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Body weight and metabolic risk factors in patients with type 2 diabetes on a self-selected high-protein low-carbohydrate diet.
Alzahrani, AH, Skytte, MJ, Samkani, A, Thomsen, MN, Astrup, A, Ritz, C, Chabanova, E, Frystyk, J, Holst, JJ, Thomsen, HS, et al
European journal of nutrition. 2021;(8):4473-4482
Abstract
PURPOSE We previously reported beneficial glucoregulatory effects of a fully provided carbohydrate-reduced, high-protein (CRHP) diet in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, in which patients maintained their body weight. Here, we investigated physiological changes during an additional 6-month period on a self-selected and self-prepared CRHP diet. METHODS Twenty-eight patients with T2DM were instructed to consume a CRHP diet (30% of energy from carbohydrate and 30% from protein) for 24 weeks, after an initial 2 × 6-week trial when all food was prepared and provided to them. Patients received dietary advice every 2 weeks. At weeks 0, 6, 12 and 36, they underwent a 3-h intravenous glucose tolerance test, a 4-h mixed meal test, and a 48-h continuous glucose monitoring. Liver, muscle, pancreas, and visceral fat contents were measured by magnetic resonance imaging. RESULTS During the 24-week self-selected diet period (weeks 12-36), body weight, visceral fat, liver fat, and glycated haemoglobin were maintained at the same levels achieved at the end of the fully provided diet period, and were still lower than at baseline (P < 0.05). Postprandial insulinaemia and insulin secretion were significantly greater (P < 0.05). At week 36, fasting insulin and C-peptide levels increased (P < 0.01) and daily glycaemia decreased further (P < 0.05) when compared with the end of the fully provided diet period. CONCLUSION Substituting dietary carbohydrate for protein and fat has metabolic benefits in patients with T2DM. These beneficial effects are maintained or augmented over the next 6 months when patients self-select and self-prepare this diet in a dietitian-supported setting. TRIAL REGISTRATION ClinicalTrials.gov NCT02764021.
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Effects of a highly controlled carbohydrate-reduced high-protein diet on markers of oxidatively generated nucleic acid modifications and inflammation in weight stable participants with type 2 diabetes; a randomized controlled trial.
Skytte, MJ, Samkani, A, Astrup, A, Larsen, TM, Frystyk, J, Poulsen, HE, Henriksen, T, Holst, JJ, Andersen, O, Madsbad, S, et al
Scandinavian journal of clinical and laboratory investigation. 2020;(5):401-407
Abstract
Carbohydrate-restricted diets are increasingly recognized as options for dietary management of type 2 diabetes mellitus (T2DM). We investigated the effects of a carbohydrate-reduced high-protein (CRHP) and a conventional diabetes (CD) diet on oxidative stress and inflammation in weight stable individuals with T2DM. We hypothesized that the CRHP diet would improve markers of oxidatively generated RNA and DNA modifications as well as inflammatory parameters. Thirty participants with T2DM were randomized to 6 weeks of CRHP or CD dietary treatment (30/50 energy percentage (E%) carbohydrate, 30/17E% protein, 40/33E% fat), followed by a cross-over to the opposite diet for a subsequent 6-week period. All meals were provided during the study and body weight was controlled. Diurnal urine samples were collected after 4 weeks on each diet and oxidatively generated RNA and DNA modifications were measured as 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), respectively. Fasting concentrations of soluble urokinase plasminogen activator receptor, high-sensitivity C-reactive protein, tumor necrosis factor alpha and interleukin-6 were measured before and after 6 weeks of interventions. Compared with the CD diet, the CRHP diet increased 24-hour urinary excretion of 8-oxoGuo by 9.3% (38.6 ± 12.6 vs. 35.3 ± 11.0 nmol/24 h, p = .03), whereas 8-oxodG did not differ between diets (24.0 ± 9.5 vs. 24.8 ± 11.1 nmol/24 h, p = .17). Changes in plasma inflammatory parameters did not differ between CRHP and CD diets, all p ≥ .2. The clinical implications of increased RNA oxidation following a CRHP diet as well as long-term effects of carbohydrate-restriction on markers of oxidatively generated nucleic acid modifications should be a field of future study.
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The differential plasma proteome of obese and overweight individuals undergoing a nutritional weight loss and maintenance intervention.
Oller Moreno, S, Cominetti, O, Núñez Galindo, A, Irincheeva, I, Corthésy, J, Astrup, A, Saris, WHM, Hager, J, Kussmann, M, Dayon, L
Proteomics. Clinical applications. 2018;(1)
Abstract
PURPOSE The nutritional intervention program "DiOGenes" focuses on how obesity can be prevented and treated from a dietary perspective. We generated differential plasma proteome profiles in the DiOGenes cohort to identify proteins associated with weight loss and maintenance and explore their relation to body mass index, fat mass, insulin resistance, and sensitivity. EXPERIMENTAL DESIGN Relative protein quantification was obtained at baseline and after combined weight loss/maintenance phases using isobaric tagging and MS/MS. A Welch t-test determined proteins differentially present after intervention. Protein relationships with clinical variables were explored using univariate linear models, considering collection center, gender and age as confounding factors. RESULTS Four hundred and seventy three subjects were measured at baseline and end of the intervention; 39 proteins were longitudinally differential. Proteins with largest changes were sex hormone-binding globulin, adiponectin, C-reactive protein, calprotectin, serum amyloid A, and proteoglycan 4 (PRG4), whose association with obesity and weight loss is known. We identified new putative biomarkers for weight loss/maintenance. Correlation between PRG4 and proline-rich acidic protein 1 variation and Matsuda insulin sensitivity increment was showed. CONCLUSION AND CLINICAL RELEVANCE MS-based proteomic analysis of a large cohort of non-diabetic overweight and obese individuals concomitantly identified known and novel proteins associated with weight loss and maintenance.
