RT journal article
T1 Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance
A1 González-Domínguez, Álvaro
A1 Belmonte, Thalía
A1 Domínguez Riscart, Jesús
A1 Ruiz-Ocaña, Pablo
A1 Muela-Zarzuela, Inés
A1 Sáez-Benito Godino, Ana
A1 Montañez-Martínez, Raúl
A1 Mateos Bernal, Rosa María
A1 Lechuga Sancho, Alfonso María
A2 Materno-Infantil y Radiología
K1 Childhood obesity
K1 Inflammasome activation
K1 Insulin resistance
K1 Oral glucose tolerance test
K1 Oxidative stress
AB Background Insulin resistance (IR) is considered the main driver of obesity related metabolic complications, and is related to oxidative stress and inflammation, which in turn promote each other. There is currently no specific definition of IR in children, rather, that for adult population is used by pediatric endocrinologists instead. Altered insulin secretion dynamics are associated with worse metabolic profiles and type 2 diabetes mellitus development, thus we aimed to test whether insulin response relates to oxidative stress and inflammation in children.Methods We conducted a case–control study, including 132 children classified as follows: 33 children without obesity (Lean); 42 with obesity but no IR according to the American Diabetes Association criteria for adults (OBIR-); 25 with obesity and IR and an early insulin response to an oral glucose tolerance test (OGTT) (EP-OBIR +); 32 with obesity, IR, and a late insulin peak (LP-OBIR +); and studied variables associated with lipid and carbohydrate metabolism, oxidative stress, inflammation and inflammasome activation.Results The measured parameters of children with obesity, IR, and an early insulin response were similar to those of children with obesity but without IR. 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 that identifies children with obesity suffering oxidative stress and inflammasome activation more specifically. Uric acid could be mediating this pathological inflammatory response by activating NLRP3 in peripheral blood mononuclear cells.
YR 2023
FD 2023-08
LK http://hdl.handle.net/10498/29283
UL http://hdl.handle.net/10498/29283
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-nov-2026