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

Diurnal pattern of plasma endothelin-1: effect on endothelium-dependent vasodilatation in patients with stable angina pectoris

This study included two groups of patients: Group I included 20 patients with stable angina pectoris [SA] [18 men and 2 women, aged 50.51 +/- 8.29 years] and group II included 20 healthy subjects [17 males and 3 females, aged 48.11 +/- 6.31 years] taken as a control group. Flow-mediated vasodilatation [FMD] of the brachial artery [a surrogate for endothelium-dependent vasodilatation] was determined by ultrasound at 8 a.m. and 8 p.m. Also, carotid artery intima-media thickness [IMT] was determined by ultrasound. The plasma levels of C- reactive protein [CRP] and ET-1 were determined at 8 a.m. and 8 p.m. The study included that the normal subjects had diurnal variation in endothelium-dependent vasodilatation that may counteract other, potentially adverse, diurnal variations in the hemodynamic and other parameters. In contrast, patients with SA showed a loss of this protective mechanism. No diurnal variation in plasma CRP was found to explain this finding. Diurnal variation in plasma ET-1 levels is likely one of the mechanisms involved in the pathogenesis of this phenomenon

Serum testosterone and carotid atherosclerosis in men with type 2 diabetes: is there a link?

This study included 50 male patients with type 2 diabetes aged 56.2 +/- 7.8 years, with a body mass index [BMI] of 28.3 +/- 2.6 kg/m 2, a duration of diabetes 10.6 +/- 6.4 years; in addition, 25 age- matched lean healthy subjects were taken as a control group. Body mass index [BMI], waist to hip ratio [WHR], plasma lipids, homeostasis model assessment of insulin resistance [HOMA-IR], plasminogen activator inhibitor-1 antigen [PAI-1 Ag] and plasma total testosterone [T] were assessed. Carotid intima-media thickness [IMT] and plaque score [PS] were evaluated by ultrasound. The study concluded that total serum testosterone is inversely associated with carotid atherosclerosis determined by ultrasonographically evaluated carotid IMT and PS in men with type 2 diabetes. Low serum testosterone is associated with an adverse cardiovascular risk profile in these patients

Plasma soluble tumor necrosis factor alpha receptor 2 in obese subjects with impaired glucose tolerance

A total of 55 subjects participated in this study; 20 obese subjects with normal glucose tolerance [NGT], 20 obese subjects with impaired glucose tolerance [IGT] and 15 lean healthy control subjects with NGT. Body mass index [BMI], waist to hip ratio [WHR], plasma lipids and homeostasis model assessment of insulin resistance [HOMA-IR] were assessed. Plasma tumor necrosis factor-alpha [TNF-alpha] and soluble tumor necrosis factor receptor 2 [sTNFR2] were assessed by enzyme- linked immunosorbent assay [ELISA]. The study concluded that obese IGT subjects are more insulin resistant compared with the matched obese NGT subjects. The further increase in insulin resistance in IGT group is not due to the increase in plasma TNF-alpha and may be due to up-regulation of TNF-alpha system manifested by the increased plasma sTNFR2 levels. Therefore, sTNFR2 might be a better marker of TNF- alpha action in insulin-resistant states such as obese IGT subjects than the circulating cytokine itself

Insulin resistance and hyperinsulinemia: independent relation to left ventricular mass in humans

