Altered Insulin Secretion Dynamics Relates to Oxidative Stress and Inflammasome Activation in Children with Obesity and Insulin Resistance

Abstract

Background Insulin resistance (IR) is considered the main driver of obesity related metabolic complications, and is related with oxidative stress and inflammation which in turn promote each other. However, there is still no specific definition of IR in children. Altered insulin secretion dynamics are also related with worse metabolic profiles and type 2 diabetes mellitus development, thus we aimed to test whether if insulin response relates with oxidative stress and inflammation.Methods We conducted a case-control study, including 132 children (33 controls; 42 with obesity but no IR; 25 with obesity and IR and an early insulin response to OGTT; 32 with obesity, IR, and a late insulin peak), and studied variables related with lipid and carbohydrate metabolism, oxidative stress, inflammation and inflammasome activationResults Children with obesity and IR with an early insulin response, behaved much like those without IR an almost every parameter. It was late responders who presented an impaired antioxidant system and elevated oxidative damage in erythrocytes and plasma, and inflammasome activation at their white blood cells, despite lower classical inflammation markers. Increased uric acid levels seems to be one of the underlying mechanisms for inflammasome activation.Conclusions It is insulin response to an OGTT what better identifies children with obesity suffering oxidative stress and inflammasome activation. Uric acid could be mediating this pathological inflammatory response by activating NLRP3 in peripheral blood mononuclear cells.