(17/472) Demand, appropriateness and prescribing of 'lifestyle drugs': a consultation survey in general practice.
BACKGROUND: The simultaneous launch of orlistat and sildenafil in 1998 provoked much media attention, particularly around the role of lifestyle drugs and their potential costs if controls were not established. Fears were also expressed that primary care would be overwhelmed by demand, and little information was available about the attitude of GPs to their new role as prescribers of lifestlye drugs. Partly in response to these concerns, tight prescribing guidelines and licensed indications, for sildenafil and orlistat, respectively, were issued. OBJECTIVE: Our aim was to describe levels of demand for orlistat and sildenafil in general practice, whether this demand was translated into a prescription, adherence to prescribing guidelines/licensed indications and the GP perception of appropriateness of an NHS prescription for either of these drugs. METHOD: We carried out an observational study in primary care conducted over a 6-week period during 1999. Twenty-seven GPs were recruited, each from a different practice. All GP consultations were recorded for the study period and the GP completed a structured questionnaire each time sildenafil or orlistat were discussed in a consultation. RESULTS: Sildenafil was discussed in 0.5% (68/13 394) of consultations and orlistat in 0.3% (42/13 394). GPs thought that a corresponding NHS prescription would be highly appropriate in 57 and 74% of cases, respectively, although for both lifestyle drugs, nearly 20% of GPs thought such prescriptions were inappropriate. An NHS prescription was issued in 43% of consultations in which sildenafil had been discussed and 33% in which orlistat had been discussed. Five out of 29 NHS sildenafil prescriptions were issued to patients failing to fulfil the requirements of prescribing guidelines; similarly, one out of 14 orlistat prescriptions fell outside licensed indications. There were four examples of NHS prescriptions for sildenafil which were given even when the GP thought the drug to be inappropriate, whereas orlistat was never given when the GP thought it inappropriate. CONCLUSIONS: Levels of demand for the two lifestyle drugs, sildenafil and orlistat, were modest when compared with earlier media predictions. Neither was there evidence that GP was pitted against patient in their negotiation concerning a lifestyle drug NHS prescription since most GPs agreed with their patients that such a prescription was appropriate. Prescribing guidelines and licensed indications were generally adhered to, but the modest level of demand raises questions about expanding the guidelines for sildenafil. (+info)
(18/472) Anti-obesity effect of dietary diacylglycerol in C57BL/6J mice: dietary diacylglycerol stimulates intestinal lipid metabolism.
We examined the long-term effects of dietary diacylglycerol (DG) and triacylglycerol (TG) with similar fatty acid compositions on the development of obesity in C57BL/6J mice. We also analyzed the expression of genes involved in lipid metabolism at an early stage of obesity development in these mice. Compared with mice fed the high-TG diet, mice fed the high-DG diet accumulated significantly less body fat during the 8-month study period. Within the first 10 days, dietary DG stimulated beta-oxidation and lipid metabolism-related gene expression, including acyl-CoA oxidase, medium-chain acyl-CoA dehydrogenase, and uncoupling protein-2 in the small intestine but not in the liver, skeletal muscle, or brown adipose tissue, suggesting the predominant contribution of intestinal lipid metabolism to the effects of DG. Furthermore, analysis of digestion products of [(14)C]DG and those of [(14)C]TG revealed that the radioactivity levels detected in fatty acid, 1-monoacylglycerol, and 1,3-DG in intestinal mucosa were significantly higher after intrajejunal injection of DG rather than TG. Thus, dietary DG reduces body weight gain that accompanies the stimulation of intestinal lipid metabolism, and these effects may be related to the characteristic metabolism of DG in the small intestine. (+info)
(19/472) Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance.
BACKGROUND: Conjugated linoleic acids (CLAs), a group of fatty acids shown to have beneficial effects in animals, are also used as weight loss supplements. Recently, we reported that the t10c12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms. The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance. METHODS AND RESULTS: In a double-blind placebo-controlled trial, 60 men with metabolic syndrome were randomized to one of 3 groups receiving t10c12 CLA, a CLA mixture, or placebo for 12 weeks. Insulin sensitivity (euglycemic clamp), serum lipids, in vivo lipid peroxidation (determined as urinary 8-iso-PGF(2alpha) [F2-isoprostanes]), 15-ketodihydro PGF(2alpha), plasma vitamin E, plasma C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 were assessed before and after treatment. Supplementation with t10c12 CLA markedly increased 8-iso-PGF(2alpha) (578%) and C-reactive protein (110%) compared with placebo (P<0.0001 and P<0.01, respectively) and independent of changes in hyperglycemia or dyslipidemia. The increases in 8-iso-PGF(2alpha), but not in C-reactive protein, were significantly and independently related to aggravated insulin resistance. Oxidative stress was related to increased vitamin E levels, suggesting a compensatory mechanism. CONCLUSIONS: t10c12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men. The oxidative stress seems closely related to induced insulin resistance, suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance. These unfavorable effects of t10c12 CLA might be of clinical importance with regard to cardiovascular disease, in consideration of the widespread use of dietary supplements containing this fatty acid. (+info)
(20/472) Paradoxical effect of sibutramine on autonomic cardiovascular regulation.
BACKGROUND: Sibutramine, a serotonin and norepinephrine transporter blocker, is widely used as an adjunctive obesity treatment. Norepinephrine reuptake inhibition with sibutramine conceivably could exacerbate arterial hypertension and promote cardiovascular disease. METHODS AND RESULTS: In 11 healthy subjects (7 men, age 27+/-2 years, body mass index 23.1+/-0.7 kg/m2), we compared the effect of sibutramine or matching placebo (ingested 26, 14, and 2 hours before testing) on cardiovascular responses to autonomic reflex tests and to a graded head-up tilt test. In addition, we tested sibutramine in combination with metoprolol. Testing was conducted in a double-blind and crossover fashion. Supine systolic blood pressure was 113+/-3 mm Hg with placebo, 121+/-3 mm Hg with sibutramine (P<0.001 versus placebo), and 111+/-2 mm Hg with the combination of sibutramine and metoprolol. Similarly, sibutramine increased upright blood pressure. Sibutramine substantially increased upright heart rate. This effect was abolished with metoprolol. The blood pressure response to cold pressor and handgrip testing was attenuated with sibutramine compared with placebo. Furthermore, sibutramine decreased low-frequency oscillations of blood pressure and plasma norepinephrine concentrations in the supine position. CONCLUSIONS: The cardiovascular effect of the antiobesity drug sibutramine results from a complex interaction of peripheral and central nervous system effects. The inhibitory clonidine-like action of sibutramine on the central nervous system attenuates the peripheral stimulatory effect. Our findings strongly suggest that current concepts regarding the action of sibutramine on the sympathetic nervous system should be reconsidered. (+info)
(21/472) acp Best Practice No 168. The investigation and management of obesity.
Obesity is a chronic condition characterised by an excess of body fat. It is a complex disorder of appetite regulation and energy metabolism controlled by specific biological factors. In the past 10 years, great progress has been made in the scientific understanding of the pathophysiology of obesity and the interactions between genetic predisposition to weight gain and the environment. This article will review the current understanding of the pathophysiology and the approach to the investigation and management of obesity. (+info)
(22/472) New antiobesity agents in type 2 diabetes: overview of clinical trials with sibutramine and orlistat.
Besides genetic predisposition, obesity is the most important risk factor for the development of type 2 diabetes mellitus. Even modest weight reduction can improve blood glucose control in overweight subjects. After failure of lifestyle modifications, antiobesity drugs such as orlistat, a potent and selective inhibitor of gastric and pancreatic lipases that reduces lipid intestinal absorption, or sibutramine, a noradrenaline and 5-hydroxytryptamine reuptake inhibitor that regulates food intake, may be considered to favour weight loss and/or weight maintenance. Several placebo-controlled studies have recently demonstrated that both drugs are able to promote weight loss in obese type 2 diabetic patients treated with diet alone, sulphonylureas, metformin or insulin. The greater weight reduction as compared to placebo was associated with a significant reduction of glycated haemoglobin levels and/or of the doses of classical antihyperglycaemic agents, especially in good responders who lost at least 10% of initial body weight. In addition, vascular risk factors associated to insulin resistance were also reduced after weight loss. These antiobesity agents may also contribute to delay or prevent the progression from impaired glucose tolerance to overt type 2 diabetes in at risk obese individuals ("Xenical in the prevention of diabetes in obese subjects" trial). Large long-term prospective studies, such as the "Sibutramine cardiovascular and diabetes outcome study" should better determine the place of pharmacological anti-obesity strategy in the overall management of obese patients with impaired glucose tolerance or type 2 diabetes. (+info)
(23/472) Impact of carbohydrate and fat intake on weight-reducing efficacy of orlistat.
BACKGROUND: Orlistat treatment of obesity results in a poor long-term weight loss (< 5%) in about 30% of patients. AIM: Total energy and macronutrient intake were examined to assess the effect of a change in eating habits on weight loss. METHODS: Sixty-two patients consumed a hypocaloric diet, together with orlistat (3 x 120 mg/day), for 72 weeks, with a maximal fat allowance of 30% of the energy intake. At regular intervals, food diaries were recorded. RESULTS: Fifty-six patients completed the study and lost 8.5 +/- 0.88 kg (P < 0.001). Energy intake was approximately 1500 kcal/day during the entire study period. In three sub-groups established according to weight loss (1, < 5%; 2, > 5% and < 10%; 3, > 10%), fat intake was within the recommended range in all groups during the first 6 months, but thereafter only in group 3. All groups increased their carbohydrate consumption, with the greatest increase in group 1, which could account for the rapid regain of initially lost body weight in this group. CONCLUSION: At the beginning of a weight management programme in conjunction with orlistat, a low fat intake is advised for an efficient reduction in body weight. Subsequently, in patients with poor long-term weight loss, dietary recommendations must also consider carbohydrate restriction to ensure an adequate hypocaloric diet. (+info)
(24/472) Acarviosine-simmondsin, a novel compound obtained from acarviosine-glucose and simmondsin by Thermus maltogenic amylase and its in vivo effect on food intake and hyperglycemia.
Simmondsin was modified with acarviosine-glucose using the transglycosylation activity of Thermus maltogenic amylase to synthesize a novel compound with both antiobesity and hypoglycemic activity. The LC/MS and 13C NMR analyses confirmed that the structure of the major transglycosylation product was acarviosine-simmondsin (Acv-simmondsin), in which acarviosine was attached to the glucose moiety of simmondsin by an alpha-(1,6)-glycosidic linkage. It was found that Acv-simmondsin was a potent competitive inhibitor of alpha-glucosidase with the Ki value of 0.69 microM and a mixed type inhibitor of alpha-amylase with the Ki and KI of 20.78 microM and 26.31 microM, respectively. The administration of Acv-simmondsin (0.1 g/100 g diet/day) to mice for 5 days significantly reduced food intake by 35%, compared to 25% with simmondsin in control obese mice. Acv-simmondsin (50 mg/kg BW) suppressed the postprandial blood glucose response to sucrose (1 g/kg BW) by 74%, compared to 71% with acarbose, in normal rats. (+info)