Publications by authors named "Mathias Ried-Larsen"

73 Publications

Impact of intensive lifestyle intervention on gut microbiota composition in type 2 diabetes: a analysis of a randomized clinical trial.

Gut Microbes 2022 Jan-Dec;14(1):2005407

Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Type 2 diabetes (T2D) management is based on combined pharmacological and lifestyle intervention approaches. While their clinical benefits are well studied, less is known about their effects on the gut microbiota. We aimed to investigate if an intensive lifestyle intervention combined with conventional standard care leads to a different gut microbiota composition compared to standard care alone treatment in individuals with T2D, and if gut microbiota is associated with the clinical benefits of the treatments. Ninety-eight individuals with T2D were randomized to either an intensive lifestyle intervention combined with standard care group (N = 64), or standard care alone group (N = 34) for 12 months. All individuals received standardized, blinded, target-driven medical therapy, and individual counseling. The lifestyle intervention group moreover received intensified physical training and dietary plans. Clinical characteristics and fecal samples were collected at baseline, 3-, 6-, 9-, and 12-month follow-up. The gut microbiota was profiled with 16S rRNA gene amplicon sequencing. There were no statistical differences in the change of gut microbiota composition between treatments after 12 months, except minor and transient differences at month 3. The shift in gut microbiota alpha diversity at all time windows did not correlate with the change in clinical characteristics, and the gut microbiota did not mediate the treatment effect on clinical characteristics. The clinical benefits of intensive lifestyle and/or pharmacological interventions in T2D are unlikely to be explained by, or causally related to, changes in the gut microbiota composition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/19490976.2021.2005407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8726663PMC
December 2021

": Understanding (dis)engagement in Physical Activity Among Individuals With Type 2 Diabetes Using a Practice Theory Approach.

Qual Health Res 2021 Dec 29:10497323211064598. Epub 2021 Dec 29.

Centre for Applied Research in Mental Health Care (CARMEN), Mental Health Centre Glostrup, Copenhagen University Hospital, Copenhagen, Denmark.

Lack of physical activity (PA) is common among individuals with type 2 diabetes (T2D). We apply a practice theory approach to investigate PA engagement in the context of T2D. Data were collected through semi-structured individual interviews ( = 23) and focus groups ( = 3x6) and analyzed by deductive-inductive reflexive thematic analysis using a practice theory framework. Forty-one purposefully selected individuals with T2D (29 men) between the ages of 54 and 77 years were included. The analysis resulted in three main themes informed by five subthemes, reflecting the key elements of practice theory (i.e., meanings, materialities, and competencies). One overarching theme identified PA engagement as an unsustainable and insurmountable project in constant and unequal competition with the practice of physical inactivity. To increase PA among individuals with T2D, future PA interventions and strategies should aim to establish a stronger link between PA and everyday life practices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/10497323211064598DOI Listing
December 2021

Protective potential of high-intensity interval training on cardiac structure and function after COVID-19: protocol and statistical analysis plan for an investigator-blinded randomised controlled trial.

BMJ Open 2021 11 18;11(11):e048281. Epub 2021 Nov 18.

Centre for Physical Activity Research (CFAS), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

Introduction: COVID-19 is associated with a marked systemic inflammatory response with concomitant cardiac injury and remodelling, but it is currently unknown whether the latter is reversible. Given that high-intensity interval training (HIIT) is a powerful stimulus to improve cardiorespiratory fitness while also eliciting marked anti-inflammatory effects, it may be an important countermeasure of reducing cardiopulmonary morbidity following COVID-19.

Methods And Analysis: 40 COVID-19 survivors who have been discharged from hospital will be included in this investigator-blinded randomised study with a 12-week HIIT intervention. Patients will be 1:1 block-randomised by sex to either a supervised HIIT exercise group or standard care (control group). The main hypothesis is that a 12-week HIIT scheme is a safe way to improve loss of cardiac mass and associated cardiorespiratory fitness, despite hypothesised limited HIIT-induced changes in conventional lung function indices per se. Ultimately, we hypothesise that the HIIT scheme will reduce post-COVID-19 symptoms and improve quality of life.

Ethics And Dissemination: This study is approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-20033733, including amendments 75068 and 75799) and registered at ClinicalTrials.gov (NCT04647734, pre-results). The findings will be published in a peer-reviewed journal, including cases of positive, negative and inconclusive results. NCT04549337.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-048281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602927PMC
November 2021

Association of Cycling With All-Cause and Cardiovascular Disease Mortality Among Persons With Diabetes-Reply.

JAMA Intern Med 2021 12;181(12):1678-1679

Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamainternmed.2021.6272DOI Listing
December 2021

Discordance Between Glucose Levels Measured in Interstitial Fluid in Venous Plasma After Oral Glucose Administration: A Analysis From the Randomised Controlled PRE-D Trial.

Front Endocrinol (Lausanne) 2021 5;12:753810. Epub 2021 Oct 5.

