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.

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