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.

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.

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.

Age, neck circumference (NC), fasting blood glucose (FPG) and glycosylated hemoglobin (HbA_1c) 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 (r_s=-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.

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.

随着慢性代谢性疾病的发病率逐年增加，已威胁全民健康，目前非编码RNA与内分泌代谢相关疾病的研究已成为国内外研究热点，其中长链非编码RNA核富集转录体（lncRNA NEAT1）及微小RNA（miRNA）-182-5p在2型糖尿病（T2DM）合并代谢相关脂肪性肝病（MAFLD）中的研究鲜有报道。

探讨T2DM合并MAFLD患者lncRNA NEAT1、miRNA-182-5p在肝纤维化发生、发展中的机制及临床意义。

纳入2021年10月—2022年6月在内蒙古科技大学包头医学院第一附属医院内分泌科就诊的T2DM患者236例为研究对象，同时纳入49名健康志愿者为健康对照组。收集研究对象一般资料与实验室检测结果。测定内脏脂肪面积（VFA）、皮下脂肪面积（SFA）。采集外周血，测定lncRNA NEAT1、miRNA-182-5p。将T2DM患者其分为T2DM合并非MAFLD组（n=82）与T2DM合并MAFLD组（n=154）。进一步根据肝纤维化指数（FIB-4）将T2DM合并MAFLD组分为肝纤维化低危亚组（n=55）、肝纤维化中危亚组（n=69）、肝纤维化高危亚组（n=30）。采用Spearman秩相关分析探究肝纤维化高危亚组lncRNA NEAT1、miRNA-182-5p表达水平的相关性，采用多因素有序Logistic回归分析探究T2DM合并MAFLD患者肝纤维化风险的影响因素。

健康对照组年龄、颈围（NC）、空腹血糖（FPG）、糖化血红蛋白（HbA_1c）低于T2DM合并MAFLD组、T2DM合并非MAFLD组，白蛋白（Alb）高于T2DM合并MAFLD组、T2DM合并非MAFLD组（P<0.05）；T2DM合并MAFLD组BMI、腰围（WC）、VFA、SFA、稳态模型评估胰岛素抵抗指数（HOMA-IR）、三酰甘油（TG）、血尿酸（SUA）、lncRNA NEAT1高于健康对照组、T2DM合并非MAFLD组，血小板计数（PLT）低于健康对照组、T2DM合并非MAFLD组，总胆固醇（TC）低于健康对照组（P<0.05）；T2DM合并非MAFLD组HOMA-IR、lncRNA NEAT1高于健康对照组，miRNA-182-5p高于健康对照组、T2DM合并MAFLD组，丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）低于健康对照组、T2DM合并MAFLD组（P<0.05）。肝纤维化低危亚组VFA、SFA、AST、lncRNA NEAT1低于肝纤维化中危亚组、肝纤维化高危亚组，PLT、miRNA-182-5p高于肝纤维化中危亚组、肝纤维化高危亚组，BMI、WC、NC低于肝纤维化高危亚组，TC高于肝纤维化高危亚组（P<0.05）；肝纤维化中危亚组PLT、miRNA-182-5p高于肝纤维化高危亚组，AST、lncRNA NEAT1低于肝纤维化高危亚组（P<0.05）。Spearman秩相关分析结果显示，肝纤维化高危亚组患者lncRNA NEAT1与miRNA-182-5p呈负相关（r_s=-0.438，P<0.05）。多因素有序Logistic回归分析结果显示，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）是T2DM合并MAFLD患者肝纤维化风险的影响因素。

外周血lncRNA NEAT1、miRNA-182-5p与T2DM合并MAFLD患者并发肝纤维化密切相关，为该病的早期预测及诊治提供依据。