Background The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. Methods We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). Results The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P = 0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.

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The recognition of obesity as a disease was in theory established in 1948 by WHO's (World Health Organization) taking on the International Classification of Diseases but the early highlighting of the potential public health problem in the United States and the United Kingdom 35 years ago was considered irrelevant elsewhere. The medical profession disregarded obesity as important despite the new evidence and WHO data set out in the 1980s. Only in 1995 did WHO find greater problems of overweight than underweight in many developing countries but it required the first special obesity consultation in 1997 and particularly the Millennium burden of disease analyses to suddenly highlight its crucial role in the current unmanageable and escalating medical costs globally. Governments now recognize the overwhelming industrial developments that guarantee an escalating epidemic but neither they nor WHO know how to engage in changing the societal framework to promote routine spontaneous physical activity and a transformation of the food system so that low energy-density food of high nutrient quality becomes the norm.

Objective: To briefly review the current understanding of the aetiology and prevention of chronic diseases using a life course approach, demonstrating the lifelong influences on the development of disease. Design: A computer search of the relevant literature was done using Medline-'life cycle' and 'nutrition' and reviewing the articles for relevance in addressing the above objective. Articles from references dated before 1990 were followed up separately. A subsequent search using Clio updated the search and extended it by using 'life cycle', 'nutrition' and 'noncommunicable disease' (NCD), and 'life course'. Several published and unpublished WHO reports were key in developing the background and arguments. Setting: International and national public health and nutrition policy development in light of the global epidemic in chronic diseases, and the continuing nutrition, demographic and epidemiological transitions happening in an increasingly globalized world. Results of review:There is a global epidemic of increasing obesity, diabetes and other chronic NCDs, especially in developing and transitional economies, and in the less affluent within these, and in the developed countries. At the same time, there has been an increase in communities and households that have coincident under-and over-nutrition. Conclusions: The epidemic will continue to increase and is due to a lifetime of exposures and influences. Genetic predisposition plays an unspecified role, and with programming during fetal life for adult disease contributing to an unknown degree. A global rise in obesity levels is contributing to a particular epidemic of type 2 diabetes as well as other NCDs. Prevention will be the most cost-effective and feasible approach for many countries and should involve three mutually reinforcing strategies throughout life, starting in the antenatal period.

OBJECTIVE: To assess the ef®cacy and tolerability of orlistat (Xenical 1 ) in producing and maintaining weight loss over a 12-month period. DESIGN: Patients were randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with a low-energy diet, for 12 months. SETTING: Five centres in the UK. SUBJECTS: 228 obese adult patients with body mass index between 30 and 43 kgam 2 and mean weight 97 kg (range 74 ± 144 kg). INTERVENTIONS: All patients were prescribed a low-energy diet, providing 30% of energy from fat, designed to produce an individually tailored energy de®cit of approximately 600 kcaladay, for a run-in period of 4 weeks and then 12 months, plus orlistat 120 mg or placebo three times daily. MAIN OUTCOME MEASURES: Change in body weight (the primary ef®cacy parameter), waist circumference and adverse events were reviewed regularly, together with serum lipids, insulin, glucose and plasma levels of fat-soluble vitamins and b b carotene. RESULTS: Based on an intent-to-treat analysis, after 1 y of treatment patients receiving orlistat had lost an average of 8.5% of their initial body weight compared with 5.4% for placebo-treated patients; 35% of the orlistat group lost at least 5% of body weight compared with 21% of the placebo group (P`0.05), and 28% and 17%, respectively (P 0.04) lost at least 10% of body weight. Orlistat-treated patients showed signi®cant decreases (P`0.05) in serum levels of total cholesterol, low density lipoprotein cholesterol, and in the low density lipoprotein : high density lipoprotein ratio in comparison with placebo. Both groups had similar adverse-event pro®les, except for gastrointestinal events, which were 26% more frequent in the orlistat group but were mostly mild and transient. To maintain normal plasma levels of fat-soluble vitamins, supplements of vitamins A, D and E were given to 1.8%, 8.0% and 3.6%, respectively, of orlistattreated patients, compared with 0.9% of placebo-treated patients for each vitamin type. After 1 y, the decrease in vitamin E and b b carotene was signi®cantly greater in orlistat-treated patients compared with those receiving placebo (P`0.001). No signi®cant change was found in the mean vitamin E : total cholesterol ratio in either group after 52 weeks. Conclusions: Orlistat, in conjunction with a low-energy diet, produced greater and more frequent signi®cant weight loss than placebo during 1 y of treatment. One-third of orlistat-treated patients achieved clinically relevant weight loss ( ! 5% initial body weight). There was also an improvement in relevant serum lipid parameters. Fat-soluble vitamin supplements may be required during chronic therapy. Orlistat was well tolerated and offers a promising new approach to the long-term management of obesity.

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1. The capacity ofr thermoregulation and thermogenesis in lean and genetically obese (ob/ob) mice has been investigated. 2. At 4 degrees C ob/ob mice rapidly die of hypothermia, because of a reduced capacity for cold-induced thermogenesis, but the animals are able to survive if previously adapted to 12 degrees C. 3. At all environmental temperatures between 30 degrees C and 10 degrees C the body temperature of ob/ob mice is 2.0-2.5 degrees C below that of lean animals. This may be due to a lower "setting" for body temperature. 4. At 34 degrees C the oxygen consumption of obese mice is greater than that of the lean animals while at 30 degrees C it is similar. When the environmental temperature is below 30 degrees C the oxygen consumption of the lean mice is greater. The obese animals therefore expend less energy on thermoregulatory thermogenesis. 5. The capacity for non-shivering thermogenesis was measured in lean and obese mice by investigating the effect of an injection of L-nor-adrenaline (1000 microgram/kg body weight) on the metabolic rate at 31 degrees C. Non-shivering thermogenesis was reduced by one-half in the obese animals. 6. One cause of the obesity of the ob/ob mouse is its high metabolic efficiency. We suggest that this high metabolic efficiency is due, at least in part, to less energy being expended on thermoregulatory thermogenesis.

Overweight and obesity increase the risks of diabetes and cardiovascular disease (CVD). This has been shown to be reversed with weight loss. A systematic review and meta-analysis were performed to determine the effect of weight loss in the primary prevention of CVD. PubMed, Embase and the Cochrane Library databases were searched electronically through to May 2013. Randomized controlled trials assessing weight loss and cardiovascular risk factors and outcomes were included. A random effects meta-analysis, with sub-group analyses for degree of weight loss, and age were performed. Because few studies reported clinical outcomes of CVD, analyses were limited to cardiovascular risk factors (83 studies). Interventions that caused any weight loss significantly reduced systolic blood pressure (-2.68 mmHg, 95% CI -3.37, -2.11), diastolic blood pressure (-1.34 mmHg, 95% CI -1.71, -0.97), low-density lipoprotein cholesterol (-0.20 mmol L(-1) , 95% CI -0.29, -0.10), triglycerides (-0.13 mmol L(-1) , 95% CI -0.22, -0.03), fasting plasma glucose (-0.32 mmol L(-1) , 95% CI -0.43, -0.22) and haemoglobin A1c(-0.40%, 95% CI -0.52, -0.28) over 6-12 months. Significant changes remained after 2 years for several risk factors. Similar results were seen in sub-group analyses. Interventions that cause weight loss are effective at improving cardiovascular risk factors at least for 2 years. © 2016 World Obesity.