Publications by authors named "Pernille Auerbach"

14 Publications

  • Page 1 of 1

Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial.

Lancet Diabetes Endocrinol 2021 09 21;9(9):563-574. Epub 2021 Jul 21.

Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

Background: Semaglutide is an effective treatment for type 2 diabetes; however, 20-30% of patients given semaglutide 1·0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea.

Methods: We did a 40-week, randomised, active-controlled, parallel-group, double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics in ten countries. Participants (≥18 years) with inadequately controlled type 2 diabetes (HbA 8·0-10·0%) with metformin and with or without sulfonylurea were randomly assigned (1:1) by an interactive web-response system to 2·0 mg or 1·0 mg once-weekly semaglutide. Participants, site personnel, the clinical study group, and investigators were masked to the randomised treatment. Outcomes included change from baseline at week 40 in HbA (primary outcome) and bodyweight (secondary confirmatory outcome), evaluated through trial product estimand (no treatment discontinuation or without rescue medication) and treatment policy estimand (regardless of treatment discontinuation or rescue medication) strategies. This study is registered with ClinicalTrials.gov, NCT03989232; EudraCT, 2018-004529-96; and WHO, U1111-1224-5162.

Findings: Between June 19 and Nov 28, 2019, of 1515 adults assessed for eligibility, 961 participants (mean age 58·0 years [SD 10·0]; 398 [41%] women) were included. Participants were randomly assigned to once-weekly semaglutide 2·0 mg (n=480 [50%]) or 1·0 mg (n=481 [50%]); 462 (96%) patients in the semaglutide 2·0 mg group and 471 (98%) in the semaglutide 1·0 mg group completed the trial. Mean baseline HbA was 8·9% (SD 0·6; 73·3 mmol/mol [SD 6·9]) and BMI was 34·6 kg/m (SD 7·0). Mean change in HbA from baseline at week 40 was -2·2 percentage points with semaglutide 2·0 mg and -1·9 percentage points with semaglutide 1·0 mg (estimated treatment difference [ETD] -0·23 percentage points [95% CI -0·36 to -0·11]; p=0·0003; trial product estimand) and -2·1 percentage points with semaglutide 2·0 mg and -1·9 percentage points with semaglutide 1·0 mg (ETD -0·18 percentage points [-0·31 to -0·04]; p=0·0098; treatment policy estimand). Mean change in bodyweight from baseline at week 40 was -6·9 kg with semaglutide 2·0 mg and -6·0 kg with semaglutide 1·0 mg (ETD -0·93 kg [95% CI -1·68 to -0·18]; p=0·015; trial product estimand) and -6·4 kg with semaglutide 2·0 mg and -5·6 kg with semaglutide 1·0 mg (ETD -0·77 kg [-1·55 to 0·01]; p=0·054; treatment policy estimand). Gastrointestinal disorders were the most commonly reported adverse events (163 [34%] in the 2·0 mg group and 148 [31%] in the 1·0 mg group). Serious adverse events were similar between treatment groups, reported for 21 (4%) participants given semaglutide 2·0 mg and 25 (5%) participants given semaglutide 1·0 mg. Three deaths were reported during the trial (one in the semaglutide 1·0 mg group and two in the semaglutide 2·0 mg group).

Interpretation: Semaglutide 2·0 mg was superior to 1·0 mg in reducing HbA, with additional bodyweight loss and a similar safety profile. This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control.

Funding: Novo Nordisk.
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http://dx.doi.org/10.1016/S2213-8587(21)00174-1DOI Listing
September 2021

Effects of Dietary Self-Monitoring, Physical Activity, Liraglutide 3.0 mg, and Placebo on Weight Loss in the SCALE IBT Trial.

Obes Facts 2020 16;13(6):572-583. Epub 2020 Nov 16.

Washington Center for Weight Management and Research, Arlington, Virginia, USA.

Introduction: Individuals who enroll in intensive behavioral therapy (IBT) programs are asked to make several lifestyle changes simultaneously. However, few studies have examined the relative effects of adherence to different treatment components on weight loss.

Objective: This secondary analysis of the SCALE IBT trial assessed adherence to the medication regimen, dietary self-monitoring, and physical activity recommendations and their relative contributions to weight change in individuals with obesity who were provided with IBT combined with either liraglutide 3.0 mg or placebo.

