ABSTRACT
Background: The development of cachexia is a particular predictor of adverse prognosis in chronic heart failure [CHF]. Less is known about anabolic metabolism in CHF. Leptin -the hormone product of obesity gene has been shown to inhibit food intake, increase energy expenditure and fat oxidation. Insulin sensitivity and secretion is related to leptin. Leptin has been reported also to stimulate proliferation of CD4 T cells and increases cytokine production. The study aimed to investigate leptin. Insulin sensitivity and tumor necrosis factor-alpha [TNF-alpha] in chronic heart failure with and without cachexia
Methods: We studied 31 male patients with CHF, mean age [59.87 +/- 6.91 years], mean New York Heart Association Functional Class [2.52 +/- 0.81], mean left ventricular ejection fraction [LVEF] [0.33+0.08] and 13 male healthy control subjects, mean age [59.87 +/- 6.91]. Of the CHF patients, 14 were cachectic [cCHF] with non-oedematous weight loss >7.5% over at least6 months and 17 non-cachectic. Serum insulin was measured by enzyme immunoassay, insulin sensitivity was assessed by intravenous glucose tolerance. Serum leptin and TNF were meas ured using commercially available ELISA kit
Results: Compared with the healthy control subjects, patients had elevated levels of leptin, fasting insulin and TNF-alpha [P<0.001], with reduced insulin sensitivity [P<0.001]. Both ncCHF and cCHF subgroups had higher leptin and TNF levels than the control group [P<0.001]. The cCHF subgroup-compared with ncCHF subgroup-showed reduced leptin and fasting insulin levels [P<0.001 and P<0.01] respectively and elevated TNF-alpha levels [P<0.001]. In both patients and control subjects there was a positive correlation between leptin and fasting insulin levels [r=0.59, P<0.001 and r=0.54, P<0.05] respectively. The relative risk of incidence of cCHF in NYHA Functional class [I and II] versus NYHA Functional class [III and IV] was 0.427 [P<0.05]
Conclusion: CHF is hyperleptinaemic state and is associated with decreased insulin sensitivity and elevated fasting plasma insulin levels. The state of cardiac cachexia is associated with higher TNF-alpha levels and more worse NYHA Functional Class. Leptin and TNF-alpha may be valid targets for novel therapeutic interventions in patients with CHF
ABSTRACT
It has been proposed that renin angiotensin system [RAS] plays a pivotal and perhaps obligatory role in the initiation and progression of ventricular hypertrophy. Glucose and insulin level are associated with left ventricular mass [LVM] in insulin resistant individuals. Antihypertensive drugs always have ditferent effects on glucose insulin levels, RAS and on LVM. To evaluate whether the effect of antihypertensives [Losartan or Ramipril] on LVM are associated with its effects on plasma glucose, insulin and aldosterone we compared their effects on these parameters in a group of insulin resistant, obese hypertensive patients. A total of 20 obese, non diabetic hypertensives who were 45 +/- 4 years had a body mass index of 31.5 +/- 2.5 Kg/m2, were free of coronary or valvular heart disease and had normal left ventricular [LV] function were randomized to treatment with losartan , 50mg daily [n=10]or ramipril 5 mg daily [n=10]. Echocardiograpic left ventricular mass [LVM] corrected for height [LVM/height] and plasma aldosterone [PA] were measured after 4 weeks of washout and 6 months of treatment. Baseline characteristics were similar in both groups. Losartan and ramipril effectively reduced blood pressure while both did not affect significantly fasting plasma glucose or insulin levels. Both ramipril and losartan significantly reduced LVM/ height. In obese hypertensive individuals adequate and similar blood pressure control was achieved with losartan and ramipril, also, in obese hypertensive patients both losartan and ramipril led to a significant regression of left ventricular mass associated with significant decreased plasma aldosterone level
ABSTRACT
Aim: Graves'-related ophthamopathy [GRO] is an organ -specific autoimmune disease passing into two stages, the stage of active inflammatory disease, which is treated conservatively by anti-inflammatory drugs or radiotherapy, and the inactive fibrotic stage, which is treated surgically. It is rather difficult to distinguish inflammatory from noninflammatory stages. The aim of the present work was to study some proinflammatory cytokines as sICAM, IL-2, and IFN-gamma serum levels, and peripheral blood T-cell subsets, together with orbital Ultrasonography in patients with GRO and their relation to clinical activity score [CAS] and relevant clinical parameters. Subjects and Fourty patients with GRO were enrolled, 30 of whom had inactive GRO and 10 cases had active GRO according to the clinical activity score, in addition to 10 healthy volunteers as a control group. Thorough clinical evaluation and orbital ulttrasonography were done for all patients. Laboratory work included measurement of sICAM, IL-2, IFN-gamma in serum and T-cell subsets in peripheral blood for patients and control. It was found that age, sex, smoking habit, or thyroid hormone status are not different in patients having active compared to inactive GRO, while the duration of the disease was significantly different, being shorter in those having active GRO. Extraocular muscle hyporeflectivity, as shown by orbital ultra-sonography, was significantly correlated with clinical activity score [P <0.01]. Serum sICAM-1, IL-2, and IFN-gamma levels were high in patients compared to controls [40.4=/=5 pg/ml versus 10.4 +/- 3.08 pg/ml, 440 +/- 187.6 pg/ml versus 65.8'24.3 pg/ml, and 479=/=160.3 pg/ml versus 116.4 +/- 24.0 pg/ml, respectively], and those having active GRO showed higher levels compared to those with inactive GRO [46.2 +/- 4.6 pg/ml versus 38.4 +/- 3.4 pg/ml, 707 +/- 149 pg/ml versus 351 +/- 87.6 pg/ml and 705.3 +/- 108.2 pg/ml versus 404.2 +/- 86.5 pg/ml, respectively]. T-cell subsets studied [CD3, CD4, and CD8] in peripheral blood were not different in patients with active GRO compared to those with inactive GRO [75.5 +/- 6.19% versus 71.8 +/- 5.53%, 58.4 +/- 4.62% versus 53.7+7.26%, and 14.8'6.05% versus 14.8 +/- 3.18%, respectively]. Conclusions: It is concluded that the duration of the eye disease and orbital utrasonography added to the clinical activity score could help distinguish patients with active Graves'-related ophthalmopathy, while serum levels of slCAM-1, IL-2, and IFN-gamma as single measurements, or peripheral blood T-cell subset pattern are of little help in this respect