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.