Methods: SCALE IBT was a double-blinded, multicenter, randomized controlled trial comparing 56-week weight losses in individuals with obesity who received liraglutide 3.0 mg (n = 142) or placebo (n = 140), as an adjunct to IBT. Adherence to dietary self-monitoring, physical activity, and medication usage (liraglutide or placebo) were measured during the 56-week treatment period. A regression model was used to estimate the relative contribution of adherence to each treatment component to weight loss at week 56.

Results: The proportion of individuals who adhered to each intervention component decreased over time. Compared with non-adherence, complete adherence to dietary self-monitoring and physical activity recommendations were associated with estimated weight changes of -7.2% (95% CI -10.4 to -4.0; p < 0.0001) and -2.0% (95% CI -3.2 to -0.8; p = 0.0009), respectively. Complete adherence to liraglutide predicted an additional weight loss of -6.5% (95% CI -10.2 to -2.9; p = 0.0005) relative to individuals who did not adhere to the medication regimen, while adherence to placebo did not have a statistically significant effect on weight loss (p = 0.33).

Conclusions: High adherence to dietary self-monitoring and use of liraglutide 3.0 mg was associated with clinically relevant weight loss with IBT and adjunctive pharmacotherapy. The effect of adherence to physical activity was significant but smaller.
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http://dx.doi.org/10.1159/000511130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802504PMC
April 2021

Low-Grade Inflammation Is Not Present in Former Obese Males but Adipose Tissue Macrophage Infiltration Persists.

Biomedicines 2020 May 14;8(5). Epub 2020 May 14.

Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, 2200N Copenhagen, Denmark.

Macrophage infiltration in two subcutaneous adipose tissue depots and systemic low-grade inflammation were studied in post-obese (PO), obese (O), and control (C) subjects. Young males were recruited into PO: ( = 10, weight-loss avg. 26%, BMI: 26.6 ± 0.7, mean ±SEM kg/m), O: ( = 10, BMI: 33.8 ± 1.0kg/m) and C: ( = 10, BMI: 26.6 ± 0.6 kg/m). PO and C were matched by BMI. Blood and abdominal and gluteal subcutaneous adipose tissue were obtained in the overnight fasted state. Plasma concentrations of IL-6 and CRP were higher ( < 0.05) in O than in PO and C, TNF-α was higher ( < 0.05) only in O compared to PO and IL-18 was similar between groups. The number of CD68 macrophages was higher ( < 0.05) in the gluteal than the abdominal depot, and higher ( < 0.05) in O and PO compared to C in both depots. The content of CD163 macrophages was similar between depots but was higher ( < 0.05) in PO compared to C and O in the gluteal depot. In post obese men with a long-term sustained weight loss, systemic low-grade inflammation was similar to non-obese controls despite a higher subcutaneous adipose tissue CD68 macrophage content. Interestingly, the anti-inflammatory CD163 macrophage adipose tissue content was consistently higher in post obese than obese and controls.
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http://dx.doi.org/10.3390/biomedicines8050123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277299PMC
May 2020

A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity.

N Engl J Med 2020 05 31;382(22):2117-2128. Epub 2020 Mar 31.

From the Department of Pediatrics and Center for Pediatric Obesity Medicine, University of Minnesota Medical School, Minneapolis (A.S.K.); Novo Nordisk, Søborg, Denmark (P.A.); Pediatric Endocrinology, Hospital Ángeles Puebla, Puebla City, Mexico (M.B.-P.); the Department of Pediatrics, Division of Pediatric Endocrinology, Universitair Ziekenhuis Brussel, Brussels (I.G.); Novo Nordisk, Plainsboro, NJ (P.M.H.); the Division of Pediatrics, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm (C.M.); the Division of Pediatric Endocrinology and Diabetes, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY (L.D.M.); Novo Nordisk, Bengaluru, India (N.P.); and the Center for Pediatric Research in Obesity and Metabolism, Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh (S.A.).

Background: Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity.

Methods: In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56.

Results: A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, -0.22; 95% confidence interval [CI], -0.37 to -0.08; P = 0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, -4.64 percentage points) and for body weight (estimated difference, -4.50 kg [for absolute change] and -5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the trial treatment (13 [10.4%] vs. 0). Few participants in either group had serious adverse events (3 [2.4%] vs. 5 [4.0%]). One suicide, which occurred in the liraglutide group, was assessed by the investigator as unlikely to be related to the trial treatment.