Hyperinsulinemia and insulin resistance may contribute to the development of cardiac hypertrophy which is a major cardiovascular risk factor. In humans, however, the evidence is inconclusive. Antihypertensive drugs have different effects on insulin metabolism, sensitivity, and on left ventricular mass [LVM]. To study the association between LVM and insulin resistance as well as some other cardiovascular risk factors. Also, to compare the effects of two drugs [Atenolol, lisinopril], which have different effects on insulin sensitivity on LVM. The study included four groups: Group [I] control group included 10 healthy lean females aged 35.7+3.4 years. Group [II] included 28 obese normotensive female patients aged 35.39+3.9 1 years, body mass index [BMI] 36.18+3.93 Kg/m2. Group [III] included 28 newly diagnosed obese hypertensive female patients aged 35.85+ 7.8 years, BMI 39.34+4.12 Kg/m2. Group [IV] included 28 newly diagnosed lean hypertensive female patients aged 34.36+4.45 years, BMI 22.98+1.60 Kg/m2. Patients in groups III and IV were randomized to treatment with atenolol or lisinopril [14 patients in each group]. The following parameters were assessed BMI, WHR, systolic and diastolic blood pressure, fasting plasma glucose and insulin, fasting insulin resistance index [FIRI], LVM and left ventricular mass index [LVMI]. Obese and hypertensive patients had significant increase in insulin resistance, LVM and LVMI compared to controls [P<0.05]. Abdominal obesity as repesented by WHR, was directly associated with insulin resistance, LVM, and LVMI [r = 0.749, P<0.001; r = 0.523,P<0.O01; r = 0.656, P<0.001 respectively]. LVM was positively correlated with systolic and diastolic blood pressure, BMI. WHR, and insulin resistance [r = 0.749, P<0.001; r = 0.639, P<0.001; r = 0.224, P = 0.041, r = 0.523, P<0.001; r = 0.509, P<0.001 respectively]. After adjustment for systemic blood pressure and obesity, LVM was independently associated with insulin resistance [P<0.001]; Lisinopril, but not atenolol was associated with favorable effect on insulin resistance and led to more significant regression of LVM in lean [P<0.001] and obese [p = 0:004] hypertesnive patients. LVM has a positive independent correlation with hyperinsulinemia and insulin resistance. Hyperinsulinemia has independent role in promoting left ventricular hypertrophy. Agents and maneuvers which improve insulin sensitivity might be beneficial in management of left ventricular hypertrnphy and other deleterious effects of hyperinsulinemia

Plasma adrenomedullin, a new predictor of prognosis and severity in patients with dilated cardiomyopathy and heart failure

Adrenomedullin, a potent endogenous vasodilating and natriuretic peptide, may play an important role in the pathophysiology of chronic heart failure associated with dilated cardiomyopathy. To determine the changes of plasma adrenomedullin [AM] in patients with heart failure due to dilated cardiomyopathy of ischemic and idiopathic etiology before and after treatment and the relations between plasma AM and some hormones involved in the pathophysiology of heart failure as plasma renin activity [PRA], atrial natriuretic peptide [ANP] and aldosterone as well as some echocardiographic parameters. Also, the predictive value of AM in assessment of severity of heart failure was evaluated. Design 44 patients with symptomatic dilated cardiomyopathy due to is chemic and idiopathic etiology [24 females and 20 males], aged 53.37 +/- 9.38 years and matched to 13 healthy volunteers [8 females and 5 males] aged 54.3 +/- 8.6 years. Cases were classified according to the New York Heart Association [NYHA] functional classification into: 12 cases class 1, 10 cases class 11, 13 cases class III and 9 cases class IV Cases were subjected to thorough history, clinical and laboratory investigations with special stress on plain x-ray chest, ECG, and echocardiography to exclude other etiologies of heart failure. Assay of plasma AM, PRA, ANP and aldosterone was done. Plasma AM, PRA, ANP and aldosterone were significantly higher in patients compared to controls [27.91 +/- 15.19 Vs 11.1 7 +/- 1.55 pmol/L 2.20 +/- 1.48 Vs 0.35 +/- 0.10 ng/L/s; 16.61 +/- 61 Vs 5.57 +/- 1.16fmol/ml, 686.81 +/- 442.78 Vs 176 +/- 18.5 pmol/L respectively] and plasma levels of these hormones increased with the severity of heart failure. There was significant correlation between AM and both PRA, ANP and aldosterone [r=0.650, P<0.001; r=0.612, P<0.001; r=0.677, P<0.001 respectively]. Also there was significant correlation between plasma AM and both ejection fraction [EF] and fractional shortening percentage [FS%] [r=-0.781, P<0.001; r=-863, P<0.001 respectively], Plasma AM decreased in response to treatment of heart failure. Class of heart failure could be predicted in 82.5% of cases by assessment of plasma AM. Plasma AM increases in patients with heart failure due to dilated cardiomyopathy in proportion to the severity of heart failure along with some hormones known to modulate the development of heart failure. AM has a high predictive value in the assessment of the severity of heart failure, Stratification of patients regarding severity of heart failure can be facilitated by plasma AM measurements which could reasonably included in the routine clinical workup of patients with CHF

