Interleukin-39 is a novel cytokine associated with type 2 diabetes mellitus and positively correlated with body mass index.

INTRODUCTION: It is suggested that cytokines play a key role in the pathogenesis of type 2 diabetes mellitus (T2DM). Therefore, this study explored two recently discovered cytokines, interleukin (IL)-37 (anti-inflammatory) and IL-39 (pro-inflammatory), in T2DM due to limited data in this context. METHODS: Serum IL-37 and IL-39 levels were determined in 106 T2DM patients and 109 controls using enzyme-linked immunosorbent assay kits. RESULTS: Serum levels (median and interquartile range) of IL-37 (79 [47-102] vs. 60 [46-89] ng/L; probability [p] = .04) and IL-39 (66 [59-69] vs. 31 [19-42] ng/L; p < .001) were significantly elevated in T2DM patients compared to controls. As indicated by the area under the curve (AUC), IL-39 (AUC = 0.973; p < .001) was more predictable for T2DM than IL-37 (AUC = 0.582; p = .039). Elevated levels of IL-39 were significantly associated with T2DM (odds ratio = 1.30; p < .001), while IL-37 did not show this association. Classification of IL-37 and IL-39 levels by demographic and clinical characteristics of patients revealed some significant differences including gender (IL-39), body mass index (BMI; IL-37 and IL-39) and diabetic neuropathy (IL-39). BMI was positively correlated with IL-39 (correlation coefficient [rs ] = 0.27; p = .005) and glycosylated haemoglobin (rs  = 0.31; p = .001), and negatively correlated with age at onset (rs  = -0.24; p = .015). CONCLUSIONS: IL-37 and IL-39 levels were elevated in the serum of T2DM patients. Besides, IL-39 is proposed to be a novel cytokine associated with T2DM and positively correlated with BMI.

Interleukin-40 is a promising biomarker associated with type 2 diabetes mellitus risk.

Interleukin (IL)-40 is a recently identified cytokine with a proposed role in the pathogenesis of inflammatory diseases. Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by low-grade inflammation. Therefore, it can be suggested that IL-40 may be involved in the pathogenesis of T2DM, but this topic has not been explored. The current study evaluated the potential of IL-40 as a biomarker for T2DM. Serum IL-40 levels were determined in 106 patients with T2DM and 109 healthy controls using an enzyme-linked immunosorbent assay kit. Median (interquartile range) IL-40 levels were significantly higher in patients than in controls (2.82 [2.58-3.25] vs. 1.22 [0.93-1.42] ng/L; probability [p] < 0.001). When IL-40 levels were stratified according to age, gender, disease duration, body mass index, diabetic neuropathy, fasting plasma glucose or glycated hemoglobin, no significant differences were found in each stratum. Receiver operating characteristic curve analysis showed that IL-40 was an excellent predictor in discriminating between T2DM patients and controls (area under the curve = 0.989; 95% confidence interval = 0.973-1.00; p < 0.001). Age- and gender-adjusted multinomial logistic regression analysis estimated an odds ratio of 53.36 (95% confidence interval = 12.52-227.45; p < 0.001) for IL-40 in T2DM. IL-40 level was negatively correlated with age (correlation coefficient = -0.274; p = 0.005) and onset age (correlation coefficient = -0.203; p = 0.037). In conclusion, IL-40 was up-regulated in the serum of T2DM patients, and can be considered as a reliable biomarker in distinguishing patients with T2DM from healthy controls.