Conclusions: In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy. (Funded by Novo Nordisk; NN8022-4180 ClinicalTrials.gov number, NCT02918279.).
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http://dx.doi.org/10.1056/NEJMoa1916038DOI Listing
May 2020

Liraglutide 3.0 mg and Intensive Behavioral Therapy (IBT) for Obesity in Primary Care: The SCALE IBT Randomized Controlled Trial.

Obesity (Silver Spring) 2020 03;28(3):529-536

Washington Center for Weight Management and Research, Arlington, Virginia, USA.

Objective: Previous studies have shown additive weight loss when intensive behavioral therapy (IBT) was combined with weight-loss medication. The present multisite study provides the first evaluation, in primary care, of the effect of the Centers for Medicare and Medicaid Services-based IBT benefit, delivered alone (with placebo) or in combination with liraglutide 3.0 mg.

Methods: The Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes (SCALE) IBT was a 56-week, randomized, double-blind, placebo-controlled, multicenter trial in individuals with obesity who received liraglutide 3.0 mg (n = 142) or placebo (n = 140) as an adjunct to IBT.

Results: At week 56, mean weight loss with liraglutide 3.0 mg plus IBT was 7.5% and 4.0% with placebo combined with IBT (estimated treatment difference [95% CI]-3.4% [-5.3% to -1.6%], P = 0.0003). Significantly more individuals on liraglutide 3.0 mg than placebo achieved ≥ 5% weight loss (61.5% vs. 38.8%; odds ratio [OR] 2.5% [1.5% to 4.1%], P = 0.0003), > 10% weight loss (30.5% vs. 19.8%; OR 1.8% [1.0% to 3.1%], P = 0.0469), and > 15% weight loss (18.1% vs. 8.9%; OR 2.3% [1.1% to 4.7%], P = 0.0311). Liraglutide 3.0 mg in combination with IBT was well tolerated, with no new safety signals identified.

Conclusions: In a primary care setting, Centers for Medicare and Medicaid Services-based IBT produced clinically meaningful weight loss at 56 weeks, enhanced by the addition of liraglutide 3.0 mg.
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http://dx.doi.org/10.1002/oby.22726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065111PMC
March 2020

Pro12Ala Ala carriers exhibit greater improvements in peripheral insulin sensitivity in response to 12 weeks of aerobic exercise training.

Physiol Genomics 2019 06 10;51(6):254-260. Epub 2019 May 10.

Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark.

The Ala allele of Pro12Ala ( rs1801282 ) is associated with greater improvements to the glucose metabolism in exercise studies, but whether this extends to peripheral insulin sensitivity is unknown. Our objective was to investigate the effect of Pro12Ala on exercise-induced changes in peripheral insulin sensitivity. A total of 124 (91 Pro homozygotes and 33 Ala carriers) previously physically inactive healthy young men and women with overweight or class 1 obesity who completed a 12 wk aerobic exercise intervention were included in the analysis. All participants underwent a hyperinsulinemic euglycemic clamp before and after the 12 wk intervention. The prescribed exercise frequency was 5-7 days/wk, and the exercise energy expenditure was 2,100 4,200 kcal/wk for men and 1,600 kcal/wk for women. Insulin sensitivity improved significantly in both genotype groups. However, Ala carriers had a 1.13-fold (95% confidence interval 1.01; 1.26, = 0.032) greater improvement in insulin sensitivity from baseline compared with Pro homozygotes. Our data support that Pro12Ala modifies the effect of aerobic exercise on peripheral insulin sensitivity.
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http://dx.doi.org/10.1152/physiolgenomics.00101.2018DOI Listing
June 2019

Gaps to bridge: Misalignment between perception, reality and actions in obesity.

Diabetes Obes Metab 2019 08 3;21(8):1914-1924. Epub 2019 May 3.

Department of Psychological Sciences, University of Liverpool, Liverpool, UK.

Aims: Despite increased recognition as a chronic disease, obesity remains greatly underdiagnosed and undertreated. We aimed to identify international perceptions, attitudes, behaviours and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs).

Materials And Methods: An online survey was conducted in 11 countries. Participants were adults with obesity and HCPs who were primarily concerned with direct patient care.

