Association Between Interleukin-10 Gene (-1082g/A) Polymorphism and Type 2 Diabetes, Diabetes-Related Traits, and Microvascular Complications in the Croatian Population.

Interleukin (IL)-10 is an anti-inflammatory cytokine, and a decrease in its secretion is associated with obesity, metabolic syndrome and type 2 diabetes. However, it has not been established whether the intensity of the immune response during diabetes-associated chronic inflammation affects the development and/or progression of type 2 diabetes and its microvascular complications. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP)-1082G/A for IL-10 gene in development of diabetes type 2 and its complications. DNA was extracted from blood cells of 240 overweight/obese subjects for IL-10 genotyping. Based on the presence of diabetes type 2, patients were divided in two groups: experimental group of 144 patients with diabetes type 2 and control group of 96 age- and gender-matched subjects without diabetes. Compared to control group, diabetic group had higher levels of leukocytes (p=0.012), fibrinogen (p=0.049) and plasminogen activator inhibitor-1 (PAI-1) (p=0.009), and lower levels of albumin (p=0.001). There were no differences in the frequency of SNP-1082G/A for IL-10 gene between the two groups (p=0.654). When considering diabetes related traits in all subjects in relation to specific genotype, a group with homozygous (AA) genotype had higher values of the mean fasting glucose (p<0.000001), HbA1c (p<0.000001) and HOMA-IR (p=0.003632), while the mean HOMA-B value (p=0.000178) was lower when compared to the groups with GG and GA genotypes. There was no difference in devel-opment of diabetic nephropathy, retinopathy and polyneuropathy between the IL-10 polymorphism genotypes. In conclusion, obese diabetes type 2 patients had an increased inflammation activity com-pared to obese non-diabetic individuals. There was no association of the investigated polymorphisms and development of type 2 diabetes and its microvascular complications. However, diabetes related traits clearly depended on the presence of specific IL-10 genotype.

Postoperative immunosuppression markers and the occurrence of sepsis in patients with benign and malignant disease.

AIM: To investigate associations between the postoperative immune response and the levels of extracellular circulating DNA (cDNA), C-reactive protein (CRP), neutrophil/lymphocyte (N/L) ratio, and regulatory T (Treg) cells in the peripheral blood and their role as potential predictors of postoperative septic complications. METHODS: This was a prospective observational study involving 115 adult patients who underwent elective surgery. Patients were divided into three groups: with benign disease, with malignant disease, and with malignant disease and administration of dexamethasone. Serum CRP levels, N/L ratio, monocyte human leukocyte antigen-DR (HLA-DR) expression, proportion of Treg cells, and cDNA levels were measured at different time points before and after surgery. RESULTS: All patients had increased CRP levels after surgery. Septic patients had higher serum CRP levels at baseline. Compared with the other groups, the dexamethasone group had significantly higher CRP levels before and after surgery, a significantly higher N/L ratio before surgery, a significantly lower rise in the N/L ratio after surgery, and a significantly lower HLA-DR expression at baseline, which remained stable after surgery. In the malignant-disease group, we observed a significant postoperative decrease in the HLA-DR expression. CONCLUSIONS: Our results suggest that the immunosuppressive effect of surgery and the presence of a malignant disease may contribute to a higher risk of postoperative sepsis. Preoperative CRP levels may be a reliable predictor of sepsis in oncological patients.

Kinetics of changes in serum concentrations of procalcitonin, interleukin-6, and C- reactive protein after elective abdominal surgery. Can it be used to detect postoperative complications?

Postoperative increase in inflammation biologic markers is associated with a nonspecific inflammatory response to a surgical injury. We investigated the kinetics of changes in serum concentrations of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6) after abdominal surgeries and we focused on the behaviour of those markers in the case of development of the systemic inflammatory response syndrome (SIRS). In the single centre we conducted a prospective observational study and we included patients admitted to the ICU after elective abdominal surgery. A total of 41 patients were included and 8 (19.5%) of them had clinical and laboratory signs of SIRS. Sepsis was confirmed in one of the patients, a 72-year old patient operated due to having an abdominal aortic aneurysm. Plasma concentrations of PCT, CRP and IL-6 were measured in all the patients before surgery and at the postoperative day 1 (POD1), postoperative day 2 (POD2) and postoperative day 3 (POD3). Systemic release of PCT, CRP and IL-6 was present in all the measured time points after the abdominal surgery. Median concentrations of IL-6 (100.4 pg/mL) and PCT (1, 17 pg/mL) production were measured highest at POD1 and the median of CRP (147 mg/L) was measured at highest POD2. A larger increase of all three measured markers was found in patients with SIRS compared to those without. IL-6 at POD1 and POD2 was a good predictor of SIRS (areas under curves were 0.71 and 0.765, respectively), showing the highest accuracy among investigated markers at those time points. CRP at POD3 was a good predictor of SIRS (AUC was 0.76). A cut-off of 95 mg/mL in the level of CRP at POD3 yielded a sensitivity of 87.5% and specificity of 66.7% in detecting SIRS. IL-6 and CRP were the best in detecting postoperative SIRS after abdominal surgery with the highest area under ROC curve. This study is showing that PCT is not a good marker of SIRS caused only by surgical injury without sepsis.