A Critical Appraisal of the Diagnostic and Prognostic Utility of the Anti-Inflammatory Marker IL-37 in a Clinical Setting: A Case Study of Patients with Diabetes Type 2

Background: The role of the cytokine interleukin-37 (IL-37) has been recognized in reversing inflammation-mediated metabolic costs. The aim was to evaluate the clinical utility of this cytokine as a diagnostic and prognostic marker in patients with type 2 diabetes (T2D). Methods: We included 170 older (median: 66 years) individuals with T2D (females: 95) and classified as primary care attenders to assess the association of factors that describe patients with plasma IL-37 levels (expressed as quartiles) using multinomial regression models. We determined the diagnostic ability of IL-37 cut-offs to identify diabetes-related complications or patient subgroups by using Receiver Operating Characteristic analysis (c-statistics). Results: Frailty status was shown to have a suppressive effect on IL-37 circulating levels and a major modifying effect on associations of metabolic and inflammatory factors with IL-37, including the effects of treatments. Situations in which IL-37 reached a clinically significant discriminating ability included the model of IL-37 and C-Reactive Protein in differentiating among diabetic patients with low–normal/high BMI ((<25/≥25 kg/m(2)), and the model of IL-37 and Thyroid Stimulating Hormone in discriminating between women with/without metabolic syndrome. Conclusions: The study has revealed limitations in using classical approaches in determining the diagnostic and prognostic utility of the cytokine IL-37 in patients with T2D and lain a foundation for new methodology approaches.