Skip to main content
SpringerLink
Log in

Association between experience of insulin resistance and long-term cardiovascular disease risk: findings from the Korean Genome and Epidemiology Study (KOGES)

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Although the correlation between insulin resistance (IR) and cardiovascular disease (CVD) risk is well-established, the impact of changes in IR status over time has received little attention. This study aimed to investigate the effect of IR on CVD risk in a large prospective cohort of middle-aged Korean adults.

Methods

We assessed 3597 participants from the Korean Genome and Epidemiology Study (KoGES). Participants were categorized as having IR if their HOMA-IR was ≥2.5 at least once during the exposure period. Multivariate Cox proportional hazards regression analysis was performed to assess hazard ratios (HRs) with 95% CIs for incident CVD after adjusting for confounders.

Results

Among a total of 3597 participants, 2259 did not have IR and 1138 had IR. The cumulative incidence rate of CVD in the IR group was significantly higher than that in the non-IR group (log-rank test, p = 0.015). Compared to the non-IR group, the HR and 95% CI for incident CVD in the IR group was 1.40 (1.07–1.83) in the unadjusted model. The presence of IR during the exposure period was significantly associated with a higher risk of incident CVD after adjusting for age, sex, body mass index, diabetes, hypertension, dyslipidemia, C-reactive protein, physical activity, alcohol intake, and smoking status (HR = 1.37; 95% CI: 1.01–1.84).

Conclusion

Individuals who have experienced IR have a consistently higher likelihood of developing CVD than those who have never had IR. More intensive efforts should be made to prevent IR in middle-aged and older adults.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Data analyzed in this study were obtained from the Korean Genome and Epidemiology Study (4851-302) and are available at the following website: https://www.kdca.go.kr/contents.es?mid=a40504010000.

References

  1. R. Jagannathan, S.A. Patel, M.K. Ali, K.M.V. Narayan, Global updates on cardiovascular disease mortality trends and attribution of traditional risk factors. Curr. Diab. Rep. 19(7), 44 (2019)

    Article  PubMed  Google Scholar 

  2. B. Dahlof, Cardiovascular disease risk factors: epidemiology and risk assessment. Am. J. Cardiol. 105(1 Suppl), 3A–9A (2010)

    Article  PubMed  Google Scholar 

  3. J.I. Shin, J. Oh, H.C. Kim, D. Choi, Y.S. Yoon, Current state of cardiovascular research in Korea. Circ. Res. 125(12), 1141–1145 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. H.C. Kim, Epidemiology of cardiovascular disease and its risk factors in Korea. Glob. Health Med. 3(3), 134–141 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  5. V. Ormazabal, S. Nair, O. Elfeky, C. Aguayo, C. Salomon, F.A. Zuniga, Association between insulin resistance and the development of cardiovascular disease. Cardiovasc. Diabetol 17(1), 122 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. S.-F. Tsai, C.-T. Yang, W.-J. Liu, C.-L. Lee, Development and validation of an insulin resistance model for a population without diabetes mellitus and its clinical implication: a prospective cohort study. eClinicalMedicine 58, 101934 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  7. A. Di Pino, R.A. DeFronzo, Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents. Endocrine Rev. 40(6), 1447–1467 (2019)

    Article  Google Scholar 

  8. C.F. Semenkovich, Insulin resistance and atherosclerosis. J. Clin. Invest. 116(7), 1813–1822 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. I.M. Vladu, M. Fortofoiu, D. Clenciu, M.C. Fortofoiu, R. Padureanu, L. Radu, S.T.T. Cojan, P.M. Radulescu, V. Padureanu, Insulin resistance quantified by the value of HOMA-IR and cardiovascular risk in patients with type 2 diabetes. Exp. Ther. Med. 23(1), 73 (2022)

