Proinflammatory cytokines and endothelial dysfunction in obese subjects: effect of weight reduction

Obesity is associated with an increased risk of developing atherosclerosis, which may be mediated, at least in part, by increased secretion of proinflammatory cytokines by adipose tissue. The aim of present study was to determine whether circulating levels of inflammatory cytokines and intercellular adhesion molecule-1 [sICAM-1] are elevated in obese subjects and whether they could be reduced by a substantical decrease in body weight. Forty-two healthy obese subjects [22 females and 20 males, age range 25 to 40 years, body mass index 35.2 +/- 3.64 Kg/m2, waist to hip ratio 0.883+0.085, and 20 age and sex matched normal weight controls were studied. Compared with nonobese subjects, obese subjects had increased basal concentrations of tumor necrosis factor-alpha [TNF-alpha]. [P<0.001], interleukin-6 [IL-6], [P<0.001] and sICAM-1 [P<0.001]. Flow mediated dilatation [FMD] was impaired in obese subjects when compared to lean controls [7.52% +/- 3.05 Vs 10.28% +/- 1.64, P<0.001]. Concentrations of TNF-alpha and lL-6 were related [P<0.001] to visceral obesity, as well as to slCAM-1 levels and FMD. After one year of a multidisciplinary program of weight reduction [diet, exercise, behavioral counseling], all obese women lost at least 10% of their original weight. Compared with baseline, sustained weight loss was associated with reduction of cytokines [TNF-alpha, IL-6] [P<0.001] and sICAM-1 [P = 0.001] concentrations in addition to improvement of FMD [P<0.001]. In obese subjects, endothelial activation and dysfunction correlates with visceral body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating endothelial dysfunction in obese subjects

Relationship between plasma homocysteine level and some cardiovascular risk factors in patients with type 2 diabetes

High plasma homocysteine [Hcy] concentration is risk factor for cardiovascular disease. Insulin resistance has been hypothesized to play an important role in the development of atherosclerotic disease. The information on the association between insulin resistance, other cardiovascular risk factors and plasma Hcy in type 2 diabetes is limited. The aim of our study was to assess the impact of insulin resistance and other cardiovascular risk factors on plasma total Hcy levels in patients with type 2 diabetes. The study included 40 patients with type 2 diabetes [aged 42.0 +/- 4.1 years] and 15 healthy controls, matched in age and sex with the patients. The following parameters were assessed: fasting plasma glucose [FPG], fasting plasma insulin [FPI], homeostasis model assessment of insulin resistance [HOMA-IR], serum total cholesterol, triglycerides, HDL-C, LDL-C and plasma total Hcy. Our study revealed significant increase in SBP, FPG, FPI, HOMA-IR, and total Hcy in type 2 diabetic patients compared to control group [137 +/- 4 vs 123 +/- 5 mmHg, 103 +/- 10.1 vs 83.2 +/- 6.9 mg/dl; 20.1 +/- 4.1 vs 8.8 +/- 3.1 mu/L, 5.8 +/- 0.8 vs 1.93 +/- 0.26, 13.6 +/- 1.2 vs 7.6 +/- 0.8 umol/L, respectively, all P<0.001]. As regard serum lipids our results revealed significant increase in total cholesterol, triglycerides and LDL-C but significant decrease in HDL-C in type 2 diabetic patients compared to control group [210 +/- 39 vs 160 +/- 21 mg/dl, 220 +/- 29 vs 106 +/- 10 mg/dl, 129 +/- 28 vs 88 +/- 21 mg/dl, 40 +/- 11 vs 52 +/- 16 mg/dl, respectively, all P<0.05]. In patients with type 2 diabetes there was significant positive correlation between total Hcy and SBP, FPG, FPI, HOMA-IR, total cholesterol and LDL-C [r = 327, P = 0.005, r = 240, P = 0.049, r = 0.513, P<0.001; r = 0.601, P<0.001, r = 0.241, P = 0.048; r = 0.250, P = 0.040 respectively], but there was significant negative correlation between total Hcy and HDL-C [r = -0.301, P = 0.009]. Increases in total homocysteine levels in type 2 diabetes are associated with insulin resistance and other cardiovascular riskfactors. Thus insulin resistance may be an important determinant of Hcy levels in those patients