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

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

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%.

Full Text

Restricted Access

About the authors

I. A. Bondar

Novosibirsk State Medical University

Email: oyushabelnikova@yandex.ru
ORCID iD: 0000-0003-4641-3874
SPIN-code: 6633-8947

MD, Professor

Russian Federation, Novosibirsk

O. Yu. Shabelnikova

Novosibirsk Regional Clinical Hospital

Author for correspondence.
Email: oyushabelnikova@yandex.ru
ORCID iD: 0000-0003-3906-4784
SPIN-code: 5941-4815

Candidate of Medical Sciences

Russian Federation, Novosibirsk

References

  1. International Diabetes Federation. IDF Diabetes Atlas, 10th edn. Brussels, Belgium; 2021. URL: https://www.diabetesatlas.org
  2. Дедов И.И., Шестакова М.В., Викулова О.К. и др. Сахарный диабет в Российской Федерации: динамика эпидемиологических показателей по данным Федерального регистра сахарного диабета за период 2010–2022 гг. Сахарный диабет. 2023; 26 (2): 104–23 [Dedov I.I., Shestakova M.V., Vikulova O.K. et al. Diabetes mellitus in the Russian Federation: dynamics of epidemiological indicators according to the Federal Register of Diabetes Mellitus for the period 2010–2022. Diabetes mellitus. 2023; 26 (2): 104–23 (in Russ.)]. doi: 10.14341/DM13035
  3. Wong N.D., Sattar N. Cardiovascular risk in diabetes mellitus: epidemiology, assessment and prevention. Nat Rev Cardiol. 2023; 20 (10): 685–95. doi: 10.1038/s41569-023-00877-z
  4. Yun J.S., Ko S.H. Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes. Metabolism. 2021; 123: 154838. doi: 10.1016/j.metabol.2021.154838
  5. Gast K.B., Tjeerdema N., Stijnen T. et al. Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PLoS One. 2012; 7 (12): e52036. doi: 10.1371/journal.pone.0052036
  6. Kim K.S., Lee Y.M., Lee I.K. et al. Paradoxical Associations of Insulin Resistance With Total and Cardiovascular Mortality in Humans. J Gerontol A Biol Sci Med Sci. 2015; 70 (7): 847–53. doi: 10.1093/gerona/glu194
  7. Mahajan A., Taliun D., Thurner M. et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat Genet. 2018; 50 (11): 1505–13. doi: 10.1038/s41588-018-0241-6
  8. van der Harst P., Verweij N. Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease. Circ Res. 2018; 122 (3): 433–43. doi: 10.1161/CIRCRESAHA.117.312086
  9. Rivera N.V., Carreras-Torres R., Roncarati R. et al. Assessment of the 9p21.3 locus in severity of coronary artery disease in the presence and absence of type 2 diabetes. BMC Med Genet. 2013; 14: 11. doi: 10.1186/1471–2350-14-11
  10. Geoghegan G., Simcox J., Seldin M.M. et al. Targeted deletion of Tcf7l2 in adipocytes promotes adipocyte hypertrophy and impaired glucose metabolism. Mol Metab. 2019; 24: 44–63. doi: 10.1016/j.molmet.2019.03.003
  11. Chen X., Ayala I., Shannon C. et al. The Diabetes Gene and Wnt Pathway Effector TCF7L2 Regulates Adipocyte Development and Function. Diabetes. 2018; 67 (4): 554–68. doi: 10.2337/db17-0318
  12. Wingard M.C., Frasier C.R., Singh M. et al. Heart failure and diabetes: role of ATM. Curr Opin Pharmacol. 2020; 54: 27–35. doi: 10.1016/j.coph.2020.06.007
  13. Su Y., Swift M. Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Ann Intern Med. 2000; 133 (10): 770–8. doi: 10.7326/0003-4819-133-10-200011210-00009
  14. Rawshani A., Rawshani A., Franzén S. et al. Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2018; 379 (7): 633–44. doi: 10.1056/NEJMoa1800256
  15. Zabala A., Darsalia V., Holzmann M.J. et al. Risk of first stroke in people with type 2 diabetes and its relation to glycaemic control: A nationwide observational study. Diabetes Obes Metab. 2020; 22 (2): 182–90. doi: 10.1111/dom.13885
  16. Ali M.K., Pearson-Stuttard J., Selvin E. et al. Interpreting global trends in type 2 diabetes complications and mortality. Diabetologia. 2022; 65 (1): 3–13. doi: 10.1007/s00125-021-05585-2
  17. Zhao M., Song L., Sun L. et al. Associations of Type 2 Diabetes Onset Age With Cardiovascular Disease and Mortality: The Kailuan Study. Diabetes Care. 2021; 44 (6): 1426–32. doi: 10.2337/dc20-2375
  18. Sharma A., Zheng Y., Ezekowitz J.A. et al. Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine. Diabetes Care. 2022; 45 (1): 204–12. doi: 10.2337/dc20-2806
  19. Stidsen J.V., Christensen D.H., Henriksen J.E. et al. Risk of cardiovascular events associated with pathophysiological phenotypes of type 2 diabetes. Eur J Endocrinol. 2022; 187 (2): 279–91. doi: 10.1530/EJE-22-0020
  20. Sousa A.G., Marquezine G.F., Lemos P.A. et al. TCF7L2 polymorphism rs7903146 is associated with coronary artery disease severity and mortality. PLoS One. 2009; 4 (11): e7697. doi: 10.1371/journal.pone.0007697
  21. Bielinski S.J., Pankow J.S., Folsom A.R. et al. TCF7L2 single nucleotide polymorphisms, cardiovascular disease and all-cause mortality: the Atherosclerosis Risk in Communities (ARIC) study. Diabetologia. 2008; 51 (6): 968–70. doi: 10.1007/s00125-008-1004-1
  22. Satirapoj B., Tasanavipas P., Supasyndh O. Role of TCF7L2 and PPARG2 Gene Polymorphisms in Renal and Cardiovascular Complications among Patients with Type 2 Diabetes: A Cohort Study. Kidney Dis (Basel). 2019; 5 (4): 220–7. doi: 10.1159/000497100

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Russkiy Vrach Publishing House