Results: A total of 14 502 PwO and 2785 HCPs completed the survey. Most PwO (68%) and HCPs (88%) agreed that obesity is a disease. However, 81% of PwO assumed complete responsibility for their own weight loss and only 44% of HCPs agreed that genetics were a barrier. There was a median of three (mean, six) years between the time PwO began struggling with excess weight or obesity and when they first discussed their weight with an HCP. Many PwO were concerned about the impact of excess weight on health (46%) and were motivated to lose weight (48%). Most PwO (68%) would like their HCP to initiate a conversation about weight and only 3% were offended by such a conversation. Among HCPs, belief that patients have little interest in or motivation for weight management may constitute a barrier for weight management conversations. When discussed, HCPs typically recommended lifestyle changes; however, more referrals and follow-up appointments are required.

Conclusions: Our international dataset reveals a need to increase understanding of obesity and improve education concerning its physiological basis and clinical management. Realization that PwO are motivated to lose weight offers an opportunity for HCPs to initiate earlier weight management conversations.
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http://dx.doi.org/10.1111/dom.13752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767048PMC
August 2019

Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction.

Nat Commun 2014 Mar 19;5:3485. Epub 2014 Mar 19.

1] Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA [2] Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.

We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonstrate that endotrophin plays a pivotal role in shaping a metabolically unfavourable microenvironment in adipose tissue during consumption of a high-fat diet (HFD). Endotrophin serves as a powerful co-stimulator of pathologically relevant pathways within the 'unhealthy' adipose tissue milieu, triggering fibrosis and inflammation and ultimately leading to enhanced insulin resistance. We further demonstrate that blocking endotrophin with a neutralizing antibody ameliorates metabolically adverse effects and effectively reverses metabolic dysfunction induced during HFD exposure. Collectively, our findings demonstrate that endotrophin exerts a major influence in adipose tissue, eventually resulting in systemic elevation of pro-inflammatory cytokines and insulin resistance, and the results establish endotrophin as a potential target in the context of metabolism and cancer.
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http://dx.doi.org/10.1038/ncomms4485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076823PMC
March 2014

Calibrated image-derived input functions for the determination of the metabolic uptake rate of glucose with [18F]-FDG PET.

Nucl Med Commun 2014 Apr;35(4):353-61

Departments of aClinical Physiology, Nuclear Medicine and PET bAnesthesiology, Rigshospitalet cDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen dDepartment of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark.

Purpose: We investigated the use of a simple calibration method to remove bias in previously proposed approaches to image-derived input functions (IDIFs) when used to calculate the metabolic uptake rate of glucose (K(m)) from dynamic [(18)F]-FDG PET scans of the thigh. Our objective was to obtain nonbiased, low-variance K(m) values without blood sampling.

Materials And Methods: We evaluated eight previously proposed IDIF methods. K(m) values derived from these IDIFs were compared with Km values calculated from the arterial blood samples (gold standard). We used linear regression to extract calibration parameters to remove bias. Following calibration, cross-validation and bootstrapping were used to estimate the mean square error and variance.

Results: Three of the previously proposed methods failed mainly because of zero-crossings of the IDIF. The remaining five methods were improved by calibration, yielding unbiased Km values. The method with the lowest SD yielded an SD of 0.0017/min--that is, below 10% of the muscle K(m) value in this study.

Conclusion: Previously proposed IDIF methods can be improved by using a simple calibration procedure. The calibration procedure may be used in other studies, thus obviating the need for arterial blood sampling, once the calibration parameters have been established in a subgroup of participants. The method has potential for use in other parts of the body as it is robust with regard to partial volume effects.
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http://dx.doi.org/10.1097/MNM.0000000000000063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940375PMC
April 2014

Appetite regulation in overweight, sedentary men after different amounts of endurance exercise: a randomized controlled trial.

J Appl Physiol (1985) 2013 Dec 19;115(11):1599-609. Epub 2013 Sep 19.

Departments of Biomedical Sciences and.

