ESPE Abstracts

Introduction: Metabolically unhealthy obesity (МUO), characterized by cytokine-induced adipopathy with the development of persistent meta-inflammation, is the main cause of metabolically associated diseases of civilization, which are associated with the formation of a diseasome of insulin-resistant diseases.

Objective: to investigate the contribution of clinical and genetic predictors to the development of MUO in children methods 350 obese children aged 6-18 were examined. The main group (n = 204) consisted of children with MUO. The control group (n = 146) included children with metabolically healthy obesity (MHО). The clinical and genetic examination of obese children conducted by us was characterized by the involvement of full genome sequencing (CeGat, Germany) and subsequent bioinformatics and statistical analysis of 795 prognostic markers. Wald analysis was used with the calculation of the predictive coefficient (PC), a statistical hypothesis testing method in the Python software package version 3.8.10 was used to predict the risk of MUO.

Results: The most informative clinical and genetic indicators for predicting metabolically unhealthy obesity were: a decrease in serum adiponectin ≤7 μg/ml (PC=+10.1); increased IL-6≥4.01 pg/ml (PC=+6.9); steatohepatosis according to fibroelastography more than grade 2 (PC=+5.6); increased AST ≥21.7 UI/L (PC=+5.4); reduction of 25-hydroxycholecalciferol ≤21.9 ng/ml (PC=+4.6); osteopenia according to densitometry (+4.6); increase in DBP≥80 percentiles (PС=+4.5); increased fat mass index (FMI) ≥12.3 kg/m2 (PC=+4.4); hyperleptinemia≥28 ng/ml (PC=+4.2); hepatomegaly according to ultrasound examination (PC=+4); increase in waist circumference (WC)≥99 percentile (PC=+3.9); TT genotype SNV rs1800139 LRP1 (PC=+3.9); TT genotype SNV rs2307111 POC5 (PC=+3.8); basal hyperinsulinemia ≥ 18 μU/ml (PC=+3.7); an increase in insulin-like growth factor type 1≥ 174 ng/ml (PC=+3.3); increased C reactive protein (CRP) ≥ mg/l (PC=+3.3); increase of IL-1β ≥2.7 pg/ml (PC=+3.2); increased SBP ≥ 85 percentiles (+3.2); reduction of HDL cholesterol ≤30 percentiles (PC=+2.7); increase in APRI ratio (ACT/platelets) ≥ 0.08 (PC=+2.4); increase in antimüllerian hormone ≥ 69.8 ng/ml (PC=+2.1); obesity level above the 95th percentile ≥ 119% (PC=+2.1); increase in the WC/HC ratio ≥0.81 (PC=+1.7); increase in the ratio of WC/Height ratio ≥0.53 (PC=+1.2); increased LDL cholesterol ≥84 percentile (PC=+1); increased TG ≥ 87 percentile (PC=+0.7).

Conclusion: Meta-inflammation in metabolically unhealthy obesity has an adiponectin-deficient. Proinflammatory IL-6 is one of the potential mediators linking obesity-induced meta-inflammation to insulin and leptin resistance. Genetic predictors of MUO are TT genotype SNV rs1800139 LRP1 and SNV rs2307111 POC5.

Keywords: diseasome of insulin-resistant diseases, metabolically unhealthy obesity, children, prediction.