Exploring the Relationship between Plasma Adiponectin, Gender, and Underlying Diseases in Severe Illness

Abstract

Adiponectin is low in obesity, plays a crucial role in metabolic health, and, moreover, possesses immunoregulatory properties. However, studies examining its levels in patients with systemic inflammatory response syndrome (SIRS) or sepsis have yielded conflicting results. While females typically have higher systemic adiponectin levels than males, research on sex-specific associations in this context is limited. In this study of 156 SIRS/sepsis patients, including those with liver cirrhosis, we aimed to explore the relationship between plasma adiponectin, body mass index (BMI), gender, disease severity, and underlying etiological conditions. Our findings revealed that patients with liver cirrhosis, who are susceptible to infections, exhibited elevated circulating adiponectin levels, irrespective of sex. When excluding cirrhosis patients, plasma adiponectin levels were similar between male SIRS/sepsis patients and controls but lower in female patients compared to female controls. Plasma adiponectin was inversely related to BMI in female but not male patients. Further analysis within the non-cirrhosis subgroup demonstrated no significant differences in adiponectin levels between sexes among SIRS, sepsis, and septic shock patients. Ventilation, dialysis, and vasopressor therapy had no discernible impact on adiponectin levels in either sex. A negative correlation between adiponectin and C-reactive protein (CRP) existed in males only. Notably, patients with pancreatitis showed the lowest plasma adiponectin concentrations, although sex-specific differences were not significant. Infection with Gram-negative or Gram-positive bacteria had minimal effects on plasma adiponectin levels in both sexes. However, infection with the severe acute respiratory syndrome coronavirus type 2 led to decreased adiponectin levels in females exclusively. Multivariate analysis considering all factors affecting plasma adiponectin levels in males or females identified BMI in females and CRP levels in males to predict plasma adiponectin levels in SIRS/sepsis patients. Additionally, our study observed a trend where the 25 patients who did not survive had higher plasma adiponectin levels, particularly among males. In summary, our investigation highlights the influence of underlying diseases and sex on plasma adiponectin levels in SIRS/sepsis patients, shedding light on potential implications for disease management and prognosis.

Keywords: COVID-19; adiponectin; liver cirrhosis; pancreatitis; sex; survival.

Figure 1

Adiponectin in the plasma of controls and systemic inflammatory response syndrome (SIRS)/sepsis patients. (a) Plasma adiponectin levels of the 22 controls and the 156 SIRS/sepsis patients; (b) Plasma adiponectin levels of the 109 male and 47 female SIRS/sepsis patients; (c) Plasma adiponectin levels of 32 SIRS/sepsis patients with and 124 SIRS/sepsis patients without liver cirrhosis; (d) Plasma adiponectin levels of 11 female controls and 38 female SIRS/sepsis patients when patients with liver cirrhosis were excluded; (e) Plasma adiponectin levels of 11 male controls and 86 male SIRS/sepsis patients when patients with liver cirrhosis were excluded; (f) Plasma adiponectin levels of 22 controls and 124 SIRS/sepsis patients of both sexes when patients with liver cirrhosis were excluded. Statistical test used: Mann–Whitney-U-test.

Figure 2

Adiponectin in the plasma of patients with systemic inflammatory response syndrome (SIRS)/sepsis stratified according to the underlying diseases and causes of SIRS/sepsis. (a) Plasma adiponectin of patients categorized according to the SIRS criteria and to the Sepsis-3 definition as SIRS (27 patients), sepsis (33 patients), and septic shock (64 patients); (b) Plasma adiponectin levels of SIRS/sepsis patients with pancreatitis (31 patients) or cholangiosepsis (9 patients); (c) Plasma adiponectin levels of SIRS/sepsis patients with pneumonia (41 patients) or urinary tract infections (14 patients); (d) Plasma adiponectin of 23 SIRS/sepsis patients with SARS-CoV-2 infection (Yes) and patients not infected by this virus (No). Statistical tests used: Kruskal–Wallis test (a), Mann–Whitney-U-test (b–d).

Figure 3

Adiponectin in the plasma of patients with SIRS/sepsis is stratified by type of bacterial infection. A total of 44 patients with no bacterial infections, 51 Gram-negative infected patients, 15 patients with Gram-positive bacteria, and 14 patients with Gram-negative and Gram-positive bacteria. Statistical test used: Kruskal–Wallis test.

Figure 4

Association of plasma adiponectin with survival. (a) Plasma adiponectin levels of the 99 systemic inflammatory response syndrome (SIRS)/sepsis patients who survived and the 25 patients who did not survive; (b) Plasma adiponectin levels of the 84 SIRS/sepsis patients who survived and the 18 patients who did not survive when patients with COVID-19 and liver cirrhosis were excluded. Statistical test used: Mann–Whitney-U-test; (c) Receiver operating characteristic curve for non-survival of male SIRS/sepsis patients (13 patients died and 57 survived) with COVID-19 and liver cirrhosis were excluded.