Introduction
Type 2 diabetes mellitus (T2DM) belongs to the group of chronic metabolic and chronic inflammatory diseases. Interleukin 38 (IL-38) is a novel member of the interleukin 1 (IL-1) cytokine family, and it has anti-inflammatory activity. Recently, we found that IL-38 can alleviate inflammation and liver inflammatory damage caused by obesity [1]. However, the role of IL-38 in T2DM has not yet been determined. In order to explore the clinical significance of IL-38 in T2DM, we measured the serum IL-38 concentration of normal subjects and T2DM patients, and analysed its relationship with insulin resistance (IR), anthropometric measurements, and metabolic parameters.
Material and methods
Forty patients with T2DM and 40 healthy controls in The Affiliated Hospital of Ningbo University School of Medicine were chosen for this study. The weight, height, and body mass index (BMI) of all subjects were recorded using standard anthropometric methods. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by a designated nurse using a mercury sphygmomanometer. The levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), and fasting blood glucose (FBG) in T2DM and healthy controls were determined using an automatic biochemical analyser. High-performance liquid chromatography was used to determine the level of glycated haemoglobin A1c (HbA1c). The concentration of fasting insulin (FINS) was determined by electrochemiluminescence immunoassay. IR was estimated using homeostasis model assessment of insulin resistance (HOMA-IR): HOMA-IR = FINS (μU/mL) × FBG (mmol/L)/22.5. Enzyme-linked immunosorbent assays (ELISA) were used to determine the serum levels of IL-38 and interleukin 17 (IL-17) of the subjects. All statistical analyses were performed using GraphPad Prism 9.0 software. Data were presented as mean ± SD. The unpaired t test was used for comparative analysis of the 2 groups. Correlations between IL-38 and variables were assessed by Pearson correlation analysis. p < 0.05 was considered statistically significant.
Results
As shown in Supplementary File — Table S1, there were no statistically differences in gender distribution, age, height, and DBP between the T2DM patients and the healthy control subjects (p > 0.05). The BMI, SBP, and body weight of the T2DM patients were higher than those of the control subjects, with a statistically significant difference (p < 0.05). The levels of TC, TG, HbA1c, LDL, FBG, FINS, HOMA-IR, and CRP of the T2DM patients were significantly higher than those of the control subjects (p < 0.05). The HDL was not statistically different between the 2 groups (p > 0.05) (Supplementary File—Tab. S2).
As shown in Figure 1, we detected serum IL-38 and IL-17 levels by ELISA. The serum IL-38 levels in T2DM patients were significantly lower than those in the control group (p < 0.001, Fig. 1A). Conversely, serum IL-17 levels in T2DM patients were significantly higher than those in healthy people (p < 0.0001, Fig. 1B). Pearson correlation analysis showed that serum IL-38 levels in T2DM patients were negatively correlated with SBP (r = −0.3144, p < 0.05, Fig. 1C) and IL-17 (r = –0.5496, p < 0.001, Fig. 1D).
Discussion
IL-38 is a newly discovered anti-inflammatory cytokine, being the 10th new member of the IL-1 family. Yu et al. [2] found that the expression of IL-38 was increased in the umbilical cord and placenta of patients with gestational diabetes mellitus. In this study, we found that the serum IL-38 levels in T2DM patients were reduced and the serum IL-17 levels were increased. Correlation analysis showed that IL-38 levels in T2DM patients were negatively correlated with SBP and IL-17.
Conclusions
Our study suggests that the serum IL-38 level is helpful in the diagnosis of T2DM. Further studies are needed to expand the current findings, especially to explore the exact mechanism of IL-38 in the pathogenesis of T2DM.
Funding
This study was supported by the National Natural Science Foundation of China (81970735), the Clinical Research and Application Project of Zhejiang Health Science and Technology Program (2022KY1148), and the Natural Science Foundation of Ningbo (2021J246, 202003N4115, 202003N4118).