Weight loss induced by endurance exercise is often disappointing, possibly due to an increase in energy intake mediated through greater appetite. The aim of this study was to evaluate fasting, postprandial, and postexercise appetite regulation after an intervention prescribing two amounts of endurance exercise. Sixty-four sedentary, overweight, healthy young men were randomized to control (CON), moderate-dose (MOD: ≈ 30 min/day), or high-dose (HIGH: ≈ 60 min/day) endurance exercise for 12 wk. Along with subjective appetite ratings, plasma ghrelin, glucagon, insulin, peptide YY3-36, glucose, free fatty acids, and glycerol were measured during fasting and in relation to a breakfast meal and an acute bout of exercise, both at baseline and at follow-up. Ad libitum lunch energy intake was evaluated 3 h after the breakfast meal. Despite different amounts of endurance exercise, the subjects lost similar amounts of fat mass (MOD: 4.2 ± 0.5 kg; HIGH: 3.7 ± 0.5 kg). Fasting and postprandial insulin decreased ≈ 20% in both exercise groups (P < 0.03 vs. CON). Appetite measurements were not upregulated in the fasting and postprandial states. On the contrary, fasting and postprandial ratings of fullness and postprandial PYY3-36 increased in HIGH (P < 0.001 vs. CON). Ad libitum lunch energy intake remained unchanged over the course of the intervention. In both exercise groups, plasma ghrelin increased in relation to acute exercise after training. Thus neither moderate nor high doses of daily endurance exercise increased fasting and postprandial measures of appetite, but a high dose of exercise was associated with an increase in fasting and meal-related ratings of fullness and satiety.
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http://dx.doi.org/10.1152/japplphysiol.00680.2013DOI Listing
December 2013

Compliance with physical exercise: using a multidisciplinary approach within a dose-dependent exercise study of moderately overweight men.

Scand J Public Health 2014 Feb 16;42(1):38-44. Epub 2013 Sep 16.

1Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Aims: Sixty-one healthy, sedentary, moderately overweight young men participated in a randomised controlled trial to examine the effects of two different doses of endurance exercise on health behaviour and exercise compliance.

Methods: Participants were randomised to a sedentary control group, a moderate (MOD; 300 kcal/day) or a high-dose (HIGH; 600 kcal/day) endurance exercise group for 12 weeks. A sub-set of the subjects were interviewed using pre-determined, qualitative questions to elucidate physical activity and health behaviour. In combination with the Theory of Planned Behaviour (TPB), a post hoc thematic analysis was conducted to connect qualitative and quantitative data in a joint analysis.

Results: Of the subjects interviewed, exercise compliance expressed as 95% CI was [96.8; 103%] in the MOD group and [82.9; 99.6%] in the HIGH group. The different doses of daily exercise equally improved various metabolic health parameters. The MOD group was untroubled by the exercise load and had a positive attitude towards exercise. The HIGH group expressed increased fatigue, less positivity and perceived exercise as time-consuming. The MOD group described themselves as more energetic, and thereby may have increased physical activity levels in areas of their everyday lives that were not related to the intervention.

Conclusions: A multidisciplinary approach provided explanations for similar effects of two different doses of exercise. This could not have been determined via either qualitative or quantitative methodology alone. The preconditions of the TBP were fulfilled, and it represents a methodological model to explain the high degree of compliance and motivation to exercise.
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http://dx.doi.org/10.1177/1403494813504505DOI Listing
February 2014

Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men.

Am J Physiol Regul Integr Comp Physiol 2013 Sep 10;305(5):R490-8. Epub 2013 Jul 10.

Department of Biomedical Sciences, University of Copenhagen, Denmark.

Obese individuals are characterized by low circulating adiponectin concentrations and an increased number of macrophages in adipose tissue, which is believed to be causally associated with chronic low-grade inflammation and insulin resistance. Regular physical exercise decreases overall morbidity in obese subjects, which may be due to modulations of inflammatory pathways. In this randomized clinical trial we investigated the separate effects of endurance training-induced weight loss, diet-induced weight loss, and endurance training per se (without weight loss) on plasma adiponectin multimer composition (Western blotting) and adipose tissue macrophage content (immunohistochemistry) in young, moderately overweight men. Weight loss and endurance training per se decreased whole body fat percentage in an additive manner. No intervention-induced changes were observed for plasma total adiponectin. Surprisingly, endurance training, irrespectively of any associated weight loss, shifted the adiponectin multimer distribution toward a lower molecular weight (21% decrease in HMW/LMW, P = 0.015), whereas diet-induced weight loss shifted the distribution toward a higher molecular weight (42% increase in HMW/MMW, P < 0.001). Furthermore, endurance training per se increased the number of anti-inflammatory CD163⁺ macrophages [from 12.7 ± 2.1 (means ± SE) to 16.1 ± 3.1 CD163⁺ cells/100 adipocytes, P = 0.013], whereas diet-induced weight loss tended to decrease CD68⁺ macrophages in subcutaneous abdominal adipose tissue. Thus regular physical exercise influences systemic and adipose tissue inflammatory pathways differently than diet-induced weight loss in younger, moderately overweight men. Our data suggest that some of the health benefits of a physically active lifestyle may occur through modulations of anti- rather than pro-inflammatory pathways in young, overweight men.
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http://dx.doi.org/10.1152/ajpregu.00575.2012DOI Listing
September 2013

Body fat loss and compensatory mechanisms in response to different doses of aerobic exercise--a randomized controlled trial in overweight sedentary males.

