Endocrine Abstracts

Background: Prediabetes (PD) is a significant risk factor diabetes mellitus (DM) and as such, behavioral interventions are the primary management for PD. High blood glucose levels alter circulating NLRP3 inflammasome complex activity and correlated interleukins (ILs). There is limited data available on the activity of NLRP3 inflammasome and ILs in sera of patients with PD that may or may have not developed DM. This interventional study assessed the effects of NLRP3 inflammasome activation on DM development in PD individuals who followed a six-month behavioral intervention program.

Methods: This interventional study included 67 Saudi adults, 20 males and 47 females, (mean age = 41.9±8.0 years, mean BMI = 33.15±5.5 kg/m²). Overnight-fasting serum samples were collected at baseline and at 6-month follow-up. Serum levels of NLRP3, capsase-1 and correlated ILs (IL-1α, IL-1β, IL-18, IL-33 and IL-37) were assessed using commercially available immunoassay kits at both visits.

Results: IL-1α levels significantly increased in the PD group that developed T2DM after 6 months of intervention (baseline: 0.6 (0.5–0.8), follow-up: 1.0 (0.9–1.4); P= 0.046), IL-33 levels significantly decreased in the PD group that reverted to normal after 6 months of intervention (baseline: 3.2 (0.7–4.0), follow-up: 0.8 (0.6–2.1); P<0.001), IL-37 levels significantly decreased in the PD group that remained PD after 6 months of intervention (baseline: 4.2 (2.1–10.7), follow-up: 2.9 (2.1–2.9); P<0.001) and NLRP3 levels significantly decreased in the PD group that remained PD after 6 months of intervention (baseline: 0.13 (0.1–0.22), follow-up: 0.11 (0.07–0.18); P= 0.01). In all participants with PD, after 6 months of intervention IL-33 levels significantly decreased (baseline: 3.2 (2.9–3.9), follow-up: 0.9 (0.6–3.0); P= 0.001), IL-37 levels significantly decreased (baseline: 3.0 (2.1–8.5), follow-up: 2.9 (2.1–3.0); P= 0.008) and NLRP3 levels significantly decreased (baseline: 0.1 (0.1–0.2), follow-up: 0.1 (0.1–0.2); P= 0.05). Results also showed a positive overtime correlation between NLRP3 and both IL-1α (r= 0.3, P= 0.001) and IL-33 (r= 0.03, P= 0.028).

Conclusion: Glycemic control positively changed NLRP3 inflammasome complex activation post-behavioral intervention program in PD individuals and this maybe pivotal in reversing the detrimental metabolic and pro-inflammatory states.

Keywords: prediabetes, type 2 diabetes mellitus, lifestyle interventions, NLRP3, inflammasome, interleukins, inflammatory disease, chronic inflammation