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Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial.
Gudbergsen, H, Overgaard, A, Henriksen, M, Wæhrens, EE, Bliddal, H, Christensen, R, Nielsen, SM, Boesen, M, Knop, FK, Astrup, A, et al
The American journal of clinical nutrition. 2021;(2):314-323
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Abstract
BACKGROUND Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). OBJECTIVE To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. METHODS The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. RESULTS In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. CONCLUSIONS In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.
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Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics.
Valsesia, A, Chakrabarti, A, Hager, J, Langin, D, Saris, WHM, Astrup, A, Blaak, EE, Viguerie, N, Masoodi, M
Scientific reports. 2020;(1):9236
Abstract
Weight loss aims to improve glycemic control in obese but strong variability is observed. Using a multi-omics approach, we investigated differences between 174 responders and 201 non-responders, that had lost >8% body weight following a low-caloric diet (LCD, 800 kcal/d for 8 weeks). The two groups were comparable at baseline for body composition, glycemic control, adipose tissue transcriptomics and plasma ketone bodies. But they differed significantly in their response to LCD, including improvements in visceral fat, overall insulin resistance (IR) and tissue-specific IR. Transcriptomics analyses found down-regulation in key lipogenic genes (e.g. SCD, ELOVL5) in responders relative to non-responders; metabolomics showed increase in ketone bodies; while proteomics revealed differences in lipoproteins. Findings were consistent between genders; with women displaying smaller improvements owing to a better baseline metabolic condition. Integrative analyses identified a plasma omics model that was able to predict non-responders with strong performance (on a testing dataset, the Receiving Operating Curve Area Under the Curve (ROC AUC) was 75% with 95% Confidence Intervals (CI) [67%, 83%]). This model was based on baseline parameters without the need for intrusive measurements and outperformed clinical models (p = 0.00075, with a +14% difference on the ROC AUCs). Our approach document differences between responders and non-responders, with strong contributions from liver and adipose tissues. Differences may be due to de novo lipogenesis, keto-metabolism and lipoprotein metabolism. These findings are useful for clinical practice to better characterize non-responders both prior and during weight loss.
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A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss.
Greenway, FL, Aronne, LJ, Raben, A, Astrup, A, Apovian, CM, Hill, JO, Kaplan, LM, Fujioka, K, Matejkova, E, Svacina, S, et al
Obesity (Silver Spring, Md.). 2019;(2):205-216
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OBJECTIVE This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity. METHODS The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥ 27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss. RESULTS Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks. CONCLUSIONS Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.
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Prevotella-to-Bacteroides ratio predicts body weight and fat loss success on 24-week diets varying in macronutrient composition and dietary fiber: results from a post-hoc analysis.
Hjorth, MF, Blædel, T, Bendtsen, LQ, Lorenzen, JK, Holm, JB, Kiilerich, P, Roager, HM, Kristiansen, K, Larsen, LH, Astrup, A
International journal of obesity (2005). 2019;(1):149-157
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BACKGROUND/OBJECTIVES Individuals with high pre-treatment bacterial Prevotella-to-Bacteroides (P/B) ratio have been reported to lose more body weight on diets high in fiber than subjects with a low P/B ratio. Therefore, the aim of the present study was to examine potential differences in dietary weight loss responses between participants with low and high P/B. SUBJECTS/METHODS Eighty overweight participants were randomized (52 completed) to a 500 kcal/d energy deficit diet with a macronutrient composition of 30 energy percentage (E%) fat, 52 E% carbohydrate and 18 E% protein either high (≈1500 mg calcium/day) or low ( ≤ 600 mg calcium/day) in dairy products for 24 weeks. Body weight, body fat, and dietary intake (by 7-day dietary records) were determined. Individuals were dichotomized according to their pre-treatment P/B ratio derived from 16S rRNA gene sequencing of collected fecal samples to test the potential modification of dietary effects using linear mixed models. RESULTS Independent of the randomized diets, individuals with high P/B lost 3.8 kg (95%CI, 1.8,5.8; P < 0.001) more body weight and 3.8 kg (95% CI, 1.1, 6.5; P = 0.005) more body fat compared to individuals with low P/B. After adjustment for multiple covariates, individuals with high P/B ratio lost 8.3 kg (95% CI, 5.8;10.9, P < 0.001) more body weight when consuming above compared to below 30 g fiber/10MJ whereas this weight loss was 3.2 kg (95% CI, 0.8;5.5, P = 0.008) among individuals with low P/B ratio [Mean difference: 5.1 kg (95% CI, 1.7;8.6, P = 0.003)]. Partial correlation coefficients between fiber intake and weight change was 0.90 (P < 0.001) among individuals with high P/B ratio and 0.25 (P = 0.29) among individuals with low P/B ratio. CONCLUSIONS Individuals with high P/B lost more body weight and body fat compared to individuals with low P/B, confirming that individuals with a high P/B are more susceptible to weight loss on a diet rich in fiber.
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Weight loss at your fingertips: personalized nutrition with fasting glucose and insulin using a novel statistical approach.
Ritz, C, Astrup, A, Larsen, TM, Hjorth, MF
European journal of clinical nutrition. 2019;(11):1529-1535
Abstract
BACKGROUND/OBJECTIVES Precision medicine is changing the way people are diagnosed and treated into a more personalized approach. Using a novel statistical approach, we demonstrate how two diets cause differential weight loss depending on pre-treatment fasting plasma glucose (FPG) and fasting insulin (FI) levels. SUBJECTS/METHODS One hundred and eighty-one overweight people with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in dietary fiber and whole grain or an Average Danish (Western) Diet (ADD) for 26 weeks. All foods were provided free of charge. Body weight was measured throughout the study and blood was drawn before randomization from where FPG and FI were analyzed. Weight was described by linear mixed models including biomarker (FPG or FI) diet group interactions. Individualized predictions were estimated as contrasts of intercepts and slopes of pre-treatment biomarkers. RESULTS Every mmol/L increase in baseline FPG predicted a between-diet difference of 3.00 (1.18;4.83, n = 181, P = 0.001) kg larger weight loss from choosing NND over ADD. For instance, a baseline FPG level of 4.7 mmol/L would lead to an average of 1.42 kg larger weight loss on NND vs. ADD (above 0.41 kg with 95% certainty), whereas the average effect size would be 8.33 kg (above 5.50 kg with 95% certainty) among subjects with FPG level of 7.0 mmol/L. Among individuals with FPG <5.6 mmol/L, each pmol/L lower baseline FI predicted a 0.039 (95% CI 0.017;0.061, n = 143, P < 0.001) kg larger weight loss from choosing NND over ADD. CONCLUSIONS Use of pre-treatment FPG and FI led to truly individualized predictions of treatment effect of introducing more fiber and whole grain in the diet on weight loss, ranging from almost no effect to losing >8 kg. These findings suggest that this novel statistical approach has great potential when re-evaluating data from existing randomized controlled trials.
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Weight loss decreases self-reported appetite and alters food preferences in overweight and obese adults: Observational data from the DiOGenes study.
Andriessen, C, Christensen, P, Vestergaard Nielsen, L, Ritz, C, Astrup, A, Meinert Larsen, T, Martinez, JA, Saris, WHM, van Baak, MA, Papadaki, A, et al
Appetite. 2018;:314-322
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People with obesity often struggle to maintain their weight loss after a weight loss period. Furthermore, the effect of weight loss on appetite and food preferences remains unclear. Hence this study investigated the effect of weight loss on subjective appetite and food preferences in healthy, overweight and obese volunteers. A subgroup of adult participants (n = 123) from the Diet Obesity and Genes (DiOGenes) study (subgroup A) was recruited from across six European countries. Participants lost ≥8% of initial body weight during an 8-week low calorie diet (LCD). Subjective appetite and food preferences were measured before and after the LCD, in response to a standardized meal test, using visual analogue rating scales (VAS) and the Leeds Food Choice Questionnaire (FCQ). After the LCD, participants reported increased fullness (p < 0.05), decreased desire to eat (p < 0.05) and decreased prospective consumption (p < 0.05) after consuming the test meal. An interaction effect (visit x time) was found for hunger ratings (p < 0.05). Area under the curve (AUC) for hunger, desire to eat and prospective consumption was decreased by 18.1%, 20.2% and 21.1% respectively whereas AUC for fullness increased by 13.9%. Preference for low-energy products measured by the Food Preference Checklist (FPC) decreased by 1.9% before the test meal and by 13.5% after the test meal (p < 0.05). High-carbohydrate and high-fat preference decreased by 11.4% and 16.2% before the test meal and by 17.4% and 22.7% after the meal (p < 0.05). No other effects were observed. These results suggest that LCD induced weight loss decreases the appetite perceptions of overweight volunteers whilst decreasing their preference for high-fat-, high-carbohydrate-, and low-energy products.
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[Personalised nutrition for weight loss in overweight patients].
Hjorth, MF, Astrup, A
Ugeskrift for laeger. 2018;(22)
Abstract
Over the past several decades numerous trials have compared various diets for the management of overweight and obesity, assuming that one diet fits all. However, it is far more likely, that different people will have different levels of success on different diets. We have investigated fasting plasma glucose (and insulin) levels as well as the microbiota Prevotella/Bacteroides-ratio as prognostic markers of weight loss during periods of characterised dietary composition. Overall, these biomarkers hold great promise for moving forward with personalised nutrition to improve weight control in obese patients.
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Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention.
Hjorth, MF, Roager, HM, Larsen, TM, Poulsen, SK, Licht, TR, Bahl, MI, Zohar, Y, Astrup, A
International journal of obesity (2005). 2018;(3):580-583
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On the basis of the abundance of specific bacterial genera, the human gut microbiota can be divided into two relatively stable groups that might have a role in personalized nutrition. We studied these simplified enterotypes as prognostic markers for successful body fat loss on two different diets. A total of 62 participants with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in fiber/whole grain or an Average Danish Diet for 26 weeks. Participants were grouped into two discrete enterotypes by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Modifications of dietary effects of pre-treatment P/B group were examined by linear mixed models. Among individuals with high P/B the NND resulted in a 3.15 kg (95% confidence interval (CI): 1.55; 4.76, P<0.001) larger body fat loss compared with ADD, whereas no differences was observed among individuals with low P/B (0.88 kg (95% CI: -0.61; 2.37, P=0.25)). Consequently, a 2.27 kg (95% CI: 0.09; 4.45, P=0.041) difference in responsiveness to the diets were found between the two groups. In summary, subjects with high P/B ratio appeared more susceptible to lose body fat on diets high in fiber and whole grain than subjects with a low P/B ratio.
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Pretreatment Fasting Plasma Glucose Modifies Dietary Weight Loss Maintenance Success: Results from a Stratified RCT.
Hjorth, MF, Due, A, Larsen, TM, Astrup, A
Obesity (Silver Spring, Md.). 2017;(12):2045-2048
Abstract
OBJECTIVE Levels of fasting plasma glucose (FPG) and fasting insulin (FI) were studied as diet-specific prognostic markers for successful weight loss maintenance in participants with overweight. METHODS After losing ≥ 8% of body weight, participants received one of three ad libitum diets for 6 months: (1) a moderate-fat diet high in monounsaturated fatty acids (MUFA); a low-fat, high-fiber diet (Nordic Nutrition Recommendations [NNR]); and the Average Danish Diet (ADD). Participants were categorized as having low (< 90 mg/dL) or high (90-105 mg/dL) FPG based on preintervention values. Median FI among those having high FPG was used as a cutoff for FI (FI ≤ 50 pmol/L; FI > 50 pmol/L). RESULTS Participants with low FPG and randomized to MUFA, NNR, and ADD regained similarly 2.1 to 2.5 kg after 6 months. By contrast, participants with high FPG and randomized to MUFA, NNR, and ADD regained 2.73 kg (95% CI 1.33 to 4.13; P < 0.001), -0.05 kg (95% CI -1.95 to 1.86; P = 0.96), and 4.16 kg (95% CI 2.27 to 6.06; P < 0.001) after 6 months, respectively, resulting in lower weight regain on NNR compared to ADD (-4.21 kg [95% CI -6.83 to -1.59]; P = 0.002) and MUFA (95% CI -2.77 kg [-5.12 to -0.43]; P = 0.020). The addition of FI strengthened these associations. CONCLUSIONS Slightly elevated pretreatment FPG determined success in dietary weight loss maintenance among overweight patients on ad libitum diets differing in macronutrient and fiber content.