    Article  CAS  PubMed  Google Scholar 

  10. M.M. Adeva-Andany, J. Martinez-Rodriguez, M. Gonzalez-Lucan, C. Fernandez-Fernandez, E. Castro-Quintela, Insulin resistance is a cardiovascular risk factor in humans. Diabetes Metab. Synd. 13(2), 1449–1455 (2019)

    Article  Google Scholar 

  11. V. Ormazabal, S. Nair, O. Elfeky, C. Aguayo, C. Salomon, F.A. Zuñiga, Association between insulin resistance and the development of cardiovascular disease. Cardiovascular Diabetol. 17(1), 122 (2018)

    Article  CAS  Google Scholar 

  12. K.B. Gast, N. Tjeerdema, T. Stijnen, J.W.A. Smit, O.M. Dekkers, Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PLOS ONE 7(12), e52036 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. M.-C. Lu, W.-C. Fang, W.-C. Li, W.-C. Yeh, Y.-H. Shieh, J.-Y. Chen, The association between insulin resistance and cardiovascular disease risk: a community-based cross-sectional study among Taiwanese people aged over 50 years. Int. J. Environ. Res. Public Health 17(19), 7195 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. S.Y. Park, J.F. Gautier, S. Chon, Assessment of insulin secretion and insulin resistance in human. Diabetes Metab. J. 45(5), 641–654 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  15. E. Bonora, G. Targher, M. Alberiche, R.C. Bonadonna, F. Saggiani, M.B. Zenere, T. Monauni, M. Muggeo, Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23(1), 57–63 (2000)

    Article  CAS  PubMed  Google Scholar 

  16. T. Wang, M. Li, T. Zeng, R. Hu, Y. Xu, M. Xu, Z. Zhao, Y. Chen, S. Wang, H. Lin, X. Yu, G. Chen, Q. Su, Y. Mu, L. Chen, X. Tang, L. Yan, G. Qin, Q. Wan, Z. Gao, G. Wang, F. Shen, Z. Luo, Y. Qin, L. Chen, Y. Huo, Q. Li, Z. Ye, Y. Zhang, C. Liu, Y. Wang, S. Wu, T. Yang, H. Deng, J. Zhao, L. Shi, G. Ning, Y. Bi, W. Wang, J. Lu, Association between insulin resistance and cardiovascular disease risk varies according to glucose tolerance status: a nationwide prospective cohort study. Diabetes Care 45(8), 1863–1872 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. T. Wang, J. Lu, L. Shi, G. Chen, M. Xu, Y. Xu, Q. Su, Y. Mu, L. Chen, R. Hu, X. Tang, X. Yu, M. Li, Z. Zhao, Y. Chen, L. Yan, G. Qin, Q. Wan, M. Dai, D. Zhang, Z. Gao, G. Wang, F. Shen, Z. Luo, Y. Qin, L. Chen, Y. Huo, Q. Li, Z. Ye, Y. Zhang, C. Liu, Y. Wang, S. Wu, T. Yang, H. Deng, J. Zhao, S. Lai, Y. Bi, R.A. DeFronzo, W. Wang, G. Ning, Association of insulin resistance and β-cell dysfunction with incident diabetes among adults in China: a nationwide, population-based, prospective cohort study. Lancet Diabetes Endocrinol 8(2), 115–124 (2020)

    Article  CAS  PubMed  Google Scholar 

  18. M.A. Abdul-Ghani, A. Jayyousi, R.A. DeFronzo, N. Asaad, J. Al-Suwaidi, Insulin resistance the link between T2DM and CVD: basic mechanisms and clinical implications. Curr. Vasc. Pharmacol. 17(2), 153–163 (2019)

    Article  CAS  PubMed  Google Scholar 

  19. S.F. Tsai, C.T. Yang, W.J. Liu, C.L. Lee, Development and validation of an insulin resistance model for a population without diabetes mellitus and its clinical implication: a prospective cohort study. EClinicalMedicine 58, 101934 (2023)

