Differential Impact Of Weight Loss And Glycemic Control On Inflammasome Signaling

Objective Interleukin (IL)-1 beta is involved in obesity-associated inflammation and in the pathogenesis of type 2 diabetes (T2D) mellitus. Our aim was to correlate serum IL-1 beta and caspase-1 levels with weight loss, glucose metabolism, and insulin resistance (IR) after bariatric surgery.Methods A total of 32 patients with morbid obesity and T2D (Ob-T2D) and 29 patients with morbid obesity and normal glucose tolerance (Ob-NGT), treated by Roux-en-Y gastric bypass, were studied before and 1 year after surgery. Sixteen healthy individuals served as a control (HC) group. IR was assessed by the oral glucose insulin sensitivity method. Plasma IL-1 beta levels and caspase-1 were measured.Results Presurgery BMI was similar in Ob-NGT and Ob-T2D. IR was progressively impaired in Ob-NGT and Ob-T2D (P < 0.0001). Fasting plasma IL-1 beta and caspase-1 levels were lower in HCs than in patients with Ob-NGT or Ob-T2D (P < 0.02; P = 0.05), and both were inversely correlated with IR (P = 0.01; P = 0.02). After surgery, BMI decreased and IR improved to a similar extent in Ob-NGT and Ob-T2D (P < 0.0001). Plasma caspase-1 concentrations normalized in both groups (P < 0.0001), whereas plasma IL-1 beta levels normalized only in Ob-NGT.Conclusions Plasma IL-1 beta and caspase-1 levels were inversely correlated with IR. Caspase-1 levels normalized after weight loss, whereas IL-1 beta normalized only in people without T2D, suggesting the persistence of a systemic inflammatory condition in people with T2D.