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Pretreatment fasting plasma glucose and insulin modify dietary weight loss success: results from 3 randomized clinical trials.
Hjorth, MF, Ritz, C, Blaak, EE, Saris, WH, Langin, D, Poulsen, SK, Larsen, TM, Sørensen, TI, Zohar, Y, Astrup, A
The American journal of clinical nutrition. 2017;(2):499-505
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Background: Which diet is optimal for weight loss and maintenance remains controversial and implies that no diet fits all patients.Objective: We studied concentrations of fasting plasma glucose (FPG) and fasting insulin (FI) as prognostic markers for successful weight loss and maintenance through diets with different glycemic loads or different fiber and whole-grain content, assessed in 3 randomized trials of overweight participants.Design: After an 8-wk weight loss, participants in the DiOGenes (Diet, Obesity, and Genes) trial consumed ad libitum for 26 wk a diet with either a high or a low glycemic load. Participants in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) Supermarket intervention (SHOPUS) trial consumed ad libitum for 26 wk the New Nordic Diet, which is high in fiber and whole grains, or a control diet. Participants in the NUGENOB (Nutrient-Gene Interactions in Human Obesity) trial consumed a hypocaloric low-fat and high-carbohydrate or a high-fat and low-carbohydrate diet for 10 wk. On the basis of FPG before treatment, participants were categorized as normoglycemic (FPG <5.6 mmol/L), prediabetic (FPG 5.6-6.9 mmol/L), or diabetic (FPG ≥7.0 mmol/L). Modifications of the dietary effects of FPG and FI before treatment were examined with linear mixed models.Results: In the DiOGenes trial, prediabetic individuals regained a mean of 5.83 kg (95% CI: 3.34, 8.32 kg; P < 0.001) more on the high- than on the low-glycemic load diet, whereas normoglycemic individuals regained a mean of 1.44 kg (95% CI: 0.48, 2.41 kg; P = 0.003) more [mean group difference: 4.39 kg (95% CI: 1.76, 7.02 kg); P = 0.001]. In SHOPUS, prediabetic individuals lost a mean of 6.04 kg (95% CI: 4.05, 8.02 kg; P < 0.001) more on the New Nordic Diet than on the control diet, whereas normoglycemic individuals lost a mean of 2.20 kg (95% CI: 1.21, 3.18 kg; P < 0.001) more [mean group difference: 3.84 kg (95% CI: 1.62, 6.06 kg); P = 0.001]. In NUGENOB, diabetic individuals lost a mean of 2.04 kg (95% CI: -0.20, 4.28 kg; P = 0.07) more on the high-fat and low-carbohydrate diet than on the low-fat and high-carbohydrate diet, whereas normoglycemic individuals lost a mean of 0.43 kg (95% CI: 0.03, 0.83 kg; P = 0.03) more on the low-fat and high-carbohydrate diet [mean group difference: 2.47 kg (95% CI: 0.20, 4.75 kg); P = 0.03]. The addition of FI strengthened these associations.Conclusion: Elevated FPG before treatment indicates success with dietary weight loss and maintenance among overweight patients consuming diets with a low glycemic load or with large amounts of fiber and whole grains. These trials were registered at clinicaltrials.gov as NCT00390637 (DiOGenes) and NCT01195610 (SHOPUS), and at ISRNCT.com as ISRCTN25867281 (NUGENOB).