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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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Plasma metabolites and lipids predict insulin sensitivity improvement in obese, nondiabetic individuals after a 2-phase dietary intervention.
Meyer, A, Montastier, E, Hager, J, Saris, WHM, Astrup, A, Viguerie, N, Valsesia, A
The American journal of clinical nutrition. 2018;(1):13-23
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Abstract
BACKGROUND Weight loss in obese individuals aims to reduce the risk of type 2 diabetes by improving glycemic control. Yet, significant intersubject variability is observed and the outcomes remain poorly predictable. OBJECTIVE The aim of the study was to predict whether an individual will show improvements in insulin sensitivity above or below the median population change at 6 mo after a low-calorie-diet (LCD) intervention. DESIGN With the use of plasma lipidomics and metabolomics for 433 subjects from the Diet, Obesity, and Genes (DiOGenes) Study, we attempted to predict good or poor Matsuda index improvements 6 mo after an 8-wk LCD intervention (800 kcal/d). Three independent analysis groups were defined: "training" (n = 119) for model construction, "testing" (n = 162) for model comparison, and "validation" (n = 152) to validate the final model. RESULTS Initial modeling with baseline clinical variables (body mass index, Matsuda index, total lipid concentrations, sex, age) showed limited performance [area under the curve (AUC) on the "testing dataset" = 0.69; 95% CI: 0.61, 0.77]. Significantly better performance was achieved with an omics model based on 27 variables (AUC = 0.77; 95% CI: 0.70, 0.85; P = 0.0297). This model could be greatly simplified while keeping the same performance. The simplified model relied on baseline Matsuda index, proline, and phosphatidylcholine 0-34:1. It successfully replicated on the validation set (AUC = 0.75; 95% CI: 0.67, 0.83) with the following characteristics: specificity = 0.73, sensitivity = 0.68, negative predictive value = 0.60, and positive predictive value = 0.80. Marginally lower performance was obtained when replacing the Matsuda index with homeostasis model assessment of insulin resistance (AUC = 0.72; 95% CI: 0.64, 0.80; P = 0.08). CONCLUSIONS Our study proposes a model to predict insulin sensitivity improvements, 6 mo after LCD completion in a large population of overweight or obese nondiabetic subjects. It relies on baseline information from 3 variables, accessible from blood samples. This model may help clinicians assessing the large variability in dietary interventions and predict outcomes before an intervention. This trial was registered at www.clinicaltrials.gov as NCT00390637.
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Acute Effects of Dietary Carbohydrate Restriction on Glycemia, Lipemia and Appetite Regulating Hormones in Normal-Weight to Obese Subjects.
Samkani, A, Skytte, MJ, Thomsen, MN, Astrup, A, Deacon, CF, Holst, JJ, Madsbad, S, Rehfeld, JF, Krarup, T, Haugaard, SB
Nutrients. 2018;(9)
Abstract
Postprandial responses to food are highly dependent on the macronutrient composition of the diet. We investigated the acute effects of transition from the recommended moderately high carbohydrate (HC) diet towards a carbohydrate-reduced high-protein (CRHP) diet on postprandial glycemia, insulinemia, lipemia, and appetite-regulating hormones in non-diabetic adults. Fourteen subjects, including five males (Mean ± SD: age 62 ± 6.5; BMI 32 ± 7.6 kg/m²; hemoglobin A1c (HbA1c) 40 ± 3.0 mmol/mol; HOMA2-IR 2.1 ± 0.9) were included in this randomized, cross-over study. Iso-caloric diets were consumed for two consecutive days with a median wash-out period of 21 days (range 2⁻8 weeks) between diets (macronutrient energy composition: CRHP/HC; 31%/54% carbohydrate, 29%/16% protein, 40%/30% fat). Postprandial glucose, insulin secretion rate (ISR), triglycerides (TGs), non-esterified fatty acids (NEFAs), and satiety ratings were assessed after ingestion of breakfast (Br) and lunch (Lu), and gut hormones and glucagon were assessed after ingestion of Br. Compared with the HC diet, the CRHP diet reduced peak glucose concentrations (Br 11%, p = 0.024; Lu 11%, p < 0.001), glucose excursions (Br 80%, p = 0.20; Lu 85%, p < 0.001), and ISR (Br 31%; Lu 64%, both p < 0.001) whereas CRHP, as compared with HC, increased glucagon-like peptide-1 (Br 27%, p = 0.015) and glucagon values (Br 249%, p < 0.001). NEFA and TG levels increased in the CRHP diet as compared with the HC diet after Br, but no difference was found after Lu (NEFA Br 22%, p < 0.01; TG Br 42%, p = 0.012). Beta-cell glucose sensitivity, insulin clearance, cholecystokinin values, and subjective satiety ratings were unaffected. It is possible to achieve a reduction in postprandial glycemia and insulin without a deleterious effect on beta-cell glucose sensitivity by substituting part of dietary carbohydrate with iso-caloric protein and fat in subjects without type 2 diabetes mellitus (T2DM). The metabolic effects are more pronounced after the second meal.
