Correlation of lncRNA NEAT1 and miRNA-182-5p with the Risk of Liver Fibrosis in Type 2 Diabetes Mellitus Patients with MAFLD

Abstract

Background With the incidence of chronic metabolic diseases rising by year, which has threatened the national health, the study of non-coding RNA and endocrine metabolism-related diseases has become a research hotspot at home and abroad, while lncRNA NEAT1 and miRNA-182-5p in type 2 diabetes mellitus (T2DM) combined with metabolic-related fatty liver disease (MAFLD) has been rarely reported. Objective To investigate the mechanism and clinical significance of lncRNA NEAT1 and miRNA-182-5p in the development of liver fibrosis in T2DM patients with MAFLD. Methods A total of 236 T2DM patients admitted to the endocrinology department of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from October 2021 to June 2022 were included as the study subjects, and 49 healthy people were included as the healthy control group. General information and laboratory test results of the subjects were collected. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured. Peripheral blood was collected and lncRNA NEAT1, miRNA-182-5p were determined. T2DM patients were divided into the T2DM with non-MAFLD group (n=82) and T2DM with MAFLD group (n=154). T2DM with MAFLD group was further divided into the low-risk subgroup (n=55), medium-risk subgroup (n=69) and high-risk subgroup (n=30) according to the liver fibrosis index (FIB-4). In addition, healthy people were selected as the healthy control group (n=49). Spearman rank correlation analysis was used to explore the correlation of lncRNA NEAT1 and miRNA-182-5p expression levels in the high-risk subgroup of liver fibrosis, and multilevel ordinal Logistic regression was used to explore the influencing factors of liver fibrosis risk in T2DM patients with MAFLD. Results Age, neck circumference (NC), fasting blood glucose (FPG) and glycosylated hemoglobin (HbA1c) in the healthy control group were lower than those in the T2DM with non-MAFLD and T2DM with MAFLD groups, the albumin (Alb) in the healthy control group was higher than that in the T2DM with non-MAFLD and T2DM with MAFLD groups (P<0.05). BMI, waist circumference (WC), VFA, SFA, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), serum uric acid (SUA) and lncRNA NEAT1 in the T2DM with MAFLD group were higher than those in the healthy control group and T2DM with non-MAFLD group, platelet count (PLT) was lower than that of the healthy control group and T2DM with non-MAFLD group, total cholesterol (TC) was lower than that of the healthy control group (P<0.05). HOMA-IR and lncRNA NEAT1 in the T2DM with non-MAFLD groups were higher than those in the healthy control group, miRNA-182-5p was higher than that in the healthy control group and T2DM with MAFLD group, alanine aminotransferase (ALT) and aspartate transferase (AST) were lower than those in the healthy control group and T2DM with MAFLD group (P<0.05). VFA, SFA, AST and lncRNA NEAT1 in the low-risk subgroup were lower than those in the medium-risk subgroup and high-risk subgroup, PLT and miRNA-182-5p were higher than those in the medium-risk subgroup and high-risk subgroup, BMI, WC and NC were lower than those in the high-risk subgroup, TC was higher than that in the high-risk group of liver fibrosis (P<0.05). PLT and miRNA-182-5p in the medium-risk subgroup were higher than the high-risk subgroup, AST and lncRNA NEAT1 were lower than those in the high risk group (P<0.05). Spearman rank correlation analysis showed that lncRNA NEAT1 was significantly negatively correlated with miRNA-182-5p in the high-risk subgroup of liver fibrosis (rs=-0.438, P<0.05). The results of multilevel ordinal Logistic regression analysis showed that lncRNA NEAT1 (OR=1.326, 95%CI=1.087-1.616), VFA (OR=1.019, 95%CI=1.006-1.033), miRNA-182-5p (OR=0.083, 95%CI=0.027-0.257), PLT (OR=0.956, 95%CI=0.942-0.970), AST (OR=1.048, 95%CI=1.022-1.075) were the risk factors of liver fibrosis in T2DM patients with MAFLD. Conclusion Peripheral blood lncRNA NEAT1 and miRNA-182-5p are closely related to the complicated liver fibrosis in T2DM patients with MAFLD, providing a new basis for the early prediction, diagnosis and treatment of the disease.

Keywords

• type 2 diabetes mellitus|metabolic-related fatty liver disease|neat1|mirna-182-5p|hepatic fibrosis|root cause analysis