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Comprehensive treatment of microvascular angina in overweight women - a randomized controlled pilot trial.
Bove, KB, Nilsson, M, Pedersen, LR, Mikkelsen, N, Suhrs, HE, Astrup, A, Prescott, E
PloS one. 2020;(11):e0240722
Abstract
AIMS: Coronary microvascular dysfunction (CMD) carries a poor cardiovascular prognosis and may explain angina in women without obstructive coronary artery disease (CAD). Currently, no evidence-based treatment for CMD exists. We investigated whether reducing cardiovascular risk factors improves symptoms and microvascular function in women with non-endothelial dependent CMD and no obstructive CAD. METHODS We randomized 62 women aged 40-75, with body mass index (BMI) >25 kg/m2, angina ≥monthly, and coronary flow velocity reserve (CFVR) ≤2.5 to a 24-week intervention comprising low energy diet, exercise training, and optimized treatment of hypertension, dyslipidemia and diabetes or to control. Patients were assessed before randomization and after 24 weeks. Primary outcomes were CFVR assessed by transthoracic Doppler stress-echocardiography and angina burden by Seattle Angina Questionnaire (SAQ). Secondary outcomes were exercise capacity, body composition, glycemic control, myocardial function, and anxiety and depression symptoms. RESULTS Fifty-six participants (90%) completed the study. Median (IQR) age was 65.2 (57.1;70.7) years, BMI was 30.1 (28.4;32.7) kg/m2. The intervention resulted in relevant improvement in angina symptoms (9-21-point increase on SAQ-scales (all p<0.01)) but had no effect on CFVR (p = 0.468). Mean (CI) weight loss was 9.6 (7.80;11.48) kg, (p<0.0001). There was a significant mean (CI) decrease in depression symptoms = 1.16 (0.22;2.12), triglycerides = 0.52 (0.25;0.78) mmol/L, total cholesterol = 0.55 (0.12;0.98) mmol/L, and HbA1c in diabetics = 27.1 (1.60;52.6) mmol/mol but no effect on other secondary outcomes. CONCLUSION A major weight loss and intensified risk factor control resulted in significantly improved angina burden but no improvement of coronary microvascular function among women with microvascular angina.
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Preoperative weight loss program targeting women with overweight and hypertrophy of the breast - a pilot study.
Geiker, NR, Horn, J, Astrup, A
Clinical obesity. 2017;(2):98-104
Abstract
Among women with hypertrophic breasts, the clear majority are overweight or obese. Owing to increased risk of complications, women with a body mass index (BMI) above 25 kg m -2 are precluded from reduction mammaplasty. The primary aim was to investigate if intensive weight loss could ready women with overweight for breast reduction surgery. Six women, all overweight [BMI 30.9 {28.5; 35.8} kg m -2 ] with symptomatic hypertrophy of the breast, were included a 12-week weight loss program. All women desired reduction mammaplasty and were motivated for preoperational weight loss. The first 8 weeks consisted of a formula-based diet supplying 800 kcal daily, in the subsequent 4 weeks regular foods were reintroduced increasing the intake to 1200 kcal daily. Five women completed the trial, and achieved a median (range) weight loss of 10.2 (6.5; 19) kg. Initial breast volume was 1100-2500 mL per breast, this was reduced by 300 (200; 500) mL after the intervention; equivalent to approximately 19%. Waist, hip, upper arm and thorax circumference were significantly reduced following weight loss. At end of study, all the women still suffered from symptomatic breast hypertrophy to substantiate reduction mammaplasty. Surgeries were performed 2 months thereafter. A 12-week intensive preoperative weight loss program enabled women with obesity for breast reduction surgery. Breast size was reduced proportionally more than total weight loss among women with hypertrophy.
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Long-term weight-loss maintenance in obese patients with knee osteoarthritis: a randomized trial.
