Plasma GLP-1 (Glucagon-like Peptide-1) Depletion Is Correlated with Dysregulation of Adipocytokine in Type 2 Diabetic Patients With or Without Metabolic-Associated Fatty Liver Disease (MAFLD): A Cross-Sectional Study Related to Gender-Sex Disparities

The triad association among type 2 diabetes mellitus (T2DM), metabolic associated fatty liver disease (MAFLD), and incretin secretion dysfunction, including GLP-1 (glucagon-like peptide-1) secretion dysfunction, maintains a critical cardiovascular risk and liver-related mortality. The aim of this study is to establish interactions between the GLP-1 plasma levels and metabolic syndrome clusters and adipokines profile (leptin, adiponectin, resistin) and proinflammatory cytokines (TNFα, IL-6, IL1β, IL-17) in diabetic subjects with or without MAFLD. The data revealed that insulin resistance (HOMA-IR) is present in all groups. MAFLD is more common in men than in women. The average FLI score in group IV was ≥70, confirming the diagnosis of MAFLD. The disorder of GLP-1 secretion is more pronounced in women than in men. HOMA-IR is negatively associated with plasma GLP-1 depletion in the MAFLD, T2DM, and MAFLD + T2DM groups. Adiponectin levels are decreased in all groups, as for GLP-1. In contrast, leptin, resistin, TNFα, IL-6, IL-1β, and IL-17 levels show an inverse correlation with GLP-1. GLP-1 accurately reflects metabolic and inflammatory status in subjects with MAFLD, T2DM, and diabetes-steatosis. The applied multivariate linear regression model confirms a highly significant association between MAFLD and GLP-1. It appears that plasma GLP-1 can be considered as biomarker in MAFLD and T2DM related to sex-gender disparities. Longitudinal studies are required to confirm these data.