Showing papers by "Arne Astrup published in 2009"
TL;DR: Liraglutide treatment over 20 weeks is well tolerated, induces weight loss, improves certain obesity-related risk factors, and reduces prediabetes.
926 citations
TL;DR: A systematic review with meta‐analysis of randomized, controlled trials of calcium (supplements or dairy) in healthy subjects, where faecal fat excretion was measured, found that dietary calcium intake is inversely related to body weight and body fat mass.
Abstract: Observational studies have found that dietary calcium intake is inversely related to body weight and body fat mass. One explanatory mechanism is that dietary calcium increases faecal fat excretion. To examine the effect of calcium from dietary supplements or dairy products on quantitative faecal fat excretion, we performed a systematic review with meta-analysis. We included randomized, controlled trials of calcium (supplements or dairy) in healthy subjects, where faecal fat excretion was measured. Meta-analyses used random-effects models with changes in faecal fat excreted expressed as standardized mean differences, as the studies assessed the same outcome but measured in different ways. An increased calcium intake resulted in increased excretion of faecal fat by a standardized mean difference of 0.99 (95% confidence intervals: 0.63-1.34; P < 0.0001; expected to correspond to approximately 2g day(-1)) with moderate heterogeneity (I(2) = 49.5%) indicating some inconsistency in trial outcomes. However, the dairy trials showed homogeneous outcomes (I(2)=0%) indicating consistency among these trials. We estimated that increasing the dairy calcium intake by 1241 mg day(-1) resulted in an increase in faecal fat of 5.2 (1.6-8.8) g day(-1). In conclusion, dietary calcium has the potential to increase faecal fat excretion to an extent that could be relevant for prevention of weight (re-)gain. Long-term studies are required to establish its potential contribution.
259 citations
TL;DR: Increased insulin secretion precedes the development of peripheral insulin resistance, mitochondrial dysfunction and obesity in response to overfeeding, suggesting a role for insulin per se as well GIP, in the developmentof peripheral insulin Resistance and obesity.
Abstract: A high-fat, high-calorie diet is associated with obesity and type 2 diabetes. However, the relative contribution of metabolic defects to the development of hyperglycaemia and type 2 diabetes is controversial. Accumulation of excess fat in muscle and adipose tissue in insulin resistance and type 2 diabetes may be linked with defective mitochondrial oxidative phosphorylation. The aim of the current study was to investigate acute effects of short-term fat overfeeding on glucose and insulin metabolism in young men. We studied the effects of 5 days’ high-fat (60% energy) overfeeding (+50%) versus a control diet on hepatic and peripheral insulin action by a hyperinsulinaemic euglycaemic clamp, muscle mitochondrial function by 31P magnetic resonance spectroscopy, and gene expression by qrt-PCR and microarray in 26 young men. Hepatic glucose production and fasting glucose levels increased significantly in response to overfeeding. However, peripheral insulin action, muscle mitochondrial function, and general and specific oxidative phosphorylation gene expression were unaffected by high-fat feeding. Insulin secretion increased appropriately to compensate for hepatic, and not for peripheral, insulin resistance. High-fat feeding increased fasting levels of plasma adiponectin, leptin and gastric inhibitory peptide (GIP). High-fat overfeeding increases fasting glucose levels due to increased hepatic glucose production. The increased insulin secretion may compensate for hepatic insulin resistance possibly mediated by elevated GIP secretion. Increased insulin secretion precedes the development of peripheral insulin resistance, mitochondrial dysfunction and obesity in response to overfeeding, suggesting a role for insulin per se as well GIP, in the development of peripheral insulin resistance and obesity.
257 citations
TL;DR: Short and long sleeping times are associated with a higher risk of developing type 2 diabetes/IGT, independent of several covariates, and results suggest that sleep duration may represent a novel risk factor for type 2abetes/IGt.
180 citations
TL;DR: This review will endeavor to provide an update of the literature from 1993 to the present with respect to the role of dietary fat and obesity, metabolic syndrome and diabetes, and emerging Data from cross-sectional, prospective cohort and interventional studies will be evaluated.