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Weight loss predictability by plasma metabolic signatures in adults with obesity and morbid obesity of the DiOGenes study.
Stroeve, JH, Saccenti, E, Bouwman, J, Dane, A, Strassburg, K, Vervoort, J, Hankemeier, T, Astrup, A, Smilde, AK, van Ommen, B, et al
Obesity (Silver Spring, Md.). 2016;(2):379-88
Abstract
OBJECTIVE Aim is to predict successful weight loss by metabolic signatures at baseline and to identify which differences in metabolic status may underlie variations in weight loss success. METHODS In DiOGenes, a randomized, controlled trial, weight loss was induced using a low-calorie diet (800 kcal) for 8 weeks. Men (N = 236) and women (N = 431) as well as groups with overweight/obesity and morbid obesity were studied separately. The relation between the metabolic status before weight loss and weight loss was assessed by stepwise regression on multiple data sets, including anthropometric parameters, NMR-based plasma metabolites, and LC-MS-based plasma lipid species. RESULTS Maximally, 57% of the variation in weight loss success can be predicted by baseline parameters. The most powerful predictive models were obtained in subjects with morbid obesity. In these models, the metabolites most predictive for weight loss were acetoacetate, triacylglycerols, phosphatidylcholines, specific amino acids, and creatine and creatinine. This metabolic profile suggests that high energy metabolism activity results in higher amounts of weight loss. CONCLUSIONS Possible predictive (pre-diet) markers were found for amount of weight loss for specific subgroups.
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Influence of SNPs in nutrient-sensitive candidate genes and gene-diet interactions on blood lipids: the DiOGenes study.
Brahe, LK, Ängquist, L, Larsen, LH, Vimaleswaran, KS, Hager, J, Viguerie, N, Loos, RJ, Handjieva-Darlenska, T, Jebb, SA, Hlavaty, P, et al
The British journal of nutrition. 2013;(5):790-6
Abstract
Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene-diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP-diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect) ,and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP-dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of 20.26 mmol/l per A-allele/protein unit (95% CI 20.38, 20.14, P=0.000043). In conclusion, we investigated SNP-diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration.
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Change in proportional protein intake in a 10-week energy-restricted low- or high-fat diet, in relation to changes in body size and metabolic factors.
Stocks, T, Taylor, MA, Angquist, L, Macdonald, IA, Arner, P, Holst, C, Oppert, JM, Martinez, JA, Rössner, S, Polak, J, et al
Obesity facts. 2013;(3):217-27
Abstract
OBJECTIVE To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. METHODS Obese adults (n = 771) were randomised to a 600 kcal energy-deficient low-fat (20-25 fat%) or high-fat (40-45 fat%) diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (<-2 /-2 to 2/>2) on outcomes. RESULTS The low-fat group with >2 prot% increase lost 1.1 kg more weight (p = 0.03) and reduced cholesterol by 0.25 mmol/l more (p = 0.003) than the high-fat group with >2 prot% decrease. These differences were 2.5-fold and 1.8-fold greater than the differences between the low-fat and high-fat groups while not considering prot% change. The high-fat group reduced plasma triglycerides more than the low-fat group, but not compared to those in the low-fat group with >2 units prot% increase (p fat-protein interaction = 0.01). CONCLUSIONS Under energy restriction, participants on a low-fat diet who had increased the percentage energy intake from protein showed the greatest reduction in weight and cholesterol, and a triglyceride reduction equally large to that of participants on a high-fat diet.
