RT journal article T1 Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity A1 González Domínguez, Alvaro A1 Millán-Martínez, María A1 Domínguez-Riscart, Jesús A1 Lechuga Sancho, Alfonso María A1 González-Domínguez, Raúl A2 Materno-Infantil y Radiología K1 childhood obesity K1 insulin resistance K1 trace elements K1 insulin secretion profile K1 delayed hyperinsulinemia K1 oral glucose tolerance test AB Background: Trace elements and heavy metals have proven pivotal roles in childhoodobesity and insulin resistance. However, growing evidence suggests that insulin resistance couldencompass distinct phenotypic subtypes. Methods: Herein, we performed a comprehensive metallomicscharacterization of plasma samples from children and adolescents with obesity and concomitantinsulin resistance, who were stratified as early (N = 17, 11.4 2.4 years), middle (N = 16,11.8 1.9 years), and late (N = 33, 11.7 2.0 years) responders according to the insulin secretionprofile in response to an oral glucose tolerance test. To this end, we employed a high-throughputmethod aimed at determining the biodistribution of various essential and toxic elements by analyzingtotal metal contents, metal-containing proteins, and labile metal species. Results: Compared with theearly responders, participants with delayed glucose-induced hyperinsulinemia showed a worsenedinsulin resistance (HOMA-IR, 4.5 vs. 3.8) and lipid profile (total cholesterol, 160 vs. 144 mg/dL;LDL-cholesterol, 99 vs. 82 mg/dL), which in turn was accompanied by sharpened disturbances inthe levels of plasmatic proteins containing chromium (4.8 vs. 5.1 g/L), cobalt (0.79 vs. 1.2 g/L),lead (0.021 vs. 0.025 g/L), and arsenic (0.077 vs. 0.17 g/L). A correlation analysis demonstrated aclose inter-relationship among these multielemental perturbations and the characteristic metaboliccomplications occurring in childhood obesity, namely impaired insulin-mediated metabolism ofcarbohydrates and lipids. Conclusions: These findings highlight the crucial involvement that alteredmetal homeostasis and exposure may have in regulating insulin signaling, glucose metabolism, anddyslipidemia in childhood obesity. PB MDPI SN 2072-6643 YR 2023 FD 2023 LK http://hdl.handle.net/10498/32441 UL http://hdl.handle.net/10498/32441 LA eng DS Repositorio Institucional de la Universidad de Cádiz RD 10-nov-2026