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case-control·pediatrics, endocrinology, immunology, clinical nutrition, preclinical research·PMC10440893

Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance

Journal of Translational Medicine · 9 authors, 11 centres

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AGENT 01 · STRUCTURED SUMMARY

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TL;DR

The groups were: non-IR (OBIR-), IR with an early insulin peak (EP-OBIR+), and IR with a late peak (LP-OBIR+).

Full summary

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THE GROUPS WERE

non-IR (OBIR-), IR with an early insulin peak (EP-OBIR+), and IR with a late peak (LP-OBIR+). They also had a more atherogenic lipid profile. The study is limited by its cross-sectional design, single-center recruitment, and the use of adult IR criteria. The findings suggest that the timing of insulin secretion during an OGTT is a more specific identifier of children with obesity who have underlying oxidative stress and pathological inflammation.

STUDY TYPE

case-control

SPECIALTY

pediatrics

SUMMARISED BY

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100% · A

ORIGINAL PAPER

PMC10440893

Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance

Journal of Translational Medicine

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ABSTRACT

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. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12967-023-04337-7.

CITATION EXPORT

Álvaro González-Domínguez, Thalía Belmonte, Jesús Domínguez-Riscart et al.. Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance. Journal of Translational Medicine. (2023). https://doi.org/10.1186/s12967-023-04337-7

AUTHORS

9 · 11 CENTRES

Álvaro González-Domínguez, Thalía Belmonte, Jesús Domínguez-Riscart, Pablo Ruiz-Ocaña, Inés Muela-Zarzuela, Ana Saez-Benito, Raúl Montañez-Martínez, Rosa M. Mateos, Alfonso M. Lechuga-Sancho

1https://ror.org/02s5m5d51grid.512013.4Grupo de Inflamación, Nutrición, Metabolismo y estrés Oxidativo, Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), c/Doctor Marañón, 3 - Edificio Andrés Segovia, 11002 Cádiz, Spain
2grid.420395.90000 0004 0425 020XTranslational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain
3https://ror.org/00ca2c886grid.413448.e0000 0000 9314 1427CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain
4https://ror.org/040xzg562grid.411342.10000 0004 1771 1175Unidad de Endocrinología Pediátrica y Diabetes, Servicio de Pediatría, Hospital Universitario Puerta del Mar, Cádiz, Spain
5Unidad de Endocrinología Pediátrica y Diabetes, Servicio de Pediatría, Hospital Universitario de Jerez, Jerez de la Frontera, Spain
6https://ror.org/02s5m5d51grid.512013.4Grupo de Inflamación y Metabolismo Durante el Envejecimiento, Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain
7https://ror.org/040xzg562grid.411342.10000 0004 1771 1175Servicio de Análisis Clínicos, Hospital Universitario Puerta del Mar, Cádiz, Spain
8https://ror.org/02s5m5d51grid.512013.4Grupo de Diabetes Mellitus - Autoinmunidad y complicaciones crónicas, Implicaciones Patológicas, clínicas y terapéuticas, Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain
9https://ror.org/02s5m5d51grid.512013.4Grupo de Daño cerebral Perinatal, Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain
10https://ror.org/04mxxkb11grid.7759.c0000 0001 0358 0096Departamento de Biomedicina, Facultad de Ciencias, Biotecnología y Salud Pública y Salud Pública, Universidad de Cádiz, Puerto Real, Spain
11https://ror.org/04mxxkb11grid.7759.c0000 0001 0358 0096Departamento Materno Infantil y Radiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain