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Clinical Research

The obesity paradox in younger adult patients with sepsis: analysis of the MIMIC-IV database

Abstract

Background

The obesity paradox suggests that individuals with obesity may have a survival advantage against specific critical illnesses, including sepsis. However, whether this paradox occurs at younger ages remains unclear. Therefore, we aimed to investigate whether obesity could improve survival in younger adult patients with sepsis.

Methods

We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients with Sequential Organ Failure Assessment score ≥2 and suspected infection at the time of ICU admission were identified as having sepsis, following the Sepsis-3 definition. Individuals were classified into the obesity (BMI ≥30 kg/m²) and non-obesity (BMI <30 kg/m²) groups. Patients aged <50 and ≥50 years were categorized as younger adult patients and older patients, respectively.

Results

Of 73,181 patients in the MIMIC-IV ICU database, 18,120 satisfied the inclusion criteria: 2642 aged <50 years and 15,478 aged ≥50 years. The Kaplan–Meier curve showed that obesity was not associated with an improved mortality rate among younger adult patients with sepsis (log-rank test: P = 0.197), while obesity exhibited a survival benefit in older patients with sepsis (log-rank test: P < 0.001). After propensity score matching, in-hospital mortality did not differ significantly between the obesity and non-obesity groups (13.3% vs. 12.2%; P = 0.457) in the younger adult patients with sepsis. Multivariate logistic regression analysis revealed that BMI was not an independent risk factor for in-hospital mortality in younger adult patients with sepsis (underweight: adjusted odds ratio [aOR] 1.72, P = 0.076; overweight: aOR 0.88, P = 0.437; obesity: aOR 0.93, P = 0.677; and severe obesity: aOR 1.22, P = 0.580, with normal weight as the reference).

Conclusion

Contrary to findings regarding older patients with sepsis, our findings suggest that the obesity paradox does not apply to younger adult patients with sepsis.

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Fig. 1: Flowchart of study participant enrollment.
Fig. 2: Kaplan-Meier survival curves of patients with sepsis.

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Data availability

The dataset analyzed in the current study is available on the MIMIC-IV website (https://physionet.org/content/mimiciv/2.2/).

References

  1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Liu V, Escobar GJ, Greene JD, Soule J, Whippy A, Angus DC, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. Jama. 2014;312:90–2.

    Article  CAS  PubMed  Google Scholar 

  3. Torio CM, Moore BJ. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2013. In. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Agency for Healthcare Research and Quality (US), Rockville (MD), 2006.

  4. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the global burden of disease study. Lancet. 2020;395:200–11.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ramón-Arbués E, Martínez-Abadía B, Gracia-Tabuenca T, Yuste-Gran C, Pellicer-García B, Juárez-Vela R, et al. Prevalence of overweight/obesity and its association with diabetes, hypertension, dyslipidemia and metabolic syndrome: a cross-sectional study of a sample of workers in Aragón, Spain. Nutr Hosp. 2019;36:51–9.

    PubMed  Google Scholar 

  6. Gomis R, Artola S, Conthe P, Vidal J, Casamor R, Font B. Prevalence of type 2 diabetes mellitus in overweight or obese outpatients in Spain. OBEDIA Study. Med Clin (Barc). 2014;142:485–92.

    Article  PubMed  Google Scholar 

  7. Zhang L, Zhang WH, Zhang L, Wang PY. Prevalence of overweight/obesity and its associations with hypertension, diabetes, dyslipidemia, and metabolic syndrome: a survey in the suburban area of Beijing, 2007. Obes Facts. 2011;4:284–9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Nguyen NT, Magno CP, Lane KT, Hinojosa MW, Lane JS. Association of hypertension, diabetes, dyslipidemia, and metabolic syndrome with obesity: findings from the National Health and Nutrition Examination Survey, 1999 to 2004. J Am Coll Surg. 2008;207:928–34.

    Article  PubMed  Google Scholar 

  9. Sun X, Yan AF, Shi Z, Zhao B, Yan N, Li K, et al. Health consequences of obesity and projected future obesity health burden in China. Obes (Silver Spring). 2022;30:1724–51.

    Article  Google Scholar 

  10. Wang HE, Griffin R, Judd S, Shapiro NI, Safford MM. Obesity and risk of sepsis: a population-based cohort study. Obes (Silver Spring). 2013;21:E762–9.

    Article  CAS  Google Scholar 

  11. Kaplan JM, Nowell M, Lahni P, Shen H, Shanmukhappa SK, Zingarelli B. Obesity enhances sepsis-induced liver inflammation and injury in mice. Obes (Silver Spring). 2016;24:1480–8.

