| 1. |
- Delling, Lotta, et al.
(författare)
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Feasibility of bariatric surgery as a strategy for secondary prevention in cardiovascular disease: a report from the Swedish obese subjects trial.
- 2010
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Ingår i: Journal of obesity (Online). - : Hindawi Limited. - 2090-0716 .- 2090-0708. ; 2010
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Forskningsöversikt (refereegranskat)abstract
- Aims. Evaluation of bariatric surgery as secondary prevention in obese patients with ischemic heart disease (IHD). Methods. Analysis of data from 4047 subjects in the Swedish Obese Subjects (SOSs) study. Thirty-five patients with IHD are treated with bariatric surgery (n = 21) or conventional treatment (n = 14). Mean follow-up is 10.8 years. Results. Bariatric surgery resulted in sustained weight loss during the study period. After 2 years, the surgery group displayed significant reductions in cardiovascular risk factors, relief from cardiorespiratory symptoms, increments in physical activity, and improved quality of life. After 10 years, recovery from hypertension, diabetes, physical inactivity, and depression was still more common in the surgery group. There were no signs of increased cardiovascular morbidity or mortality in the surgery group. Conclusion. Bariatric surgery appears to be a safe and feasible treatment to achieve long-term weight loss and improvement in cardiovascular risk factors, symptoms, and quality of life in obese subjects with IHD.
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| 2. |
- Elias, Erik, 1979, et al.
(författare)
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Central nervous system lipocalin-type prostaglandin D2-synthase is correlated with orexigenic neuropeptides, visceral adiposity and markers of the hypothalamic-pituitary-adrenal axis in obese humans.
- 2011
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Ingår i: Journal of neuroendocrinology. - : Wiley. - 1365-2826 .- 0953-8194. ; 23:6, s. 501-7
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Tidskriftsartikel (refereegranskat)abstract
- Lipocalin-type prostaglandin D2-synthase (L-PGDS) is the main producer of prostaglandin D2 (PGD2) in the central nervous system (CNS). Animal data suggest effects of central nervous L-PGDS in the regulation of food intake and obesity. No human data are available. We hypothesised that a role for CNS L-PGDS in metabolic function in humans would be reflected by correlations with known orexigenic neuropeptides. Cerebrospinal fluid (CSF) and serum samples were retrieved from 26 subjects in a weight loss study, comprising a 3-week dietary lead-in followed by 12-weeks of leptin or placebo treatment. At baseline, CSF L-PGDS was positively correlated with neuropeptide Y (NPY) (ρ=0.695, P<0.001, n=26) and galanin (ρ=0.651, P<0.001) as well as visceral adipose tissue (ρ=0.415, P=0.035). Furthermore, CSF L-PGDS was inversely correlated with CSF leptin (ρ=-0.529, P=0.005) and tended to correlate inversely with s.c. adipose tissue (ρ=-0.346, P=0.084). As reported earlier, leptin treatment had no effect on weight loss and did not affect CSF L-PGDS or NPY levels compared to placebo. After weight loss, the change of CSF L-PGDS was significantly correlated with the change of CSF NPY levels (ρ=0.604, P=0.004, n=21). Because of the correlation between baseline CSF L-PGDS levels and visceral adipose tissue, we examined associations with hypothalamic-pituitary-adrenal (HPA) axis components. Baseline CSF L-PGDS was correlated with corticotrophin-releasing hormone (ρ=0.764, P<0.001) and β-endorphin (ρ=0.491, P<0.001). By contrast, serum L-PGDS was not correlated with any of the measured variables either at baseline or after treatment. In summary, CSF L-PGDS was correlated with orexigenic neuropeptides, visceral fat distribution and central HPA axis mediators. The importance of these findings is unclear but could suggest a role for CSF L-PGDS in the regulation of visceral obesity by interaction with the neuroendocrine circuits regulating appetite and fat distribution. Further interventional studies will be needed to characterise these interactions in more detail.
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| 3. |
- Eskandari, Davoud, et al.
