Type 2 diabetes mellitus (T2DM) is a multifactorial non-communicable disease that is characterized by insulin resistance and chronic sub-clinical inflammation. Among the emerging inflammatory markers observed to be associated with β-cell damage is interleukin 1β (IL1β), a proinflammatory cytokine that modulates important metabolic processes including insulin secretion and β-cell apoptosis. The present systematic review and meta-analysis gathers available evidence on the emerging role of IL1β in T2DM. PubMed and Embase were searched for human studies that assessed 1L1β in T2DM individuals from 2016-2021. Thirteen studies (N=2680; T2DM=1182, controls=1498) out of 523 were included in the systematic review and only 3 studies in the meta-analysis. Assays were the most commonly used quantification method and lipopolysaccharides as the most common stimulator for IL1β upregulation. Random and fixed effects meta-analysis showed non-significant mean differences of IL1β concentrations between the T2DM and controls. Given the high heterogeneity and small subset of studies included, caution is advised in the interpretation of results. The present systematic review and meta-analysis highlights the limited evidence available that could implicate 1L1β as a potent biomarker for T2DM. Standardization of 1L1β assays with larger sample sizes are encouraged in future observational and prospective studies.

Inflammasome activation of the nucleotide-binding domain, leucine-rich–containing family, and pyrin domain–containing-3 (NLRP3) has been observed to be involved in the pathogenesis of numerous inflammatory diseases, including prediabetes (PD) and type 2 diabetes mellitus (T2DM). Varying levels of glycemia can trigger inflammasome activation; yet, limited studies have reported the associations between NLRP3 levels or other circulating interleukins (ILs) and glycemic status. This study investigated the differences and associations between serum levels of NLRP3 and IL-1α, IL-1β, IL-33 and IL-37 in Arab adults with PD and T2DM. A total of 407 Saudi adults (151 males and 256 females) (mean age = 41.4 ± 9.1 years and mean BMI = 30.7 ± 6.4 kg/m2) were included. Overnight-fasting serum samples were collected. The participants were stratified according to T2DM status. Serum levels of NLRP3 and ILs of interest were assessed using commercially available assays. In all participants, age- and BMI-adjusted circulating levels of IL-37 were significantly higher in the T2DM group (p = 0.02) than in healthy controls (HC) and the PD group. A general linear model analysis revealed that NLRP3 levels were significantly influenced by T2DM status; age; and ILs 18, 1α and 33 (p-values 0.03, 0.04, 0.005, 0.004 and 0.007, respectively). IL-1α and triglycerides significantly predicted NLRP3 levels by as much as 46% of the variance perceived (p < 0.01). In conclusion, T2DM status significantly influenced NLRP3 expression and other IL levels in varying degrees. Whether these altered levels of inflammasome markers can be favorably reversed through lifestyle interventions needs to be investigated prospectively in the same population.

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