Differences and Associations of NLRP3 Inflammasome Levels with Interleukins 1α, 1β, 33 and 37 in Adults with Prediabetes and Type 2 Diabetes Mellitus

Abstract

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.

Acute Glycemic Control in Prediabetes Individuals Favorably Alters Serum NLRP3 Inflammasome and Related Interleukins

“…However, the IL-1α levels significantly increased in participants who developed T2DM. This is consistent with our recent cross-sectional study, in which we found that the circulatory IL-1α levels were drastically influenced by T2DM [ 31 ]. Legiawati et al found that the IL-1α levels were higher in T2DM patients with HbA1c levels above 7% [ 32 ], while Khalil et al recorded higher serum IL-1α levels in T2DM patients infected with the hepatitis C virus [ 33 ].…”

“…These results are of great significance, as obesity is an important contributing factor in diabetes and this could be seen in this study, in which the weight of the PD group that developed T2DM was already higher than those of the PD group that reverted to normal and the group that remained PD. Circulatory NLRP3 is a potential inflammatory biomarker in various inflammatory diseases [ 31 , 43 ]. These results support our recent cross-sectional study [ 31 ], in which we aimed to evaluate the differences in NLRP3 inflammasomes and related ILs in a cohort of PD and T2DM participants.…”

“…Circulatory NLRP3 is a potential inflammatory biomarker in various inflammatory diseases [ 31 , 43 ]. These results support our recent cross-sectional study [ 31 ], in which we aimed to evaluate the differences in NLRP3 inflammasomes and related ILs in a cohort of PD and T2DM participants. We found higher NLRP3 levels only in the female PD group.…”

“…We found higher NLRP3 levels only in the female PD group. That being said, the results still need to be taken cautiously, as the general linear model results indicated that the gender factor was not significant in predicating NLRP3 levels; however, T2DM status, age, IL-18, IL-1α and 33 did [ 31 ]. To date, no studies have investigated the effect of lifestyle modification and glycemic control on serum NLRP3 levels.…”

Predicting the risk of subclinical atherosclerosis based on interpretable machine models in a Chinese T2DM population

“…Long-term studies have shown that AS has a complex pathogenesis, primarily attributed to lipoprotein retention in the arterial wall and chronic inflammation ( 34 , 35 ). Hyperglycemia leads to increased inflammasome activity, upregulated nucleotide-binding oligomerization domain-like receptor 3, and ultimately elevated pro-inflammatory interleukin1β and interleukin 18 levels ( 36 ). Our study further confirms that SCAS in T2DM is a chronic inflammatory condition.…”