Christensen, P, Henriksen, M, Bartels, EM, Leeds, AR, Meinert Larsen, T, Gudbergsen, H, Riecke, BF, Astrup, A, Heitmann, BL, Boesen, M, et al
The American journal of clinical nutrition. 2017;(3):755-763
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Abstract
Background: A formula low-energy diet (LED) reduces weight effectively in obese patients with knee osteoarthritis, but the role of LED in long-term weight-loss maintenance is unclear.Objective: We aimed to determine the effect of intermittent LED compared with daily meal replacements on weight-loss maintenance and number of knee replacements over 3 y.Design: The design was a randomized trial with participants aged >50 y who had knee osteoarthritis and a body mass index [BMI (in kg/m2)] ≥30. Participants were recruited from the osteoarthritis outpatient clinic at Copenhagen University Hospital in Frederiksberg, Denmark; they had previously completed a 68-wk lifestyle intervention trial and achieved an average weight loss of 10.5 kg (10% of initial body weight). Participants were randomly assigned to either the intermittent treatment (IN) group with LED for 5 wk every 4 mo for 3 y or to daily meal replacements of 1-2 meals for 3 y [regular (RE) group]. Attention by dietitians and the amount of formula products were similar. Primary outcomes were changes in body weight and proportion of participants receiving knee replacements. Outcomes were analyzed on the intention-to-treat-population with the use of baseline-carried-forward imputation for missing data.Results: A total of 153 participants (means ± SDs: BMI: 33.3 ± 4.6; age: 63.8 ± 6.3 y; 83% women) were recruited between June and December 2009 and randomly assigned to the IN (n = 76) or RE (n = 77) group. A total of 53 and 56 participants, respectively, completed the trial. Weight increased by 0.68 and 1.75 kg in the IN and RE groups, respectively (mean difference: -1.06 kg; 95% CI: -2.75, 0.63 kg; P = 0.22). Alloplasty rates were low and did not differ (IN group: 8 of 76 participants; RE group: 12 of 77 participants; P = 0.35).Conclusions: After a mean 10% weight-loss and 1-y maintenance, additional use of daily meal replacements or intermittent LED resulted in weight-loss maintenance for 3 y. These results challenge the commonly held assumption that weight regain in the long term is inevitable. This trial was registered at clinicaltrials.gov as NCT00938808.
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Personalized weight loss strategies-the role of macronutrient distribution.
Martinez, JA, Navas-Carretero, S, Saris, WH, Astrup, A
Nature reviews. Endocrinology. 2014;(12):749-60
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A large number of different dietary approaches have been studied in an attempt to achieve healthy, sustainable weight loss among individuals with overweight and obesity. Restriction of energy intake is the primary method of producing a negative energy balance leading to weight loss. However, owing to the different metabolic roles of proteins, carbohydrates and lipids in energy homeostasis, diets of similar overall energy content but with different macronutrient distribution can differentially affect metabolism, appetite and thermogenesis. Evidence increasingly suggests that the fuel values of calories provided by distinct macronutrients should be considered separately, as metabolism of specific molecular components generates differences in energy yield. The causes of variation in individual responses to various diets are currently under debate, and some evidence suggests that differences are associated with specific genotypes. This Review discusses all available systematic reviews and meta-analyses, and summarizes the results of relevant randomized controlled intervention trials assessing the influence of macronutrient composition on weight management. The initial findings of research into personalized nutrition, based on the interactions of macronutrient intake and genetic background and its potential influence on dietary intervention strategies, are also discussed.
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Effects of weight loss and long-term weight maintenance with diets varying in protein and glycemic index on cardiovascular risk factors: the diet, obesity, and genes (DiOGenes) study: a randomized, controlled trial.
