Hepatokines are a variety of proteins secreted by the liver, a key organ involved in systemic metabolism and endocrine, directly affect the liver glycolipid metabolism, and play an important role in the development of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM). Ectodysplasin A (EDA) is a newly discovered hepatokine, which is considered to be strongly related to diabetes, obesity and insulin resistance.

To assess the relationship between serum EDA level and the risk of NAFLD in patients with T2DM.

One hundred and thirty T2DM patients, including 74 males (56.92%) and 56 females (43.08%), with a mean age of (55.6±12.4) years, were recruited from Department of Endocrinology, Affiliated Hospital of Jiangsu University between November 2017 and November 2020. Baseline data, results of glucose tolerance test, insulin response test, C-peptide response to glucagon test, and color Doppler ultrasound of the abdomen were collected. Baseline data were compared between patients with ultrasound-detected NAFLD (n=80) and those without (n=50). Pearson correlation analysis was used to evaluate the correlation between serum EDA and the other clinical and biochemical indices. Multiple linear regression analysis was used to explore the influencing factors of EDA level. Multivariate Logistic regression analysis was used to explore the effect of EDA level on the risk of NAFLD.

Compared with non-NAFLD group, NAFLD group had much younger mean age, shorter mean duration of T2DM, but significantly higher mean levels of BMI, fasting insulin (FIns), 2-hour postprandial insulin responses (2 hIns), fasting C-peptide (FCP), 2-hour postprandial C-peptide (2 hCP), homeostasis model assessment of insulin resistance (HOMA-IR), triacylglycerol (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood uric acid (SUA), urea nitrogen (BUN), and EDA level (P<0.05). Pearson correlation analysis showed that the serum EDA level was positively correlated with age, FIns, 2 hIns, HOMA-IR, and AST (r=0.222, 0.186, 0.233, 0.204, 0.189, P<0.05). Multiple linear regression analysis showed that age〔β=1.957, 95%CI (0.412, 3.502), P=0.013〕, WHR〔β=-328.845, 95%CI (-638.903, -18.788), P=0.038〕, 2 hIns〔β=0.523, 95%CI (0.036, 1.011), P=0.036〕 and AST〔β=2.148, 95%CI (0.520, 3.776), P=0.010〕were independently associated with EDA (P<0.05). Multivariate Logistic regression analysis demonstrated that EDA was still associated with NAFLD after adjusting for multiple confounding factors〔OR=1.006, 95%CI (1.002, 1.010), P=0.007〕.

In T2DM patients with NAFLD, the level of serum EDA was significantly increased, and potentially associated with elevated risk of NAFLD, which suggests that serum EDA level may play a role in the development of NAFLD in T2DM. Our study may provide a theoretical basis for early screening or treatment of NAFLD.

肝脏作为全身代谢的关键器官及内分泌器官，可分泌多种蛋白质（肝脏因子），直接影响肝脏葡萄糖及脂代谢，对非酒精性脂肪性肝病（NAFLD）与2型糖尿病（T2DM）的发生及发展具有重要作用。Ectodysplasin A（EDA）是一种新发现的肝脏因子，近年来被认为与糖尿病、肥胖和胰岛素抵抗密切相关。

探讨T2DM患者血清EDA水平与NAFLD发生风险的相关性。

选取2017年11月至2020年11月于江苏大学附属医院内分泌科就诊的T2DM患者130例为研究对象，其中男74例（56.92%）、女56例（43.08%），平均年龄（55.6±12.4）岁。收集患者的基线资料，行糖耐量试验、胰岛素及C肽兴奋试验；采用全身彩色多普勒诊断仪器对所有患者进行腹部超声检查，依据超声结果将患者分为NAFLD组（n=80）和非NAFLD组（n=50），比较两组患者基线资料的差异。采用Pearson相关性分析评估血清EDA与各指标的相关性；采用多元线性回归分析探讨T2DM患者血清EDA水平的影响因素；采用多因素Logistic回归分析探究T2DM患者血清EDA水平对NAFLD发生风险的影响。

NAFLD组患者年龄、T2DM病程低于非NAFLD组，而体质指数（BMI）、空腹胰岛素（FIns）、餐后2 h胰岛素（2 hIns）、空腹C肽（FCP）、餐后2 hC肽（2 hCP）、稳态模型评估胰岛素抵抗指数（HOMA-IR）、三酰甘油（TG）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、血尿酸（SUA）、尿素氮（BUN）、EDA水平高于非NAFLD组（P<0.05）。Pearson相关性分析结果显示，T2DM患者血清EDA水平与年龄、FIns、2 hIns、HOMA-IR、AST呈正相关（r=0.222、0.186、0.233、0.204、0.189，P<0.05）。多元线性回归分析结果显示，年龄〔β=1.957，95%CI（0.412，3.502），P=0.013〕、腰臀比（WHR）〔β=-328.845，95%CI（-638.903，-18.788），P=0.038〕、2 hIns〔β=0.523，95%CI（0.036，1.011），P=0.036〕、AST〔β=2.148，95%CI（0.520，3.776），P=0.010〕是T2DM患者EDA血清水平的影响因素。多因素Logistic回归分析结果显示，在校正多个混杂因素后，血清EDA水平仍是T2DM患者发生NAFLD的影响因素〔OR=1.006，95%CI（1.002，1.010），P=0.007〕。

T2DM合并NAFLD患者血清EDA水平显著增高，且血清EDA水平升高可能是T2DM患者发生NAFLD的危险因素，提示T2DM患者血清EDA水平变化可能在NAFLD的发生和发展中起作用，可为NAFLD的早期筛查或治疗提供理论依据。