Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Epidemiology and Population Health

Early mortality and cardiovascular disease, varied association with body mass index and its changes in insulin-treated diabetes: a nationwide study

Abstract

Background/Objectives

We investigated the hazards of cardiovascular diseases (CVDs) and all-cause death during follow-up according to baseline body mass index (BMI) and percent change in BMI among adults with insulin-treated diabetes.

Subjects/Methods

Using the Korean National Health Insurance Service datasets (2002–2017), the hazards of myocardial infarction (MI), stroke, and all-cause mortality during follow-up were analyzed according to baseline BMI and percent change in BMI among adults with insulin-treated diabetes and without baseline CVD and/or malignancy (N = 44,055).

Results

At baseline, 67.3% of total subjects were either obese or overweight. During a mean 3.8 years, 1,081 MI and 1,562 stroke cases developed; 2,847 deaths occurred over a mean 3.9 years. Compared with normal weight, overweight and obesity were associated with lower hazards of outcomes [hazard ratio (95% CI): 0.836 (0.712–0.981), 0.794 (0.687–0.917) for MI; 0.829 (0.726–0.946), 0.772 (0.684–0.870) for stroke; 0.740 (0.672–0.816), 0.666 (0.609–0.728) for death, respectively]. Underweight was associated with a higher hazard of all-cause death during follow-up [hazard ratio (95% CI): 2.035 (1.695–2.443)]. When the group with minimum absolute value for percent change in BMI was set as a reference, the relative reduction in BMI was associated with increased hazards of MI, stroke, and all-cause death, and relative increase in BMI was associated with increased hazards of stroke and all-cause death during follow-up.

Conclusions

Among adults with insulin-treated diabetes, a high prevalence of overweight and obesity was observed, and baseline BMI category was inversely associated with CVD incidence and all-cause death during follow-up. Both weight loss and gain were associated with increased CVD incidence and all-cause death during follow-up, showing a U-shaped relationship between weight change and outcome. Stable body weight might be a predictor of a lower risk of CVDs and premature death among individuals with insulin-treated diabetes.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1
Fig. 2: Adjusted hazard ratios and 95% confidence intervals for incidence of myocardial infarction, stroke, and all-cause death during follow-up according to percent change in body mass index.

References

  1. Lind M, Svensson AM, Kosiborod M, Gudbjörnsdottir S, Pivodic A, Wedel H, et al. Glycemic control and excess mortality in type 1 diabetes. N Engl J Med. 2014;371:1972–82.

    Article  Google Scholar 

  2. Tancredi M, Rosengren A, Svensson AM, Kosiborod M, Pivodic A, Gudbjörnsdottir S, et al. Excess mortality among persons with type 2 diabetes. N Engl J Med. 2015;373:1720–32.

    CAS  Article  Google Scholar 

  3. Gagnum V, Stene LC, Leivestad T, Joner G, Skrivarhaug T. Long-term mortality and end-stage renal disease in a type 1 diabetes population diagnosed at age 15-29 years in norway. Diabetes Care. 2017;40:38–45.

    Article  Google Scholar 

  4. Lee YB, Han K, Kim B, Lee SE, Jun JE, Ahn J, et al. Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study. Cardiovasc Diabetol. 2019;18:157.

    Article  Google Scholar 

  5. Svane J, Lynge TH, Pedersen-Bjergaard U, Jespersen T, Gislason GH, Risgaard B, et al. Cause-specific mortality in children and young adults with diabetes mellitus: a Danish nationwide cohort study. Eur J Prev Cardiol. 2019:2047487319836550.

  6. Edqvist J, Rawshani A, Adiels M, Bjorck L, Lind M, Svensson AM, et al. BMI, mortality, and cardiovascular outcomes in type 1 diabetes: findings against an obesity paradox. Diabetes Care. 2019;42:1297–304.

    Article  Google Scholar 

  7. Kilpatrick ES, Rigby AS, Atkin SL. Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes: “double diabetes” in the Diabetes Control and Complications Trial. Diabetes Care. 2007;30:707–12.

