Endocrine Abstracts

Background and aims: 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 62 obese patients (mean age 45±10 years; BMI 41.7±4.5 kg/m²) undergoing GBS and 62 healthy, age-matched control subjects (mean age 45±10 years; BMI 23.5±1.8 kg/m²). 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 HOMA-IR={fasting glucose (mmol/l) * fasting insulin (μU/ml)}/22.5. Liver biopsies taken during GBS were evaluated using NASH-CRN scoring system (NAS score) and Steatosis, Activity and Fibrosis scoring (SAF score).

Results: GBS patients showed higher glucose, insulin and HOMA-IR levels (all P<0.001) compared to controls. Among GBS patients, according to the SAF score, patients with non-alcoholic steatohepatitis (NASH) had higher glucose levels compared to those without. Besides, with an increasing grade of inflammation patients had higher HOMA-IR and insulin levels (P<0.05), an association that is independent from age, BMI and cholesterol (F(2,48)=3309; P=0.045). Ballooning was not associated with HOMA-IR, insulin or glucose levels, whereas an association between steatosis grade and HOMA-IR levels was lost after controlling for age and BMI. An increasing grade of fibrosis was correlated with insulin and HOMA-IR levels (r_s=0.256, P=0.048 and r_s=0.255, P=0.049; respectively).

Conclusion: This study showed 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 was associated with higher IR. For fibrosis, a trend toward higher IR with higher grade of fibrosis was found. Whether this finding reflects a subgroup of patients with more severe adiposity-related consequences or whether this results from a direct effect of hepatic inflammation (and fibrosis) on IR needs to be further investigated.