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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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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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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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Markers of metabolic health in children differ between weekdays--the result of unhealthier weekend behavior.
Hjorth, MF, Damsgaard, CT, Michaelsen, KF, Astrup, A, Sjödin, A
Obesity (Silver Spring, Md.). 2015;(4):733-6
Abstract
OBJECTIVE The aim of this study was to investigate whether indicators of metabolic health fluctuate during the week in a group of children posing unhealthier physical activity, sedentary time, and sleep during weekends compared to weekdays. METHODS A total of 807 eight- to eleven-year-old children had valid metabolic health markers from one, two, or three measurements contributing 2190 to 2240 observations of metabolic health markers. The weekly variation was tested using linear mixed models. RESULTS Homeostatic model assessment of insulin resistance (HOMAIR), triglycerides, leptin (all P < 0.001), and adiponectin (P = 0.03) decreased from Monday to Friday, whereas ghrelin increased (P < 0.001). HOMAIR , triglycerides, and leptin were 35%, 28%, and 33% higher on Mondays compared to Fridays, respectively, and ghrelin was 7% lower on Mondays compared to Fridays (all P < 0.001). CONCLUSIONS The large weekly variation in HOMAIR , triglycerides, and leptin was likely the result of unhealthier behaviors during weekends. These findings have public health relevance and raise methodological issues that should ideally be taken into account in future studies.
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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.
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Early weight loss while on lorcaserin, diet and exercise as a predictor of week 52 weight-loss outcomes.
Smith, SR, O'Neil, PM, Astrup, A, Finer, N, Sanchez-Kam, M, Fraher, K, Fain, R, Shanahan, WR
Obesity (Silver Spring, Md.). 2014;(10):2137-46
Abstract
OBJECTIVE To identify an early treatment milestone that optimizes sensitivity and specificity for predicting ≥5% weight loss at Week (W) 52 in patients with and without type 2 diabetes on lorcaserin or placebo. METHODS Post hoc area under the curve for receiver operating characteristic analyses of data from three phase 3 trials comparing lifestyle modification+placebo with lifestyle modification+lorcaserin. A total of 6897 patients (18-65 years; BMI, 30-45 or 27-29.9 kg/m(2) with ≥1 comorbidity) were randomized to placebo or lorcaserin 10 mg bid. Changes (baseline to W52) in cardiometabolic parameters were assessed. RESULTS Response (≥5% weight loss from baseline) at W12 was a strong predictor of W52 response. Lorcaserin patients with a W12 response achieved mean W52 weight losses of 10.6 kg (without diabetes) and 9.3 kg (with diabetes). Proportions achieving ≥5% and ≥10% weight loss at W52 were 85.5% and 49.8% (without diabetes), and 70.5% and 35.9% (with diabetes). Lorcaserin patients who did not achieve a W12 response lost 3.2 kg (without diabetes) and 2.8 kg (with diabetes) at W52. Responders had greater improvements in cardiometabolic risk factors than the modified intent-to-treat (MITT) population, consistent with greater weight loss. CONCLUSIONS ≥5% weight loss by W12 predicts robust response to lorcaserin at 1 year.
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A multicentre weight loss study using a low-calorie diet over 8 weeks: regional differences in efficacy across eight European cities.
Papadaki, A, Linardakis, M, Plada, M, Larsen, TM, van Baak, MA, Lindroos, AK, Pfeiffer, AF, Martinez, JA, Handjieva-Darlenska, T, Kunešová, M, et al
Swiss medical weekly. 2013;:w13721
Abstract
PRINCIPLES The efficacy of low-calorie diets (LCDs) has not been investigated in large-scale studies or among people from different regions, who are perhaps unaccustomed to such methods of losing weight. The aim of the present study was to investigate changes in obesity measures among overweight/obese adults from eight European cities (from Northern, Central and Southern Europe) during the 8-week LCD phase of the DiOGenes study (2006-2007), a family-based, randomised, controlled dietary intervention. METHODS 938 overweight/obese adults completed baseline examinations and underwent an 8-week LCD, providing 3.3-4.2 MJ/day to replace all meals. Anthropometric measurements and body composition were assessed at baseline and post-LCD. RESULTS 773 (82.4%) adults (mean age, 43.1 y) completed the LCD successfully. The highest drop-out rate was observed in Southern (24.9%) and the lowest in Northern (13.3%) European cities. Overall, the LCD induced favourable changes in all outcomes, including an approximate 11.0% reduction in body weight and body fat percentage. Changes in outcomes differed significantly between regions, with North- and Central-European cities generally achieving higher percentage reductions in most anthropometric measurements assessed. Nonetheless, participants in Southern Europe reduced their body fat percentage significantly more than participants in Northern Europe (-11.8 vs. -9.5%, P = 0.017). CONCLUSIONS The LCD significantly improved anthropometric and body composition measurements in all cities participating in DiOGenes.