(författare)
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Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study
- 2014
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 44:1, s. 140-149
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Tidskriftsartikel (refereegranskat)abstract
- Carbonic anhydrase inhibition reduces apnoeic events in sleep disordered breathing. Zonisamide inhibits carbonic anhydrase, and induces weight loss in obese patients. This study explored the relative influence of these two properties, which may both alleviate obstructive sleep apnoea (OSA). Continuous positive airway pressure (CPAP) was used as a standard care comparator. 47 patients with moderate-to-severe OSA and a body mass index of 27-35 kg.m(-2) were randomised to receive either zonisamide, placebo or CPAP for 4 weeks. The open extension phase (20 weeks) compared CPAP and zonisamide. Polysomnography, biochemistry and symptoms were evaluated. At 4 weeks, zonisamide reduced apnoea/hypopnoea index (AHI) by a mean +/- SD 33 +/- 39% and oxygen desaturation index by 28 +/- 31% (p=0.02 and 0.014, respectively; placebo adjusted). The mean compliance adjusted reduction of AHI after zonisamide and CPAP was 13 and 61%, respectively, (p=0.001) at 24 weeks. Body weight was marginally changed at 4 weeks, but reduced after zonisamide and increased after CPAP at 24 weeks (-2.7 +/- 3.0 kg versus 2.3 +/- 2.0 kg, p<0.001). Zonisamide decreased bicarbonate at 4 and 24 weeks. Side-effects were more common after zonisamide. Zonisamide reduced OSA independent of body weight potentially by mechanisms related to carbonic anhydrase inhibition. The effect was less pronounced than that obtained by CPAP.
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| 4. |
- Gummesson, Anders, 1973, et al.
(författare)
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Intestinal Permeability Is Associated With Visceral Adiposity in Healthy Women.
- 2011
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Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381.
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Tidskriftsartikel (refereegranskat)abstract
- Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates to key metabolic dysfunctions including insulin resistance, hepatic steatosis, and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and in experimental rodent models of gut inflammation suggest that impaired gut barrier function with increased leakage of gut-derived antigens may drive visceral lipid deposition. The aim of this study was to determine whether increased intestinal permeability is associated with visceral adiposity in healthy humans. Normal to overweight female subjects were recruited from a population-based cohort. Intestinal permeability was assessed using the ratio of urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n = 67), we found a positive correlation between waist circumference and S/M excretion within a time frame of urine collection consistent with permeability of the lower gastrointestinal tract (6-9 hours post-ingestion; P = 0.022). These results were followed up in study 2 (n = 55) in which we used computed tomography and dual energy X-ray absorptiometry to measure visceral and subcutaneous fat areas of the abdomen, liver fat content, and total body fat of the same women. The S/M ratio from the 6-12 h urine sample correlated with visceral fat area (P = 0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total body fat. This novel finding of an association between intestinal permeability and visceral adiposity and liver fat content in healthy humans suggests that impaired gut barrier function should be further explored as a possible mediator of excess visceral fat accumulation and metabolic dysfunction.
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| 5. |
- Kellis, Dimitrios, 1982, et al.
(författare)
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Associations between obstructive sleep apnea and CT-determined abdominal and liver fat content in severe obese subjects
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: Obstructive Sleep Apnea (OSA) is a common co-morbidity in obese patients. OSA is also frequently associated with various metabolic complications. In this study, we have evaluated the associations between measures of OSA and abdominal and liver fat subjects with untreated OSA. Methods: A total of 470 subjects (73% females) were examined during a screening process at the Obesity unit at the Sahlgrenska University Hospital. OSA was determined by the ApneaLink system and visceral and liver fat content were determined by CT using a two slice technique at the liver and L4-5 level. The included subjects had a mean age of 42.4 years (SD: 13.5 years), mean weight of 116.6 kg (SD: 20.3 kg), and a mean BMI of 40.8 kg/m2 (SD: 5.7 kg/m2). From the ApneaLink examinations the Apnea - Hypopnea Index (AHI), Respiratory Distress Index (RDI), Oxygen Desaturation Index (ODI) and mean oxygen saturation (SO2) was determined. From the CT examinations visceral adipose tissue mass (VAT) and hepatic fat content (HFC) was determined. Results: VAT was strongly correlated to AHI, RDI, ODI, and SO2 (r = 0.397, 0.388, 0.449, and )0.424 respectively, P < 0.001). There was also a correlation between HFC and AHI, RDI, ODI, and SO2 (r = 0.193, 0.198, 0.214, and 0.173 respectively, P < 0.001). Conclusion: The present study demonstrates that untreated OSA in severe obesity is associated to both measures of visceral fat and hepatic fat content. Evaluations of abdominal fat content should be considered in obese subjects with OSA.
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| 6. |
- Lundén, A, et al.
