Skip to main content

Is There an Obesity Paradox in Critical Illness? Epidemiologic and Metabolic Considerations

Abstract

Purpose of Review

Obesity represents a global epidemic with serious implications in public health due to its increasing prevalence and its known association with a high morbidity and mortality burden. However, a growing number of data support a survival benefit of obesity in critical illness. This review summarizes current evidence regarding the obesity paradox in critical illness, discusses methodological issues and metabolic implications, and presents potential pathophysiologic mechanisms.

Recent Findings

Data from meta-analyses and recent studies corroborate the obesity-related survival benefit in critically ill patients as well as in selected populations such as patients with sepsis and acute respiratory distress syndrome, but not trauma. However, this finding warrants a cautious interpretation due to certain methodological limitations of these studies, such as the retrospective design, possible selection bias, the use of BMI as an obesity index, and inadequate adjustment for confounding variables. Main pathophysiologic mechanisms related to obesity that could explain this phenomenon include higher energy reserves, inflammatory preconditioning, anti-inflammatory immune profile, endotoxin neutralization, adrenal steroid synthesis, renin-angiotensin system activation, cardioprotective metabolic effects, and prevention of muscle wasting.

Summary

The survival benefit of obesity in critical illness is supported from large meta-analyses and recent studies. Due to important methodological limitations, more prospective studies are needed to further elucidate this finding, while future research should focus on the pathophysiologic role of adipose tissue in critical illness.

This is a preview of subscription content, access via your institution.

Fig. 1

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Seidell JC, Halberstadt J. The global burden of obesity and the challenges of prevention. Ann Nutr Metab. 2015;66(Suppl 2):7–12. https://doi.org/10.1159/000375143.

    Article  CAS  PubMed  Google Scholar 

  2. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–81. https://doi.org/10.1016/s0140-6736(14)60460-8.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377:13–27. https://doi.org/10.1056/NEJMoa1614362.

    Article  PubMed  Google Scholar 

  4. Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10. https://doi.org/10.1016/j.metabol.2018.09.005.

    Article  CAS  PubMed  Google Scholar 

  5. World Health Organization. Obesity and overweight fact sheet. In: WHO Media Centre. Cited February 16, 2018. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed November 25, 2019.

  6. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32:1431–7. https://doi.org/10.1038/ijo.2008.102.

    Article  CAS  Google Scholar 

  7. Dixon JB. The effect of obesity on health outcomes. Mol Cell Endocrinol. 2010;316:104–8. https://doi.org/10.1016/j.mce.2009.07.008.

    Article  CAS  PubMed  Google Scholar 

  8. Bhaskaran K, Dos-Santos-Silva I, Leon DA, Douglas IJ, Smeeth L. Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3.6 million adults in the UK. Lancet Diabetes Endocrinol. 2018;6:944–53. https://doi.org/10.1016/s2213-8587(18)30288-2.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kim DD, Basu A. Estimating the medical care costs of obesity in the United States: systematic review, meta-analysis, and empirical analysis. Value Health. 2016;19:602–13. https://doi.org/10.1016/j.jval.2016.02.008.

    Article  PubMed  Google Scholar 

  10. 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. https://doi.org/10.1097/ccm.0000000000001310.

    Article  PubMed  Google Scholar 

  11. De Jong A, Verzilli D, Sebbane M, Monnin M, Belafia F, Cisse M, et al. Medical versus surgical ICU obese patient outcome: a propensity-matched analysis to resolve clinical trial controversies. Crit Care Med. 2018;46:e294–301. https://doi.org/10.1097/ccm.0000000000002954.

    Article  PubMed  Google Scholar 

  12. Schetz M, De Jong A, Deane AM, Druml W, Hemelaar P, Pelosi P, et al. Obesity in the critically ill: a narrative review. Intensive Care Med. 2019;45:757–69. https://doi.org/10.1007/s00134-019-05594-1.

    Article  PubMed  Google Scholar 

  13. Oliveros H, Villamor E. Obesity and mortality in critically ill adults: a systematic review and meta-analysis. Obesity (Silver Spring). 2008;16:515–21. https://doi.org/10.1038/oby.2007.102.

