INFLUÊNCIA DO POLIMORFISMO DO GENE FTO E DO HISTÓRICO FAMILIAR DE DIABETES SOBRE O SISTEMA NERVOSO AUTÔNOMO DE ADOLESCENTES

Abstract

Metabolic diseases, such as diabetes mellitus (DM) and obesity, are associated with changes that can damage various organ systems, including the autonomic nervous system (ANS) and cardiovascular system. The literature links the development of metabolic diseases to genetic factors, with different genes identified as involvement, including the FTO gene, which has polymorphisms associated with these pathologies and their complications. Most complications are diagnosed late, once the damage has already occurred. It is believed that changes in several physiological parameters can be detected early in patients with FTO gene polymorphism, even in the absence of detectable laboratory changes. Thus, this study aimed to evaluate the presence of the mutant FTO gene and early changes in adolescents with a family history of DM, as well as to assess the gene's influence on autonomic disorders and cardiovascular functions. For this purpose, 115 non-diabetic adolescents with a family history of DM were included and divided into three groups based on genotypes related to the FTO gene. These individuals underwent genetic testing for genotypic determination, followed by a comparison of results between the AA, AT, and TT groups, alongside assessments of blood glucose levels, anthropometric measurements, and Heart Rate Variability analysis obtained through electrocardiograms. The results showed no anthropometric or laboratory changes between the groups, nor significant differences between males and females. However, electrocardiographic evaluations revealed autonomic dysfunction in groups carrying the mutant gene A, particularly in indices related to heart rate variability (HRV), which is an important organic adaptive mechanism. Evaluating the mean RR and SDNN parameters indicated that carriers of the mutant allele, especially in homozygosity, exhibited reduced HRV indices compared to the other genotypes. Furthermore, carriers of the FTO gene polymorphism demonstrated increased sympathetic activation and decreased parasympathetic activity in cardiac modulation. This conclusion was based on sleep quality index evaluations, which were significantly worse in individuals with the mutant gene; the cardiac stress index, which was higher in those with the mutation; and assessments of cardiac parameters SD1, SD2, RMSSD, LF, and HF, all indicating greater sympathetic activity and lower parasympathetic activity. These results suggest that this polymorphism is linked to direct changes in the ANS functioning, which in turn leads to cardiovascular autonomic changes. Collectively, these findings support the identification of the FTO gene as a relevant biomarker for the early detection of potential complications stemming from chronic diseases in individuals with a family history of diabetes, serving as a valuable tool for predicting cardiovascular and metabolic health.