Circulating interleukin-33 levels in obesity and type 2 diabetes: a systematic review and meta-analysis

Obesity and type 2 diabetes (T2D) are increasingly prevalent worldwide, and there is a critical need for novel interventions. Interleukin-33 (IL-33), an anti-inflammatory cytokine that regulates metabolism, is a promising biomarker for these conditions. The goal of this systematic review and meta-analysis is to examine the role of IL-33 in obesity and T2D, assessing its potential in predicting disease progression. A systematic search was performed on Scopus, Web of Science, and PubMed up until May 30, 2023. Each study was assessed for quality and sources of bias using the relevant critical appraisal checklists. Meta-analyses were conducted to compare IL-33 levels in individuals with obesity and T2D versus healthy controls (HC), and in obesity alone versus HC. Eighteen studies were included in the systematic review, and nine qualified for meta-analyses. The analyses showed insufficient evidence to suggest a significant difference in IL-33 levels between individuals with T2D and HC (mean difference, MD = -79.95, 95% CI [-241.38; 81.48]), with substantial heterogeneity across the studies observed (I² = 97.1%, τ² = 33,549.15). Similarly, there was insufficient evidence to suggest a significant difference between nondiabetic individuals with obesity and HC (MD = -7.31, 95% CI [-25.74; 11.13]), and heterogeneity was noted (I² = 86.2%, τ² = 342.45). There is insufficient evidence to indicate significant differences in IL-33 levels in individuals with T2D or obesity compared with HC. The results suggest a need for improved IL-33 measurement methods to reduce heterogeneity, enhancing understanding of the role of IL-33 in obesity and T2D, and informing future research and therapeutic strategies.NEW & NOTEWORTHY Our research finds an inconclusive relationship between IL-33 serum levels in individuals with type 2 diabetes (T2D) and nondiabetic individuals with obesity. In addition, we note a potential gender association with IL-33 serum levels. Further studies with larger cohorts are required to assess the significance of serum IL-33 in T2D and obesity. Urgent standardization is needed in IL-33 quantification and reporting methods for reliable comparisons.