    Article  CAS  Google Scholar 

  12. Vachharajani V, Russell JM, Scott KL, Conrad S, Stokes KY, Tallam L, et al. Obesity exacerbates sepsis-induced inflammation and microvascular dysfunction in mouse brain. Microcirculation. 2005;12:183–94.

    Article  CAS  PubMed  Google Scholar 

  13. Petronilho F, Giustina AD, Nascimento DZ, Zarbato GF, Vieira AA, Florentino D, et al. Obesity exacerbates sepsis-induced oxidative damage in organs. Inflammation. 2016;39:2062–71.

    Article  CAS  PubMed  Google Scholar 

  14. Kuperman EF, Showalter JW, Lehman EB, Leib AE, Kraschnewski JL. The impact of obesity on sepsis mortality: a retrospective review. BMC Infect Dis. 2013;13:377.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sakr Y, Alhussami I, Nanchal R, Wunderink RG, Pellis T, Wittebole X, et al. Being overweight is associated with greater survival in ICU patients: results from the intensive care over nations audit. Crit Care Med. 2015;43:2623–32.

    Article  PubMed  Google Scholar 

  16. Pepper DJ, Demirkale CY, Sun J, Rhee C, Fram D, Eichacker P, et al. Does obesity protect against death in sepsis? A retrospective cohort study of 55,038 adult patients. Crit Care Med. 2019;47:643–50.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wang S, Liu X, Chen Q, Liu C, Huang C, Fang X. The role of increased body mass index in outcomes of sepsis: a systematic review and meta-analysis. BMC Anesthesiol. 2017;17:118.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yeo HJ, Kim TH, Jang JH, Jeon K, Oh DK, Park MH, et al. Obesity paradox and functional outcomes in sepsis: a multicenter prospective study. Crit Care Med. 2023;51:742–52.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ahima RS. Adipose tissue as an endocrine organ. Obes (Silver Spring). 2006;14:242s–9s.

    Article  CAS  Google Scholar 

  20. Hillenbrand A, Xu P, Zhou S, Blatz A, Weiss M, Hafner S, et al. Circulating adipokine levels and prognostic value in septic patients. J Inflamm (Lond). 2016;13:30.

    Article  PubMed  Google Scholar 

  21. Niedziela J, Hudzik B, Niedziela N, Gąsior M, Gierlotka M, Wasilewski J, et al. The obesity paradox in acute coronary syndrome: a meta-analysis. Eur J Epidemiol. 2014;29:801–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med. 2006;34:15–21.

    Article  PubMed  Google Scholar 

  23. Abbate LM, Perman SM, Clambey ET, Van Pelt RE, Ginde AA. Age modifies the association between obesity and mortality in individuals hospitalized with severe sepsis. J Am Geriatr Soc. 2016;64:882–3.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Michels EHA, Butler JM, Reijnders TDY, Cremer OL, Scicluna BP, Uhel F, et al. Association between age and the host response in critically ill patients with sepsis. Crit Care. 2022;26:385.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Johnson AEW, Bulgarelli L, Shen L, Gayles A, Shammout A, Horng S, et al. MIMIC-IV, a freely accessible electronic health record dataset. Sci Data. 2023;10:1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Johnson A, Bulgarelli L, Pollard T, Horng S, Celi LA, Mark R. MIMIC-IV (version 2.2). PhysioNet. https://doi.org/10.13026/6mm1-ek67 (2023).

  27. Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43:1130–9.

    Article  PubMed  Google Scholar 

  28. Bai L, Huang J, Wang D, Zhu D, Zhao Q, Li T, et al. Association of body mass index with mortality of sepsis or septic shock: an updated meta-analysis. J Intensive Care. 2023;11:27.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Saini A, Al-Shanti N, Stewart CE. Waste management - cytokines, growth factors and cachexia. Cytokine Growth Factor Rev. 2006;17:475–86.

    Article  CAS  PubMed  Google Scholar 

  30. Hasselgren PO, Fischer JE. The ubiquitin-proteasome pathway: review of a novel intracellular mechanism of muscle protein breakdown during sepsis and other catabolic conditions. Ann Surg. 1997;225:307–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pepper DJ, Sun J, Welsh J, Cui X, Suffredini AF, Eichacker PQ. Increased body mass index and adjusted mortality in ICU patients with sepsis or septic shock: a systematic review and meta-analysis. Crit Care. 2016;20:181.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Karampela I, Christodoulatos GS, Dalamaga M. The role of adipose tissue and adipokines in sepsis: inflammatory and metabolic considerations, and the obesity paradox. Curr Obes Rep. 2019;8:434–57.

