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Effects of 1 year of exercise training versus combined exercise training and weight loss on body composition, low-grade inflammation and lipids in overweight patients with coronary artery disease: a randomized trial.
Pedersen, LR, Olsen, RH, Anholm, C, Astrup, A, Eugen-Olsen, J, Fenger, M, Simonsen, L, Walzem, RL, Haugaard, SB, Prescott, E
Cardiovascular diabetology. 2019;(1):127
Abstract
BACKGROUND Dyslipidaemia and low-grade inflammation are central in atherogenesis and linked to overweight and physical inactivity. Lifestyle changes are important in secondary prevention of coronary artery disease (CAD). We compared the effects of combined weight loss and interval training with interval training alone on physical fitness, body composition, dyslipidaemia and low-grade inflammation in overweight, sedentary participants with CAD. METHODS Seventy CAD patients, BMI 28-40 kg/m2 and age 45-75 years were randomised to (1) 12 weeks' aerobic interval training (AIT) at 90% of peak heart rate three times/week followed by 40 weeks' AIT twice weekly or (2) a low energy diet (LED) (800-1000 kcal/day) for 8-10 weeks followed by 40 weeks' weight maintenance including AIT twice weekly and a high-protein/low-glycaemic load diet. Effects of the intervention were evaluated by physical fitness, body weight and composition. Dyslipidaemia was described using both biochemical analysis of lipid concentrations and lipoprotein particle subclass distribution determined by density profiling. Low-grade inflammation was determined by C-reactive protein, soluble urokinase-type plasminogen activator receptor and tumour necrosis factor α. Effects on continuous outcomes were tested by mixed-models analysis. RESULTS Twenty-six (74%) AIT and 29 (83%) LED + AIT participants completed the study. At baseline subject included 43 (78%) men; subjects averages were: age 63 years (6.2), body weight 95.9 kg (12.2) and VO2peak 20.7 mL O2/kg/min (4.9). Forty-six (84%) had pre-diabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). LED + AIT reduced body weight by 7.2 kg (- 8.4; - 6.1) and waist circumference by 6.6 cm (- 7.7; - 5.5) compared to 1.7 kg (- 0.7; - 2.6) and 3.3 cm (- 5.1; - 1.5) after AIT (within-group p < 0.001, between-group p < 0.001 and p = 0.018, respectively). Treatments caused similar changes in VO2peak and lowering of total cholesterol, triglycerides, non-HDL cholesterol and low-grade inflammation. A shift toward larger HDL particles was seen following LED + AIT while AIT elicited no change. CONCLUSIONS Both interventions were feasible. Both groups obtained improvements in VO2peak, serum-lipids and inflammation with superior weight loss and greater central fat loss following LED + AIT. Combined LED induced weight loss and exercise can be recommended to CAD patients. Trial registration NCT01724567, November 12, 2012, retrospectively registered (enrolment ended in April 2013).
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High intake of dairy during energy restriction does not affect energy balance or the intestinal microflora compared with low dairy intake in overweight individuals in a randomized controlled trial.
Bendtsen, LQ, Blædel, T, Holm, JB, Lorenzen, JK, Mark, AB, Kiilerich, P, Kristiansen, K, Astrup, A, Larsen, LH
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2018;(1):1-10
Abstract
During weight loss, dairy calcium is proposed to accelerate weight and fat-mass loss through increased fecal fat excretion. The primary objective was to investigate if a high-dairy energy-restricted diet is superior to low dairy in terms of changes in body weight, body composition, and fecal fat excretion over 24 weeks. Secondary objectives included fecal energy and calcium excretion, resting energy expenditure, blood pressure, lipid metabolism, and gut microbiota. In a randomized, parallel-arm intervention study, 11 men and 69 women (body mass index, 30.6 ± 0.3 kg/m2; age, 44 ± 1 years) were allocated to a 500-kcal (2100 kJ) -deficit diet that was either high (HD: 1500 mg calcium/day) or low (LD: 600 mg calcium/day) in dairy products for 24 weeks. Habitual calcium intake was ∼1000 mg/day. Body weight loss (HD: -6.6 ± 1.3 kg, LD: -7.9 ± 1.5 kg, P = 0.73), fat-mass loss (HD: -7.8% ± 1.3%, LD: -8.5% ± 1.1%, P = 0.76), changes in fecal fat excretion (HD: -0.57 ± 0.76 g, LD: 0.46 ± 0.70 g, P = 0.12), and microbiota composition were similar for the groups over 24 weeks. However, total fat-mass loss was positively associated with relative abundance of Papillibacter (P = 0.017) independent of diet group. Consumption of a high-dairy diet did not increase fecal fat or accelerate weight and fat-mass loss beyond energy restriction over 24 weeks in overweight and obese adults with a habitual calcium intake of ∼1000 mg/day. However, this study indicates that Papillibacter is involved in body compositional changes.
