Tumor necrosis factor-alpha serum levels, weight loss and tissue oxygenation in chronic obstructive pulmonary disease.

weight loss has been recognized as a feature of advanced emphysema and a factor of poor prognosis, but its mechanisms remain obscure. Studies have demonstrated high serum concentrations of TNF-a (cachexin) in chronic obstructive pulmonary disease (COPD) patients with emphysema. Pink puffers (PP) COPD patients have worse tissue oxygenation when compared with blue bloaters (BB) COPD patients. Consequently, PP patients would become cachectic, whereas BB patients with better tissue oxygenation would not. The aim of this study is to test the hypothesis that malnutrition in emphysema is a cytokine-mediated marker of chronic progressive tissue hypoxia. Thirty male COPD patients, without clinical or laboratory evidence of infection and severe air way obstruction (FEV1 < 1.5 l) were allocated: 16 as pink puffers (PP) and 14 as blue bloaters (BB). Lung function measurements included FEV1, FVC, RV, TLC, DLCO and arterial blood gases on room air. TNF-a serum levels were measured by immunoenzymic method (ELISA). Tissue oxygenation was assessed from oxygen delivery (DO2), PvO2 and oxygen extraction ratio (O2ER) obtained after right heart catheterization with Swan Ganz catheter. PP patients demonstrated lower DLCO and higher TLC, FRC and PaO2 from BB. We found that oxygen delivery was better in our BB than in PP patients (CI 2.9 +/- 0.2 vs 2.5 +/- 0.4 l/min/m2--P < 0.01, DO2 16.1 +/- 2.1 vs 13.1 +/- 0.2 ml/min/kg--P < 0.001) and the same was found for tissue oxygenation (PvO2 34.6 +/- 2.9 vs 31.2 +/- 3.8 mmHg--P < 0.01, O2ER 0.27 +/- 0.02 vs 0.34 +/- 0.06%--P < 0.001). The TNF-a values were higher in PP (31.3 +/- 26 pg/ml vs 15.2 +/- 9.9 pg/ml--P < 0.05) and their percent fat-free mass (%FFM) was 49.6 +/- 11.5 vs 42 +/- 8%--P < 0.001. We found that COPD patients with lower DO2 had increased TNF-a levels; but the correlations between TNF-a serum levels and PvO2 or O2ER were not statistically significant. TNF-a levels were elevated in PP patients with tissue hypoxia and may be a factor contributing to the weight loss of these patients.

Diet and exercise for weight loss: a review of current issues.

Obesity is a fast growing epidemic that is primarily due to environmental influences. Nutrition and exercise represent modifiable factors with a major impact on energy balance. Despite considerable research, there remains continued debate regarding the energy content and the optimal macronutrient distribution for promoting healthy and effective weight loss. Low-fat diets have been advised for many years to reduce obesity. However, their effectiveness has been recently challenged, partly because the prevalence of obesity continues to rise despite reductions in fat intake. There are also concerns regarding the methodology of clinical trials showing benefits of fat reduction on weight loss. Although often viewed as a fad diet, very low-carbohydrate (ketogenic) diets are very popular and several recent clinical trials indicate they are more effective at promoting short-term weight loss and improving characteristics of the metabolic syndrome than low-fat diets. However, there is a need to obtain long-term safety and efficacy data. Clearly, weight loss can be achieved with a variety of diet interventions but the effects on other health-related aspects also need to be considered and studied in more detail. Exercise can have positive effects on weight loss, weight control and overall general health, although debate exists concerning the most effective mode, duration and intensity of exercise required to achieve these effects. Importantly, any effective weight control treatment must consider a life-long plan or there will likely be weight regain. Perhaps the most challenging, but rewarding, question that faces researchers is how to predict individual responses to diet and exercise interventions.

Does intentional weight loss affect mortality rate?

Short-term studies indicate that intentional weight loss among obese persons significantly improves physiologic variables. Hence, it is logical to conjecture that intentional weight loss would lead to long-term benefits and increased longevity. Herein, we review recent epidemiologic studies that investigate the weight loss-mortality association using a conservative analytic approach that included distinguishing between intentional and unintentional weight loss, adjusting for potential confounders, and excluding unhealthy subjects. On balance, results indicate that intentional weight loss appears to neither increase nor decrease mortality rate. Discussion focuses on the problems of addressing this important public health question with observational data.

Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance.

OBJECTIVE: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. RESEARCH METHODS AND PROCEDURES: Twenty-four insulin-resistant obese subjects with varying degrees of glucose tolerance completed a 6-month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6)] and highly sensitive C-reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. RESULTS: Participants had a 6.9 +/- 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 +/- 3 vs. 23.6 +/- 3 ng/mL, p = 0.01) and IL-6 (2.75 +/- 1.51 vs. 2.3 +/- 0.91 pg/mL, p = 0.012). TNF-alpha levels tended to decrease (2.3 +/- 0.2 vs. 1.9 +/- 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C-reactive protein (r = 0.466, p < 0.05). DISCUSSION: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL-6 and a tendency toward a decrease in circulating TNF-alpha, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.

Performance of two self-report measures for evaluating obesity and weight loss.

OBJECTIVES: To evaluate performance of the obesity and weight-loss Quality-of-Life (OWLQOL) and Weight-Related Symptoms (WRSM) measures. RESEARCH METHODS AND PROCEDURES: Four studies of obese persons 18 to 75 years of age were analyzed: a 12-week initial validation study, a clinical trial using blinded endpoint data at 50 to 83 weeks, and community studies conducted in the U.S. and Europe. Fifty-six initial validation study subjects visited 1 week after screening to evaluate reproducibility. RESULTS: Overall, 6107 obese persons completed one assessment, 291 completed follow-up at 12 weeks, and 642 at >50 weeks. Psychometric analyses resulted in a 17-item OWLQOL with a single score tested on five samples that was internally consistent (alpha values > 0.90) and reproducible (intraclass correlation coefficient > 0.95). The OWLQOL score (higher is better) was associated, as expected, with the symptom measure (lower is better, -0.54), generic quality of life measure (0.53), and measures of physical (0.40) and mental functioning (0.47). The 20-item WRSM was internally consistent (alpha = 0.87) and reproducible (intraclass correlation coefficient = 0.83). The OWLQOL discriminated between genders (p < 0.001), presence of disability days (p < 0.05), levels of BMI (p < 0.05), and levels of symptom bothersomeness (p < 0.001). Evaluation at 12 weeks yielded an effect size for > or = 2.5% weight loss of 0.77 for the OWLQOL and -0.54 for the WRSM. At > or = 50 weeks for > or = 10% weight change, effect sizes were 1.63 and -0.73, respectively. DISCUSSION: The OWLQOL and WRSM are brief, valid, reproducible, and responsive self-reported outcomes for evaluating obesity and weight loss.

Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C.

Niemann-Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is the result of deficient intracellular cholesterol movement. We investigated the effects of tamoxifen and vitamin E (D-alpha tocopherol) treatment on patterns of weight loss and motor function in the mouse model of Niemann-Pick C disease (Npc1-/- mice). Tamoxifen has multiple metabolic effects, including reducing oxidative damage, while vitamin E primarily has this property. Npc1-/- mice were identified and treatment was initiated at an approximate age of 21 days. Tamoxifen suspended in peanut oil was administered via intraperitoneal injection (weekly, at a dose calculated to deliver 0.023 microg/g/day). Vitamin E (25 IU) was administered orally via gavage once a week. weight loss and Rota-Rod performance were analyzed by using Kaplan-Meyer survival curves. Tamoxifen treatment by itself significantly delayed weight loss (an endpoint of neurodegeneration) in male and female mice compared to untreated controls. Motor function was evaluated by performance on a Rota-Rod. Tamoxifen maintained Rota-Rod performance for about an extra week. Vitamin E treatment significantly delayed weight loss in females only. Rota-Rod performance was maintained slightly longer in mice treated with vitamin E. Simultaneous use of both treatments did not delay weight loss longer than tamoxifen-only treatment but had a greater effect than either treatment alone on Rota-Rod performance and demonstrated a significant positive effect on the early "learning curve" portion of the Rota-Rod evaluations. We found significant but relatively small improvements in rate of disease progression by treating Npc1-/- mice with tamoxifen and/or vitamin E. Some sex differences in response and an early improvement in Rota-Rod performance suggest areas for further study.

Ultrasound parameters of calcaneal bone density in girls with anorexia nervosa.

