Serum lipidomics in type 2 diabetes mellitus patients with simple fatty liver or nonalcoholic steatohepatitis

Objective To understand the profile of serum lipid composition in type 2 diabetes mellitus (T2DM) patients with nonalcoholic simple fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), and to screen potential serum markers of NASH. Methods A total of 40 patients with T2DM and comorbid non-alcoholic fatty liver disease (NAFLD) who underwent liver biopsy were selected from September 2014 to October 2017 in the Department of Endocrinology, the Third Central Hospital of Tianjin. According to the results of liver biopsy (SAF score), they were divided into NAFL group (22 cases) and NASH group (18 cases). Medical profiles of the two groups were extracted and compared, ultra-high performance liquid chromatography-mass spectrometry was used for serum lipidomics analysis. T test was used to determine statistical significance between the groups. Logistic stepwise regression analysis and receiver operating characteristic (ROC) curve analysis were used to screen potential serum markers for NASH in T2DM. Results The liver stiffness, NASH score, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyltransferase (GGT), fasting blood glucose and serum ferritin levels were higher in NASH group than those in NAFL group (t=-2.76--2.06, all P<0.05). Phosphatidylcholine (35∶4)[PC (35∶4)], PC (36∶1) [PC (18∶1/18∶0)], PC (38∶3), PC (44∶5), phosphatidyl-ethnolamine (36∶2)[PE (36∶2)], PE (34∶1) c[PE-NMe2 (18∶1/16∶0)], PE (34∶1) [PE(20∶1/14∶0)], phosphatidyl serine (33∶0) [PS(33∶0)], triglyceride (54∶2)[TG (54∶2)], sphingomyelin (37∶1)[SM (37∶1)], SM (39∶1), SM (40∶1), glucosylceramide (40∶2)[GlcCer (40∶2)] were higher in NASH group than those in NAFL group (t=-2.930--1.380, all P<0.05). The levels of PC (38∶5),PC (38∶6),TG (52∶4),TG (54∶4),TG (54∶5),TG (57∶6), TG (58∶4), TG (60∶6) decreased in NASH group (t=1.982-2.431, all P<0.05); The levels of PC (36∶1) [PC (19∶1/17∶0)], PE (38∶1), PE (39∶1), TG (52∶1), N-palmitoyl phenylalanine were significantly higher in NASH group than those in NAFL group, with statistically significant differences (-3.789--2.837, P<0.005). Logistic stepwise regression analysis showed that increased PC (36∶1) and PE (38∶1) were risk factors for NASH progression in patients with T2DM complicated with NAFLD [P=0.026, 0.013, OR (95%CI): 1.213 (1.076-1.301), 1.119 (1.015-1.243)]. ROC curve analysis showed that the areas under curves of PC (36∶1) and PE (38∶1) were 0.803 and 0.785, respectively, with sensitivity 94.4% and specificity 72.7%, all higher than those of ALT, AST and GGT (the areas under the curve were 0.689, 0.734 and 0.741, the sensitivity was 72.2%, 77.8% and 77.8%, and the specificity was 68.2%, 63.6% and 68.2% respectively). Conclusions In patients with type 2 diabetes, glycero phospholipids, sphingolipids and TG changed significantly in NASH compared with NAFL. In patients with T2DM and fatty liver, PC (36∶1) and PE(38∶1) might be potential bio markers for NASH diagnosis. Key words: Diabetes mellitus, type 2; Fatty liver; Lipidomics