Abstract: Research Group 2002; Ornish, 2005]. However, it is impossible to draw final conclusions from these studies in that they do not have a higher fat control group, they often incorporated additional lifestyle interventions, and there is difficulty in maintaining the very low fat diets, which leads to high drop out rates. Despite the findings of post hoc analyses of these trials that show that adherence to a high fiber, low fat diet is the strongest predictor of weight loss and decreased risk of type 2 diabetes (T2DM) [Lindstrom et al., 2006a], unified recommendations are difficult and the public is left with mixed messages [Bravata et al., 2003]. This review will endeavor to provide an update of the literature from 1993 to the present with respect to the role of dietary fat and obesity, metabolic syndrome and diabetes. Data from cross-sectional, prospective cohort and interventional studies will be evaluated, and emerging data on the role of genetic regulation of the response to dietary fat will be presented.
159 citations
TL;DR: The data suggest that as a supplement to a fat-rich meal in patients with type 2 diabetes, whey protein seems to outperform other proteins in terms of postprandial lipemia improvement, possibly because of the formation of fewer chylomicrons or increased clearance of chylomaticrons.
137 citations
TL;DR: Only caffeine was thermogenic in the given dose and caused no haemodynamic side effects, and the sample size was probably too small to detect any appetite suppressant properties of the treatments.
Abstract: To investigate the effect of three different food ingredients tyrosine, green tea extract (GTE) and caffeine on resting metabolic rate and haemodynamics, and on ad libitum energy intake (EI) and appetite. Twelve healthy, normal weight men (age: 23.7±2.6 years, mean±s.d.) participated in a four-way crossover, randomized, placebo-controlled, double-blind study. Treatments were administered as tablets of 500 mg GTE, 400 mg tyrosine, 50 mg caffeine, or placebo, and were separated by >3-day washout. The acute thermogenic response was measured in a ventilated hood system for 4 h following ingestion. Blood pressure, heart rate (HR), and subjective appetite sensations were assessed hourly and ad libitum EI 4 h post-dose. Caffeine induced a thermogenic response of 6% above baseline value (72±25 kJ per 4 h, mean±s.e.) compared to placebo (P<0.0001). The thermogenic responses to GTE and tyrosine were not significantly different from placebo. Tyrosine tended to increase 4-h respiratory quotient by 1% compared to placebo (0.01±0.005, P=0.05). Ad libitum EI was not significantly different between treatments but was reduced by 8% (−403±183 kJ), 8% (−400±335 kJ) and 3% (−151±377 kJ) compared to placebo after intake of tyrosine, GTE and caffeine, respectively. No significant difference in haemodynamics was observed between treatments. Only caffeine was thermogenic in the given dose and caused no haemodynamic side effects. The sample size was probably too small to detect any appetite suppressant properties of the treatments. Further investigations are required.
115 citations
TL;DR: There is insufficient evidence that an exchange of sugar for non‐sugar carbohydrates in the context of a reduced‐fat ad libitum diet or energy‐restricted diet results in lower body weights and no convincing evidence for a role of GI independent of GL.
Abstract: The role of dietary sugars in the current obesity epidemic is much debated and opposing views can be found in the lay as well as scientific literature. Here we have reviewed the recent scientific literature on consumption of sugars and body weight. Main focus was on three questions: (i) What is the evidence that intake of dietary sugars is associated with higher body weight than intake of non-sugar carbohydrates? (ii) What is the evidence that sugars in liquid form are associated with higher body weight than sugars in solid form? (iii) What is the evidence that diets with a low glycaemic index (GI) or glycaemic load (GL) are associated with lower body weight than diets high in GI or GL? We conclude that (i) there is insufficient evidence that an exchange of sugar for non-sugar carbohydrates in the context of a reduced-fat ad libitum diet or energy-restricted diet results in lower body weights; (ii) observational studies suggest a possible relationship between consumption of sugar-sweetened beverages and body weight, but there is currently insufficient supporting evidence from randomized controlled trials of sufficient size and duration; (iii) at this moment there is insufficient evidence to support a difference between liquid and solid sugar intake in body-weight control and (iv) there is some, although not consistent, evidence for a lower body weight on diets with a lower GL, but the effect is likely to be small. There is currently no convincing evidence for a role of GI independent of GL.