(författare)
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Validation of the Obesity-related Problem Scale version 3
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: The Obesity-related Problem scale (OP) is a quality of life instrument developed to measure the impact of obesity on psychosocial functioning. Subjects are asked how bothered they are by their obesity in specific social situations. A new version of the instrument (OP V3) has been developed. Eight more items were added. Also, an avoidance scale (AV) was added to each item, measuring avoidance of social activities. Thus, the OP V3 contains both a distress and an avoidance scale. The aim of the present study was to investigate the construct validity of OP V3. Methods: One eighty subjects, BMI 40.7˘ 5.3 kg/m2, completed the OP V3. The construct validity of OP V3 was studied by means of exploratory factor analyses. Internal consistency reliability, floor and ceiling effects, concurrent validity and known group validation were also examined. SF-36 was used to evaluate the concurrent validity. Results: Scale internal consistency reliability was high for both the distress and avoidance scales (Cronbach’s alpha = 0.95 for both). Floor and ceiling effects were small. Exploratory factor analyses confirmed the homogeneity and stability of the construct. Psychometric results were cross-validated and replicated in subgroups by gender, age and BMI. Multitrait-Multimethod analysis showed moderate associations between the OP V3 scales and the SF-36 scales. Correlations ranged from )0.32 to )0.58, P < 0.001. As expected, OP V3 scales were most highly correlated with Social functioning, Mental health and Vitality (r = )0.51 to )0.58, P < 0.001). Conclusions: Results confirm that OP V3 is a psychometrically valid measure of the impacts of obesity on psychosocial functioning.
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| 7. |
- Marshall, N.S., et al.
(författare)
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Changes in sleep duration and changes in weight in obese patients: The Swedish Obese Subjects Study
- 2010
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Ingår i: Sleep and Biological Rhythms. - : Springer Science and Business Media LLC. - 1479-8425 .- 1446-9235. ; 8:1, s. 63-71
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Tidskriftsartikel (refereegranskat)abstract
- Sleep duration has been linked to obesity and/or weight gain in a number of cross-sectional and longitudinal observational studies. The Swedish Obese Subjects Study (SOS) is a non-randomized controlled trial of surgical interventions (surgical group) for weight-loss compared with standard conservative weight loss management (control group). We investigated whether changes in sleep duration were associated with weight loss in severely obese patients. This is a longitudinal treatment study reanalyzed as two 10-year cohorts, surgical (n= 1139) and control (n= 952). Self-reported habitual sleep duration, body weight, total cholesterol, HDL (high density lipoprotein) cholesterol, triglycerides, fasting glucose, and blood pressure were measured at baseline, 2 years, and 10 years. At baseline patients were obese (inclusion: body mass index [BMI]≥34 for men and ≥38 for women) and middle aged (37–60 years). The surgical group had substantially greater weight reduction after 10 years (–19.1 kg) compared with the control group (+1.2 kg). Changes in sleep duration between baseline, 2 years, and 10 years were not associated with body mass or with changes in weight in either cohort. Changes in cardiovascular disease (CVD) risk factors were not associated with changes in sleep duration. Changes in sleep duration over 2 and 10 years were not associated with weight loss in these obese patients. The data from the SOS study offers no support to the hypothesis that sleep-duration modification is associated with obesity reduction in severely obese people.
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| 8. |
- Marshall, N.S., et al.
(författare)
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Self-reported sleep apnoea and mortality in patients from the Swedish Obese Subjects study
- 2011
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 38:6, s. 1349-1354
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Tidskriftsartikel (refereegranskat)abstract
- Sleep apnoea is associated with increased mortality in sleep clinic and community population groups. It is unclear whether a clinical report of sleep apnoea results in additional mortality risk in patients with severe obesity. The Swedish Obese Subjects (SOS) study is a nonrandomised controlled trial of bariatric surgery versus conventional treatment for the treatment of severe obesity and its complications (mean±sd body mass index 41±5 kg·m−2). The presence or absence of sleep apnoea (witnessed pauses in breathing) was determined by self-reporting at baseline in 3,953 patients who were observed for 54,236 person-yrs (mean 13.5 maximum 21.0 yrs). Sleep apnoea was reported by 934 (23.6%) patients at baseline and was a significant univariate predictor of mortality (hazard ratio (95% CI) 1.74 (1.40–2.18)). In a range of multivariate models of mortality risk, controlling for ≤16 other potential confounders and established mortality risk factors, sleep apnoea remained a significant prognostic factor (fully adjusted model 1.29 (1.01–1.65)). Self-reported sleep apnoea is an independent prognostic marker of all-cause mortality in obese patients.