Endoscopic variceal ligation versus endoscopic injection sclerotherapy: a prospective study comparing efficacy and safety endoscopic

Patients who have bled from esophageal varices remain at risk for rebleeding. There is interest in methods that would enable rapid control of active bleeding and eradication of esophageal varices. This study included two groups of patients with similar clinical and endoscopic characteristics. One group [28 patients] received endoscopic variceal ligation [EVL] and the second group [22 patients] received endoscopic injection sclerotherapy [EIS]. We compared both methods in terms of efficacy in controlling acute variceal bleeding, associated complications, eradication of varices, recurrence of varices during follow-up, and changes in portal vein blood flow after variceal eradication. Both EVL and EIS were comparable in control of active variceal bleeding [78.6% Vs 81.8%; p= 0.776] and eradication of varices [82.1% Vs 86.4%; p = 0.686]. Rebleeding was more probable to occur with ETS than EVL [7.1% Vs 27.3%; p = 0.054]. ElS was associated with more complications [54.5% Vs 14.3%, p = 0.002]. EVL required less number of endoscopic sessions to eradicate varices [3.82 +/- 0.98 Vs 4.86 +/- 1.36, p = 0.004] but was associated with more recurrence of varices during follow-up period of 8-12 months [35.7% Vs 9.1%], P = 0.029]. The changes in portal vein blood flow were transient after eradication of varices by both procedures. We conclude that while EVL and ElS are equally effective in controlling acute variceal bleeding and eradication of varices, ligation treatment shows greater advantages in the short-term follow up regarding the number of endoscopic sessions required to eradicate varices and the incidence of comp1ications, but is associated with more frequent recurrence of varices in the longer term, These two aspects should be considered for evaluation in the cost/benefits ratio arid quality of life analysis All patients should have frequent endoscopic evaluations [every three or four months] throughout the first year of follow-up

Effects of age and short-term fasting on plasma leptin in obese women and its association with some metabolic cardiovascular risk factors

The study included 22 female obese subjects with body mass index [BMI] ranged from 32-43 Kgm/m2 and age 20-56 years. The effect of 24 h fasting on serum leptin, insulin, and glucose was determined. Also, the correlation between serum leptin and some metabolic risk factors for cardiovascular disease such as lipoproteins and abdominal visceral fat was evaluated. We found that the magnitude of decrease in leptin concentration. with 24 h fasting was much greater than the possible associated loss of body weight induced by fasting. This suggests that other factors modulate leptin secretion other than total adipose mass. The ability of progressive fasting to suppress plasma leptin levels despite a minimal change in adipose mass suggests that ongoing caloric deficiency supersedes total energy reserve in setting chronic levels of satiety and thermogenesis. This regulatory mechanism might have conferred a survival advantage in environments characterized by rapid changes in food availability. Significant correlations were found between abdominal visceral fat measured by computed tomography [CT] and total serum cholesterol, HDL-cholesterol, and triglycerides. However, no association was found between plasma leptin concentrations and both abdominal visceral fat and waist/hip ratio. Also, there was no association between plasma leptin and plasma lipid concentrations. Since plasma leptin concentrations were not related to alterations of plasma lipoprotein concentrations and abdominal visceral which are known risk factors for cardiovascular disease, it does not seem relevant to include leptinemia in the set of metabolic risk factors for cardiovascular disease. Circulating leptin level reflects total adipos tissue mass rather than a combination of adipose tissue mass and distribution