Adiposopathy: how do diet, exercise and weight loss drug therapies improve metabolic disease in overweight patients?

An increase in bodyweight is generally associated with an increased risk of excessive fat-related metabolic diseases (EFRMD), including Type 2 diabetes mellitus, hypertension and dyslipidemia. However, not all patients who are overweight have EFRMD, and not all patients with EFRMD are significantly overweight. The adipocentric paradigm provides the basis for a unifying, pathophysiological process whereby fat gain in susceptible patients leads to fat dysfunction ('sick fat'), and wherein pathological abnormalities in fat function (adiposopathy) are more directly related to the onset of EFRMD than increases in fat mass (adiposity) alone. But just as worsening fat function worsens EFRMD, improved fat function improves EFRMD. Peroxisome proliferator-activated receptor-gamma agonists increase the recruitment, proliferation and differentiation of preadipocytes ('healthy fat') and cause apoptosis of hypertrophic and dysfunctional (including visceral) adipocytes resulting in improved fat function and improved metabolic parameters associated with EFRMD. Weight loss interventions, such as a hypocaloric diet and physical exercise, in addition to agents such as orlistat, sibutramine and cannabinoid receptor antagonists, may have favorable effects upon fat storage (lipogenesis and fat distribution), nutrient metabolism (such as free fatty acids), favorable effects upon adipose tissue factors involved in metabolic processes and inflammation, and enhanced 'cross-talk' with other major organ systems. In some cases, weight loss therapeutic agents may even affect metabolic parameters and adipocyte function independently of weight loss alone, suggesting that the benefit of these agents in improving EFRMD may go beyond their efficacy in weight reduction. This review describes how adiposopathy interventions may affect fat function, and thus improve EFRMD.     

Can metabolic function and physical fitness improve without weight loss for inactive,obese, Hispanic adolescents? A feasibility study

Introduction: A case series that examines the effects of a 12-week combined resistance and aerobic training program for four sedentary obese, Hispanic adolescents without weight loss. Subjects/Methods: Baseline and post-intervention anthropometric, metabolic and physical fitness measures were obtained. Body composition, hepatic, visceral, and intramuscular fat contents were analyzed via imaging. Fasting levels of alanine transaminase (ALT), insulin, glucose, free fatty acids, triglycerides, high- and low-density lipoproteins (LDL), and C-reactive protein were obtained via blood samples. Results: Two subjects decreased their glucose levels by 1.86% and 4.06%. Subjects 1, 3, and 4 increased their lean body mass by 4.12%, 9.70%, and 5.48%. ALT was reduced 13.0%, 16.0%, and 35.7% for subjects 2, 3, and 4, respectively. LDLs were reduced by 37.7%, 4.5%, and 7.5% for subjects 1, 2, and 3. Triglycerides were reduced by 25.4%, 37.8%, and 4.6% for subjects 1, 2, and 3. Visceral fat reductions by 16.5%, 14.2%, and 13.0% occurred for subjects 1, 2, and 3. C-reactive protein was reduced for subjects 1, 2, and 3 by 19.4%, 16.3%, and 32.0%. Conclusion: Expected directions of change were made for most indicators of metabolic function and body composition, but measures of physical fitness improved for all four subjects.     

Ribavirin therapeutic drug monitoring: why,when and how?

Recent studies suggest the potential interest of ribavirin therapeutic drug monitoring to improve sustain virological response rate in hepatitis C virus‐infected patients. The present review details the pharmacokinetic properties of ribavirin, suggesting that it may be a good candidate for therapeutic drug monitoring, the different possible strategies and the analytical methods that could be employed.     

Abdominal obesity and metabolic syndrome: exercise as medicine?

Background

Metabolic syndrome is defined as a cluster of at least three out of five clinical risk factors: abdominal (visceral) obesity, hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) and insulin resistance. It is estimated to affect over 20% of the global adult population. Abdominal (visceral) obesity is thought to be the predominant risk factor for metabolic syndrome and as predictions estimate that 50% of adults will be classified as obese by 2030 it is likely that metabolic syndrome will be a significant problem for health services and a drain on health economies.Evidence shows that regular and consistent exercise reduces abdominal obesity and results in favourable changes in body composition. It has therefore been suggested that exercise is a medicine in its own right and should be prescribed as such.

Purpose of this review

This review provides a summary of the current evidence on the pathophysiology of dysfunctional adipose tissue (adiposopathy). It describes the relationship of adiposopathy to metabolic syndrome and how exercise may mediate these processes, and evaluates current evidence on the clinical efficacy of exercise in the management of abdominal obesity. The review also discusses the type and dose of exercise needed for optimal improvements in health status in relation to the available evidence and considers the difficulty in achieving adherence to exercise programmes.

Conclusion

There is moderate evidence supporting the use of programmes of exercise to reverse metabolic syndrome although at present the optimal dose and type of exercise is unknown. The main challenge for health care professionals is how to motivate individuals to participate and adherence to programmes of exercise used prophylactically and as a treatment for metabolic syndrome.