    Article  Google Scholar 

  14. Hogue CW Jr, Stearns JD, Colantuoni E, Robinson KA, Stierer T, Mitter N, et al. The impact of obesity on outcomes after critical illness: a meta-analysis. Intensive Care Med. 2009;35:1152–70. https://doi.org/10.1007/s00134-009-1424-5.

    Article  PubMed  Google Scholar 

  15. •• Zhao Y, Li Z, Yang T, Wang M, Xi X. Is body mass index associated with outcomes of mechanically ventilated adult patients in intensive critical units? A systematic review and meta-analysis. PLoS One 2018;13:e0198669. Doi:https://doi.org/10.1371/journal.pone.0198669. This large meta-analysis of 23 studies from 4 continents and 199,421 critically ill patients receiving mechanical ventilation demonstrated that obese had lower ICU, hospital, short- and long-term mortality compared to non-obese, while obese and severely obese had lower hospital mortality compared to normal weight patients. It is the most recent meta-analysis that supports the obesity paradox in critically ill patients, despite showing that obesity is associated with longer duration of mechanical ventilation and ICU stay.

  16. • 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. Doi:https://doi.org/10.1007/s13679-019-00360-2. This review highlights recent insights in the metabolic responses to sepsis and the obesity paradox and summarizes current evidence on the role of adipose tissue and adipokines in sepsis severity and outcome.

  17. 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. https://doi.org/10.1186/s13054-016-1360-z.

    Article  PubMed  PubMed Central  Google Scholar 

  18. • Ni YN, Luo J, Yu H, Wang YW, Hu YH, Liu D et al. Can body mass index predict clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome? A meta-analysis. Crit Care 2017;21:36. Doi:https://doi.org/10.1186/s13054-017-1615-3. This meta-analysis exploring the association of BMI with outomes of adult patients with ARDS included 5 multicenter studies from the USA and found that obese and morbidly obese had lower mortality compared to normal weight patients.

  19. Carbone S, Canada JM, Billingsley HE, Siddiqui MS, Elagizi A, Lavie CJ. Obesity paradox in cardiovascular disease: where do we stand? Vasc Health Risk Manag. 2019;15:89–100. https://doi.org/10.2147/vhrm.s168946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. De Schutter A, Lavie CJ, Milani RV. The impact of obesity on risk factors and prevalence and prognosis of coronary heart disease-the obesity paradox. Prog Cardiovasc Dis. 2014;56:401–8. https://doi.org/10.1016/j.pcad.2013.08.003.

    Article  PubMed  Google Scholar 

  21. Vareldzis R, Naljayan M, Reisin E. The incidence and pathophysiology of the obesity paradox: should peritoneal dialysis and kidney transplant be offered to patients with obesity and end-stage renal disease? Curr Hypertens Rep. 2018;20:84. https://doi.org/10.1007/s11906-018-0882-y.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Akinnusi ME, Pineda LA, El Solh AA. Effect of obesity on intensive care morbidity and mortality: a meta-analysis. Crit Care Med. 2008;36:151–8. https://doi.org/10.1097/01.ccm.0000297885.60037.6e.

    Article  PubMed  Google Scholar 

  23. •• 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. Doi:https://doi.org/10.1186/s12871-017-0405-4. This systematic review and meta-analysis pooled data from 8 studies and 9696 patients with sepsis and showed that overweight, but not obese and morbidly obese, had significantly lower mortality.

  24. Zhi G, Xin W, Ying W, Guohong X, Shuying L. “Obesity paradox” in acute respiratory distress syndrome: asystematic review and meta-analysis. PLoS One. 2016;11:e0163677. https://doi.org/10.1371/journal.pone.0163677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu T, Chen JJ, Bai XJ, Zheng GS, Gao W. The effect of obesity on outcomes in trauma patients: a meta-analysis. Injury. 2013;44:1145–52. https://doi.org/10.1016/j.injury.2012.10.038.

    Article  PubMed  Google Scholar 

  26. Harris K, Zhou J, Liu X, Hassan E, Badawi O. The obesity paradox is not observed in critically ill patients on early enteral nutrition. Crit Care Med. 2017;45:828–34. https://doi.org/10.1097/ccm.0000000000002326.