105 citations
TL;DR: How close cannabinoid receptor antagonists are to the ideal anti‐obesity drug, with respect to their mechanisms of action, clinical effectiveness and safety is discussed.
Abstract: The discovery of cannabinoids, with the well-known stimulatory effect of Cannabis sativa on appetite, has offered a new drug target for obesity treatment. Cannabinoids act on two different receptors: CB1 receptors which are sited in the brain and many peripheral tissues, and CB2 receptors which are primarily found in immune system cells. Cannabinoid receptor antagonists act centrally by blocking CB1 receptors, thereby reducing food intake. Moreover, they probably also act peripherally by increasing thermogenesis and therefore energy expenditure, as has been suggested by animal experiments. Despite these promising mechanisms of action, recent clinical studies examining the effect of the two CB1 receptor antagonists rimonabant and taranabant showed that the attained weight loss did not exceed that attained with other currently approved anti-obesity medications. Moreover, potentially severe psychiatric adverse effects limit their clinical use. As several new CB1 receptor antagonists are presently undergoing development, it remains to be elucidated to what extent they differ in terms of efficacy and safety. This review primarily discusses how close cannabinoid receptor antagonists are to the ideal anti-obesity drug, with respect to their mechanisms of action, clinical effectiveness and safety.
88 citations
TL;DR: The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored.
Abstract: Background: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these genes with obesity and metabolic traits. Methodology/Principal Findings: In a population of 166 200 young men examined at the draft boards, obese men (n=726, BMI$31.0 kg/m 2 ) and a randomly selected group (n=831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49). Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat-BMI (OR=1.08, CI=1.01–1.16). The SNPs were associated with a number of physiological variables; most importantly 5HT2C rs3813929 T-allele was associated with glucose (OR=4.56, CI=1.13–18.4) and acute insulin response (OR=0.65, CI=0.44–0.94) in S-49. COMT rs4680 GG-genotype was associated with glucose (OR=1.04, CI=1.00–1.09). Except for an association between 5HT2A rs6311 and totalcholesterol at both surveys, significant in S-46 (OR=2.66, CI=1.11–6.40), no significant associations were observed for the other phenotypes. Significant associations were obtained when combined genotype of 5HT2C rs3813929 and COMT rs4680 were examined in relation to BMI (OR=1.12, CI=1.03–1.21), fat-BMI (OR=1.22, CI=1.08–1.38), waist (OR=1.13, CI=1.04– 1.22), and cholesterol (OR=5.60, CI=0.99–31.4). Analyses of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) revealed, a 12.3% increased frequency of 5HT2C rs3813929 T-allele and an 11.6% increased frequency of COMT rs4680 GGgenotype in individuals with IGT or T2D (x 2 , p=0.05 and p=0.06, respectively). Examination of the combined genotypes of 5HT2C and COMT showed a 34.0% increased frequency of IGT or T2D (x 2 , p=0.01). Conclusions: The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored.
73 citations
TL;DR: The FTO rs9939609 may interact with the macronutrient composition in weight loss diets in various ways; carriers of the A allele on LF diet appear to have a lower risk for drop out, and TT individuals have a smaller decrease in REE and greater decrease in HOMA-β and HomA-IR on LF than on HF diet.