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| 9. |
- Ryan, Donna H, et al.
(författare)
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Nonsurgical weight loss for extreme obesity in primary care settings: results of the Louisiana Obese Subjects Study.
- 2010
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Ingår i: Archives of internal medicine. - : American Medical Association (AMA). - 1538-3679 .- 0003-9926. ; 170:2, s. 146-54
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Effective primary care practice (PCP) treatments are needed for extreme obesity. The Louisiana Obese Subjects Study (LOSS) tested whether, with brief training, PCPs could effectively implement weight loss for individuals with a body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 40 to 60. METHODS: The LOSS, a 2-year (July 5, 2005, through January 30, 2008) randomized, controlled, "pragmatic clinical trial" trained 7 PCPs and 1 research clinic in obesity management. Primary outcome measure was year-2 percentage change from baseline weight. Volunteers (597) were screened and randomized to intensive medical intervention (IMI) (n = 200) or usual care condition (UCC) (n = 190). The UCC group had instruction in an Internet weight management program. The IMI group recommendations included a 900-kcal liquid diet for 12 weeks or less, group behavioral counseling, structured diet, and choice of pharmacotherapy (sibutramine hydrochloride, orlistat, or diethylpropion hydrochloride) during months 3 to 7 and continued use of medications and maintenance strategies for months 8 to 24. RESULTS: The mean age of participants was 47 years; 83% were women, and 75% were white. Retention rates were 51% for the IMI group and 46% for the UCC group (P = .30). After 2 years, the results were as follows: (1) among 390 randomized participants, 31% in the IMI group achieved a 5% or more weight loss and 7% achieved a 20% weight loss or more, compared with 9% and 1% of those in the UCC group. (2) The mean +/- SEM baseline observation carried forward analysis showed a weight loss of -4.9% +/- 0.8% in IMI and -0.2 +/- 0.3% in UCC. (3) Last observation carried forward analysis showed a weight loss of -8.3% +/- 0.79% for IMI, whereas UCC was -0.0% +/- 0.4%. (4) A total of 101 IMI completers lost -9.7% +/- 1.3% (-12.7 +/- 1.7 kg), whereas 89 UCC completers lost -0.4% +/- 0.7% (-0.5 +/- 0.9 kg); (P < .001 for all group differences). Many metabolic parameters improved. CONCLUSION: Primary care practices can initiate effective medical management for extreme obesity; future efforts must target improving retention and weight loss maintenance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00115063.
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| 10. |
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| 11. |
- Smith, SR, et al.
(författare)
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The effect of orlistat 60 mg on changes in body composition over a 24 week treatment: a randomized, placebo-controlled, multicenter study
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: A paucity of data exists on the effects of 60 mg orlistat on changes in body composition, particularly visceral adipose tissue (VAT). Methods: Overweight and obese adults (BMI 25–34.9) with a waist circumference >88 cm (women) or >102 cm (men) were randomized to either orlistat 60 mg (n = 61) or placebo (n = 62) tid for 6 months to examine changes in body composition. Subjects were encouraged to maintain a hypocaloric (-500 kcals/day), low fat (30% calories from fat) diet and were encouraged to exercise. Change from baseline for VAT (kg) by CT was examined at 12 and 24 weeks by ANCOVA. Change from baseline in total fat mass (FM) by EchoMRI, body weight, and waist circumference were examined across multiple time points beginning at week 2 using repeated measure analysis. Results: Mean changes from baseline for all variables were significant in both groups. VAT reduction was greater with orlistat compared to placebo at 12 (LS mean ± SE; )0.50 ± 0.06 vs. )0.32 ± 0.06, P < 0.05) and 24 weeks ()0.62 ± 0.08 vs. )0.32 ± 0.08 P < 0.01). A significantly greater reduction was observed over the 24 weeks in the orlistat group for FM and body weight, as compared to placebo (Group effect P < 0.05), but not waist circumference. Conclusion: Orlistat 60 mg provided significantly greater reductions in weight, FM and VAT across 24 weeks, compared to placebo. The reductions in VAT were relatively stable from 12 to 24 weeks in placebo subjects, whereas VAT reduction in orlistat-treated subjects continued over the 24 week duration.