Am J Physiol Regul Integr Comp Physiol 2012 Sep 1;303(6):R571-9. Epub 2012 Aug 1.

Department of Biomedical Sciences, University of Copenhagen, Denmark.

The amount of weight loss induced by exercise is often disappointing. A diet-induced negative energy balance triggers compensatory mechanisms, e.g., lower metabolic rate and increased appetite. However, knowledge about potential compensatory mechanisms triggered by increased aerobic exercise is limited. A randomized controlled trial was performed in healthy, sedentary, moderately overweight young men to examine the effects of increasing doses of aerobic exercise on body composition, accumulated energy balance, and the degree of compensation. Eighteen participants were randomized to a continuous sedentary control group, 21 to a moderate-exercise (MOD; 300 kcal/day), and 22 to a high-exercise (HIGH; 600 kcal/day) group for 13 wk, corresponding to ∼30 and 60 min of daily aerobic exercise, respectively. Body weight (MOD: -3.6 kg, P < 0.001; HIGH: -2.7 kg, P = 0.01) and fat mass (MOD: -4.0 kg, P < 0.001 and HIGH: -3.8 kg, P < 0.001) decreased similarly in both exercise groups. Although the exercise-induced energy expenditure in HIGH was twice that of MOD, the resulting accumulated energy balance, calculated from changes in body composition, was not different (MOD: -39.6 Mcal, HIGH: -34.3 Mcal, not significant). Energy balance was 83% more negative than expected in MOD, while it was 20% less negative than expected in HIGH. No statistically significant changes were found in energy intake or nonexercise physical activity that could explain the different compensatory responses associated with 30 vs. 60 min of daily aerobic exercise. In conclusion, a similar body fat loss was obtained regardless of exercise dose. A moderate dose of exercise induced a markedly greater than expected negative energy balance, while a higher dose induced a small but quantifiable degree of compensation.
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http://dx.doi.org/10.1152/ajpregu.00141.2012DOI Listing
September 2012

Endurance training per se increases metabolic health in young, moderately overweight men.

Obesity (Silver Spring) 2012 Nov 22;20(11):2202-12. Epub 2012 Mar 22.

Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

Health benefits of physical activity may depend on a concomitant weight loss. In a randomized, controlled trial, we compared the effects of endurance training with or without weight loss to the effect of weight loss induced by an energy-reduced diet in 48 sedentary, moderately overweight men who completed a 12-week intervention program of training (T), energy-reduced diet (D), training and increased diet (T-iD), or control (C). An energy deficit of 600 kcal/day was induced by endurance training or diet in T and D and a similar training regimen plus an increased dietary intake of 600 kcal/day defined the T-iD group. Primary end point was insulin sensitivity as evaluated by HOMA-IR (mainly reflecting hepatic insulin sensitivity) and hyperinsulinemic, isoglycemic clamps (primarily reflecting peripheral insulin sensitivity). Body mass decreased in T and D by 5.9 ± 0.7 and 5.3 ± 0.7 kg, respectively, whereas T-iD and C remained weight stable. Total and abdominal fat mass were reduced in an additive manner in the T-iD, D, and T groups by 1.9 ± 0.3/0.2 ± 0.1, 4.4 ± 0.7/0.5 ± 0.1, and 7.7 ± 0.8/0.9 ± 0.1 kg, respectively. HOMA-IR was improved in T, D, and T-iD, whereas insulin-stimulated glucose clearance and suppression of plasma nonesterified fatty acids (NEFAs) were increased only in the two training groups. Thus, loss of fat mass (diet or training induced) improves hepatic insulin sensitivity, whereas peripheral insulin sensitivity in skeletal muscle and adipose tissue is increased by endurance training only. This demonstrates that endurance training per se increases various metabolic health parameters and that endurance training should preferably always be included in any intervention regimen for improving metabolic health in moderately overweight men.
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http://dx.doi.org/10.1038/oby.2012.70DOI Listing
November 2012
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