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Effect of trans fatty acid intake on LC-MS and NMR plasma profiles.
Gürdeniz, G, Rago, D, Bendsen, NT, Savorani, F, Astrup, A, Dragsted, LO
PloS one. 2013;(7):e69589
Abstract
BACKGROUND The consumption of high levels of industrial trans fatty acids (TFA) has been related to cardiovascular disease, diabetes and sudden cardiac death but the causal mechanisms are not well known. In this study, NMR and LC-MS untargeted metabolomics has been used as an approach to explore the impact of TFA intake on plasma metabolites. METHODOLOGY/PRINCIPAL FINDINGS In a double-blinded randomized controlled parallel-group study, 52 overweight postmenopausal women received either partially hydrogenated soybean oil, providing 15.7 g/day of TFA (trans18:1) or control oil with mainly oleic acid for 16 weeks. Subsequent to the intervention period, the subjects participated in a 12-week dietary weight loss program. Before and after the TFA intervention and after the weight loss programme, volunteers participated in an oral glucose tolerance test. PLSDA revealed elevated lipid profiles with TFA intake. NMR indicated up-regulated LDL cholesterol levels and unsaturation. LC-MS profiles demonstrated elevated levels of specific polyunsaturated (PUFA) long-chain phosphatidylcholines (PCs) and a sphingomyelin (SM) which were confirmed with a lipidomics based method. Plasma levels of these markers of TFA intake declined to their low baseline levels after the weight loss program for the TFA group and did not fluctuate for the control group. The marker levels were unaffected by OGTT. CONCLUSIONS/SIGNIFICANCE This study demonstrates that intake of TFA affects phospholipid metabolism. The preferential integration of trans18:1 into the sn-1 position of PCs, all containing PUFA in the sn-2 position, could be explained by a general up-regulation in the formation of long-chain PUFAs after TFA intake and/or by specific mobilisation of these fats into PCs. NMR supported these findings by revealing increased unsaturation of plasma lipids in the TFA group. These specific changes in membrane lipid species may be related to the mechanisms of TFA-induced disease but need further validation as risk markers. TRIAL REGISTRATION Registered at clinicaltrials.gov as NCT00655902.
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Effects of soy supplementation on blood lipids and arterial function in hypercholesterolaemic subjects.
Hermansen, K, Hansen, B, Jacobsen, R, Clausen, P, Dalgaard, M, Dinesen, B, Holst, JJ, Pedersen, E, Astrup, A
European journal of clinical nutrition. 2005;(7):843-50
Abstract
BACKGROUND Studies on soy supplementation suggest a cardioprotective potential. OBJECTIVE To examine the effects on LDL cholesterol and arterial function as a result of dietary enrichment with soy supplementation. DESIGN A Randomized, double blind, parallel intervention trial. SETTING Department of Endocrinology and Metabolism C, Aarhus University Hospital, and Department of Human Nutrition, The Royal Veterinary and Agricultural University, Denmark. SUBJECTS In all, 100 hypercholesterolaemic but otherwise healthy subjects were included in the study of which 89 completed it. INTERVENTIONS Subjects were randomly assigned to 24 weeks of daily intake of either a soy supplement, Abalon (30 g soy protein, 9 g cotyledon fibre and 100 mg isoflavones) or placebo (30 g of casein). The soy supplement and placebo were provided in two sachets daily that were stirred in water. Fasting plasma lipids, TNF-alpha, homocysteine, insulin sensitivity, homeostasis model assessment (HOMA-IR), serum insulin, serum glucose, blood pressure as well as Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and plasma lipids to a fat-rich meal were recorded before and after the intervention. In a sub study in 32 subjects, arterial dilatory capacity, compliance, and distensibility were recorded before and after the intervention. RESULTS In the main study, no difference in fasting plasma lipid levels or insulin sensitivity was found between soy-based supplement and placebo. A significant postprandial increase in GIP to the meal test was observed in the soy group (P < 0.05). In a substudy, no difference between the groups in changes in flow-mediated vasodilatation (P = 0.84) was detected, while the soy supplementation caused a reduction in LDL and total cholesterol. CONCLUSIONS No significant effects on blood lipids were observed in the main study to a soy supplementation in hypercholesterolaemic subjects after 24 weeks. In the substudy, the soy supplementation, however, reduced LDL and total cholesterol but did not influence markers of arterial function.