Osteoporosis is common in patients with anorexia nervosa (AN), but ultrasound has so far been scarcely used to detect it We measured calcaneal broadband ultrasound attenuation (BUA) and velocity of sound (VOS) in 26 AN girls (mean age 15.1+/- 1.5 years) using a Cuba Clinical device (McCue Ultrasonics, UK). Basic anthropometric (body weight, height and body mass index--BMI) and clinical data (mean duration of AN, number of absent cycles, weight loss) were collected. All of the girls reported that they did at least one hour's vigorous exercise a day. BUA was significantly lower (p<0.004) and VOS significantly higher (p<0.0001) in comparison with reference data. Body weight and BMI at the time of the measurements were significantly lower than the reference data (p<0.0001). There were no correlations between body weight or height and BUA or VOS, but there was a slight correlation between BUA and BMI (r=0.4, p<0.05) and a slight inverse correlation between VOS, body weight and BMI (r=-0.48 and r=-0.43, p<0.01). VOS slightly correlated with weight loss (r=0.4, p<0.05), significantly with the weekly number of exercise hours (r=0.48, p<0.01). The duration of AN, the number of missed cycles and the percentage of weight loss did not correlate with BUA, and neither the duration of AN nor the number of missed cycles correlated with VOS. The low BUA value could be attributed to poor nutrition, and substantial physical activity may lead to the increase in VOS. In conclusion, girls with AN have low BUA and high VOS values, neither of which correlate with the duration of AN or the number of missed cycles.

Comparison of high-fat and high-protein diets with a high-carbohydrate diet in insulin-resistant obese women.

AIMS/HYPOTHESIS: A diet low in saturated fatty acids and rich in wholegrains, vegetables and fruit is recommended in order to reduce the risk of obesity, cardiovascular disease and type 2 diabetes mellitus. However there is widespread interest in high-fat ("Atkins Diet") and high-protein ("Zone Diet") alternatives to the conventional high-carbohydrate, high-fibre approach. We report on a randomised trial that compared these two alternative approaches with a conventional diet in overweight insulin-resistant women. METHODS: Ninety-six normoglycaemic, insulin-resistant women (BMI >27 kg/m(2)) were randomised to one of three dietary interventions: a high-carbohydrate, high-fibre (HC) diet, the high-fat (HF) Atkins Diet, or the high-protein (HP) Zone Diet. The experimental approach was designed to mimic what might be achieved in clinical practice: the recommendations involved advice concerning food choices and were not prescriptive in terms of total energy. There were supervised weight loss and weight maintenance phases (8 weeks each), but there was no contact between the research team and the participants during the final 8 weeks of the study. Outcome was assessed in terms of body composition and indicators of cardiovascular and diabetes risk. RESULTS: Body weight, waist circumference, triglycerides and insulin levels decreased with all three diets but, apart from insulin, the reductions were significantly greater in the HF and HP groups than in the HC group. These observations suggest that the popular diets reduced insulin resistance to a greater extent than the standard dietary advice did. When compared with the HC diet, the HF and HP diets were shown to produce significantly (p<0.01) greater reductions in several parameters, including weight loss (HF -2.8 kg, HF -2.7 kg), waist circumference (HF -3.5 cm, HF -2.7 cm) and triglycerides (HF -0.30 mmol/l, HF -0.22 mmol/l). LDL cholesterol decreased in individuals on the HC and HP diets, but tended to fluctuate in those on the HF diet to the extent that overall levels were significantly lower in the HP group than in the HF group (-0.28 mmol/l, 95% CI 0.04-0.52, p=0.02). Of those on the HF diet, 25% showed a >10% increase in LDL cholesterol, whereas this occurred in only 13% of subjects on the HC diet and 3% of those on the HP diet. CONCLUSIONS/INTERPRETATION: In routine practice a reduced-carbohydrate, higher protein diet may be the most appropriate overall approach to reducing the risk of cardiovascular disease and type 2 diabetes. To achieve similar benefits on a HC diet, it may be necessary to increase fibre-rich wholegrains, legumes, vegetables and fruits, and to reduce saturated fatty acids to a greater extent than appears to be achieved by implementing current guidelines. The HF approach appears successful for weight loss in the short term, but lipid levels should be monitored. The potential deleterious effects of the diet in the long term remain a concern.