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Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease

  • Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

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.

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Authors and Affiliations

  1. Department of Disease Control and Homeostacis, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Masaru Sakurai, Toshinari Takamura, Tsuguhito Ota, Hitoshi Ando, Hiroshi Akahori, Kyosuke Kaji & Shuichi Kaneko

  2. Department of Human Pathology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

    Motoko Sasaki & Yasuni Nakanuma

  3. Department of Epidemiology and Public Health, Kanazawa Medical University, Kanazawa, Japan

    Katsuyuki Miura

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  1. Masaru Sakurai
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  2. Toshinari Takamura
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  3. Tsuguhito Ota
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Sakurai, M., Takamura, T., Ota, T. et al. Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease. J Gastroenterol 42, 312–317 (2007). https://doi.org/10.1007/s00535-006-1948-

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