1579-P: Impact of Adipose Tissue Insulin Sensitivity on Hepatic Insulin Sensitivity Preservation in Longitudinal Observation of Patients with NAFLD

Abstract

Hepatic insulin resistance associated with NAFLD is a major pathogenesis of type 2 diabetes and its complications. In addition to reducing lipids in the liver, identifying the factors that may preserve hepatic insulin sensitivity (H-IS) is crucial. In this study, we investigated the factors that may preserve H-IS in patients with NAFLD in longitudinal observations. Comprehensively, putative biomarkers in blood and urine, body composition, tissue-specific lipid accumulation and insulin sensitivity by 1H-MRS and hyperinsulinemic euglycemic clamp, respectively, and pathological diagnosis using liver biopsy were assessed in patients with NAFLD (n=62) at baseline. After more than one year of general treatment, consented 36 patients (average age 51.3±11.2, men n=21, diabetes n=23) were subjected to the same assessment as baseline. To investigate the indices associated with H-IS, all indices were compared between upper and lower one third patients of Δ% suppression of endogenous glucose production (EGP) (+11.5±4.0 vs. -10.9±5.1%, respectively). As results, body weight, fasting plasma glucose, HbA1c, muscle and adipose tissue insulin sensitivity, visceral fat, and adiponectin levels were significantly improved in improved H-IS group. Interestingly, Δhepatic lipid content or fibrosis index was not different between the improved and worsened H-IS groups. Furthermore, simple regression analysis with Δ% suppression of EGP and all indices revealed that Δ% suppression of free fatty acid, visceral fat area, and adiponectin levels were significantly associated with Δ% suppression of EGP. Multiple regression analysis with Δ% suppression of EGP and these three indices showed that only Δ% suppression of free fatty acid significantly associated with Δ% suppression of EGP. Taken together, not only lipid volume but also the quality of accumulated lipid is important to preserve hepatic insulin sensitivity in patients with NAFLD. Disclosure F.Shigiyama: None. S.Hiruma: None. N.Kumashiro: Research Support; Terumo Corporation, LifeScan Diabetes Institute, Sumitomo Dainippon Pharma Co., Ltd., Speaker's Bureau; Daiichi Sankyo, Novo Nordisk.