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.

Hyperglycemia associated with prediabetes (PD) alters NLRP3 inflammasome activity and related interleukins, yet no study has evaluated the expression of the NLRP3 inflammasome complex and related interleukins in individuals with a PD condition that did or did not develop type 2 diabetes mellitus (T2DM). This study investigated the effect of 6 months of lifestyle modification on the expression of the NLRP3 inflammasome and related interleukins (1α, 1β, 18, 33 and 37) in the sera of individuals with a PD condition that did or did not develop T2DM. This interventional study included 67 Saudi adults (mean age = 41.9 ± 8.0 years, mean BMI = 33.2 ± 5.5 kg/m²). Overnight-fasting serum samples were collected at baseline and at the 6-month follow-up. Serum levels of NLRP3, capsase-1 and related ILs were analyzed at both visits using commercially available immunoassay kits. Results showed that IL-1α increased in the PD group that developed T2DM (p = 0.046), IL-33 decreased in the PD group that reverted to normal (p < 0.001) and NLRP3 decreased in the PD group that remained PD (p = 0.01). Results also showed a positive over-time correlation between NLRP3 and both IL-1α and IL-33 (p < 0.001 and p = 0.028, respectively). In conclusion, glycemic control favorably altered NLRP3 inflammasome complex activity, and lifestyle modification in PD individuals is crucial in reversing harmful metabolic and inflammatory phenotypes.

Interleukin-8 (IL-8) is a critical biomarker associated with inflammation and disability in both adults and newborns. Conventional detection methods are often labor-intensive, time-consuming, and require highly trained personnel. Non-Faradaic impedimetric biosensors offer a label-free, rapid, and direct approach for IL-8 detection. While previous studies have primarily focused on capacitance and phase changes, the potential of other impedimetric parameters remains underexplored. In this study, a gold interdigitated electrode (Au-IDE)-based non-Faradaic biosensor was developed for IL-8 detection, evaluating multiple impedimetric parameters, including capacitance, impedance magnitude (Z_mod), real impedance (Z_real), and imaginary impedance (Z_imag). Among these, Z_imag exhibited the lowest limit of detection (LoD) at 90 pg/mL, followed by Z_mod at 120 pg/mL, and capacitance at 140 pg/mL, all significantly below the clinical threshold of 600 pg/mL. In contrast, Z_real displayed the highest LoD at 1.3 ng/mL. Sensitivity analysis revealed that Z_imag provided the highest sensitivity at 13.1 kΩ/log (ng/mL), making it the most effective parameter for detecting IL-8 at low concentrations. The sensitivity of Z_mod and Z_real was lower, while capacitance sensitivity was measured at 20 nF/log (ng/mL). These findings highlight the importance of investigating alternative impedimetric parameters beyond capacitance to optimize biosensor performance for biomarker detection. This study demonstrates that non-Faradaic biosensors, despite their capacitive-based nature, can achieve enhanced sensitivity and detection limits by leveraging additional impedimetric parameters, offering a promising approach for rapid and effective IL-8 detection.

Vitamin D (VD) deficiency has been associated with inflammation and dysregulation of the immune system. The NLRP3 inflammasome, a critical immune response component, plays a pivotal role in developing inflammatory diseases. VD hinders NLRP3 inflammasome activation and thus exerts anti-inflammatory effects. This study aimed to analyze the effect of VD deficiency on circulating levels of NLRP3 inflammasomes (NLRP3 and caspase–1) and associated interleukins (IL–1α, IL–1β, IL–18, IL–33 and IL–37) in Saudi adults. Methods: A total of 338 Saudi adults (128 males and 210 females) (mean age = 41.2 ± 9.1 years and mean BMI 31.2 ± 6.5 kg/m²) were included. Overnight-fasting serum samples were collected. Participants were stratified according to their VD status. Serum levels of NLRP3 inflammasomes and interleukins of interest were assessed using commercially available immuno-assays. Individuals with VD deficiency had significantly lower mean 25(OH)D levels than those with a normal VD status (29.3 nmol/L vs. 74.2 nmol/L, p < 0.001). The NLRP3 levels were higher in the VD-deficient group than their VD-sufficient counterparts (0.18 vs. 0.16, p = 0.01). Significant inverse associations were observed between NLRP3 levels with age (r = −0.20, p = 0.003) and BMI (r = −0.17, p = 0.01). Stepwise regression analysis identified insulin (β = 0.38, p = 0.005) and NLRP3 (β = −1.33, p = 0.03) as significant predictors of VD status, explaining 18.3% of the variance. The findings suggest that the VD status modestly regulates NLRP3 inflammasome and interleukin activities. This may provide novel insights into the pathogenesis and management of inflammatory disorders.