Endocrine Abstracts

Background: Obesity induced inflammation is a key component in the pathogenesis of insulin resistance (IR). In addition, obesity-related non-alcoholic fatty liver disease (NAFLD) also seems to contribute to IR development. Until now, however, it is unclear which, if any component of NAFLD specifically associates with IR. Therefore, the aim is to assess if individual components of NAFLD contribute to IR in obese patients undergoing gastric bypass surgery (GBS).

Subjects and methods: This cross-sectional study included 73 obese patients (mean age 45±11 years; BMI 42.2±4.8 kg/m²) undergoing GBS. Glucose levels were analysed by hexokinase method and insulin levels with electrochemiluminescence. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) was calculated with following formula

Liver biopsies taken during GBS were evaluated using Steatosis, Activity and Fibrosis scoring (SAF score).

Main results: Among GBS patients, according to the SAF score, patients with non-alcoholic steatohepatitis (NASH) had higher glucose levels compared to those without. Besides, patients with a higher grade of inflammation had higher HOMA-IR and insulin levels compared to those with a lower inflammation grade (P<0.05), an association that was independent from age and BMI (F(2,67)=5517; P=0.006). Patients with no fibrosis had lower glucose levels (P=0.037) and a trend towards lower insulin (P=0.079) and HOMA-IR (P=0.088) levels compared to patients with a higher grade of fibrosis. Ballooning and steatosis grade were not associated with HOMA-IR.

Conclusion: This study shows that within an insulin resistant group of obese patients, the level of IR correlates with histopathologic subcomponents of NAFLD. Specifically, whereas steatosis and ballooning are not associated with HOMA-IR, a higher grade of hepatic inflammation is associated with higher IR. For fibrosis, a trend towards higher IR with higher grade of fibrosis is found. Whether this finding reflects a subgroup of patients with more severe adiposity-related consequences, such as whole-body systemic inflammation, or whether this results from a direct effect of hepatic inflammation (and fibrosis) on IR needs to be further investigated.