Risks of mortality for various phenotypes in patients with type 2 diabetes mellitus in the Novosibirsk region

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a disease with high prevalence and early mortality, and identifying groups at risk for adverse outcomes is important in secondary prevention.

AIM: To study clinical, metabolic and genetic risk factors for deaths in various clinical phenotypes in patients with type 2 diabetes mellitus in the Novosibirsk region.

MATERIALS AND METHODS: A prospective cohort study was conducted of 2507 patients with T2DM. The follow-up duration was 6.3±2.5 years. Depending on the level of C-peptide and the HOMA-IR index, patients were divided into 3 phenotypes: insulinopenic (n=288), classic (n=1921), insulin-resistant (n=298). Fatal outcome for the period from 2014 to 31.12.2022 was recorded in 592 patients (23.6%). DNA isolation and genotyping of structural variants of the TCF7L2(rs7903146), ATM(rs11212617) genes were performed by PCR.

RESULTS: The main cause of death in patients with T2DM in all phenotypes was CVD (63.8%). Patients with an insulin-resistant phenotype had a significantly shorter duration of diabetes at the time of death, 12.3±5.5 years, compared with the classic and insulinopenic phenotype (p<0.001). Risk factors for mortality from all causes according to multivariate Cox regression analysis (OR) were the duration of T2DM (1.043, p<0.001), the level of HbA1c (1.131, p<0.001), creatinine (1.013, p=0.002), the T allele of the TCF7L2(rs7903146) gene (OR=1.431, p=0.017) and allele C of the ATM(rs11212517) gene (OR=1.509, p=0.007). Predictors of cardiovascular death were HbA1c (OR=1.129, p=0.001), duration of diabetes (OR=1.041, p=0.002), creatinine level (OR=1.015, p=0.004), the T allele of the TCF7L2(rs7903146) gene (OR=1.719, p=0.005) and allele C of the ATM gene (OR=1.539, p=0.024).

CONCLUSION: The study found that patients with an insulin-resistant had a poor prognosis. The main predictor of general and cardiovascular death was HbA1c. The T allele of the TCF7L2(rs7903146) gene increased the risk of overall mortality by 43.1%, the C allele of the ATM(rs11212617) gene by 50.9%.

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