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Leptin independently predicts development of future sepsis and determines survival in the acute phase
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Idrottsmedicin.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.ORCID iD: 0000-0002-5325-2688
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.ORCID iD: 0000-0003-2475-7131
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective: To determine if levels of the adipocyte-derived hormones leptin and adiponectin (adipokines) predict sepsis development and if intra-individual changes in circulating levels from baseline to the acute phase affect outcome.

Method: A nested case-referent study within the framework of the Northern Sweden Health and Disease Study (NSHDS) and the Northern Sweden Maternity Cohort (NSMC). Patients aged 18 years or more with documented sepsis within 24 hours after admission to the intensive care unit (ICU) were included if they had participated in a health survey and donated blood samples prior to the sepsis event, and if possible also had stored plasma from the acute phase. Two matched referents free of known sepsis were selected for each case. Baseline and acute phase plasma leptin and adiponectin levels were determined. The associations between adipokines and sepsis and its severity and outcome were determined.

Results: We identified 57 men and 97 women with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in the health survey, and 83% of them had also samples from the acute septic phase. Hyperleptinemia associated with a future sepsis event (OR 1.77, 95% CI 1.04-3.00, P=0.03), with stronger associations with severe sepsis and septic shock than with sepsis. High leptin levels were also associated with hospital death in the fully adjusted model. Leptin remained associated with sepsis in men (P=0.02), but not in women (P=0.36), after stratification and adjustment for BMI. In the acute phase, leptin increased more in men than in women (P=0.001), and high leptin levels were associated with increased risk for in-hospital death in women (OR 4.18, 95%CI 1.17-15.00, P=0.03), while being protective in men (OR 0.05, 95% CI 0.01-0.48, P=0.01). Adiponectin did not associate with sepsis or outcome.

Conclusions: Hyperleptinemia independently predicted the development of sepsis, and an unfavourable outcome in men. Adiponectin was not associated with sepsis development.

Keyword [en]
sepsis, leptin, adiponectin, case-referent study, sex
National Category
Anesthesiology and Intensive Care
URN: urn:nbn:se:umu:diva-95811OAI: diva2:761115
Available from: 2014-11-05 Created: 2014-11-05 Last updated: 2015-09-15Bibliographically approved
In thesis
1. Severe sepsis: epidemiology and sex-related differences in inflammatory markers
Open this publication in new window or tab >>Severe sepsis: epidemiology and sex-related differences in inflammatory markers
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background.  Sepsis is a syndrome associated with high mortality rates, substantial morbidity and high costs of care. The incidents of sepsis is reported to be high and controversy exists whether gender affect severity or outcome. Little is known about factors determining suscepti­bility for developing the syndrome and severity of the syndrome once developed. Early detection and adequate antibiotic administration are the mainstay of treatment and means to identify patients with particular high risk of adverse outcome are desirable. There are data to suggest that the course of sepsis and outcome from the syndrome may be influenced by inherited differences in the immunological response among humans

Aims: Paper I: Assess incidence and outcome for ICU-treated sepsis patients in this region; Paper II: Assess if there are gender differences related to characteristics, aspects of treatment or out­come in sepsis in this region. Paper III: Assess the association of baseline levels of leptin and adiponectin and future sepsis event, and association of these adipokines in the cute phase and sepsis severity and outcome. Paper IV: Assess association of baseline levels of mannose-binding lectin (MBL) and future sepsis event, and MBL levels in the acute phase in relation to sepsis severity and outcome.

Results. Paper I:  Overall ICU mortality rate was 25%, while the ICU mortality for patients with septic shock was 58% in this retrospective single university hospital cohort analysis. Cardio­vascular disease and diabetes were the most prevalent comorbidities among patients who died during hospital stay.  Paper II:  No gender-related differences in mortality or length of stay was found in this prospective single center observational study. Differences in aspects of treatment were related to differences in site of infection. Men had more often infections in skin and skin-structures, whereas women more often had abdominal infections. Early organ dysfunction asses­sed as SOFA score at admission was a stronger predictor for hospital mortality for women than for men. The discrepancy was related to the SOFA coagulation-sub score.  Paper III: In this nes­ted case-referent study hyperleptinemia at baseline predicted a first-ever sepsis event, even after adjustment for BMI and other cardiovascular risk factors. Hyperleptinemia in the acute sepsis phase was associated with reduced risk of in-hospital death in men, but associated with increased risk of in-hospital   death in women.  Paper IV: In the same matched cohort as in Paper III high baseline levels of MBL predicted a first ever sepsis event. High MBL levels in the acute phase or an increase from baseline to the acute phase associate with increased in-hospital death in women but not in men. Low MBL levels was not identified as a risk for acute sepsis or in-hospital death.

Conclusions. Mortality from severe sepsis is high, equally affecting men and women. There are differences in patient characteristics and inflammatory markers, which associate with in-hospital mortality differentially in men and women. Aspects of gender should be mandatory, and genetic analysis are desired in future sepsis research.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2014. 110 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1680
Severe sepsis, Leptin, Adiponectin, Mannose-binding lectin, Sex
National Category
Anesthesiology and Intensive Care
Research subject
urn:nbn:se:umu:diva-96214 (URN)978-91-7601-149-2 (ISBN)
Public defence
2014-12-04, Sal B, Unod T, 9 tr, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Available from: 2014-11-13 Created: 2014-11-12 Last updated: 2014-11-13Bibliographically approved

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