Abstract: Background:The A risk allele of rs9939609 of the fat mass- and obesity-associated gene (FTO) increases body fat mass.Objective:To examine whether FTO rs9939609 affects obese individuals' response to a high-fat, low-carbohydrate (CHO) (HF) or low-fat, high-CHO (LF), hypo-energetic diet and whether the effect of the FTO variant depends on dietary fat and CHO content.Design:In a 10-week, European, multi-centre dietary intervention study 771 obese women and men were randomized to either LF (20-25% of energy (%E) from fat, 60-65%E from CHO) or HF (40-45%E from fat, 40-45%E from CHO), hypo-energetic diet (measured resting metabolic rate multiplied by 1.3-600 kcal day(-1)). Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation as % of REE (FatOx), insulin release (HOMA-beta) and a surrogate measure of insulin resistance (HOMA-IR) were measured at baseline and after the intervention. In all, 764 individuals were genotyped for FTO rs9939609.Results:For A-allele carriers the drop-out rate was higher on HF than LF diet (in AT, P=0.002; in AT/AA combined, P=0.003). Among those individuals completing the intervention, we found no effect of FTO rs9939609 genotype on Deltaweight, DeltaFM, DeltaFFM, DeltaWC or DeltaFatOx. However, participants with TT had a smaller reduction in REE on LF than on HF diet (75 kcal/24 h; interaction: P=0.0055). These individuals also showed the greatest reduction in HOMA-beta and HOMA-IR (interaction: P=0.0083 and P=0.047).Conclusion:The FTO rs9939609 may interact with the macronutrient composition in weight loss diets in various ways; carriers of the A allele on LF diet appear to have a lower risk for drop out, and TT individuals have a smaller decrease in REE and greater decrease in HOMA-beta and HOMA-IR on LF than on HF diet.International Journal of Obesity advance online publication, 18 August 2009; doi:10.1038/ijo.2009.159.
TL;DR: There is a significant association between the decrease in body fat mass and the change in appetite sensations, predicting a 5.8-mm increase in desire to eat and a 3.6-mm decrease in fullness per kg fat loss.
TL;DR: The results suggest that, whereas haptoglobin and transferrin respond more rapidly and are more susceptible to the acute change in energy balance, a Reduction in hs-CRP and IL-6 seems to be achieved by a reduction in FM when a new steady state has been established.
Abstract: To dissociate the possible differential effects of negative energy balance and reduction in body fat mass (FM) on inflammatory markers: C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), haptoglobin, transferrin and the adipokines leptin and adiponectin. Thirty-three obese subjects (BMI: 34.0±3.1 kg/m2, age: 43.0±10.5 years, mean±s.d., 16 men) participated in a 20-week controlled dietary intervention divided into four periods. Weight reduction was induced by an 8-week low energy diet (3.4 MJ d−1) (LED-1) followed by a 4-week weight maintenance program (M-1). Subsequently participants underwent an additional 4-week LED (4.2 MJ d−1) (LED-2) followed by a final 4-week weight maintenance diet (M-2). Blood samples and anthropometrics were assessed at baseline and after LED-1, M-1, LED-2 and M-2. Body weight was significantly reduced by 13% (13.7±4.0 kg, P<0.0001) after LED-1. However, a reduction in high-sensitive CRP (hs-CRP) by 35% (−1.1 (95% CI: −2.5:0.2) mg l−1, P=0.02) only became apparent after LED-2, which produced an additional weight loss of 2.9 kg compared to baseline, and it was maintained after M-2 (−1.0 (−1.4:0.4) mg l−1, P=0.02). Also IL-6 was reduced by 21% (−0.6 (−2.4:0.2) ng l−1, P=0.02) after M-2. The reductions in hs-CRP and IL-6 were both associated with reduction in FM but not body weight. Haptoglobin, transferrin and leptin were significantly reduced after both LED-1 and LED-2, but increased during weight maintenance. Adiponectin was not significantly changed during the intervention. The results suggest that, whereas haptoglobin and transferrin respond more rapidly and are more susceptible to the acute change in energy balance, a reduction in hs-CRP and IL-6 seems to be achieved by a reduction in FM when a new steady state has been established.
TL;DR: Catechin/caffeine combinations at these dosages and mode of application had non-significant acute effects on EE and fat oxidation, and the maximum observed effect on EE of about 2 % could still be meaningful for energy balance over much longer period of exposure.
