Dataset Information

Altered insulin secretion dynamics relate 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 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.

SUBMITTER: Gonzalez-Dominguez A

PROVIDER: S-EPMC10440893 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

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

González-Domínguez Álvaro Á Belmonte Thalía T Domínguez-Riscart Jesús J Ruiz-Ocaña Pablo P Muela-Zarzuela Inés I Saez-Benito Ana A Montañez-Martínez Raúl R Mateos Rosa M RM Lechuga-Sancho Alfonso M AM

Journal of translational medicine 20230820 1

<h4>Background</h4>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 in ...[more]

PMID: 37599368

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Project description:IntroductionChildhood obesity is increasing worldwide and presents as a global health issue due to multiple metabolic comorbidities. About 1% of adolescents with obesity develop type 2 diabetes (T2D); however, little is known about the genetic and pathophysiological background at young age. The objective of this study was to assess the prevalence of impaired glucose regulation (IGR) in a large cohort of children and adolescents with obesity and to characterize insulin sensitivity and insulin secretion. We also wanted to investigate adolescents with insulin secretion disorder more closely and analyze possible candidate genes of diabetes in a subcohort.MethodsWe included children and adolescents with obesity who completed an oral glucose tolerance test (OGTT, glucose + insulin) in the outpatient clinic. We calculated Matsuda index, the area under the curve (AUC (Ins/Glu)), and an oral disposition index (ISSI-2) to estimate insulin resistance and beta-cell function. We identified patients with IGR and low insulin secretion (maximum insulin during OGTT < 200 mU/l) and tested a subgroup using next generation sequencing to identify possible mutations in 103 candidate genes.ResultsThe total group consisted of 903 children and adolescents with obesity. 4.5% showed impaired fasting glucose, 9.4% impaired glucose tolerance, and 1.2% T2D. Matsuda index and Total AUC (Ins/Glu) showed a hyperbolic relationship. Out of 39 patients with low insulin secretion, we performed genetic testing on 12 patients. We found five monogenetic defects (ABCC8 (n = 3), GCK (n = 1), and GLI2/PTF1A (n = 1)).ConclusionUsing surrogate parameters of beta-cell function and insulin resistance can help identify patients with insulin secretion disorder. A prevalence of 40% mutations of known diabetes genes in the subgroup with low insulin secretion suggests that at least 1.7% of patients with adolescent obesity have monogenic diabetes. A successful molecular genetic diagnosis can help to improve individual therapy.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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