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[The CARMEN trial: increased intake of carbohydrates--simple or complex--and unchanged blood lipids in overweight subjects].
Raben, A, Astrup, A, Vasilaras, TH, Prentice, AM, Zunft, HJ, Formiguera, X, Verboeket-van de Venne, WP, Poppitt, SD, Seppelt, B, Johnston, S, et al
Ugeskrift for laeger. 2002;(5):627-31
Abstract
INTRODUCTION The purpose was to investigate the long-term effect of ad libitum low-fat, high-carbohydrate diets with mainly simple or complex carbohydrates on body weight and blood lipids. MATERIAL AND METHODS A six-months controlled randomised multicentre trial with the participation of five European centres. A total of 398 moderately obese subjects (BMI: 30.4 +/- 2.7 kg/m2, mean +/- SD) were randomised to four groups: Control diet group with normal macronutrient intake, a low-fat/high simple carbohydrate group, a low-fat/high complex carbohydrate group and a seasonal control group. RESULTS After six months we found a drop in body weight of 1.7 kg (p < 0.05) in the simple and of 2.6 kg (p < 0.001) in the complex carbohydrate group compared with the control diet group. Fat mass decreased by 1.9 kg (p < 0.05) and 2.4 kg (p < 0.001) in the simple and complex carbohydrate group, respectively, compared with the control diet group. There were no significant changes or group differences in fasting blood lipids, glucose, insulin, or leptin. DISCUSSION The results show that it is favourable to replace dietary fat by carbohydrates (simple or complex) in relation to body weight regulation. No detrimental effects were seen on blood lipids in contrast to previous contentions. Our results underline the importance of a low-fat/high-carbohydrate diet in the management of obesity and the ensuing health problems.
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The role of dietary fat in the prevention and treatment of obesity. Efficacy and safety of low-fat diets.
Astrup, A
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 2001;:S46-50
Abstract
BACKGROUND Does dietary fat play a central role in weight gain and development of obesity? Do low-fat diets have adverse effects on blood lipids? OBJECTIVE AND DESIGN To answer these questions we have reviewed the evidence linking the dietary fat content to energy balance and obesity, and examined the efficacy and safety of ad libitum low fat, high carbohydrate/protein diets in the prevention and management of obesity. RESULTS Physiological studies have provided insight into the mechanisms by which the macronutrients differ in their effect on energy balance: (1) energy from fat is less satiating than energy from carbohydrate, and a high fat/carbohydrate ratio in the diet promotes passive overconsumption, a positive energy balance and weight gain in susceptible individuals; (2) fat is more readily absorbed from the intestine and fecal energy loss is much lower with a high dietary fat/carbohydrate ratio; (3) carbohydrate is more thermogenic than fat and energy expenditure is lower during positive energy balance produced by a diet with a high fat/carbohydrate ratio than during positive energy balance produced by a diet with a low fat/carbohydrate ratio. Randomized intervention studies comparing low fat diets to normal fat diets show that low fat diets prevent weight gain in normal weight subjects and produce weight loss in overweight individuals. In our meta-analysis of ad libitum low fat interventions we included 16 trials involving 1728 individuals. The difference in weight loss between intervention and control groups was 2.5 kg (95% CI, 1.5-3.5; P<0.0001). Weight loss was positively related to pre-treatment body weight (r=0.52, P<0.05) and to reduction in percentage energy as fat (0.37 kg/%, P<0.005). Extrapolated to a body mass index (BMI) approximately 30 kg/m(2), and assuming a 10% reduction in dietary fat, the predicted weight loss would be 4.4 kg (95% CI, 2.0-6.8 kg), which has been confirmed in subsequent studies. Newer studies have shown that replacing some carbohydrate with protein may enhance weight loss. CONCLUSION The American Paradox, the observation that obesity prevalence is increasing despite a slight decrease in population dietary fat consumption, is easily explained by the concomitantly decreasing physical activity, which reduces fat requirements and counteracts the beneficial effect of a slight reduction in dietary fat. Low fat diets with a high content of complex carbohydrates and protein do not produce any adverse effect on cardiovascular risk factors when weight loss is allowed to occur, and they have been shown to decrease mortality among high risk subjects.