Abstract: Green tea may stimulate energy metabolism; however, it is unclear if acute effects are caused by specific catechins, caffeine or their combination. The objective of the present study was to examine the separate and combined effects of different catechins and caffeine on energy expenditure (EE) and fat oxidation over a single day. Fifteen healthy, normal-weight males received capsules containing placebo, caffeine alone (150 mg), or caffeine plus a catechin mixture (600 mg) enriched in either epigallocatechin-3-gallate (EGCG), epigallocatechin or a mix of catechins, in a randomised cross-over double-blinded design. On each test day EE, respiratory quotient (RQ) and substrate oxidation were measured under sedentary conditions in a respiratory chamber for 13.5 h. We found no significant treatment effect on EE (P = 0.20) or RQ (P = 0.68). EGCG with caffeine insignificantly raised EE and fat oxidation v. caffeine-only and placebo (EE 5.71 (SE 0.12) v. 5.68 (SE 0.14) v. 5.59 (SE 0.13) MJ/12.5 h, respectively; fat oxidation 84.8 (SE 5.2) v. 80.7 (SE 4.7) v. 76.8 (SE 4.0) g/12.5 h). Catechin/caffeine combinations at these dosages and mode of application had non-significant acute effects on EE and fat oxidation. The maximum observed effect on EE of about 2 % could still be meaningful for energy balance over much longer period of exposure. However, higher short-term effects reported in the literature may reflect variations in green tea extracts, added caffeine, or synergies with physical activity. The specific mechanisms and conditions that may underpin observed longer-term benefits of catechin-enriched green tea consumption on body composition remain to be confirmed.
TL;DR: Several gene polymorphisms associated with obesity-related phenotypes but not FTO and UCP variants may be responsible for some of the inter-individual variability in postabsorptive REE and fat-induced thermogenesis unaccounted for by FFM, FM, age and sex.
Abstract: Several obesity- and nutrient-related gene polymorphisms but not FTO and UCP variants modulate postabsorptive resting energy expenditure and fat-induced thermogenesis in obese individuals: the NUGENOB Study
TL;DR: Underreporting of dietary intake seems to be associated with not only current BMI but also with current BMI in combination with previous BMI.
Abstract: Our objectives were to estimate the degree of misreporting energy intake (El) and analyze associations with previous BM I, current BMI, or both. The study was part of the Adiposity and Genetics Study follow-up study including 309 Danish men (age 40-65 y) originally sampled from the obligatory draft board examination. Height and weight were measured at the mean ages of 20 (draft board), 33, 44, and 49 y (current age). Obesity was categorized as BMI ≥ 31 kg/m 2 . Dietary intake for 7 d and physical activity (PA) level (PAL) were self-reported. Resting metabolic rate (RMR) was measured in a ventilated hood system. By comparing El with energy expenditure and assuming energy balance, reporting accuracy (RA) was estimated as El/(RMR·PAL). A plausibility interval was calculated to encompass specific variation components of El, RMR, and PAL; the specific 95% plausibility interval was 1.00 ± 0.35. Participants were categorized as underreporters (RA ≤ 0.65), plausible reporters (0.65 1.35) of El. The relation between RA and BMI was studied through linear regression analysis. Overall, the RA was (mean ± SE) 0.76 ± 0.01. Of 309 participants, 35% underreported and 7% overreported. Whether stratified for current BMI or draft board BMI, the obese men were more likely to underreport than those who were not obese. Among those currently not obese, underreporting was more prevalent among those who were obese at the draft board examination (44%) than among those who were not (21 %). Regression analysis showed that both previous and current BMI and their combination were significantly associated with RA. Thus, underreporting of dietary intake seems to be associated with not only current BMI but also with current BMI in combination with previous BMI.
TL;DR: Increased energy efficiency--and potentially increased mitochondrial coupling--as suggested by faster recovery rates of phosphocreatine and inorganic phosphate in oxidative muscle fibers may contribute to the increased risk of obesity and type 2 diabetes in homozygous carriers of the FTO A-risk allele.
Abstract: Objective: Recent studies identified the rs9939609 A-allele of the FTO (fat mass and obesity associated) gene as being associated with obesity and type 2 diabetes. We studied the role of the A-allele in the regulation of peripheral organ functions involved in the pathogenesis of obesity and type 2 diabetes. Methods: Forty-six young men underwent a hyperinsulinemic euglycemic clamp with excision of skeletal muscle biopsies, an iv glucose tolerance test, 31phosphorous magnetic resonance spectroscopy, and 24-h whole body metabolism was measured in a respiratory chamber. Results: The FTO rs9939609 A-allele was associated with elevated fasting blood glucose and plasma insulin, hepatic insulin resistance, and shorter recovery half-times of phosphocreatine and inorganic phosphate after exercise in a primarily type I muscle. These relationships—except for fasting insulin—remained significant after correction for body fat percentage. The risk allele was not associated with fat distribution, peripheral insulin sens...