    Article  PubMed  Google Scholar 

  33. Hajri T, Gharib M, Kaul S, Karpeh MS Jr. Association between adipokines and critical illness outcomes. J Trauma Acute Care Surg. 2017;83:507–19.

    Article  CAS  PubMed  Google Scholar 

  34. Siegl D, Annecke T, Johnson BL III, Schlag C, Martignoni A, Huber N, et al. Obesity-induced hyperleptinemia improves survival and immune response in a murine model of sepsis. Anesthesiology 2014;121:98–114.

    Article  CAS  PubMed  Google Scholar 

  35. Robinson J, Swift-Scanlan T, Salyer J. Obesity and 1-year mortality in adults after sepsis: a systematic review. Biol Res Nurs. 2020;22:103–13.

    Article  PubMed  Google Scholar 

  36. Jagan N, Morrow LE, Walters RW, Plambeck RW, Wallen TJ, Patel TM, et al. Sepsis and the obesity paradox: size matters in more than one way. Crit Care Med. 2020;48:e776–e82.

    Article  PubMed  Google Scholar 

  37. Hainer V, Aldhoon-Hainerová I. Obesity paradox does exist. Diabetes Care. 2013;36:S276–81.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontology Ser A. 2006;61:1059–64.

    Article  Google Scholar 

  39. De Lorenzo A, Pellegrini M, Gualtieri P, Itani L, El Ghoch M, Di Renzo L. The risk of sarcopenia among adults with normal-weight obesity in a nutritional management setting. Nutrients. 2022;14:5295.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Roberts S, Collins P, Rattray M. Identifying and managing malnutrition, frailty and sarcopenia in the community: a narrative review. Nutrients. 2021;13:2316.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kim JW, Kim R, Choi H, Lee SJ, Bae GU. Understanding of sarcopenia: from definition to therapeutic strategies. Arch Pharm Res. 2021;44:876–89.

    Article  CAS  PubMed  Google Scholar 

  42. Cannataro R, Carbone L, Petro JL, Cione E, Vargas S, Angulo H, et al. Sarcopenia: etiology, nutritional approaches, and miRNAs. Int J Mol Sci. 2021;22:9724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Yuan S, Larsson SC. Epidemiology of sarcopenia: prevalence, risk factors, and consequences. Metabolism. 2023;144:155533.

    Article  CAS  PubMed  Google Scholar 

  44. Faulkner JA, Larkin LM, Claflin DR, Brooks SV. Age-related changes in the structure and function of skeletal muscles. Clin Exp Pharm Physiol. 2007;34:1091–6.

    Article  CAS  Google Scholar 

  45. Senior HE, Henwood TR, Beller EM, Mitchell GK, Keogh JW. Prevalence and risk factors of sarcopenia among adults living in nursing homes. Maturitas. 2015;82:418–23.

    Article  PubMed  Google Scholar 

  46. Wannamethee SG, Atkins JL. Muscle loss and obesity: the health implications of sarcopenia and sarcopenic obesity. Proc Nutr Soc. 2015;74:405–12.

    Article  PubMed  Google Scholar 

  47. Nikolich-Žugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018;19:10–9.

    Article  PubMed  Google Scholar 

  48. Martín S, Pérez A, Aldecoa C. Sepsis and immunosenescence in the elderly patient: a review. Front Med (Lausanne). 2017;4:20.

    PubMed  Google Scholar 

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Acknowledgements

We appreciate the Medical Illustration & Design (MID) team, a member of Medical Research Support Services of Yonsei University College of Medicine, for their excellent support with medical illustration.

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Contributions

KJH and PSH conceived the idea for the study. LY contributed to data curation, formal analysis, investigation, visualization, and original draft writing. AJY, JSJ, KNS, CJY, YJ, and KJH contributed to supervision. All authors contributed to the review and editing of the manuscript.

Corresponding authors

Correspondence to Se Hee Park or Jung Ho Kim.

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The authors declare no competing interests.

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The Institutional Review Board of the Beth Israel Deaconess Medical Center approved the study and waived the requirement for informed consent (IRB Protocol #2001P001699).

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Lee, Y., Ahn, S., Han, M. et al. The obesity paradox in younger adult patients with sepsis: analysis of the MIMIC-IV database. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01523-5

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