Gögebakan, O, Kohl, A, Osterhoff, MA, van Baak, MA, Jebb, SA, Papadaki, A, Martinez, JA, Handjieva-Darlenska, T, Hlavaty, P, Weickert, MO, et al
Circulation. 2011;(25):2829-38
Abstract
BACKGROUND We sought to separately examine the effects of either weight loss or diets varying in protein content and glycemic index without further changes in body weight on cardiovascular risk factors within the Diet, Obesity, and Genes study (DiOGenes). METHODS AND RESULTS DiOGenes is a pan-European controlled dietary intervention study in 932 overweight adults who first lost body weight on an 8-week low-calorie diet and were then randomized to 1 of 5 ad libitum diets for 26 weeks. The diets were either high or low protein or high or low glycemic index in 4 combinations or control. Weight loss (-11.23 kg; 95% confidence interval, -11.54 to -10.92; P<0.001) reduced high-sensitivity C-reactive protein (-1.15 mg/L; 95% confidence interval, -1.30 to -0.41; P<0.001), low- and high-density lipoprotein cholesterol, triglycerides, and blood pressure. During the 26-week weight maintenance period in the intention-to-treat analysis, the further decrease of high-sensitivity C-reactive protein blood levels was -0.46 mg/L greater (95% confidence interval, -0.79 to -0.13) in the groups assigned to low-glycemic-index diets than in those on high-glycemic-index diets (P<0.001). Groups on low-protein diets achieved a -0.25 mg/L greater reduction in high-sensitivity C-reactive protein (95% confidence interval, -0.59 to -0.17) than those on high-protein diets (P<0.001), whereas lipid profiles and blood pressure were not differently affected. CONCLUSIONS This large-scale intervention study clearly separates weight loss from dietary composition-related effects. Low-glycemic-index carbohydrates and, to a lesser extent, low-protein intake may specifically reduce low-grade inflammation and associated comorbidities in overweight/obese adults. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00390637.
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TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet.
Grau, K, Cauchi, S, Holst, C, Astrup, A, Martinez, JA, Saris, WH, Blaak, EE, Oppert, JM, Arner, P, Rössner, S, et al
The American journal of clinical nutrition. 2010;(2):472-9
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BACKGROUND Transcription factor 7-like 2 (TCF7L2) rs7903146 associates with type 2 diabetes and may operate via impaired glucagon-like peptide 1 secretion, which is stimulated more by fat than by carbohydrate ingestion. OBJECTIVE The objective was to examine the interaction between TCF7L2 rs7903146 and dietary fat and carbohydrate [high-fat, low-carbohydrate: 40-45% of energy as fat (HF); compared with low-fat, high-carbohydrate: 20-25% of energy as fat (LF)] in obese individuals' responses to a 10-wk hypoenergetic diet (-600 kcal/d). DESIGN European, obese participants (n = 771) were randomly assigned to receive an HF or an LF diet. Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation in percentage of REE (FatOx), homeostasis model assessed insulin release (HOMA-beta), and HOMA-insulin resistance (HOMA-IR) were determined at baseline and after the intervention; 739 individuals were genotyped for rs7903146. RESULTS Average weight loss was 6.9 kg with the LF and 6.6 kg with the HF (difference between diets, NS) diet. Among individuals who were homozygous for the T-risk allele, those in the HF diet group experienced smaller weight losses (Deltaweight) (2.6 kg; P = 0.009; n = 622), smaller DeltaFFM (1.6 kg; P = 0.027; n = 609), smaller DeltaWC (3.3 cm; P = 0.010; n = 608), and a smaller DeltaHOMA-IR (1.3 units; P = 0.004; n = 615) than did the LF diet group. For C allele carriers, there were no differences between the HF and LF diet groups. For the HF diet group, each additional T allele was associated with a reduced loss of FM (0.67 kg; P = 0.019; n = 609). TCF7L2 rs7903146 was not associated with DeltaREE, DeltaFatOx, DeltaHOMA-beta, or dropout. CONCLUSION Our results suggest that obese individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more sensitive to LF than to HF weight-loss diets.
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Comparing two low-energy diets for the treatment of knee osteoarthritis symptoms in obese patients: a pragmatic randomized clinical trial.