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| 12. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Effects of the microsomal triglyceride transfer protein (MTP) inhibitor JNJ-16269110 on glycemic control and body weight in subjects with type 2 diabetes mellitus (T2DM) on metformin
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: JNJ-16269110 is a novel enterocyte-targeted MTP inhibitor acting via enterically-mediated hormonal and neural mechanisms being investigated for treatment of obesity. Methods: Three hundred and fifty two subjects with T2DM (BMI 32.8 kg/m2; 54% males) were randomized to placebo, JNJ-16269110 5-mg bid, 10-mg bid or 15-mg bid for 12 weeks in a double-blind multicenter clinical trial to assess safety and efficacy of this agent. The primary efficacy endpoint was change from baseline to Week 12 in HbA1c (ITT-mixed-model). Secondary endpoints included changes in fasting plasma glucose (FPG), body weight (BW), and plasma lipids. Results: Gastrointestinal symptoms were the most common reason for early discontinuation in the JNJ-16269110 arms (2%, 12%, 9% of subjects in 5-mg, 10-mg, 15-mg bid groups, respectively, vs. 1% in placebo group). Conclusion: Compared to placebo, JNJ-16269110 10-mg and 15-mg bid improved glycemic control and reduced BW. The most common side effects were related to the astrointestinal system. Conflict of interest: K. Stenlof received funding from Johnson and Johnson as principal investigator and consultant. E. Wajs, F. Vercruysse, D. Ways, S. Ouwerkerk-Mahadevan, J. Penson, and L. Van Nueten are employees and shareholders of Johnson and Johnson. Funding: The study was funded by Johnson & Johnson Pharmaceutical Research and Development.
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| 13. |
- Stenlöf, Kaj, 1965
(författare)
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Recent Advances in the Use of Orlistat in the Treatment of Abdominal Obesity and Associated Cardiometabolic Risk Factors
- 2010
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Ingår i: Journal of Clinical Metabolism & Diabetes. - 2041-8019. ; 1:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a serious health concern in several parts of the world. During the last few years, the prevalence of abdominal obesity has attracted specific attention, as abdominal obesity and visceral obesity are associated with several important metabolic disturbances and explain most of the increased risk for cardiovascular disease (CVD) associated with obesity. Thus, in the clinical evaluation of obese patients with an increased risk for CVD, it is important to aim to reduce abdominal fat. Lifestyle interventions, including diet and physical activity, should be first-line treatments; however, pharmaceutical agents might also be considered. Not surprisingly, abdominal and visceral obesity are important targets for drug development. Orlistat is an existing pharmacological agent available for the long-term treatment of obesity. This drug inhibits gastric and pancreatic lipase degradation of triglycerides in the intestine, such that ingested triglycerides cannot be hydrolyzed or absorbed. Orlistat has been investigated in several large studies that demonstrated its efficacy and safety, and is currently available in more than 120 countries, with more than 40 million doses having been distributed worldwide (www.fda.gov/Drugs/, May 2010). The purpose of this report is to provide a short review of the available data regarding the effects of orlistat on abdominal obesity and associated metabolic disturbances.
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| 14. |
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| 15. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Significant reduction in body fat assessed by echomri in subjects treated with orlistat 60 mg for 6 months compared with placebo: relationships between changes in body composition and body weight
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: A randomised, double-blind study has demonstrated that orlistat 60 mg is significantly more effective than placebo in reducing visceral fat measured by CT (1). New data from this multicentre study are used to investigate associations between changes in body composition [EchoMRI, total fat mass; body impedance analysis (BIA), % body fat] and body weight. Methods: Adults (BMI 25–34.9 kg/m2) with a waist circumference >88 cm (women) or 102 cm (men) were randomised to receive orlistat 60 mg or placebo, 3x/day for 6 months. A reduced calorie, lower-fat diet was recommended and subjects were encouraged to exercise. Body fat was measured at baseline and weeks 2, 4, 12, and 24. Results: Demographic and baseline characteristics were similar between orlistat 60 mg (n = 62) and placebo (n = 61) groups. Conclusion: Orlistat 60 mg was significantly more effective than placebo in reducing body fat as assessed by EchoMRI and BIA. Change in total fat mass measured by EchoMRI was highly correlated with change in body weight, but the association with weight loss was less marked when measured by BIA (1). Orlistat 60 mg demonstrates a significant reduction in visceral adipose tissue at 24 weeks compared with placebo. Abstract presented at ICAO, Hong Kong, January 2010. Conflict of interest: Investigator, GlaxoSmithKline Consumer Healthcare.
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