Objective: The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-a protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNFa, 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-a protein. Serum TNF-a, sTNFR-2 (ELISA) and fasting C-peptide (RIA) were measured. Results: TNF-a 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-a (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 ¼ 0.005) were found in the obese subgroup in correlation with the fasting C-peptide level (r ¼ 0.49, P ¼ 0.003; and r ¼ 0.74, P ¼ 0.001) and the C-peptide/ blood glucose ratio (r ¼ 0.47, Spearman, P ¼ 0.005; and r ¼ 0.70, P ¼ 0.001). The cell volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-a and sTNFR-2 levels in the total group of patients (subcutaneous: r ¼ 0.52, P ¼ 0.0003; r ¼ 0.69, P , 0.0001; visceral: r ¼ 0.65, P , 0.0001; r ¼ 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-a, sTNFR-2 production and obesity-linked insulin resistance.

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References 1. Aso Y, Okumura K-I, Takebayashi K, Wakabayashi S, Inukai T: Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intima-media wall thickness in patients with type 2 diabetes.

Objective: We studied the significance of BsmI restriction enzyme polymorphism of the vitamin D receptor (VDR) gene and the XbaI and PvuII polymorphisms of the estrogen receptor (ER) gene in patients with type 2 diabetes n 49Y android type obesity with normal carbohydrate metabolism n 29 and healthy controls n 138X Methods: The distribution of genotypes in the study groups, as well as their relationship to fasting and 1 h postprandial serum C-peptide levels were analyzed. Results: Postprandial serum C-peptide levels of BB genotypes were significantly higher in the diabetes and obese groups 6X18^5X09 ngaml compared with other genotypes 2X71^2X45 vs. 1X721X97 ngamlY respectively, P 0X05X Among patients with type 2 diabetes and obese subjects, the XX allelic variant of the ER gene was more frequent P 0X00015X Postprandial C-peptide levels of subjects exhibiting XX genotype were significantly lower compared with those with Xx genotype 1X67^2X16 vs. 3X8^3X72 ngamlY P 0X021X The BBXx allelic combination of the VDR/ER receptor genes was less frequent in diabetic patients than in healthy subjects or in obese patients. The BBXx genotype was associated with significantly elevated postprandial C-peptide levels in all subjects compared with other combinations 9X65^3X14 vs. 1X35^2X82 ngamlY P 0X003X No difference was found in the distribution of the PvuII polymorphism of the ER gene or in the association with the C-peptide levels among study groups. Conclusion: Polymorphisms of the VDR/ER receptor genes might play a role in the pathogenesis of type 2 diabetes by influencing the secretory capacity of b-cells.

Objective: Human fetuin/a 2 -HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. Design: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. Methods: Serum AHSG was determined by radial immunodiffusion. Results: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-a (TNF-a), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-a, leptin levels and head circumference, body length and body weight of newborns. Conclusion: AHSG, TNF-a and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

TNF-alpha may be one of the factors contributing to insulin resistance and vascular dysfunction in patients with android obesity.

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