    CAS  Article  Google Scholar 

  8. Conway B, Miller RG, Costacou T, Fried L, Kelsey S, Evans RW, et al. Adiposity and mortality in type 1 diabetes. Int J Obes. 2009;33:796–805.

    CAS  Article  Google Scholar 

  9. Lee Y-B, Han K, Kim B, Jin S-M, Lee S-E, Jun JE, et al. High proportion of adult cases and prevalence of metabolic syndrome in type 1 diabetes mellitus population in Korea: a nationwide study. Diabetes Metab J. 2019;43:76–89.

    Article  Google Scholar 

  10. WHO expert consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363:157–63.

  11. Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol. 2009;53:1925–32.

    Article  Google Scholar 

  12. Lavie CJ, Milani RV, Ventura HO. Obesity and the “obesity paradox” in cardiovascular diseases. Clin Pharmacol Ther. 2011;90:23–5.

    CAS  Article  Google Scholar 

  13. Carnethon MR, Rasmussen-Torvik LJ, Palaniappan L. The obesity paradox in diabetes. Curr Cardiol Rep. 2014;16:446.

    Article  Google Scholar 

  14. Vestberg D, Rosengren A, Olsson M, Gudbjörnsdottir S, Svensson AM, Lind M. Relationship between overweight and obesity with hospitalization for heart failure in 20,985 patients with type 1 diabetes: a population-based study from the Swedish National Diabetes Registry. Diabetes Care. 2013;36:2857–61.

    Article  Google Scholar 

  15. Cheol Seong S, Kim YY, Khang YH, Heon Park J, Kang HJ, Lee H, et al. Data resource profile: the national health information database of the national health insurance service in South Korea. Int J Epidemiol. 2017;46:799–800.

    PubMed  Google Scholar 

  16. Lee YB, Kim DH, Kim SM, Kim NH, Choi KM, Baik SH, et al. Hospitalization for heart failure incidence according to the transition in metabolic health and obesity status: a nationwide population-based study. Cardiovasc Diabetol. 2020;19:77.

    Article  Google Scholar 

  17. Lee YH, Han K, Ko SH, Ko KS, Lee KU. Data analytic process of a nationwide population-based study using national health information database established by national health insurance service. Diabetes Metab J. 2016;40:79–82.

    Article  Google Scholar 

  18. Lee YB, Han K, Kim B, Choi MS, Park J, Kim M, et al. Risk of early mortality and cardiovascular disease according to the presence of recently diagnosed diabetes and requirement for insulin treatment: A nationwide study. J Diabetes Investig. 2021. https://doi.org/10.1111/jdi.13539. (Online ahead of print).

  19. Kim MK, Han K, Koh ES, Kim ES, Lee MK, Nam GE, et al. Blood pressure and development of cardiovascular disease in Koreans with type 2 diabetes mellitus. Hypertension. 2019;73:319–26.

    CAS  Article  Google Scholar 

  20. Kim MK, Han K, Kim HS, Park YM, Kwon HS, Yoon KH, et al. Cholesterol variability and the risk of mortality, myocardial infarction, and stroke: a nationwide population-based study. Eur Heart J. 2017;38:3560–6.

    CAS  Article  Google Scholar 

  21. Bahk J, Kim YY, Kang HY, Lee J, Kim I, Lee J, et al. Using the national health information database of the national health insurance service in Korea for monitoring mortality and life expectancy at national and local levels. J Korean Med Sci. 2017;32:1764–70.

    Article  Google Scholar 

  22. Lee YB, Han K, Kim B, Jun JE, Lee SE, Ahn J, et al. Risk of end-stage renal disease from chronic kidney disease defined by decreased glomerular filtration rate in type 1 diabetes: a comparison with type 2 diabetes and the effect of metabolic syndrome. Diabetes Metab Res Rev. 2019;35:e3197.

    PubMed  Google Scholar 

  23. Roh E, Hwang SY, Kim JA, Lee YB, Hong SH, Kim NH, et al. Body weight variability increases dementia risk among older adults: a nationwide population-based cohort study. Front Endocrinol. 2020;11:291.