Riecke, BF, Christensen, R, Christensen, P, Leeds, AR, Boesen, M, Lohmander, LS, Astrup, A, Bliddal, H
Osteoarthritis and cartilage. 2010;(6):746-54
Abstract
OBJECTIVES To evaluate in a prospective, randomized clinical trial (RCT), symptom response among obese knee osteoarthritis (OA) patients following a feasible, intensive weight-loss program for 16 weeks. METHODS Eligible patients were obese [body mass index (BMI)>30 kg/m(2)]; >50 years old, with primary knee OA. Participants were randomized to either a very-low-energy diet (VLED) or a low-energy diet (LED) (415 kcal/day and 810 kcal/day, respectively), using commercially available formula foods - only for the first 8 weeks, managed by dieticians. The 8 weeks were followed by an additional 8-week period of a hypo-energetic diet consisting of normal food plus meal replacements (1200 kcal/day). The primary endpoint was the number of patients responding according to the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) responder criterion. The statistical analysis was based on a non-responder intention-to-treat (ITT) population (baseline observation carried forward). RESULTS One hundred and ninety two patients (155 (80.7%) females) with a mean age 62.5 years [standard deviation (SD) 6.4; range 50-78 years]; average BMI 37.3 (SD 4.8) were included. At 16 weeks, similar proportions of the VLED and LED groups, 59 (61.5%), and 63 (65.6%) patients, respectively, met the OMERACT-OARSI responder criteria, with no statistical significant difference between the groups (P=0.55). Combining the groups the pooled estimate was 64% meeting the responder criteria [95% confidence interval (CI) 57%, 70%]. There was an overall reduction in pain, corresponding to an average pain reduction on the visual analogue scale (VAS) of 11.1 (95%CI 13.6, 8.5) in the combined groups. At week 16 weight loss in the combined groups was 12.8 kg (95%CI: 11.84-13.66; P<0.001). 71% lost > or =10% body weight in both diet groups, with a pooled estimate of 74% (95%CI: 68-80%). CONCLUSION No clinically significant differences were found between the 415 kcal/day and 810 kcal/day diets. A 16-week formula-diet weight-loss program resulted in a fast and effective weight loss with very few adverse events resulting in a highly significant improvement in symptoms in overweight patients with knee OA.
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Randomized, multi-center trial of two hypo-energetic diets in obese subjects: high- versus low-fat content.
Petersen, M, Taylor, MA, Saris, WH, Verdich, C, Toubro, S, Macdonald, I, Rössner, S, Stich, V, Guy-Grand, B, Langin, D, et al
International journal of obesity (2005). 2006;(3):552-60
Abstract
OBJECTIVE To investigate whether a hypo-energetic low-fat diet is superior to a hypo-energetic high-fat diet for the treatment of obesity. DESIGN Open-label, 10-week dietary intervention comparing two hypo-energetic (-600 kcal/day) diets with a fat energy percent of 20-25 or 40-45. SUBJECTS Obese (BMI >or=30 kg/m(2)) adult subjects (n = 771), from eight European centers. MEASUREMENTS Body weight loss, dropout rates, proportion of subjects who lost more than 10% of initial body weight, blood lipid profile, insulin and glucose. RESULTS The dietary fat energy percent was 25% in the low-fat group and 40% in the high-fat group (mean difference: 16 (95% confidence interval (CI) 15-17)%). Average weight loss was 6.9 kg in the low-fat group and 6.6 kg in the high-fat group (mean difference: 0.3 (95% CI -0.2 to 0.8) kg). Dropout was 13.6% (n = 53) in the low-fat group and 18.3% (n = 70) in the high-fat group (P=0.001). Among completers, more subjects lost >10% in the low-fat group than in the high-fat group ((20.8%, n = 70) versus (14.7%, n = 46), P = 0.02). Fasting plasma total, low-density lipoprotein- and high-density lipoprotein-cholesterol decreased in both groups, but more so in the low-fat group than in the high-fat group. Fasting plasma insulin and glucose were lowered equally by both diets. CONCLUSIONS The low-fat diet produced similar mean weight loss as the high-fat diet, but resulted in more subjects losing >10% of initial body weight and fewer dropouts. Both diets produced favorable changes in fasting blood lipids, insulin and glucose.