Background and Aims: Metabolic associated fatty liver disease (MAFLD) is diagnosed in patients with hepatic steatosis when they have the following three metabolic conditions: obesity/overweight, diabetes and metabolic dysregulation, either alone or in combination. There is no clarity whether subtypes of MAFLD diagnosed by different metabolic conditions carry different levels of risk for intra-and extra-hepatic organs. This study aims to depict the characteristics of these subtypes in a large population. Methods: The data were retrieved from the third National Health and Nutrition Examination Surveys of the United States. The clinical and biochemical features in different MAFLD subtypes were compared. The outcome of interest was significant and advanced fibrosis. Results: Out of 4,087 (31.24%) participants with MAFLD, 1,165 (28.51%) were diagnosed by single metabolic condition, 2,053 (50.23%) by two conditions, and 869 (21.26%) by all three metabolic conditions. With increasing numbers of metabolic conditions, participants tended to be older, were more likely to be female, and had more severe renal impairment and liver fibrosis (P<0.05). MAFLD patients with a lower number of metabolic conditions were more likely to have excessive alcohol consumption. Among MAFLD with single metabolic condition, those diagnosed by diabetes alone had the highest proportion of advanced fibrosis identified by non-invasive fibrosis models (P<0.05). Conclusion: More metabolic conditions upon the diagnosis of MALFD indicate higher risk of fibrosis. Patients with MAFLD diagnosed by diabetes alone are more likely to have advanced hepatic fibrosis than those with other metabolic conditions alone. Individualized management is required for MAFLD with different subtypes.

Aims: To identify the key differentially expressed genes (DEGs) in islet and investigate their potential pathway in the molecular process of type 2 diabetes. Methods: Gene Expression Omnibus (GEO) datasets (GSE20966, GSE25724, GSE38642) of type 2 diabetes patients and normal controls were downloaded from GEO database. DEGs were further assessed by enrichment analysis based on the Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.8. Then, by using Search Tool for the Retrieval Interacting Genes (STRING) 10.0 and gene set enrichment analysis (GSEA), we identified hub gene and associated pathway. At last, we performed quantitative real-time PCR (qPCR) to validate the expression of hub gene. Results: Forty-five DEGs were co-expressed in the three datasets, most of which were down-regulated. DEGs are mostly involved in cell pathway, response to hormone and binding. In protein–protein interaction (PPI) network, we identified ATP-citrate lyase (ACLY) as hub gene. GSEA analysis suggests low expression of ACLY is enriched in glycine serine and threonine metabolism, drug metabolism cytochrome P450 (CYP) and NOD-like receptor (NLR) signaling pathway. qPCR showed the same expression trend of hub gene ACLY as in our bioinformatics analysis. Conclusion: Bioinformatics analysis revealed that ACLY and the pathways involved are possible target in the molecular mechanism of type 2 diabetes.

Background and Aims Circadian misalignment (CM) leads to metabolic disorder. Metabolic (dysfunction) associated fatty liver disease (MAFLD) is a novel definition for fatty liver disease that requires the presence of metabolic dysfunction. As the association between CM and MAFLD remains unclear, this study is designed to explore whether there is an association between CM and MAFLD. Methods NHANES 2017–2018 database was used in this study. Liver steatosis and fibrosis were diagnosed by Fibroscan ® . CM was defined by the presence of mistimed sleep, late sleep or irregular chronotype. Propensity score matching (PSM) was used to match subjects for their age and gender. Results A total of 4552 participants were included in the study, with 2089 (45.89%) identified as MAFLD and 894 (19.64%) as CM. Participants with CM were significantly younger than those without (46.06 ± 18.06 vs 50.93 ± 17.78, p<0.001). PSM for age and gender resulted in 894 participants with CM and 892 with non-CM. CM group had higher body mass index, liver enzymes, glucose and lipid levels. The prevalence of MAFLD was higher in the CM group than the non-CM group (45.41% vs 28.48%, p<0.001). The presence of CM increased the risk of MAFLD by more than twofold. Short sleep duration (<6 hours) was not independently associated with MAFLD or fibrosis if additionally adjusting for CM. Conclusion CM is independently associated with MAFLD, while short sleep duration (<6 hours) is not an independent risk factor for MAFLD or liver fibrosis after adjusting for CM.