     

Complementary therapies in cancer patients: prevalence and patients’ motives

BACKGROUND: Data relating to the use of complementary/alternative medicine (CAM) in cancer patients have been published for a number of European countries. No recent data are available for Austria. AIM: To ascertain the extent of CAM use by cancer patients, what patients' motives are, what methods are used and who the CAM providers are. DESIGN: Self-administered questionnaire; cross-sectional study. PATIENTS AND METHODS: A sample of 231 cancer patients who had consulted the Viennese Cancer League. Chi-square and Mantel-Haenszel tests were used for the statistical evaluation. RESULTS: 27.3% of the cancer patients had received CAM therapy: 33.1% of the female and 20.5% of the male participants (p = 0.045). Those who were below the median of the age categories (53.8 years) had used CAM to a statistically higher degree (35.5% vs. 21.1%; p = 0.023). The most important motives were the enhancement of "nature" and the GPs' recommendation. CAM was administered in 44.4% of cases by the family doctor, in 39.7% by patients themselves, in 6.3% by a hospital doctor, in 6.3% by a lay-practitioner or "non-medical practitioner against payment" and in 4.8% of cases by a practising oncologist. CONCLUSION: From the high percentage of patients who use CAM without consulting a physician or who follow the advice of others, it would seem highly probable that conventional and complementary methods are rarely effectively coordinated. To rectify this we conclude that oncologists and GPs should have a basic knowledge of CAM and address the issue when counselling their cancer patients.     

Bisphosphonates for cancer patients: why, how, and when?

Bisphosphonates (BPs) are potent inhibitors of osteoclast-mediated bone resorption, and it is well accepted that tumor cells in bone, especially breast cancer and myeloma cells, can stimulate osteoclast formation and activity leading to the release of growth factors or cytokines, which will further stimulate cancer cells' growth and their secretion of osteolytic factors. BPs are now the standard treatment for cancer hypercalcemia, for which a dose of 90 mg of pamidronate or 1500 mg of clodronate is recommended; the former compound is more potent and has a longer lasting effect. Repeated pamidronate infusions exert clinically relevant analgesic effects in more than half of patients with metastatic bone pain. Recent data suggest that non-responding patients should perhaps be treated with higher doses. The optimal dose actually remains to be defined, especially as it is thought that it is probably a function of the disease stage. Regular pamidronate infusions can also achieve a partial objective response according to conventional UICC criteria and they can almost double the objective response rate to chemotherapy. Lifelong administration of oral clodronate to patients with breast cancer metastatic to bone reduces the frequency of morbid skeletal events by more than one-fourth. Two double-blind randomized placebo-controlled trials comparing monthly 90 mg pamidronate infusions to placebo infusions for 1-2 years in addition to hormone or chemotherapy in patients with at least one lytic bone metastasis have shown that the mean skeletal morbidity rate could be reduced by 30-40%. The results obtained with intravenous BPs are generally viewed as better than those obtained with oral clodronate. However, preference can be given to the oral route when BPs are started early in the process of metastatic bone disease in a patient receiving hormone therapy. According to the recently published ASCO guidelines, pamidronate 90 mg i.v. delivered over 2 h every 3-4 weeks can be recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. Furthermore, the ASCO Panel considered it "reasonable" to start i.v. BPs in women with localized pain whose bone scans were abnormal and plain radiographs normal, but not when an abnormal bone scan is asymptomatic. The pertinence of these criteria is discussed below. Because BPs are providing supportive care, reducing the rate of skeletal morbidity but evidently not abolishing it, the criteria for stopping their administration have to be different from those used for classic antineoplastic drugs, and they should not be stopped when metastatic bone disease is progressing. However, criteria to determine whether and for how long an individual patient benefits from their administration are lacking. New biochemical markers of bone resorption might help identify those patients continuing to benefit from therapy. Even better results have been achieved in patients with multiple myeloma, and the general consensus is that BPs should be started as soon as the diagnosis of lytic disease is made in myeloma patients. On the other hand, data are scanty in prostate cancer, but large-scale trials with potent BPs are ongoing or planned in such patients. Similar results to those achieved with pamidronate have been obtained with monthly 6-mg infusions of the newer BP ibandronate in patients with breast cancer metastatic to bone. The tolerance of ibandronate could be better, and the drug has the potential to be administered as a 15- to 30-min infusion. Zoledronate can also be administered safely as a 15-min 4-mg infusion, and large scale phase III trials have just been completed. These newer BPs will simplify the current therapeutic schemes and improve the cost-effectiveness ratio; they also have the potential to improve the therapeutic efficacy, at least in patients with an aggressive osteolytic disease or when given as adjuvant therapy. For that matter, initial data with clodronate indicate that they have the potential to prevent the development of bone metastases, but the use of BPs in the adjuvant setting must still be viewed as experimental.