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3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial.
le Roux, CW, Astrup, A, Fujioka, K, Greenway, F, Lau, DCW, Van Gaal, L, Ortiz, RV, Wilding, JPH, Skjøth, TV, Manning, LS, et al
Lancet (London, England). 2017;(10077):1399-1409
Abstract
BACKGROUND Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. METHODS In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. FINDINGS The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13-0·34). Liraglutide induced greater weight loss than placebo at week 160 (-6·1 [SD 7·3] vs -1·9% [6·3]; estimated treatment difference -4·3%, 95% CI -4·9 to -3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. INTERPRETATION In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. FUNDING Novo Nordisk, Denmark.
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Distinct lipid profiles predict improved glycemic control in obese, nondiabetic patients after a low-caloric diet intervention: the Diet, Obesity and Genes randomized trial.
Valsesia, A, Saris, WH, Astrup, A, Hager, J, Masoodi, M
The American journal of clinical nutrition. 2016;(3):566-75
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BACKGROUND An aim of weight loss is to reduce the risk of type 2 diabetes (T2D) in obese subjects. However, the relation with long-term glycemic improvement remains unknown. OBJECTIVE We evaluated the changes in lipid composition during weight loss and their association with long-term glycemic improvement. DESIGN We investigated the plasma lipidome of 383 obese, nondiabetic patients within a randomized, controlled dietary intervention in 8 European countries at baseline, after an 8-wk low-caloric diet (LCD) (800-1000 kcal/d), and after 6 mo of weight maintenance. RESULTS After weight loss, a lipid signature identified 2 groups of patients who were comparable at baseline but who differed in their capacities to lose weight and improve glycemic control. Six months after the LCD, one group had significant glycemic improvement [homeostasis model assessment of insulin resistance (HOMA-IR) mean change: -0.92; 95% CI: -1.17, -0.67)]. The other group showed no improvement in glycemic control (HOMA-IR mean change: -0.26; 95% CI: -0.64, 0.13). These differences were sustained for ≥1 y after the LCD. The same conclusions were obtained with other endpoints (Matsuda index and fasting insulin and glucose concentrations). Significant differences between the 2 groups were shown in leptin gene expression in adipose tissue biopsies. Significant differences were also observed in weight-related endpoints (body mass index, weight, and fat mass). The lipid signature allowed prediction of which subjects would be considered to be insulin resistant after 6 mo of weight maintenance [validation's receiver operating characteristic (ROC) area under the curve (AUC): 71%; 95% CI: 62%, 81%]. This model outperformed a clinical data-only model (validation's ROC AUC 61%; 95% CI: 50%, 71%; P = 0.01). CONCLUSIONS In this study, we report a lipid signature of LCD success (for weight and glycemic outcome) in obese, nondiabetic patients. Lipid changes during an 8-wk LCD allowed us to predict insulin-resistant patients after 6 mo of weight maintenance. The determination of the lipid composition during an LCD enables the identification of nonresponders and may help clinicians manage metabolic outcomes with further intervention, thereby improving the long-term outcome and preventing T2D. This trial was registered at clinicaltrials.gov as NCT00390637.
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Metabolic Effects of a 24-Week Energy-Restricted Intervention Combined with Low or High Dairy Intake in Overweight Women: An NMR-Based Metabolomics Investigation.
