; D008875:Middle Aged
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase