European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity.

Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.

Prevalence of endocrine disorders in obese patients: systematic review and meta-analysis.

OBJECTIVE: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. DESIGN: Systematic review and meta-analysis of the literature. METHODS: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). RESULTS: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. CONCLUSIONS: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.

[New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk : Statement of the D•A•CH Society for Prevention of Cardiovascular Diseases, the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society for Cardiology]. / Neue AHA- und ACC-Leitlinie zur Risikoreduktion von Herz-Kreislauf-Erkrankungen durch Cholesterinsenkung : Stellungnahme der D•A•CH-Gesellschaft Prävention von Herz-Kreislauf-Erkrankungen e. V., der Österreichischen Atherosklerose Gesellschaft und der Arbeitsgruppe Lipide und Atherosklerose (AGLA) der Schweizer Gesellschaft für Kardiologie.

Guidelines for the reduction of cholesterol to prevent atherosclerotic vascular events were recently released by the American Heart Association and the American College of Cardiology. The authors claim to refer entirely to evidence from randomized controlled trials, thereby confining their guidelines to statins as the primary therapeutic option. The guidelines derived from these trials do not specify treatment goals, but refer to the percentage of cholesterol reduction by statin medication with low, moderate, and high intensity. However, these targets are just as little tested in randomized trials as are the cholesterol goals derived from clinical experience. The same applies to the guidelines of the four patient groups which are defined by vascular risk. No major statin trial has included patients on the basis of their global risk; thus the allocation criteria are also arbitrarily chosen. These would actually lead to a significant increase in the number of patients to be treated with high or maximum dosages of statins. Also, adhering to dosage regulations instead of cholesterol goals contradicts the principles of individualized patient care. The option of the new risk score to calculate lifetime risk up to the age of 80 years in addition to the 10-year risk can be appreciated. Unfortunately it is not considered in the therapeutic recommendations provided, despite evidence from population and genetic studies showing that even a moderate lifetime reduction of low-density lipoprotein (LDL) cholesterol or non-HDL cholesterol has a much stronger effect than an aggressive treatment at an advanced age. In respect to secondary prevention, the new American guidelines broadly match the European guidelines. Thus, the involved societies from Germany, Austria and Switzerland recommend continuing according to established standards, such as the EAS/ESC guidelines.

[Screening for hyperlipidemia in cardiovascular high-risk patients in austrian diabetes ambulances]. / Hyperlipidämie-Screening bei kardiovaskulären Hochrisikopatienten. Beobachtungsstudie in österreichischen Diabetesambulanzen.

BACKGROUND: Incidence of coronary heart disease is 2-4 fold increased in type 2 diabetic patients and diabetic dyslipidemia is a major risk factor.To reduce cardiovascular risk in diabetes decreasing LDL-cholesterol (LDL-C) is the major goal in lipid management. Evidence-based limits for LDL-C levels are for patients without cardiovascular complications <100 mg/dl and for patients with cardiovascular complications <70 mg/dl. The aim of the present screening initiative was to investigate the status quo of LDL-C levels in consecutively recruited diabetic patients suffering cardiovascu-lardisease. METHOD: A total of 921 type 2 diabetic patients with coronary, peripheral or central vascular complications were included in 2007 in 15 Austrian diabetes centers. Level of lipids and HbA(1c) were analyzed as well as data on patient's history and medical therapy were collected. Subjects (n=355) with LDL-C level <70 mg/dl at the beginning were not further evaluated. In the remaining 566 patients with baseline LDL-C >70 mg/dl, routine treatment was followed; 231 of them had a follow-up evaluation, 335 did notattend thecenterfor routine treatment again. RESULTS: LDL-C at the beginning was < 70 mg/dl in 355 patients (38.5%), in between 70-100 mg/dl in 348 patients (37.8%) and > 100 mg/dl in 218 patients (23.7%). All butonepatientswerealreadytreatedwith lipid lowering agents at baseline, whereas 96.4% got at least one standard statin or a statin with high potency. During lipid therapythe percentage of standard statins decreased significantly (p < 0.0001), whereas the percentage of high potency statins increased significantly (p < 0.0001 ). The percentage of ezetimib also increased significantly (p < 0.0001), fibrate nearly remained constant. The median LDL-C levels decreased from 97 mg/dl at baseline to 77 mg/dl at follow-up in subjects who attended the sites for follow-up (n = 231). CONCLUSION: This screening initiative demonstrated a more successful therapy if only lipid levels were followed more consequently.

Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To investigate the efficacy and safety of topiramate in obese subjects with type 2 diabetes treated with metformin. DESIGN: This was a multicenter, double-blind, placebo-controlled trial. All subjects received a non-pharmacological program of diet, exercise and behavioral modification throughout the study; the assigned diet was 600 kcal/day less than the subject's individually calculated energy expenditure. After a 6-week single-blind placebo run-in, subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Following an 8-week titration period, subjects remained on their assigned dose for 52 weeks. However, the sponsor ended the study early in order to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. A total of 646 obese men and women (age: 18-75 years, body mass index: 27-50 kg/m(2)) with an established history of type 2 diabetes mellitus controlled by metformin monotherapy were randomized. Efficacy was assessed in a pre-determined modified intent-to-treat (MITT) population of 307 subjects whose randomization date would have allowed them to complete 24 weeks on study medication before the announcement of study termination. MEASUREMENTS: Joint primary efficacy parameters were mean percent change in weight and change in glycosylated hemoglobin (HbA(1c)) from baseline to week 24. RESULTS: Subjects in the placebo, topiramate 96 mg/day and topiramate 192 mg/day groups lost 1.7%, 4.5% (P<0.001) and 6.5% (P<0.001), respectively, of their baseline body weight and had absolute decreases in HbA(1c) of 0.1%, 0.4% (P<0.001) and 0.6% (P<0.001) (MITT, last observation carried forward). Topiramate-treated subjects also experienced statistically significant decreases in systolic blood pressure. Most common adverse events were paresthesia and events related to the central nervous system. CONCLUSIONS: Topiramate was effective for weight reduction and improvement in glycemic control in obese subjects with type 2 diabetes treated with metformin monotherapy. Further study in obese diabetics is warranted.

Sugar-, acid- and phenol contents in apple cultivars from organic and integrated fruit cultivation.

OBJECTIVE: This study was carried out to obtain data about the sugar-, acid- and phenol content of apple cultivars from organic and integrated fruit cultivation, with reference to their role in human health and especially for diet recommendations. SETTING: Styria (Austria) and Slovenia. INTERVENTIONS: HPLC, Spectral Photometry, organoleptic and olfactory tests. RESULTS: The total sugar content of most cultivars from integrated cultivation ranged between 115 and 160 g/kg. Some cultivars from organic growing reached higher values. The acid content of both cultivar types was similar. The phenol content in organically grown cultivars was much higher than that of the ones from integrated cultivation. CONCLUSION: Knowledge of the sugar content is very important for diabetic patients, owing to the assumption of general diet recommendations that 100 g fruit contain 12 g carbohydrates. This applies to most well-known cultivars like Golden Delicious or Gala, but not to most of the regional cultivars. For diabetics, it is necessary to know the carbohydrate content of food precisely, in order to adapt the amount of insulin to the ingestion. So, it is helpful to know the sugar content of each regional cultivar. Moreover, very high levels of phenolic compound in organically grown cultivars, and with it its importance for human health leads to the recommendation to eat regional fruits from organic fruit growing instead of those grown under integrated cultivation.

X-PERT: weight reduction with orlistat in obese subjects receiving a mildly or moderately reduced-energy diet: early response to treatment predicts weight maintenance.

AIM: To determine the effect of two different levels of energy deficit on weight loss in obese patients treated with orlistat. METHODS: Patients (n=430) were randomized in a 1-year, multicentre, open-label, parallel group study conducted at 23 hospital centres and university medical departments worldwide. Obese outpatients (body mass index 30--43 kg/m(2)) aged 18--70 years with a body weight of >or=90 kg and a waist circumference of >or=88 cm (women) or >or=102 cm (men) were treated with orlistat 120 mg three times daily plus a diet that provided an energy deficit of either 500 or 1,000 kcal/day for 1 year. Orlistat treatment was discontinued in patients who did not achieve >or=5% weight loss after assessment at 3 and 6 months. The primary outcome measure was change in body weight from baseline at week 52. RESULTS: Reported mean difference in energy intake between the two groups (500-1,000 kcal/day deficit) at weeks 24 and 52 was actually 111 and 95 kcal/day respectively. Of the 430 patients involved in the study, 295 achieved >or=5% weight loss at both 3 and 6 months. In this population, at week 52, weight loss from baseline was similar for patients randomized to either the 500 or the 1,000 kcal/day deficit diet (-11.4 kg vs. -11.8 kg, respectively; p=0.778). After 12 months of treatment with orlistat, 84% (n=118/141) and 85% (n=131/154) of patients in the 500 and 1,000 kcal/day deficit groups, respectively, achieved >or=5% weight loss, and 50% (n=70/141) and 53% (n=82/154) of patients, respectively, achieved >or=10% weight loss. Patients in both the diet treatment groups showed similar significant improvements in blood pressure, lipid levels and waist circumference at week 52. CONCLUSIONS: Treatment with orlistat was associated with a clinically beneficial weight loss, irrespective of the prescribed dietary energy restriction (-500 or -1000 kcal/day). Patients who achieved >or=5% weight loss at 3 months achieved long-term, clinically beneficial weight loss with orlistat plus either diet. Therefore, identifying patients who lose at least 5% weight after 3 months and who maintain this weight loss up to 6 months is a valuable treatment algorithm to select patients who will benefit most from orlistat treatment in combination with diet.

Effects of elderberry juice on fasting and postprandial serum lipids and low-density lipoprotein oxidation in healthy volunteers: a randomized, double-blind, placebo-controlled study.

BACKGROUND: In a recent pilot study, the intake of elderberry juice resulted in a significant decrease in serum cholesterol concentrations and an increase in low-density lipoprotein (LDL) stability. This study was designed to verify the preliminary results. OBJECTIVE: We investigated the impact of elderberry juice on cholesterol and triglyceride concentrations as well as antioxidant status in a cohort of young volunteers. DESIGN: Study A: The randomized, placebo-controlled trial for studying the effect of anthocyanes on lipid and antioxidant status, 34 subjects took capsules with 400 mg spray-dried powder containing 10% anthocyanes t.i.d. equivalent to 5 ml elderberry juice for 2 weeks. A subgroup of 14 subjects continued for an additional week to test for resistance to oxidation of LDL. Study B: To investigate the short-term effects on serum lipid concentrations, six subjects took a single dose of 50 ml of elderberry juice (equivalent to 10 capsules) along with a high-fat breakfast. RESULTS: In the placebo-controlled study, there was only a small, statistically not significant change in cholesterol concentrations in the elderberry group (from 199 to 190 mg/dl) compared to the placebo group (from 192 to 196 mg/dl). The resistance to copper-induced oxidation of LDL did not change within 3 weeks. In the single-dose experiment increases in postprandial triglyceride concentrations were not significantly different when the six subjects were investigated with and without elderberry juice. CONCLUSIONS: Elderberry spray-dried extract at a low dose exerts a minor effect on serum lipids and antioxidative capacity. Higher, but nutritionally relevant doses might significantly reduce postprandial serum lipids.

Effect of acarbose on weight maintenance after dietary weight loss in obese subjects.

AIMS: Acarbose is a well established antidiabetic drug and is known to exert a modest weight-lowering effect. The aim of this study was to assess the potential of acarbose to improve weight maintenance after a substantial weight loss by dietary measures in obese subjects. DESIGN: Randomised, double-blind, placebo-controlled trial of the effect of acarbose on weight change over a 6-month follow-up period. PATIENTS AND METHODS: One hundred and ten obese subjects with a BMI > or = 32 and < or = 38 kg/m2 were included in the study and underwent a 10-16-week very-low-calorie diet programme to initiate weight loss. Then, subjects were randomised to receive either acarbose or placebo for 26 +/- 2 weeks. The primary variable was body weight. The primary efficacy analysis was performed in the per-protocol population (n = 75). RESULTS: After an initial mean weight loss of 10.0 +/- 3.4 kg, 54 subjects received acarbose at increasing dosage and 56 subjects received placebo treatment. After 14 weeks of follow-up, there was no change in body weight in the two groups. After 26 weeks, completed by 37 subjects in the acarbose group and by 38 subjects in the placebo group, a small weight regain of 0.6 kg was documented in the latter, whereas no weight increase was observed under acarbose treatment (p = 0.38, analysis of covariance with initial body weight as covariable). CONCLUSION: In obese individuals who undergo a hypocaloric diet and achieve a substantial loss of body weight, acarbose treatment provides only a very modest, not significant benefit to stabilise weight reduction. Thus, acarbose is not a useful adjunct to improve weight maintenance in obese subjects after weight loss.

C242T polymorphism of the p22 phox gene is not associated with peripheral arterial occlusive disease.

Formation of reactive oxygen metabolites is vital for the microbicidal activity of phagocytes. As an unwanted side effect, these metabolites may contribute to oxidative stress in the vasculature and thus lead to arteriosclerosis. p22 phox, a component of the NADH/NADPH oxidase in phagocytes and vascular smooth muscle cells, is essential for production of reactive oxygen metabolites. Recently, a C/T polymorphism at position 242 of the p22 phox gene has been associated with coronary artery disease (CAD), suggesting a protective effect of the 242 T allele on the vasculature. In the present study, we analysed the relation of this polymorphism to peripheral arterial occlusive disease (PAOD). C242T polymorphism was determined by restriction fragment polymorphism (RFLP) analysis in 324 patients with documented PAOD and 295 control subjects without any known arterial disease. p22 phox 242 T allele frequencies and genotype distributions were not significantly different between patients and controls; the adjusted relative risk associated with the 242 T allele was 1.14 (95% CI 0.84-1.54, P=0.39), assuming an additive effect of the T allele. C242T polymorphism was not associated with the age of patients at the onset of the disease. Our data indicate that C242T polymorphism of the p22 phox gene is not associated with PAOD.

Prothrombin G20210A, factor V Leiden, and factor XIII Val34Leu: common mutations of blood coagulation factors and deep vein thrombosis in Austria.

Mutations in the gene for prothrombin (F2 20210A) and factor V (F5 1691A, factor V Leiden) are established risk factors for deep venous thrombosis (DVT). Recently, a mutation in the gene for factor XIII (F13 100T) leading to a Valine-Leucine exchange at amino acid position 34 has been reported to be protective against DVT. To analyze the role of these mutations for DVT in Austria, we analyzed their prevalence in 154 patients with documented DVT and 308 sex- and age-matched control subjects. Allele frequencies of F2 20210A, F5 1691A, and F13 100T were 0.018, 0.039, and 0.274 among controls, and 0.045, 0.120, and 0.211 among patients, respectively. Odds ratios for DVT associated with F2 20210A, F5 1691A, and F13 100T alleles were 2.5 (95% CI: 1.1-5.7), 3.4 (95% CI: 1.9-5.8), and 0.7 (95% CI: 0.5-1.0). We conclude that F2 20210A, F5 1691A, and F13 100T are common mutations in the Austrian population. F2 20210A and F5 1691 increase the risk for DVT, whereas F13 100T is associated with a decreased risk for DVT. Routinely, analysis of these mutations may help to analyze the individual risk for DVT.

Factor II G20210A and factor V G1691A gene mutations and peripheral arterial occlusive disease.

BACKGROUND: G to A mutations at positions 20210 of the prothrombin gene (F2) and 1691 of the factor V gene (F5) are established risk factors for venous thrombosis. Several factors associated with coagulation and/or fibrinolysis have been associated with arterial occlusive disease, but the role of F2 20210A and F5 1691A for arterial occlusive disease remains unclear. OBJECTIVE: To investigate if F2 20210A and F5 1691A are associated with peripheral arterial occlusive disease (PAOD). METHODS AND RESULTS: We analyzed the prevalence of F2 20210A and F5 1691A alleles in 336 patients with documented PAOD at Fontaine stage II-IV and 300 controls without vascular disease. Allele frequencies in patients and controls were 0.013 and 0.022 for F2 20210A, and 0.042 and 0.045 for F5 1691, respectively, both differences being not statistically significant. CONCLUSION: Our data suggest that mutations F2 G20210A and F5 G1691A are not associated with PAOD.

[Statins--attaining goal values--with reference to recent studies]. / Statine--Zielwerte erreichen--im Lichte neuer Studien.

Recent lipid intervention studies led to the implementation of lipid lowering therapy in the cardiovascular risk management. These secondary as well as primary prevention studies share the effect of HMG-CoA-reductase inhibition. Despite varying product properties there seem to be no major differences in risk reduction between the drugs. One could argue the main action of the statins, lipid lowering, is the most prominent mode of action. A new study (AirForce/Texas Coronary Atherosclerosis Prevention Study) extended that to patients with relatively low total cholesterol levels (mean 221 mg/dl with a slightly lowered LDL-C of 37 mg/dl, LDL-C of 150 mg/dl) successfully treated with lovastatin in primary prevention. That supports the concept to reach lipid levels as low as possible in the longer term, even if the absolute clinical event reduction in primary prevention is not so impressive. On the contrary, in secondary prevention: in the AVERT-study in patients with a 82% mean stenosis in one vessel PTCA-treated patients with conventional drug therapy were compared to such without PTCA and aggressive lipid lowering therapy (resulting LDL-C 77 mg/dl). One could be surprised that the "intervention group" was not better, though representing the usual clinical procedere. Interestingly, borderline significant (p < 0.046 at a level of significance of p < 0.045), results were in favor for the drug treated group. Such data could, if confirmed in further investigations, change cardiovascular disease management to aggressive lipid lowering prior to or instead invasive management, especially in initial therapy of CVD and diabetes mellitus type II.

Effects of intensified lifestyle modification on the need for further revascularization after coronary angioplasty.

BACKGROUND: In patients with coronary artery disease (CAD), a rate of restenosis as high as 50% is observed after percutaneous transluminal coronary angioplasty (PTCA). Frequently, this results in further revascularization procedures. Lifestyle intervention has been shown to slow the progression of CAD and to reduce cardiovascular events after myocardial infarction. However, no information exists whether such treatment influences the rate of restenosis in patients with CAD. The present study was performed to investigate the effects of an intensified lifestyle intervention on the need for further revascularization procedures in patients with established CAD after successful PTCA. DESIGN: A total of 60 patients were included and randomized to either conventional treatment by cardiologists and general practitioners or additional intensified lifestyle intervention in a diabetes and metabolism outpatient clinic for 12 months. The mean observation time after successful PTCA was 26 months. The primary outcome variable was the need for further revascularization procedures because of clinical restenosis. Secondary outcome variables were lifestyle-related measures. RESULTS: Intervention resulted in a reduction in body weight and blood pressure, and in increased physical activity. Furthermore, nutritional habits were changed towards less fat intake, and body composition changed towards a higher proportion of fat-free mass. The need for further revascularization procedures was reduced from a total of 14 out of 32 in the conventionally treated group to 3 out of 28 in the intervention group. This resulted in an event-free survival probability of 0.89 in the intervention group and 0.57 in the control group (P = 0.0055, log rank) with a resulting relative risk of 0.26 (95% CI 0.09-0.74). CONCLUSION: In conclusion, our data strongly suggest that intensified lifestyle modification is able to reduce the need for further revascularization procedures after PTCA in patients with CAD.

[Evaluation of a newly discovered LDL receptor mutation (exon 10, GAC>AAC, D271N, "FH Graz-1") in familial hypercholesterolemia-- a familystudy]. / Evaluation einer neu entdeckten LDL-Rezeptor-Mutation (Exon 10, GAC>ACC, D471N, "FH Graz-1") bei familiärer Hypercholesterinämie--eine Familienanalyse.

Heterozygous familial hypercholesterolemia (FH, prevalence 1:500) is a major cause of early atherosclerotic disease. Little is known about possible co-factors influencing individual patient's risk. We investigated this question in a large family carrying a new LDL-receptor-mutation. Genetic analysis of all exons of the LDL-receptor gene in the index case using polymerase chain reaction (PCR) and Denaturing Gradient Gel Electrophoresis (DGGE) revealed a previously unknown mutation in exon 10 (GAC > ACC, D471N, "FH Graz-1"). Investigation of 21 family members (15 females, 6 males), aged 17 to 86 years, revealed 9 female and 4 male carriers of the mutation. 7 female carriers aged 17 to 58 years show no clinical signs of macrovascular disease. An 86-year old female patient, who was asymptomatic until 85, recently suffered a transient cerebral ischemic attack. All these females were normotensive. The only hypertensive 76-year old patient (ex-smoker with a history of 15 pack years) suffers from angina pectoris. 2 male carriers of the mutation (32 and 38 years old) are asymptomatic. A 65-year old patient suffers from cardiovascular disease. A 49-year old patient had a coronary artery bypass graft after a myocardial infarction at the age of 37. Additionally he has a history of bilateral thrombendarterectomy of the carotid arteries and suffers from bilateral peripheral artery disease. This patient also carries the apoE-genotype 4/3, which might be responsible for his poor response to stain therapy, and needs extracorporal lipid elimination (LDL-C > 200 mg/dl under drug therapy). Both of his daughters are homozygous for the apoE-allele 3 and and responded well to stain therapy. Genetic analysis in patients with FH assures diagnosis, but is not sufficient to determine the individual patient's risk. A precise clinical examination remains the gold standard for individual risk evaluation.

Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Orlistat Dose-Ranging Study Group.

OBJECTIVE: To determine the weight-reducing efficacy of orlistat, a novel gastrointestinal lipase inhibitor, and to define the optimal dosage regimen and establish the tolerability of the drug when used for a 6-month treatment period. METHODS: The study was a multicentre randomised, double-blind, parallel group in design and involved 676 obese male and female subjects aged at least 18 years with a body mass index between 28 and 43 kg x m(-2) Following a 5-week placebo run-in period, subjects were randomised to receive orlistat 30 mg, 60 mg, 120 mg, 240 mg or matching placebo three times a day (tid) for 24 weeks during meals. Patients were maintained on a mildly hypocaloric diet throughout the study period. The primary efficacy parameter was body weight change over time. RESULTS: Orlistat resulted in a significantly greater mean loss of body weight than observed in the placebo group. In absolute terms, mean weight loss was greatest in the 120 mg group (9.8%). More orlistat- than placebo-treated patients lost > 10% of initial body weight (37% of the 120 mg group vs 19% of the placebo group). Orlistat was well tolerated. Predictably, in view of its known pharmacological effects, more orlistat-treated patients experienced gastrointestinal events. Mean levels of vitamins A, D and E, and beta-carotene remained within the clinical reference ranges in all treatment groups and rarely required supplementation. After 24 weeks, plasma concentrations of orlistat were either non-measurable or detected at the assay's limit of quantitation. CONCLUSION: Orlistat treatment results in a dose-dependent reduction in body weight in obese subjects and is well tolerated. Orlistat 120 mg tid represents the optimal dosage regimen.

Forearm composition contributes to differences in reactive hyperaemia between healthy men and women.

BACKGROUND: Post-ischaemic reactive hyperaemia in the forearm has been suggested as a marker of resistance vessel function. The contribution of forearm composition to the kinetics of reactive hyperaemia is largely unknown. The body composition of men and women differs in that women have a higher body fat content and less lean body mass. METHODS: In the present study, we investigated whether the kinetics of reactive hyperaemia in the forearm in 14 healthy subjects (seven men and seven women) show gender-specific differences and whether forearm composition contributes to such differences. RESULTS: Peak reactive hyperaemic flow as well as 1-min-flow debt repayment (measured by venous occlusion plethysmography) were significantly higher in male than in female study participants. This difference was explained to > 60% by gender-specific differences in forearm relative muscle mass (as determined by magnetic resonance imaging). The half-life of the reactive hyperaemic response, on the other hand, was not different between men and women and did not show an association with forearm muscle. CONCLUSION: Our results demonstrate that forearm composition must be considered if peak reactive hyperaemic or flow debt repayment is used as a target, and that dynamic measurements of the reactive hyperaemic process are more suitable to describe the function of resistance arteries than single-point observations.

[Effect of fat distribution on risk]. / Einfluss der Fettverteilung auf das Risiko.

About 10 years ago the WHO defined obesity as a separate disease whereas in Austria until now it is often regarded as a cosmetical problem only. Many diseases like those of joints and spine are correlated to the body weight and the body mass index (BMI), but macrovascular events (cardiovascular and cerebrovascular) and early death are closer associated with the waist to hip ratio (WHR), indicating an abdominal, android fat distribution. This fat distribution tends toward higher insulin levels, dys- and hyperlipidemia and disturbances in glucose metabolism which can in part explain these associations in the light of the metabolic syndrome. In conclusion, there is no healthy overweight, but not all overweight patients share the same risk.