    Article  Google Scholar 

  24. Park S, Jeon SM, Jung SY, Hwang J, Kwon JW. Effect of late-life weight change on dementia incidence: a 10-year cohort study using claim data in Korea. BMJ Open. 2019;9:e021739.

    Article  Google Scholar 

  25. Mühlhauser I, Overmann H, Bender R, Jörgens V, Berger M. Predictors of mortality and end-stage diabetic complications in patients with Type 1 diabetes mellitus on intensified insulin therapy. Diabet Med. 2000;17:727–34.

    Article  Google Scholar 

  26. Roy M, Rendas-Baum R, Skurnick J. Mortality in African-Americans with Type 1 diabetes: The New Jersey 725. Diabet Med. 2006;23:698–706.

    CAS  Article  Google Scholar 

  27. Lee S, Park HS, Kim SM, Kwon HS, Kim DY, Kim DJ, et al. Cut-off points of waist circumference for defining abdominal obesity in the Korean population. J Obes Metabolic Syndrome. 2006;15:1–9.

    Google Scholar 

  28. Kwon Y, Kim HJ, Park S, Park YG, Cho KH. Body mass index-related mortality in patients with type 2 diabetes and heterogeneity in obesity paradox studies: a dose-response meta-analysis. PLoS ONE. 2017;12:e0168247.

    Article  Google Scholar 

  29. Doehner W, Gerstein HC, Ried J, Jung H, Asbrand C, Hess S, et al. Obesity and weight loss are inversely related to mortality and cardiovascular outcome in prediabetes and type 2 diabetes: data from the ORIGIN trial. Eur Heart J. 2020;41:2668–77.

    CAS  Article  Google Scholar 

  30. Zoppini G, Verlato G, Leuzinger C, Zamboni C, Brun E, Bonora E, et al. Body mass index and the risk of mortality in type II diabetic patients from Verona. Int J Obes Relat Metab Disord. 2003;27:281–5.

    CAS  Article  Google Scholar 

  31. Gallagher D, Visser M, Sepúlveda D, Pierson RN, Harris T, Heymsfield SB. How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups? Am J Epidemiol. 1996;143:228–39.

    CAS  Article  Google Scholar 

  32. Camhi SM, Bray GA, Bouchard C, Greenway FL, Johnson WD, Newton RL, et al. The relationship of waist circumference and BMI to visceral, subcutaneous, and total body fat: sex and race differences. Obesity. 2011;19:402–8.

    Article  Google Scholar 

  33. Després JP, Couillard C, Gagnon J, Bergeron J, Leon AS, Rao DC, et al. Race, visceral adipose tissue, plasma lipids, and lipoprotein lipase activity in men and women: the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) family study. Arterioscler Thromb Vasc Biol. 2000;20:1932–8.

    Article  Google Scholar 

  34. Purnell JQ, Braffett BH, Zinman B, Gubitosi-Klug RA, Sivitz W, Bantle JP, et al. Impact of Excessive Weight Gain on Cardiovascular Outcomes in Type 1 Diabetes: Results From the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study. Diabetes Care. 2017;40:1756–62.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was performed using the database from the Korean National Health Insurance Service (KNHIS). This study used the National Health Information Database constructed by the KNHIS, and the study results do not necessarily represent the opinion of the KNHIS.

Author information

Authors and Affiliations

Authors

Contributions

Y-BL drafted the manuscript. Y-BL, KH, GK, and JHK contributed to the study design. BK and KH participated in the data analysis planning and statistical analysis. JP, MK, MSC, SMJ, and KYH performed literature searches and contributed to conception of the hypothesis. JHK critically edited the manuscript. All authors read and approved the final version of the manuscript. JHK and KH are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding authors

Correspondence to Kyungdo Han or Jae Hyeon Kim.

Ethics declarations

Competing interests

The authors declare no competing interests.

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

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lee, YB., Kim, B., Park, J. et al. Early mortality and cardiovascular disease, varied association with body mass index and its changes in insulin-treated diabetes: a nationwide study. Int J Obes 45, 2482–2489 (2021). https://doi.org/10.1038/s41366-021-00922-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-021-00922-2

Search

Quick links