TL;DR: The authors examined which types of fatty acids are present in various popular foods as compared with similar foods that contain low concentrations of trans fatty acids.
Abstract: Despite the obvious theoretical health benefits of replacing trans fatty acids with other fatty acids in food products, concern has been expressed that this change might increase the intake of saturated fatty acids. The authors examined which types of fatty acids are present in various popular foods as compared with similar foods that contain low concentrations of trans fatty acids.
TL;DR: In this paper, the authors used a combination of beta-adrenoceptors to stimulate the central and peripheral pathways of the human body to induce short-term induction of weight loss or long-term maintenance.
Abstract: Obesity is characterised by pathophysiological defects affecting both sides of the energy balance equation. Individuals with a predisposition to obesity have impaired appetite control when diets are fat-rich and energy dense. They also exhibit a lower than expected resting metabolic rate (RMR). A low RMR, in concert with a sedentary lifestyle, contributes to a low total energy output, which may lead to obesity if continued over a period of years. A low metabolic rate seems to be genetically determined, and is partly caused by low sympathetic nervous system activity. Classical treatment programmes for obesity do not provide a satisfactory long-term outcome for the majority of patients. Patients who achieve only a small weight loss during dietary therapy, and have a tendency to weight regain, are characterised by lower energy expenditure, lower sympathetic activity, and a reduced ability to mobilise fat stores, compared with patients who are more successful at losing weight. It is reasonable to improve or normalise these traits by supporting the dietary approach with pharmacological manipulation of central and peripheral pathways. Agents which stimulate adrenergic neurons are particularly suitable because they offer mechanisms for inhibiting hunger and for stimulating energy expenditure, lipolysis and fat oxidation. Sympathomimetic compounds can reduce appetite and increase energy expenditure. Energy expenditure can be increased by 5-10% via stimulation of a combination of beta-adrenoceptors; beta3-adrenoceptors may predominate during chronic therapy. This increased energy expenditure increases the relative proportion of fat oxidation; as this is not fully compensated by increased energy intake, a negative energy balance occurs. This mechanism may be responsible for the long-term weight loss efficiency of agents like ephedrine/caffeine and sibutramine. Pharmacotherapy can be used to support short-term induction of weight loss or long-term weight maintenance. In the latter case, adrenergic agents enable a greater proportion of patients to maintain a satisfactory weight loss, compared with patients treated with conventional programmes alone. Pharmacotherapy which stabilises the size of fat stores at a lower level contributes indirectly to a pronounced improvement of risk factors, leading to a decreased potential for cardiovascular disease, type 2 diabetes and associated morbidity.
Patent•
01 Jul 2009TL;DR: In this article, a method of preparing regression coefficients for predicting the quantity of a component of a lipoprotein entity in a biological sample from NMR spectral data was proposed, which is based on the regression coefficients.
Abstract: The invention concerns a method of preparing regression coefficients for predicting the quantity of a component of a lipoprotein entity in a biological sample from NMR spectral data and a method of predicting the quantity of a component of a lipoprotein entity in a biological sample from NMR spectral data, which is based on the regression coefficients. To this end, a spectrally local multivariate regression analysis is performed on the basis of a local subspectrum of an NMR spectrum and a reference quantification of the lipoprotein entity. The invention is especially useful for predicting the triacylglycerol level in chylomicrons of a patient.
Journal Article•
TL;DR: Tesofensine 0.5 mg might have the potential to produce a weight loss twice that of currently approved anti-obesity drugs, according to findings from a phase II trial, but confirmation in phase III trials is needed.
