Pre-diabetes and diabetic neuropathy are associated with low serum levels of interleukin-9

Abstract

Abstract Background Interleukin-9 (IL-9) is a cytokine that has recently been proposed to be associated with type 2 diabetes mellitus (T2DM) risk, but the role it plays in the development of pre-diabetes (PD) and diabetic neuropathy (DN) is unknown. Therefore, this study analyzed serum IL-9 levels in individuals with PD (n = 89), T2DM patients without DN (n = 66), T2DM patients with DN (n = 21), and non-diabetic controls (n = 84) using an ELISA kit. Results Serum IL-9 levels (median and interquartile range) were significantly lower in the PD (18.9 [12.6–22.1] pg/mL; probability [p] < 0.001) and T2DM (19.4 [16.3–28.0] pg/mL; p = 0.04) groups than in the control group (20.8 [19.4–25.8] pg/mL). Patients with DN also showed lower levels of IL-9 than patients without DN, but the p value was not significant (19.4 [12.5–22.7] vs. 20.6 [17.1–28.1] pg/mL; p = 0.13). IL-9 showed better diagnostic performance in PD and T2DM with DN than in T2DM without DN (area under the curve: 0.699 and 0.702 vs. 0.567, respectively). Moreover, lower levels of IL-9 were significantly associated with PD and DN risks (odds ratio = 0.86 and 0.85, respectively). Conclusions Serum IL-9 levels were significantly decreased in individuals with PD and patients with T2DM compared with HC. The decrease in IL-9 levels in T2DM patients was more pronounced in patients with DN than in patients without DN. Therefore, low levels of IL-9 can be considered as a potential biomarker associated with an increased risk of PD and DN.