The role of the <i>ADRB2</i> gene rs1042714 polymorphism in shaping the metabolic response in patients with early disturbances of carbohydrate metabolism

<jats:p>Background. Individual variability in therapeutic response at the early stages of carbohydrate metabolism disorders is largely determined by genetic factors. One of the key genes involved in the regulation of energy homeostasis is ADRB2, which encodes the β₂-adrenergic receptor. The rs1042714 polymorphism may influence tissue sensitivity to insulin and the effectiveness of therapeutic interventions. However, evidence regarding its role in the dynamics of metabolic parameters in individuals with early disturbances of carbohydrate metabolism remains limited. Aim. To investigate the effect of the ADRB2 rs1042714 polymorphism on carbohydrate metabolism indicators and their changes under different therapeutic strategies in patients with early carbohydrate metabolism disorders. Materials and methods. The study included 104 participants with risk factors for type 2 diabetes mellitus, residing in the Republic of Tatarstan. Inclusion criteria comprised a history of a single episode of elevated fasting plasma glucose and one or more risk factors for type 2 diabetes mellitus. All participants underwent ADRB2 rs1042714 genotyping. Fasting glucose, glycated hemoglobin (HbA1c), insulin, C-peptide, lipid profile, as well as HOMA-IR, HOMA-β, and their modified C-peptide – adjusted versions were assessed. Patients were randomized into two therapeutic groups – diet therapy and diet therapy plus metformin – and followed for three months. Results. Carriers of the CC, CG, and GG genotypes did not differ in age, sex, or baseline metabolic parameters (p0,05). After three months, CC carriers showed a significant decrease in fasting glucose, C-peptide, and HOMA-IR(CP) values, accompanied by an increase in HOMA-β (p0,05), indicating improved insulin sensitivity. In contrast, carriers of the minor G allele demonstrated an opposite trend – higher HOMA-IR and fasting glucose. No significant differences were observed between the diet-only and diet-plus-metformin groups (p0,05). Conclusion. The rs1042714 polymorphism of the ADRB2 gene contributes to the metabolic response characteristics in patients with early carbohydrate metabolism disorders. The CC genotype is linked to a more advantageous metabolic pattern and enhanced insulin sensitivity in peripheral tissues, while the presence of the G allele appears to contribute to the progression of insulin resistance.</jats:p>