    Article  PubMed  Google Scholar 

  27. Mukhopadhyay A, Kowitlawakul Y, Henry J, Ong V, Leong CS, Tai BC. Higher BMI is associated with reduced mortality but longer hospital stays following ICU discharge in critically ill Asian patients. Clin Nutr ESPEN. 2018;28:165–70. https://doi.org/10.1016/j.clnesp.2018.08.009.

    Article  PubMed  Google Scholar 

  28. •• Acharya P, Upadhyay L, Qavi A, Naaraayan A, Jesmajian S, Acharya S et al. The paradox prevails: outcomes are better in critically ill obese patients regardless of the comorbidity burden. J Crit Care 2019;53:25–31. Doi:https://doi.org/10.1016/j.jcrc.2019.05.004. This is an interesting retrospective review of a large US single-center database of critically ill patients exploring the possibility that differences in the comorbidity burden might explain the obesity paradox in critical illness. The authors evaluated 30 comorbidities in a cohort of 11,433 ICU patients and found that, regardless of the comorbidity burden, overweight and obese had decreased risk for hospital and 30-day mortality compared to normal weight with a consistent trend towards lower mortality with higher BMI.

  29. •• Toft-Petersen AP, Wulff J, Harrison DA, Ostermann M, Margarson M, Rowan KM et al. Exploring the impact of using measured or estimated values for height and weight on the relationship between BMI and acute hospital mortality. J Crit Care 2018;44:196–202. Doi:https://doi.org/10.1016/j.jcrc.2017.11.021. This study of 690,405 critically ill patients in the UK addresses the methodological problem of whether estimated weight and height affects the association of BMI with mortality compared to measured values. The researchers report that this association was independent of measurement or estimation of weight and height and also demonstrated a J-shaped association of BMI with mortality with the “optimal” range well above the normal BMI values, in the obesity range, supporting the obesity-related survival benefit in critical illness.

  30. Kumar SI, Doo K, Sottilo-Brammeier J, Lane C, Liebler JM. Super obesity in the medical intensive care unit. J Intensive Care Med. 2018;885066618761363:478–84. https://doi.org/10.1177/0885066618761363.

    Article  Google Scholar 

  31. • Li S, Hu X, Xu J, Huang F, Guo Z, Tong L et al. Increased body mass index linked to greater short- and long-term survival in sepsis patients: A retrospective analysis of a large clinical database. Int J Infect Dis 2019;87:109–16. Doi:https://doi.org/10.1016/j.ijid.2019.07.018. In this retrospective analysis from a US medical institution, overweight and obese critically ill patients with sepsis had lower 30-day and 1-year mortality, after adjustment for confounding factors, compared to normal weight patients.

  32. •• 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. Doi:https://doi.org/10.1097/ccm.0000000000003692. This retrospective study of a large clinical data repository of 139 US hospitals demonstrated that adult patients with sepsis and higher body mass indices had lower hospital mortality compared to normal weight patients, both in unadjusted and adjusted analyses.

  33. Gameiro J, Goncalves M, Pereira M, Rodrigues N, Godinho I, Neves M, et al. Obesity, acute kidney injury and mortality in patients with sepsis: a cohort analysis. Ren Fail. 2018;40:120–6. https://doi.org/10.1080/0886022x.2018.1430588.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Druml W, Zajic P, Winnicki W, Fellinger T, Metnitz B, Metnitz P. Association of body mass index and outcome in acutely ill patients with chronic kidney disease requiring intensive care therapy. J Ren Nutr. 2019. https://doi.org/10.1053/j.jrn.2019.09.006.

  35. Galvagno SM Jr, Pelekhaty S, Cornachione CR, Deatrick KB, Mazzeffi MA, Scalea TM, et al. Does weight matter? Outcomes in adult patients on venovenous extracorporeal membrane oxygenation when stratified by obesity class. Anesth Analg. 2019. https://doi.org/10.1213/ane.0000000000004454.

