ESPE2023 Free Communications Fat, metabolism and obesity 2 (6 abstracts)
Irs1 expression in peripheral blood associates with obesity and cardiovascular risk parameters in school-age girls
Ariadna Gómez-Vilarrubla 1 , Maria Niubó-Pallàs 1 , Berta Mas-Parés 2 , Gemma Carreras-Badosa 2 , Alexandra Bonmatí 3 , Enrique Estevez-Reinares 4 , Jose-María Martinez-Calcerrada 5 , Francis de Zegher 6 , Lourdes Ibañez 7 , Abel López-Bermejo 2 & Judit Bassols 1
1Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), Girona, Spain. 2Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), Girona, Spain. 3Gynecology, Dr. JosepTrueta Hospital, Girona, Spain. 4Pediatrics, Dr. JosepTrueta Hospital, Girona, Spain. 5Institute of Legal Medicine of Catalonia, Girona, Spain. 6Department of Development & Regeneration, University of Leuven, Leuven, Belgium. 7Sant Joan de Déu Children’s Hospital Pediatric Institute, University of Barcelona, Barcelona, Spain
Background and Aim: IRS1 (Insulin Receptor Substrate 1) is involved in the insulin signalling pathway and abnormalities thereof have been related to metabolic disorders and obesity. In obese subjects, insulin resistance has been associated with changes in IRS1 expression in peripheral in blood. Sex-based differences in cardiovascular disease are well established. Previous results from our group disclosed the association between IRS1 placental methylation with obesity parameters in school-age children. Here, we aimed to analyse IRS1 expression in peripheral blood from the same children and to study its association with obesity and cardiovascular risk parameters in boys and girls.
Methodology: The study population consisted of 94 subjects (46 girls and 48 boys; age 6.1 ± 0.9) from a prenatal cohort of healthy children who were followed up from birth to school age. Clinical data were obtained from all subjects at 1, 3, 6, and 12 months [weight, height, ponderal index (PI)] and at 6 years of age [weight, height, body mass index (BMI), waist circumference, hip circumference]. Biochemical data (insulin, HOMA-IR) and body composition (fat mass, visceral fat) were also assessed at 6 years of age. IRS1 expression was analysed in total peripheral blood samples by RT-qPCR. Associations between IRS1 blood expression and the studied parameters were analysed in all subjects and in subgroups thereof according to sex.
Results: Early postnatal growth (weight and PI at 1, 3, 6, and 12 months) was positively associated with IRS1 expression in peripheral blood (r from 0.216 to 0.316; all p <0.05) in all subjects, but the associations were stronger in girls (r from 0.309 to 0.469; all p <0.05). In addition, in girls, positive associations were observed at 6 years of age between IRS1 blood expression and obesity and cardiovascular risk parameters (weight, BMI, waist circumference, waist/hip ratio, waist/height ratio, fat mass, visceral fat, insulin and HOMA-IR index; r from 0.332 to 0.470; all p <0.01) that were not observed in boys. All the observed associations were independent for potential confounding variables in multivariate analyses.
Conclusions: Higher postnatal weight gain early in life is associated to higher IRS1 blood expression in school-age children. In school-age girls, higher IRS1 blood expression is further related to several obesity and cardiovascular risk parameters. Our results suggest that IRS1 could be a potential blood biomarker of cardiovascular risk in healthy school-age girls.
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