Risks of cardiovascular fatal outcomes in clinical phenotypes in patients with type 2 diabetes mellitus in the Novosibirsk region

Objective. To study the risks of cardiovascular fatal outcomes in clinical phenotypes in patients with type 2 diabetes mellitus (T2DM) in the Novosibirsk region. Materials and methods. A prospective cohort study was conducted on 2507 patients with T2DM. The primary survey was carried out from 2013 to 2017. The duration of observation was 6.3±2.5 years. Based on C-peptide and HOMA-IR levels, patients were classified in 3 phenotypes: insulinopenic (n=288), classic (n=1921) and insulin-resistant (n=298). During the period from 2014 to 31.12.2022, death occurred in 592 patients (23.6%). Based on K-means cluster analysis in 2507 patients with T2DM, using variables (HbA1c, age at diagnosis, body mass index, C-peptide, gender), 3 clusters were identified. DNA and genotyping of structural variants of the TCF7L2 (rs7903146) and ATM (rs11212617) genes were carried out using PCR. Results. A cluster with reduced β-cell function is associated with an increased risk of cardiovascular death by 32% (relative risk [RR]=1.320; p=0.015) and a 68.8% risk of acute heart failure compared with clusters with preserved and increased β-cell function. Multivariate Cox regression analysis revealed predictors of cardiovascular death were HbA1c (RR=1.129; p=0.001), duration of diabetes (RR=1.015; p=0.004), the T allele of the TCF7L2 (rs7903146) (RR=1.719; p=0.005) and allele C of the ATM gene (RR=1.539; p=0.024). Risk factors for sudden death were HbA1c (RR=1.138; p=0.035) and older age (RR=1.083; p=0.001). The predictor of death from chronic heart failure was HbA1c (RR=1.157; p=0.001), from acute heart failure the duration of T2DM (RR=2.527; p=0.014). Conclusion. The study revealed that a cluster with reduced β-cell function is associated with an increased risk of cardiovascular death by 32% and a 68.8% increase in the risk of acute heart failure compared to clusters with preserved and increased β-cell function. The most significant predictors of cardiovascular death were HbA1c, duration of T2DM, creatinine level and T allele of the TCF7L2 (rs7903146) increased the risk of death from cardiovascular disease by 71.9% and the C allele of the gene ATM (rs11212517) by 53.9%.