Increased Circulating Levels of Ectodysplasin A in Newly Diagnosed Type 2 Diabetic Patients.

Xia Deng,Zhensheng Cai,Yanyan Li,Ke Chen,Li Zhao,Panpan Zhang,Haoxiang Li,Chenxi Wang,Xunan Wu,Ling Yang,Zhicong Zhao,Guoyue Yuan

doi:10.3389/fendo.2021.737624

Abstract

ObjectiveEctodysplasin A (EDA), a newly discovered hepatokine, has recently been considered to be closely related to glycolipid metabolism disorders, but the pathophysiological effects of EDA are still poorly understood. This study was the first time to determine the level of serum EDA in newly diagnosed type 2 diabetes mellitus (T2DM) patients, and to explore the relationships between serum EDA levels and various metabolic indexes.MethodsA total of 184 subjects were enrolled in the study, including 92 subjects with newly diagnosed T2DM and 92 subjects with age- and sex-matched normal glucose tolerance (NGT). Serum EDA levels were determined using enzyme-linked immunosorbent assay (ELISA). Oral glucose tolerance test, glycosylated hemoglobin c (HbA1c), and insulin were also measured.ResultsSerum EDA levels were significantly increased in the T2DM group than in the NGT group (359.91 ± 117.99 vs. 265.82 ± 86.51 pg/ml, p < 0.001). Serum EDA levels were positively correlated with body mass index (BMI), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), HbA1c, 2-hour postprandial plasma glucose (2hPG), fasting plasma insulin (FIns), fasting C peptide (FCP), triglyceride (TG), HOMA-IR, and negatively correlated with high-density lipoprotein cholesterol (HDL-c) and HOMA-β (p < 0.05). Multiple stepwise regression analysis demonstrated that 2hPG and FIns were independent influencing factors of serum EDA level (p < 0.05). Logistic regression analysis showed that serum EDA level was significantly independently correlated with T2DM (p < 0.05).ConclusionsSerum EDA levels are significantly higher in T2DM patients, suggesting that EDA may play a role in the occurrence and development of T2DM.

Highlights

Diabetes is a group of metabolic diseases characterized by chronic hyperglycemia caused by a variety of reasons, of which 90% are type 2 diabetes mellitus (T2DM), and the main pathophysiological mechanisms are insulin resistance and relatively insufficient insulin secretion [1, 2]
Serum Ectodysplasin A (EDA) levels were positively correlated with body mass index (BMI), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), HbA1c, 2-hour postprandial plasma glucose (2hPG), fasting plasma insulin (FIns), fasting C peptide (FCP), triglyceride (TG), homeostasis model assessment (HOMA)-IR, and negatively correlated with high-density lipoprotein cholesterol (HDL-c) and HOMA-b (p < 0.05)
Serum EDA levels are significantly higher in T2DM patients, suggesting that EDA may play a role in the occurrence and development of T2DM

Summary

Introduction

Diabetes is a group of metabolic diseases characterized by chronic hyperglycemia caused by a variety of reasons, of which 90% are type 2 diabetes mellitus (T2DM), and the main pathophysiological mechanisms are insulin resistance and relatively insufficient insulin secretion [1, 2]. Liver is the central organ of glucose and lipid metabolism, which plays an important role in the development of T2DM [3]. In addition to the role of glucose and lipid metabolism, the latest research showed that the liver is an important endocrine organ, which can secrete thousands of proteins, of which about 25% can be released into the blood circulation [6]. Further studies have found that a variety of protein factors secreted by the liver form a regulatory network and affect the energy metabolism of the liver and other organs through inter tissue communication [7], affecting the occurrence and development of metabolic-related diseases, such as obesity, insulin resistance, diabetes, and fatty liver [8,9,10,11]. A quantitative protein expression profile based on isobaric tagging for relative and absolute quantification (iTRAQ) showed that there were 69 differentially expressed proteins in the plasma of T2DM patients compared with nondiabetic individuals, including a variety of proteins secreted by the liver and related to insulin resistance in diabetic patients, including a 2-macroglobulin, selenoprotein P, retinol binding protein 4 (RBP4) [12]

Results

Discussion

Conclusion