RESUMO
BACKGROUND: Diabetes has been shown to be an accelerating factor in the progression of atherosclerosis. The metabolic changes in diabetes contribute to modified platelet function and enhanced leukocyte-platelet aggregate formation. The attachment of activated platelets leads to the activation of leukocytes causing enhanced cytokine production and upregulation of surface adhesion molecules. Therefore, platelet-leukocyte aggregates may be of great importance in the development of cardiovascular complications. MATERIALS AND METHODS: Monocyte-platelet aggregates and monocyte Mac-1 expression were measured by flow cytometry to obtain differences between type 2 diabetic and healthy subjects. Inflammatory mediators were evaluated to assess the presence of inflammation. RESULTS: We found no signs of inflammation in type 2 diabetes; however, we observed enhanced aggregation level of monocytes and platelets. The expression of Mac-1 did not differ between diabetic and control subjects, but it was significantly higher on monocytes bearing platelets in both groups. CONCLUSIONS: Elevation of monocyte-platelet aggregates is an early marker of diabetes, which precedes the signs of inflammation. Enhanced Mac-1 expression can be observed on monocytes bearing platelets, independent from the presence of diabetes.
RESUMO
OBJECTIVE: The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume, serum TNF-alpha, soluble TNF-receptor-2 (sTNFR-2) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons. DESIGN: A cross-sectional case-control study was used. PATIENTS: Twenty-eight overweight/obese probands with normal glucose tolerance (BMI>27 kg/m(2)) and 15 lean people (BMI<25 kg/m(2)), all of them undergoing planned surgical operation, participated in the study. METHODS: Two to four grams of subcutaneous and visceral adipose tIssue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein. Serum TNF-alpha, sTNFR-2 (ELISA) and fasting C-peptide (RIA) were measured. RESULTS: TNF-alpha protein was expressed in adipocytes of both depots. The expression was evaluated visually and found to be greater in the obese patients. Significantly higher serum TNF-alpha (5.58+/-0.87 pg/ml vs 4.21+/-0.55, mean+/-s.d., P<0.01, Mann-Whitney) and sTNFR-2 levels (7.84+/-3.56 ng/ml vs 4.59+/-1.35, P=0.005) were found in the obese subgroup in correlation with the fasting C-peptide level (r=0.49, P=0.003; and r=0.74, P=0.001) and the C-peptide/ blood glucose ratio (r=0.47, Spearman, P=0.005; and r=0.70, P=0.001). The cell Volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha and sTNFR-2 levels in the total group of patients (subcutaneous: r=0.52, P=0.0003; r=0.69, P<0.0001; visceral: r=0.65, P<0.0001; r=0.63, P<0.0001) and in both subgroups. CONCLUSIONS: Adipocyte cell Volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha, sTNFR-2 production and obesity-linked insulin resistance.
