Supervisors info:
Κωνσταντίνος Γιαννούτσος, Καθηγητής, R.M Fairbanks School of Public Health, INDIANA University, Επιβλέπων
Πλουμής Πασαδάκης, Καθηγητής, Ιατρική Σχολή, Δημοκρίτειο Πανεπιστήμιο
Νικόλαος Πανταζής, ΕΔΙΠ, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Increased fat accumulation (obesity) is a risk factor for non-communicable diseases and is considered a chronic inflammatory condition. Patients undergoing hemodialysis have a survival advantage with weight gain, while the disease itself and the hemodialysis process induce the inflammatory response, which is a morbidity and mortality factor and is associated with malnutrition and protein-energy-wasting syndrome.
The aim of the study was to investigate in dialysis patients: 1) the relationship of adipokines secreted by fat tissue: adiponectin, leptin, resistin to mediators of inflammation (cytokines: IL-1β, IL-6, IL-10, IL-18, TNF-α, TGF-β, chemokine MCP-1, adhesion molecules: ICAM-1, VCAM-1, CD40L) and insulin resistance (estimated by HOMA index) and 2) the role of this secretion on survival.
Material - Methods. 54 dialysis patients (36 men, 18 women), with median age (25th, 75th percentile) 67.7 (55.2, 72.4) years old, under hemodialysis for median (25th, 75th percentile) 5.68 (1.91, 7.13) years were studied. Peripheral blood samples were obtained from all patients before the mid-week session both at the start of the study and after 6 months. Follow-up period was (median, 25th, 75th percentile) 4.1 (2.3, 8.7), range 0.6 to 12.4 years. Analysis was based on quantile regression for the median of the dependent variable (mediators of inflammation), while nonlinear models were used for survival in addition to the analog Cox models.
Results. In the initial measurements, significant explanatory variables for the median of each dependent variable were: adiponectin (μg/ml, β=7.021, p<0.001) for IL-18 (pg/ml), female gender (β=0.88, p=0.006) for CD40L (ng/ml) and ΒΜΙ (kg/m2, β=-171.54, p=0.032) for VCAM-1 (ng/ml). In the 6th month measurements, there was adiponectin (μg/ml, β=0.082, p=0.001) for IL-10 (pg/ml), leptin (ng/ml, β=8.458, p=0.060) together with ΒΜΙ (kg/m2, β=-50.23, p=0.029) and female gender (β=-252.4, p=0.07) for IL-18 (pg/ml), ΒΜΙ (kg/m2, β=-36.87, p=0.023) for ICAM-1 (ng/ml) and leptin (ng/ml, β=0.099, p=0.041) for HOMA index (mg/dl x mIU/l). About differences between 6th month and baseline measurements, in ICAM-1 (ng/ml) there was resistin (ng/ml, β=10.09, p=0.028) and in TGF-β (ng/ml) the model included leptin (ng/ml, β=1.60, p<0.001), waist circumference (cm, β=-0.929, p=0.086) and female gender (β=-25.87, p=0.041).
In survival analysis in univariate models, only age was a prognostic factor of total mortality (HR = 1.027, p = 0.023). In multivariate models, the non-linear effect of adiponectin (increased risk regarding its extreme values in subjects with less than the average BMI [26 kg / m2] or waist circumference [93 cm]) was shown. The effect of leptin was linearly favorable in both the waist circumference model (HR = 0.977, p = 0.024) and BMI one (HR=0.973, p = 0.014) as well.
Conclusions. Adiponectin is an independent prognostic factor for IL-10 and IL-18, and leptin for insulin resistance and for IL-18 and TGF-β. With respect to survival, adiponectin is characterized by a non-linear effect on thin individuals (BMI <26 kg / m2 or waist circumference <93 cm), while leptin has a favorable linear effect.