    Article  PubMed  PubMed Central  Google Scholar 

  20. Y. Kim, B.G. Han, G.E.S.G. Ko, Cohort Profile: The Korean Genome and Epidemiology Study (KoGES) Consortium. Int. J. Epidemiol. 46(2), e20 (2017)

    Article  PubMed  Google Scholar 

  21. R. Muniyappa, S. Lee, H. Chen, M.J. Quon, Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am. J. Physiol. Endocrinol. Metab. 294(1), E15–E26 (2008)

    Article  CAS  PubMed  Google Scholar 

  22. C. Yamada, T. Mitsuhashi, N. Hiratsuka, F. Inabe, N. Araida, E. Takahashi, Optimal reference interval for homeostasis model assessment of insulin resistance in a Japanese population. J. Diabetes Investig. 2(5), 373–376 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7), 412–419 (1985)

    Article  CAS  PubMed  Google Scholar 

  24. K.J. Yun, K. Han, M.K. Kim, Y.M. Park, K.H. Baek, K.H. Song, H.S. Kwon, Insulin resistance distribution and cut-off value in Koreans from the 2008–2010 Korean National Health and Nutrition Examination Survey. PLoS One 11(4), e0154593 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  25. S.H. Park, W.Y. Lee, E.J. Rhee, W.K. Jeon, B.I. Kim, S.H. Ryu, S.W. Kim, Relative risks of the metabolic syndrome according to the degree of insulin resistance in apparently healthy Korean adults. Clin. Sci. (Lond) 108(6), 553–559 (2005)

    Article  CAS  PubMed  Google Scholar 

  26. H. Han, Y. Wang, T. Li, C. Feng, C. Kaliszewski, Y. Su, Y. Wu, J. Zhou, L. Wang, G. Zong, Sleep duration and risks of incident cardiovascular disease and mortality among people with type 2 diabetes. Diabetes Care 46(1), 101–110 (2023)

    Article  PubMed  Google Scholar 

  27. P.C. Dempsey, A.V. Rowlands, T. Strain, F. Zaccardi, N. Dawkins, C. Razieh, M.J. Davies, K.K. Khunti, C.L. Edwardson, K. Wijndaele, S. Brage, T. Yates, Physical activity volume, intensity, and incident cardiovascular disease. Eur. Heart J. 43(46), 4789–4800 (2022)

    Article  PubMed  Google Scholar 

  28. A.J. Hanley, K. Williams, M.P. Stern, S.M. Haffner, Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care 25(7), 1177–1184 (2002)

    Article  PubMed  Google Scholar 

  29. E. Bonora, G. Formentini, F. Calcaterra, S. Lombardi, F. Marini, L. Zenari, F. Saggiani, M. Poli, S. Perbellini, A. Raffaelli, V. Cacciatori, L. Santi, G. Targher, R. Bonadonna, M. Muggeo, HOMA-estimated insulin resistance is an independent predictor of cardiovascular disease in type 2 diabetic subjects: prospective data from the Verona Diabetes Complications Study. Diabetes Care 25(7), 1135–1141 (2002)

    Article  PubMed  Google Scholar 

  30. P. Bjornstad, R.H. Eckel, Pathogenesis of lipid disorders in insulin resistance: a brief review. Curr. Diab. Rep. 18(12), 127 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  31. H. Ikezaki, E. Lim, L.A. Cupples, C.T. Liu, B.F. Asztalos, E.J. Schaefer, Small dense low-density lipoprotein cholesterol is the most atherogenic lipoprotein parameter in the prospective framingham offspring study. J. Am. Heart Assoc. 10(5), e019140 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. M.S. Zhou, I.H. Schulman, L. Raij, Vascular inflammation, insulin resistance, and endothelial dysfunction in salt-sensitive hypertension: role of nuclear factor kappa B activation. J Hypertens 28(3), 527–535 (2010)