  36. Ball IM, Bagshaw SM, Burns KE, Cook DJ, Day AG, Dodek PM, et al. Outcomes of elderly critically ill medical and surgical patients: a multicentre cohort study. Can J Anaesth. 2017;64:260–9. https://doi.org/10.1007/s12630-016-0798-4.

    Article  PubMed  Google Scholar 

  37. Benjamin ER, Dilektasli E, Haltmeier T, Beale E, Inaba K, Demetriades D. The effects of body mass index on complications and mortality after emergency abdominal operations: the obesity paradox. Am J Surg. 2017;214:899–903. https://doi.org/10.1016/j.amjsurg.2017.01.023.

    Article  PubMed  Google Scholar 

  38. Wacharasint P, Fuengfoo P, Rangsin R, Morakul S, Chittawattanarat K, Chaiwat O. Prevalence and impact of overweight and obesity in critically ill surgical patients: analysis of THAI-SICU study. J Med Assoc Thail. 2016;99(Suppl 6):S55–s62.

    Google Scholar 

  39. Finkielman JD, Gajic O, Afessa B. Underweight is independently associated with mortality in post-operative and non-operative patients admitted to the intensive care unit: a retrospective study. BMC Emerg Med. 2004;4:3. https://doi.org/10.1186/1471-227x-4-3.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Tafelski S, Yi H, Ismaeel F, Krannich A, Spies C, Nachtigall I. Obesity in critically ill patients is associated with increased need of mechanical ventilation but not with mortality. J Infect Public Health. 2016;9:577–85. https://doi.org/10.1016/j.jiph.2015.12.003.

    Article  PubMed  Google Scholar 

  41. Nasraway SA Jr, Albert M, Donnelly AM, Ruthazer R, Shikora SA, Saltzman E. Morbid obesity is an independent determinant of death among surgical critically ill patients. Crit Care Med. 2006;34:964–70; quiz 71. https://doi.org/10.1097/01.ccm.0000205758.18891.70.

    Article  PubMed  Google Scholar 

  42. El-Solh A, Sikka P, Bozkanat E, Jaafar W, Davies J. Morbid obesity in the medical ICU. Chest. 2001;120:1989–97. https://doi.org/10.1378/chest.120.6.1989.

    Article  CAS  PubMed  Google Scholar 

  43. Ray DE, Matchett SC, Baker K, Wasser T, Young MJ. The effect of body mass index on patient outcomes in a medical ICU. Chest. 2005;127:2125–31. https://doi.org/10.1378/chest.127.6.2125.

    Article  PubMed  Google Scholar 

  44. Cereda E, Klersy C, Hiesmayr M, Schindler K, Singer P, Laviano A, et al. Body mass index, age and in-hospital mortality: the NutritionDay multinational survey. Clin Nutr. 2017;36:839–47. https://doi.org/10.1016/j.clnu.2016.05.001.

    Article  PubMed  Google Scholar 

  45. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. Jama. 2013;309:71–82. https://doi.org/10.1001/jama.2012.113905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Barazzoni R, Sulz I, Schindler K, Bischoff SC, Gortan Cappellari G, Hiesmayr M. A negative impact of recent weight loss on in-hospital mortality is not modified by overweight and obesity. Clin Nutr. 2019. https://doi.org/10.1016/j.clnu.2019.11.007.

  47. Robinson MK, Mogensen KM, Casey JD, McKane CK, Moromizato T, Rawn JD, et al. The relationship among obesity, nutritional status, and mortality in the critically ill. Crit Care Med. 2015;43:87–100. https://doi.org/10.1097/ccm.0000000000000602.

    Article  CAS  PubMed  Google Scholar 

  48. Neeland IJ, Poirier P, Despres JP. Cardiovascular and metabolic heterogeneity of obesity: clinical challenges and implications for management. Circulation. 2018;137:1391–406. https://doi.org/10.1161/circulationaha.117.029617.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Antonopoulos AS, Tousoulis D. The molecular mechanisms of obesity paradox. Cardiovasc Res. 2017;113:1074–86. https://doi.org/10.1093/cvr/cvx106.

    Article  CAS  PubMed  Google Scholar 

  50. Dixon JB, Egger GJ, Finkelstein EA, Kral JG, Lambert GW. ‘Obesity paradox’ misunderstands the biology of optimal weight throughout the life cycle. Int J Obes. 2015;39:82–4. https://doi.org/10.1038/ijo.2014.59.