Zheng, H, Lorenzen, JK, Astrup, A, Larsen, LH, Yde, CC, Clausen, MR, Bertram, HC
Nutrients. 2016;(3):108
Abstract
We investigated the effect of a 24-week energy-restricted intervention with low or high dairy intake (LD or HD) on the metabolic profiles of urine, blood and feces in overweight/obese women by NMR spectroscopy combined with ANOVA-simultaneous component analysis (ASCA). A significant effect of dairy intake was found on the urine metabolome. HD intake increased urinary citrate, creatinine and urea excretion, and decreased urinary excretion of trimethylamine-N-oxide (TMAO) and hippurate relative to the LD intake, suggesting that HD intake was associated with alterations in protein catabolism, energy metabolism and gut microbial activity. In addition, a significant time effect on the blood metabolome was attributed to a decrease in blood lipid and lipoprotein levels due to the energy restriction. For the fecal metabolome, a trend for a diet effect was found and a series of metabolites, such as acetate, butyrate, propionate, malonate, cholesterol and glycerol tended to be affected. Overall, even though these effects were not accompanied by a higher weight loss, the present metabolomics data reveal that a high dairy intake is associated with endogenous metabolic effects and effects on gut microbial activity that potentially impact body weight regulation and health. Moreover, ASCA has a great potential for exploring the effect of intervention factors and identifying altered metabolites in a multi-factorial metabolomic study.
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High intake of regular-fat cheese compared with reduced-fat cheese does not affect LDL cholesterol or risk markers of the metabolic syndrome: a randomized controlled trial.
Raziani, F, Tholstrup, T, Kristensen, MD, Svanegaard, ML, Ritz, C, Astrup, A, Raben, A
The American journal of clinical nutrition. 2016;(4):973-981
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BACKGROUND Regular-fat cheese contains a high amount of saturated fat. Therefore, dietary guidelines in many countries recommend the consumption of reduced-fat cheese as opposed to regular-fat cheese. However, the negative effect of regular-fat cheese is still under debate. OBJECTIVES The aim was to compare the effects of regular-fat cheese with an equal amount of reduced-fat cheese and an isocaloric amount of carbohydrate-rich foods on LDL cholesterol and risk factors for the metabolic syndrome (MetS). DESIGN The study was a 12-wk randomized parallel intervention preceded by a 2-wk run-in period. A total of 164 subjects with ≥2 MetS risk factors were randomly allocated to 1 of 3 intervention groups: regular-fat cheese (REG), reduced-fat cheese (RED), or a no-cheese, carbohydrate control (CHO) group. Subjects in the REG and RED groups replaced part of their daily habitual diet with 80 g cheese/10 MJ, whereas subjects in the CHO group did the same with bread and jam corresponding to 90 g and 25 g/10 MJ, respectively. RESULTS A total of 139 subjects completed the intervention. The primary outcome, LDL cholesterol, was not significantly different between the REG and RED diets or between the REG and CHO diets. There was no significant difference in HDL cholesterol between the REG and RED diets, but HDL cholesterol tended to be higher with the REG diet than with the CHO diet (0.06 ± 0.03 mmol/L; P = 0.07). Insulin, glucose, and triacylglycerol concentrations as well as blood pressure and waist circumference did not differ significantly between the 3 diets. CONCLUSION A high daily intake of regular-fat cheese for 12 wk did not alter LDL cholesterol or MetS risk factors differently than an equal intake of reduced-fat cheese or an isocaloric amount of carbohydrate-rich foods. This trial was registered at www.clinicaltrials.gov as NCT02616471.
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Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial.
Christensen, R, Henriksen, M, Leeds, AR, Gudbergsen, H, Christensen, P, Sørensen, TJ, Bartels, EM, Riecke, BF, Aaboe, J, Frederiksen, R, et al
Arthritis care & research. 2015;(5):640-50
Abstract
OBJECTIVE To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or "no attention" (C; control group). METHODS We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria. RESULTS Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41). CONCLUSION A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program.
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A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management.