Abstract: Results from a phase II trial with Tesofensine for treatment of obesity are presented. In total 203 obese persons were randomised to treatment with Tesofensine 0.25, 0.5, or 1.0 mg, or placebo daily for 24 weeks. Treatment with Tesofensine resulted in a mean weight reduction of 4.5, 9.2 and 10.6% higher than that of placebo for 0.25, 0.5 and 1.0 mg, respectively. Tesofensine 0.5 mg might have the potential to produce a weight loss twice that of currently approved anti-obesity drugs. Findings of safety and efficacy of 0.5 mg Tesofensine need confirmation in phase III trials.
TL;DR: The elevated plasma fibronectin levels in morbidly obese subjects seem to normalize during weight loss, and it is suggested that the normalization to be mediated--at least in part--by a reduction of the insulin levels.
Abstract: In 23 morbidly obese patients we investigated the influence of a large weight loss (30.6 kg, range 17.5-90.8) on the plasma fibronectin concentrations. Further, changes in plasma fibronectin were related to serum insulin levels and to liver biochemistry. Between the measurements patients had been treated with an intermittent very-low-calorie formula diet sufficient in respect to protein, minerals and vitamins. They were investigated in weight-stable states. Before weight reduction, 14 patients (61%, 95% confidence limits 39-80%) had elevated plasma fibronectin levels. Plasma fibronectin decreased (medians 1.22 and 0.59 mumol/l before and after weight loss, p less than 0.01) and was after weight loss within the normal range in 14 patients. The change in plasma fibronectin was unassociated with the magnitude of the weight loss as well as with the reduction of overweight. The resulting plasma fibronectin levels were also uncorrelated with the body weight and with the final degree of overweight. Serum insulin decreased (p less than 0.01) during the weight reduction and the change correlated (p less than 0.05) with the change in plasma fibronectin. Serum lactate dehydrogenase, which is associated with the degree of hepatic fatty change, declined (p less than 0.01), but the individual change was unrelated with the change in plasma fibronectin. In conclusion, the elevated plasma fibronectin levels in morbidly obese subjects seem to normalize during weight loss. We suggest the normalization to be mediated--at least in part--by a reduction of the insulin levels.
01 Jan 2009
TL;DR: The phase III programme for tesofensine, with prospective psychiatric and cardiovascular endpoints, will provide better evidence of its long-term effects on morbidity and of its safety, and to request trials with hard endpoints such as mortality before launch would prevent any weight-loss compounds reaching the market.
01 Sep 2009
01 Jan 2009
TL;DR: Underreporting of dietary intake seems to be associated with not only current BMI but also with current BMI in combination with previous BMI.
Abstract: Our objectives were to estimate the degree of misreporting energy intake (EI) and analyze associations with previous BMI, current BMI, or both. The study was part of the Adiposity and Genetics Study follow-up study including 309 Danish men (age 40–65 y) originally sampled from the obligatory draft board examination. Height and weight were measured at the mean ages of 20 (draft board), 33, 44, and 49 y (current age). Obesity was categorized as BMI $ 31 kg/m 2 . Dietary intake for 7 d and physical activity (PA) level (PAL) were self-reported. Resting metabolic rate (RMR) was measured in a ventilated hood system. By comparing EI with energy expenditure and assuming energy balance, reporting accuracy (RA) was estimated as EI/(RMR×PAL). A plausibility interval was calculated to encompass specific variation components of EI, RMR, and PAL; the specific 95% plausibility interval was 1.00 6 0.35. Participants were categorized as underreporters (RA # 0.65), plausible reporters (0.65 , RA # 1.35), or overreporters (RA . 1.35) of EI. The relation between RA and BMI was studied through linear regression analysis. Overall, the RA was (mean 6 SE) 0.76 6 0.01. Of 309 participants, 35% underreported and 7% overreported. Whether stratified for current BMI or draft board BMI, the obese men were more likely to underreport than those who were not obese. Among those currently not obese, underreporting was more prevalent among those who were obese at the draft board examination (44%) than among those who were not (21%). Regression analysis showed that both previous and current BMI and their combination were significantly associated with RA. Thus, underreporting of dietary intake seems to be associated with not only current BMI but also with current BMI in combination with previous BMI. J. Nutr. 139: 2337–2343, 2009.