    Article  CAS  Google Scholar 

  51. McGee DL. Body mass index and mortality: a meta-analysis based on person-level data from twenty-six observational studies. Ann Epidemiol. 2005;15:87–97. https://doi.org/10.1016/j.annepidem.2004.05.012.

    Article  PubMed  Google Scholar 

  52. Global BMIMC, Di Angelantonio E, Bhupathiraju Sh N, Wormser D, Gao P, Kaptoge S, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016;388:776–86. https://doi.org/10.1016/s0140-6736(16)30175-1.

    Article  Google Scholar 

  53. Afzal S, Tybjaerg-Hansen A, Jensen GB, Nordestgaard BG. Change in body mass index associated with lowest mortality in Denmark, 1976-2013. Jama. 2016;315:1989–96. https://doi.org/10.1001/jama.2016.4666.

    Article  CAS  PubMed  Google Scholar 

  54. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89:2548–56. https://doi.org/10.1210/jc.2004-0395.

    Article  CAS  PubMed  Google Scholar 

  55. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85–97. https://doi.org/10.1038/nri2921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Oikonomou EK, Antoniades C. The role of adipose tissue in cardiovascular health and disease. Nat Rev Cardiol. 2019;16:83–99. https://doi.org/10.1038/s41569-018-0097-6.

    Article  PubMed  Google Scholar 

  57. Wang P, Mariman E, Renes J, Keijer J. The secretory function of adipocytes in the physiology of white adipose tissue. J Cell Physiol. 2008;216:3–13. https://doi.org/10.1002/jcp.21386.

    Article  CAS  PubMed  Google Scholar 

  58. Dalamaga M, Chou SH, Shields K, Papageorgiou P, Polyzos SA, Mantzoros CS. Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metab. 2013;18:29–42. https://doi.org/10.1016/j.cmet.2013.05.010.

    Article  CAS  PubMed  Google Scholar 

  59. Pellegrinelli V, Carobbio S, Vidal-Puig A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia. 2016;59:1075–88. https://doi.org/10.1007/s00125-016-3933-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sun K, Tordjman J, Clement K, Scherer PE. Fibrosis and adipose tissue dysfunction. Cell Metab. 2013;18:470–7. https://doi.org/10.1016/j.cmet.2013.06.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Koliaki C, Liatis S, Dalamaga M, Kokkinos A. Sarcopenic obesity: epidemiologic evidence, pathophysiology, and therapeutic perspectives. Curr Obes Rep. 2019;8:458–71. https://doi.org/10.1007/s13679-019-00359-9.

    Article  PubMed  Google Scholar 

  62. Vallianou N, Stratigou T, Christodoulatos GS, Dalamaga M. Understanding the role of the gut microbiome and microbial metabolites in obesity and obesity-associated metabolic disorders: current evidence and perspectives. Curr Obes Rep. 2019;8:317–32. https://doi.org/10.1007/s13679-019-00352-2.

    Article  PubMed  Google Scholar 

  63. Emfietzoglou R, Spyrou N, Mantzoros CS, Dalamaga M. Could the endocrine disruptor bisphenol-A be implicated in the pathogenesis of oral and oropharyngeal cancer? Metabolic considerations and future directions. Metabolism. 2019;91:61–9. https://doi.org/10.1016/j.metabol.2018.11.007.

    Article  CAS  PubMed  Google Scholar 

  64. Avgerinos KI, Spyrou N, Mantzoros CS, Dalamaga M. Obesity and cancer risk: emerging biological mechanisms and perspectives. Metabolism. 2019;92:121–35. https://doi.org/10.1016/j.metabol.2018.11.001.

    Article  CAS  PubMed  Google Scholar 

  65. Langouche L, Perre SV, Thiessen S, Gunst J, Hermans G, D'Hoore A, et al. Alterations in adipose tissue during critical illness: an adaptive and protective response? Am J Respir Crit Care Med. 2010;182:507–16. https://doi.org/10.1164/rccm.200909-1395OC.

