1361-P: Patients with Severe Nonalcoholic Steatohepatitis (NASH) Have Profound Insulin Resistance and Lipotoxicity

NASH is the more severe form of nonalcoholic fatty liver disease (NAFLD), prone to advanced fibrosis/cirrhosis. However, the metabolic profile of such patients is not well characterized. The aim of this study was to assess the cardiometabolic features of patients with NASH matched for major variables (age, gender, BMI, A1c), to people with less severe disease activity and without NAFLD. To this end, we recruited 46 patients (age: 57±1.5 years; BMI: 36.2±0.8 kg/m2; A1c: 6.8±0.2%; T2DM: 70%), from our outpatient endocrine and PCP clinics and measured liver disease activity/severity by magnetic resonance (MR) iron corrected T1 imaging (cT1). Patients were grouped based on disease activity (cT1) into those without NAFLD (non-NAFLD; n = 8; cT1 875 ms). Insulin resistance increased with the severity of NASH (HOMA-IR: non-NAFLD: 3.6±0.9 vs. mNASH: 4.3±0.7 vs. sNASH: 5.5±0.7), and so did adipose tissue IR (adipo-IR [fasting FFA x insulin]: 3.5±0.5 vs. 5.5±1.0 vs. 8.2±1.0; respectively, p=0.03). Dysfunctional adipose tissue/lipotoxicity was also evident from lower adiponectin levels (non-NAFLD: 7.4±2.4 vs. mNASH: 3.9±0.7 vs. sNASH: 3.7±0.3 µg/mL; p=0.04) and a 2-fold increase in ectopic fat/liver steatosis by MR-PDFF (mNASH: 11.2±0.9 vs. sNASH: 20.3±1.6; p