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Insulin resistance associates with hepatic lobular inflammation in subjects with obesity

(2019) ENDOCRINE CONNECTIONS. 8(9). p.1294-1301
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Abstract
Purpose: Obese subjects with nonalcoholic fatty liver disease (NAFLD) are more prone to develop additional metabolic disturbances such as systemic insulin resistance (IR) and type 2 diabetes. NAFLD is defined by hepatic steatosis, lobular inflammation, ballooning and stage of fibrosis, but it is unclear if and which components could contribute to IR. Objective: To assess which histological components of NAFLD associate with IR in subjects with obesity, and if so, to what extent. Methods: This cross-sectional study included 78 obese subjects (mean age 46 +/- 11 years; BMI 42.2 +/- 4.7 kg/m(2)). Glucose levels were analysed by hexokinase method and insulin levels with electrochemiluminescence. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) was calculated. Liver biopsies were evaluated for histological components of NAFLD. Results: A positive association between overall NAFLD Activity Score and HOMA-IR was found (r(s) = 0.259, P = 0.022). As per individual components, lobular inflammation and fibrosis stage were positively associated with HOMA-IR, glucose and insulin levels (P < 0.05), and HOMA-IR was higher in patients with more inflammatory foci or higher stage of fibrosis. These findings were independent of age, BMI, triglyceride levels, diabetes status and sex (all P < 0.043). In a combined model, lobular inflammation, but not fibrosis, remained associated with HOMA-IR. Conclusion: In this group of obese subjects, a major contributing histological component of NAFLD to the relation between NAFLD severity and IR seems to be the grade of hepatic lobular inflammation. Although no causal relationship was assessed, preventing or mitigating this inflammatory response in obesity might be of importance in controlling obesity-related metabolic disturbances.
Keywords
NAFLD, insulin resistance, hepatic inflammation, obesity, FATTY LIVER-DISEASE, SCORING SYSTEM, STEATOSIS, PROGRESSION, ALGORITHM, MECHANISM, SEVERITY, GLUCOSE, DAMAGE, NAFLD

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MLA
Van de Velde, Frederique, et al. “Insulin Resistance Associates with Hepatic Lobular Inflammation in Subjects with Obesity.” ENDOCRINE CONNECTIONS, vol. 8, no. 9, 2019, pp. 1294–301, doi:10.1530/ec-19-0366.
APA
Van de Velde, F., Bekaert, M., Geerts, A., Hoorens, A., Batens, A.-H., Shadid, S., … Lapauw, B. (2019). Insulin resistance associates with hepatic lobular inflammation in subjects with obesity. ENDOCRINE CONNECTIONS, 8(9), 1294–1301. https://doi.org/10.1530/ec-19-0366
Chicago author-date
Van de Velde, Frederique, Marlies Bekaert, Anja Geerts, Anne Hoorens, Arsène-Hélène Batens, Samiah Shadid, Margriet Ouwens, Yves Van Nieuwenhove, and Bruno Lapauw. 2019. “Insulin Resistance Associates with Hepatic Lobular Inflammation in Subjects with Obesity.” ENDOCRINE CONNECTIONS 8 (9): 1294–1301. https://doi.org/10.1530/ec-19-0366.
Chicago author-date (all authors)
Van de Velde, Frederique, Marlies Bekaert, Anja Geerts, Anne Hoorens, Arsène-Hélène Batens, Samiah Shadid, Margriet Ouwens, Yves Van Nieuwenhove, and Bruno Lapauw. 2019. “Insulin Resistance Associates with Hepatic Lobular Inflammation in Subjects with Obesity.” ENDOCRINE CONNECTIONS 8 (9): 1294–1301. doi:10.1530/ec-19-0366.
Vancouver
1.
Van de Velde F, Bekaert M, Geerts A, Hoorens A, Batens A-H, Shadid S, et al. Insulin resistance associates with hepatic lobular inflammation in subjects with obesity. ENDOCRINE CONNECTIONS. 2019;8(9):1294–301.
IEEE
[1]
F. Van de Velde et al., “Insulin resistance associates with hepatic lobular inflammation in subjects with obesity,” ENDOCRINE CONNECTIONS, vol. 8, no. 9, pp. 1294–1301, 2019.
@article{8632973,
  abstract     = {{Purpose: Obese subjects with nonalcoholic fatty liver disease (NAFLD) are more prone to develop additional metabolic disturbances such as systemic insulin resistance (IR) and type 2 diabetes. NAFLD is defined by hepatic steatosis, lobular inflammation, ballooning and stage of fibrosis, but it is unclear if and which components could contribute to IR. 
Objective: To assess which histological components of NAFLD associate with IR in subjects with obesity, and if so, to what extent. Methods: This cross-sectional study included 78 obese subjects (mean age 46 +/- 11 years; BMI 42.2 +/- 4.7 kg/m(2)). Glucose levels were analysed by hexokinase method and insulin levels with electrochemiluminescence. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) was calculated. Liver biopsies were evaluated for histological components of NAFLD. 
Results: A positive association between overall NAFLD Activity Score and HOMA-IR was found (r(s) = 0.259, P = 0.022). As per individual components, lobular inflammation and fibrosis stage were positively associated with HOMA-IR, glucose and insulin levels (P < 0.05), and HOMA-IR was higher in patients with more inflammatory foci or higher stage of fibrosis. These findings were independent of age, BMI, triglyceride levels, diabetes status and sex (all P < 0.043). In a combined model, lobular inflammation, but not fibrosis, remained associated with HOMA-IR. 
Conclusion: In this group of obese subjects, a major contributing histological component of NAFLD to the relation between NAFLD severity and IR seems to be the grade of hepatic lobular inflammation. Although no causal relationship was assessed, preventing or mitigating this inflammatory response in obesity might be of importance in controlling obesity-related metabolic disturbances.}},
  author       = {{Van de Velde, Frederique and Bekaert, Marlies and Geerts, Anja and Hoorens, Anne and Batens, Arsène-Hélène and Shadid, Samiah and Ouwens, Margriet and Van Nieuwenhove, Yves and Lapauw, Bruno}},
  issn         = {{2049-3614}},
  journal      = {{ENDOCRINE CONNECTIONS}},
  keywords     = {{NAFLD,insulin resistance,hepatic inflammation,obesity,FATTY LIVER-DISEASE,SCORING SYSTEM,STEATOSIS,PROGRESSION,ALGORITHM,MECHANISM,SEVERITY,GLUCOSE,DAMAGE,NAFLD}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1294--1301}},
  title        = {{Insulin resistance associates with hepatic lobular inflammation in subjects with obesity}},
  url          = {{http://dx.doi.org/10.1530/ec-19-0366}},
  volume       = {{8}},
  year         = {{2019}},
}

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