    Article  PubMed  Google Scholar 

  66. Langouche L, Marques MB, Ingels C, Gunst J, Derde S, Vander Perre S, et al. Critical illness induces alternative activation of M2 macrophages in adipose tissue. Crit Care. 2011;15:R245. https://doi.org/10.1186/cc10503.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Marques MB, Langouche L. Endocrine, metabolic, and morphologic alterations of adipose tissue during critical illness. Crit Care Med. 2013;41:317–25. https://doi.org/10.1097/CCM.0b013e318265f21c.

    Article  CAS  PubMed  Google Scholar 

  68. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32:593–604. https://doi.org/10.1016/j.immuni.2010.05.007.

    Article  CAS  PubMed  Google Scholar 

  69. Mittwede PN, Clemmer JS, Bergin PF, Xiang L. Obesity and critical illness: insights from animal models. Shock 2016;45:349–358. Doi:https://doi.org/10.1097/shk.0000000000000512.

  70. Karampela I, Christodoulatos GS, Kandri E, Antonakos G, Vogiatzakis E, Dimopoulos G, et al. Circulating eNampt and resistin as a proinflammatory duet predicting independently mortality in critically ill patients with sepsis: a prospective observational study. Cytokine. 2019;119:62–70. https://doi.org/10.1016/j.cyto.2019.03.002.

    Article  CAS  PubMed  Google Scholar 

  71. Wacharasint P, Boyd JH, Russell JA, Walley KR. One size does not fit all in severe infection: obesity alters outcome, susceptibility, treatment, and inflammatory response. Crit Care. 2013;17:R122. https://doi.org/10.1186/cc12794.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Stapleton RD, Dixon AE, Parsons PE, Ware LB, Suratt BT. The association between BMI and plasma cytokine levels in patients with acute lung injury. Chest. 2010;138:568–77. https://doi.org/10.1378/chest.10-0014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Maia LA, Cruz FF, de Oliveira MV, Samary CS, Fernandes MVS, Trivelin SAA, et al. Effects of obesity on pulmonary inflammation and remodeling in experimental moderate acute lung injury. Front Immunol. 2019;10:1215. https://doi.org/10.3389/fimmu.2019.01215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bornstein SR, Licinio J, Tauchnitz R, Engelmann L, Negrao AB, Gold P, et al. Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion. J Clin Endocrinol Metab. 1998;83:280–3. https://doi.org/10.1210/jcem.83.1.4610.

    Article  CAS  PubMed  Google Scholar 

  75. Torpy DJ, Bornstein SR, Chrousos GP. Leptin and interleukin-6 in sepsis. Horm Metab Res. 1998;30:726–9. https://doi.org/10.1055/s-2007-978967.

    Article  CAS  PubMed  Google Scholar 

  76. Grigoras I, Branisteanu DD, Ungureanu D, Rusu D, Ristescu I. Early dynamics of leptin plasma level in surgical critically ill patients. A prospective comparative study. Chirurgia (Bucur). 2014;109:66–72.

    CAS  Google Scholar 

  77. 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. https://doi.org/10.1186/s12950-016-0138-z.

    Article  CAS  Google Scholar 

  78. Karampela I, Kandri E, Antonakos G, Vogiatzakis E, Christodoulatos GS, Nikolaidou A, et al. Kinetics of circulating fetuin-A may predict mortality independently from adiponectin, high molecular weight adiponectin and prognostic factors in critically ill patients with sepsis: a prospective study. J Crit Care. 2017;41:78–85. https://doi.org/10.1016/j.jcrc.2017.05.004.

    Article  CAS  PubMed  Google Scholar 

  79. Dalamaga M, Karampela I. Fetuin-A to adiponectin ratio is a promising prognostic biomarker in septic critically ill patients. J Crit Care. 2018;44:134–5. https://doi.org/10.1016/j.jcrc.2017.10.040.

    Article  CAS  PubMed  Google Scholar 

  80. Kordonowy LL, Burg E, Lenox CC, Gauthier LM, Petty JM, Antkowiak M, et al. Obesity is associated with neutrophil dysfunction and attenuation of murine acute lung injury. Am J Respir Cell Mol Biol. 2012;47:120–7. https://doi.org/10.1165/rcmb.2011-0334OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Chien JY, Jerng JS, Yu CJ, Yang PC. Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis. Crit Care Med. 2005;33:1688–93. https://doi.org/10.1097/01.ccm.0000171183.79525.6b.