Pi-Sunyer, X, Astrup, A, Fujioka, K, Greenway, F, Halpern, A, Krempf, M, Lau, DC, le Roux, CW, Violante Ortiz, R, Jensen, CB, et al
The New England journal of medicine. 2015;(1):11-22
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BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P<0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.).
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A randomised trial comparing weight loss with aerobic exercise in overweight individuals with coronary artery disease: The CUT-IT trial.
Pedersen, LR, Olsen, RH, Jürs, A, Astrup, A, Chabanova, E, Simonsen, L, Wisløff, U, Haugaard, SB, Prescott, E
European journal of preventive cardiology. 2015;(8):1009-17
Abstract
BACKGROUND We aimed to compare the effect of aerobic interval training (AIT) versus a low energy diet (LED) on physical fitness, body composition, cardiovascular risk factors and symptoms in overweight individuals with coronary artery disease (CAD). METHODS AND DESIGN Seventy non-diabetic participants with CAD, a BMI>28 kg/m(2) and aged 45 to 75 years were randomised to 12 weeks' AIT at 90% peak heart rate three times a week or LED (800-1000 kcal/day) for 8-10 weeks followed by 2-4 weeks' weight maintenance diet. RESULTS Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. VO2peak (mL/kg fat free mass(0.67)/min) increased by 10.4% (p = 0.002) following AIT, whereas no change was observed after LED (-3.0%, p = 0.095). The LED group lost 10.6% body weight and 26.6% body fat mass (p < 0.001) compared to 1.6% (p = 0.002) and 5.5% (p < 0.001) following AIT. Waist circumference and visceral abdominal fat were reduced by both interventions but were most pronounced following LED (between-group, p < 0.001). Total cholesterol, non-HDL-C and triglycerides decreased significantly in both groups whereas HDL-C and blood pressure were unchanged. Six participants had their antihypertensive treatment reduced following LED (between-group, p = 0.032). Canadian Cardiovascular Society (CCS), New York Heart Association (NYHA) and anxiety scores were improved, while depressive symptoms remained unchanged. Intention-to-treat analyses including 65 participants (93%) were similar to per protocol analysis. CONCLUSION Both interventions were feasible and effective in achieving the desired effects. LED was superior in improving body composition and blood pressure, whereas effects on lipids and symptoms were similar in the two groups. Thus, both AIT and LED improve the cardiovascular risk profile in overweight individuals with contemporarily treated CAD.
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Effects of hydrolysed casein, intact casein and intact whey protein on energy expenditure and appetite regulation: a randomised, controlled, cross-over study.
Bendtsen, LQ, Lorenzen, JK, Gomes, S, Liaset, B, Holst, JJ, Ritz, C, Reitelseder, S, Sjödin, A, Astrup, A
The British journal of nutrition. 2014;(8):1412-22
Abstract
Casein and whey differ in amino acid composition and in the rate of absorption; however, the absorption rate of casein can be increased to mimic that of whey by exogenous hydrolysis. The objective of the present study was to compare the effects of hydrolysed casein (HC), intact casein (IC) and intact whey (IW) on energy expenditure (EE) and appetite regulation, and thereby to investigate the influence of amino acid composition and the rate of absorption. In the present randomised cross-over study, twenty-four overweight and moderately obese young men and women consumed three isoenergetic dietary treatments that varied in protein source. The study was conducted in a respiration chamber, where EE, substrate oxidation and subjective appetite were measured over 24 h at three independent visits. Moreover, blood and urine samples were collected from the participants. The results showed no differences in 24 h and postprandial EE or appetite regulation. However, lipid oxidation, estimated from the respiratory quotient (RQ), was found to be higher after consumption of IW than after consumption of HC during daytime (P= 0·014) as well as during the time after the breakfast meal (P= 0·008) when the food was provided. Likewise, NEFA concentrations were found to be higher after consumption of IW than after consumption of HC and IC (P< 0·01). However, there was no overall difference in the concentration of insulin or glucagon-like peptide 1. In conclusion, dietary treatments when served as high-protein mixed meals induced similar effects on EE and appetite regulation, except for lipid oxidation, where RQ values suggest that it is higher after consumption of IW than after consumption of HC.