    Article  CAS  PubMed  Google Scholar 

  33. H. Li, Y. Meng, S. He, X. Tan, Y. Zhang, X. Zhang, L. Wang, W. Zheng, Macrophages, chronic inflammation, and insulin resistance. Cells 11(19), 3001 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. A. Avogaro, M. Albiero, L. Menegazzo, S. de Kreutzenberg, G.P. Fadini, Endothelial dysfunction in diabetes: the role of reparatory mechanisms. Diabetes Care 34(Suppl 2), S285–S290 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  35. D. Eddy, L. Schlessinger, R. Kahn, B. Peskin, R. Schiebinger, Relationship of insulin resistance and related metabolic variables to coronary artery disease: a mathematical analysis. Diabetes Care 32(2), 361–366 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. I. Baik, N.H. Cho, S.H. Kim, C. Shin, Dietary information improves cardiovascular disease risk prediction models. Eur. J. Clin. Nutr. 67(1), 25–30 (2013)

    Article  CAS  PubMed  Google Scholar 

  37. J.H. Baek, H. Kim, K.Y. Kim, J. Jung, Insulin resistance and the risk of diabetes and dysglycemia in Korean general adult population. Diabetes Metab. J. 42(4), 296–307 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  38. A. Abdesselam, H. Zidoum, F. Zadjali, R. Hedjam, A. Al-Ansari, R. Bayoumi, S. Al-Yahyaee, M. Hassan, S. Albarwani, Estimate of the HOMA-IR cut-off value for identifying subjects at risk of insulin resistance using a machine learning approach. Sultan Qaboos Univ. Med. J. 21(4), 604–612 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  39. B. Kim, H.Y. Choi, W. Kim, C. Ahn, J. Lee, J.G. Kim, J. Kim, H. Shin, J.M. Yu, S. Moon, The cut-off values of surrogate measures for insulin resistance in the Korean population according to the Korean Genome and Epidemiology Study (KOGES). PLoS One 13(11), e0206994 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was conducted using data from the Korean Genome and Epidemiology Study (KoGES; 4851-302) that was undertaken by the National Research Institute of Health, Centers for Disease Control and Prevention, Ministry for Health and Welfare, Republic of Korea.

Author contributions

J.H.L. and Y.J.K. contributed to the conception and design of this study. J.H.L., H.S.L., S.Y.J., J.H.L., and Y.J.K. contributed to the acquisition, analysis, and interpretation of data and drafting of the manuscript. All authors critically revised the manuscript, provided final approval, and agreed to be accountable for all aspects of the work, while ensuring integrity and accuracy.

Funding

This work was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, and Forestry (IPET) through the High Value-added Food Technology Development Program funded by the Ministry of Agriculture, Food, and Rural Affairs (321030051HD030). The grant was awarded to Y.J.K.

Author information

Authors and Affiliations

  1. Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, 16995, Republic of Korea

    Jong Hee Lee, Byoungjin Park & Yu-Jin Kwon

  2. Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul, 03277, Republic of Korea

    Hye Sun Lee & Soyoung Jeon

  3. Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 03277, Republic of Korea

    Yong-Jae Lee

  4. Department of Family Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, 01830, Republic of Korea

    Jun-Hyuk Lee

  5. Department of Medicine, Hanyang University Graduate School of Medicine, Seoul, 04763, Republic of Korea

    Jun-Hyuk Lee

Authors
  1. Jong Hee Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hye Sun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Soyoung Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong-Jae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Byoungjin Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun-Hyuk Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu-Jin Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jun-Hyuk Lee or Yu-Jin Kwon.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

The protocol of this study was approved by the institutional review of the board of Yongin Severance Hospital (IRB number: 9-2022-0090).

Consent to participate

Informed consent was obtained from all the participants before enrollment in the registry.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, J.H., Lee, H.S., Jeon, S. et al. Association between experience of insulin resistance and long-term cardiovascular disease risk: findings from the Korean Genome and Epidemiology Study (KOGES). Endocrine 84, 481–489 (2024). https://doi.org/10.1007/s12020-023-03615-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-023-03615-0

Keywords

Search

Navigation