    Article  CAS  PubMed  Google Scholar 

  82. Li J, Papadopoulos V, Vihma V. Steroid biosynthesis in adipose tissue. Steroids. 2015;103:89–104. https://doi.org/10.1016/j.steroids.2015.03.016.

    Article  CAS  PubMed  Google Scholar 

  83. Kalupahana NS, Moustaid-Moussa N. The adipose tissue renin-angiotensin system and metabolic disorders: a review of molecular mechanisms. Crit Rev Biochem Mol Biol. 2012;47:379–90. https://doi.org/10.3109/10409238.2012.694843.

    Article  CAS  PubMed  Google Scholar 

  84. Yvan-Charvet L, Quignard-Boulange A. Role of adipose tissue renin-angiotensin system in metabolic and inflammatory diseases associated with obesity. Kidney Int. 2011;79:162–8. https://doi.org/10.1038/ki.2010.391.

    Article  CAS  PubMed  Google Scholar 

  85. Hastie CE, Padmanabhan S, Slack R, Pell AC, Oldroyd KG, Flapan AD, et al. Obesity paradox in a cohort of 4880 consecutive patients undergoing percutaneous coronary intervention. Eur Heart J. 2010;31:222–6. https://doi.org/10.1093/eurheartj/ehp317.

    Article  CAS  PubMed  Google Scholar 

  86. Goossens C, Marques MB, Derde S, Vander Perre S, Dufour T, Thiessen SE, et al. Premorbid obesity, but not nutrition, prevents critical illness-induced muscle wasting and weakness. J Cachexia Sarcopenia Muscle. 2017;8:89–101. https://doi.org/10.1002/jcsm.12131.

    Article  PubMed  Google Scholar 

  87. Derde S, Vanhorebeek I, Guiza F, Derese I, Gunst J, Fahrenkrog B, et al. Early parenteral nutrition evokes a phenotype of autophagy deficiency in liver and skeletal muscle of critically ill rabbits. Endocrinology. 2012;153:2267–76. https://doi.org/10.1210/en.2011-2068.

    Article  CAS  PubMed  Google Scholar 

  88. Vanhorebeek I, Van den Berghe G. Hormonal and metabolic strategies to attenuate catabolism in critically ill patients. Curr Opin Pharmacol. 2004;4:621–8. https://doi.org/10.1016/j.coph.2004.07.007.

    Article  CAS  PubMed  Google Scholar 

  89. Kiraly L, Hurt RT, Van Way CW, 3rd. The outcomes of obese patients in critical care. JPEN J Parenter Enteral Nutr 2011;35:29s–35s. Doi:https://doi.org/10.1177/0148607111413774.

  90. Flegal KM, Ioannidis JPA. The obesity paradox: a misleading term that should be abandoned. Obesity (Silver Spring). 2018;26:629–30. https://doi.org/10.1002/oby.22140.

    Article  Google Scholar 

  91. Nie W, Zhang Y, Jee SH, Jung KJ, Li B, Xiu Q. Obesity survival paradox in pneumonia: a meta-analysis. BMC Med. 2014;12:61. https://doi.org/10.1186/1741-7015-12-61.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Irene Karampela.

Ethics declarations

Conflict of Interest

Irene Karampela, Evangelia Chrysanthopoulou, Gerasimos Socrates Christodoulatos, and Maria Dalamaga declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

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

This article is part of the Topical Collection on Metabolism

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karampela, I., Chrysanthopoulou, E., Christodoulatos, G.S. et al. Is There an Obesity Paradox in Critical Illness? Epidemiologic and Metabolic Considerations. Curr Obes Rep 9, 231–244 (2020). https://doi.org/10.1007/s13679-020-00394-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13679-020-00394-x

Keywords

  • Body mass index
  • Critically ill
  • Mortality
  • Obese
  • Obesity paradox
  • Overweight
  • Sepsis
  • Survival