International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity最新文献

Sibutramine can produce dose-dependent increases in blood pressure and heart rate, especially during initial treatment. However, the cardiovascular effects of the drug are related to the weight loss achieved: patients who lose 5% or more of initial body weight have a reduction in blood pressure, which correlates with the degree of weight loss. Sibutramine does not exacerbate pre-existing controlled hypertension and treatment has been shown to be safe and effective in these patients. In clinical practice, it is important to observe the recommended exclusion criteria, to monitor blood pressure and heart rate and to adhere to the withdrawal criteria. This should enable the identification of those patients for whom sibutramine is not suitable while permitting the majority of patients to gain clinical benefit from treatment.

Obesity is an important risk factor for the development of type 2 diabetes. The increasing incidence of obesity accounts in large part for the emergence of type 2 diabetes. Drug treatment of hyperglycaemia and hypertension lowers the risk of diabetic complications, but many of these treatments, including sulphonylureas, insulin and beta-blockers, are associated with weight gain. There is increasing evidence that obesity may be an independent risk factor for complications in both type 2 and type 1 diabetes. Therapies to lower body weight will undoubtedly have a role in the treatment of diabetes to potentially avert weight gain associated with anti-diabetic therapies, to lower glycaemia, and possibly even to lower the risk of diabetic complications. However, many questions remain to be answered.

The prevalence of obesity is increasing globally, with nearly half a billion of the world's population now considered to be overweight or obese. The obesity epidemic is related both to dietary factors and to an increasingly sedentary lifestyle. Obesity has significant co-morbidities and these are associated with substantial health care and social costs. Of particular concern is the fact that obesity is increasing among children and adolescents. National health policymakers must take action to deal with the obesity problem. Prevention should be the primary target, but it is also important to develop strategies to treat those already affected with obesity.

Knowledge of the genetic and regulatory factors that influence energy homeostasis is advancing rapidly. There is increased understanding of the molecular signals that reach the brain with information regarding the current state of energy balance, how those signals are detected by the brain, and key neuronal systems important in translating the information into efferent responses. The identification of molecules that control food intake has generated new targets for drug development in the treatment of obesity. In view of the complexities of the energy control system, therapeutic strategies that target only one site are likely to be less effective than those targeting two or more sites.

Obesity is associated with type 2 diabetes, hypertension and hyperlipidaemia. Modest weight loss has been shown to have a beneficial effect on these cardiovascular risk factors and to improve risk factor clustering. Recent lifestyle intervention studies also suggest that modest weight loss can help to prevent two of the most common conditions associated with obesity: hypertension and type 2 diabetes. The practical problem is how to translate results from these studies into daily practice. In the studies, only a limited number of individuals maintained substantial weight loss over the follow up period. New approaches are needed to achieve and maintain weight loss.

Sibutramine-induced weight loss and weight maintenance lead to clinically relevant reductions in risk factors associated with the metabolic syndrome. Treatment with the drug decreases visceral fat, improves lipid levels, decreases glycosylated haemoglobin and decreases uric acid concentrations. Sibutramine is effective in achieving weight loss in patients with type 2 diabetes but weight loss occurs more slowly than in non-diabetic patients. The criteria for predicting response to treatment in uncomplicated patients may not be appropriate to those with type 2 diabetes. Furthermore, it is important to set realistic goals for weight loss in type 2 diabetes to avoid the risk of denying effective treatment to patients.

There has been a great deal of recent progress in our understanding of the transcriptional control of adipogenesis. Current data suggest that fat cell differentiation involves an interplay between the C/EBP family of transcription factors and PPARgamma. The thermogenic program of brown fat cells may also include a contribution from a new coactivator, PGC-1. Recent data suggests that this coactivator is responsible for activation of thermogenesis and oxidative metabolism in both brown fat and muscle. The PGC-1 dependent program includes both mitochondrial biogenesis and tissue-specific expression of uncoupling proteins.

The A-ZIP/F-1 mouse is lacking virtually all white adipose tissue. Like humans with extensive deficiencies of adipose tissue, the A-ZIP/F-1 mice develop a severe form of insulin resistant diabetes. We have studied the physiology of the A-ZIP/F-1 mice. Their adaptation to fasting is notable for its rapidity and the use of torpor, a hibernation-like state, to minimize energy needs. Transplantation of adipose tissue reversed the metabolic manifestations in the mice, demonstrating that the lack of adipose tissue is the cause of the insulin resistance. Leptin replacement is not very effective in reversing the diabetes of the A-ZIP/F-1 mice, which contrasts with its efficacy in the aP2-SREBP-lc mouse.