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Aims: The oral glucose tolerance test (OGTT) is together with haemoglobin A (HbA) gold standard for diagnosing prediabetes and diabetes. The objective of this study was to assess the concordance between glucose values obtained from venous plasma versus interstitial fluid after oral glucose administration in 120 individuals with prediabetes and overweight/obesity.

Methods: 120 adults with prediabetes defined by HbA 39-47 mmol/mol and overweight or obesity who participated in the randomised controlled PRE-D trial were included in the study. Venous plasma glucose concentrations were measured at 0, 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT) performed on three different occasions within a 26 weeks period. During the OGTT, the participants wore a CGM device (IPro2, Medtronic), which assessed glucose concentrations every five minutes.

Results: A total of 306 OGTTs with simultaneous CGM measurements were obtained. Except in fasting, the CGM glucose values were below the OGTT values throughout the OGTT period with mean (SD) differences of 0.2 (0.7) mmol/L at time 0 min, -1.1 (1.3) at 30 min, -1.4 (1.8) at 60 min, and -0.5 (1.1) at 120 min). For measurements at 0 and 120 min, there was a proportional bias with an increasing mean difference between CGM and OGTT values with increasing mean of the two measurements.

Conclusions: Due to poor agreement between the OGTT and CGM with wide 95% limits of agreement and proportional bias at 0 and 120 min, the potential for assessing glucose tolerance in prediabetes using CGM is questionable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.753810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525890PMC
October 2021

Fidelity, tolerability and safety of acute high-intensity interval training after hospitalisation for COVID-19: a randomised cross-over trial.

BMJ Open Sport Exerc Med 2021 1;7(3):e001156. Epub 2021 Sep 1.

Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark.

Objectives: Many patients with COVID-19 suffer from persistent symptoms, many of which may potentially be reversed by high-intensity interval training (HIIT). Yet, the safety and tolerability of HIIT after COVID-19 is controversial. This study aimed to investigate the fidelity, tolerability and safety of three different HIIT protocols in individuals that had recently been hospitalised due to COVID-19.

Methods: The study was a randomised cross-over trial. We compared three supervised HIIT protocols (4×4, 6×1, 10-20-30) in 10 individuals recently discharged after hospitalisation for severe COVID-19. Each HIIT protocol had a duration of 38 min and was performed with a 1-week washout between them. Outcomes included adverse events, exercise training intensity and tolerability assessed by the Likert scale (1-10).

Results: All 10 participants aged 61 (mean, SD 8) years (5 males) completed all three HIIT protocols with no adverse events. High intensities were achieved in all three protocols, although they differed in terms of time spent with a heart rate ≥85% of maximum (mean (SD); 4×4: 13.7 (6.4) min; 10-20-30: 12.1 (3.8) min; 6×1: 6.1 (5.6) min; p=0.03). The three protocols were all well tolerated with similar Likert scale scores (mean (SD); 4×4: 8 (2), 10-20-30: 8 (2), 6×1: 9 (2), p=0.72).

Conclusion: Our findings indicate that recently hospitalised individuals for severe COVID-19 may safely tolerate acute bouts of supervised HIIT as per protocol. This warrants future studies testing the potential of regular HIIT as a rehabilitation strategy in this context.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjsem-2021-001156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413475PMC
September 2021

Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial.

Med Sci Sports Exerc 2022 Jan;54(1):38-46

The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, DENMARK.

Introduction/purpose: The increased risk of fractures with type 2 diabetes (T2D) is suggested to be caused by decreased bone turnover. Current international guidelines recommend lifestyle modifications, including exercise, as first-line treatment for T2D. The aim of this study was to investigate the effects of an exercise-based lifestyle intervention on bone turnover and bone mineral density (BMD) in persons with T2D.

Methods: Persons with T2D were randomized to either a 12-month lifestyle intervention (n = 64) or standard care (n = 34). The lifestyle intervention included five to six weekly aerobic training sessions, half of them combined with resistance training. Serum markers of bone turnover (osteocalcin, N-terminal propeptide of type-I procollagen, reflecting bone formation, and carboxyterminal collagen I crosslinks, reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up.

Results: From baseline to follow-up, s-propeptide of type-I procollagen increased by 34% (95% confidence interval [CI], 17%-50%), serum-carboxyterminal collagen I crosslink by 36% (95% CI, 1%-71%), and s-osteocalcin by 31% (95% CI, 11-51%) more in the lifestyle intervention group compared with standard care. Loss of weight and fat mass were the strongest mediators of the increased bone turnover. Bone mineral density was unaffected by the intervention (ΔBMD, 0.1%; 95% CI, -1.1% to 1.2%).

Conclusions: A 12-month intensive exercise-based lifestyle intervention led to a substantial but balanced increase in bone turnover in persons with T2D. The increased bone turnover combined with a preserved BMD, despite a considerable weight loss, is likely to reflect improved bone health and warrants further studies addressing the impact of exercise on risk of fractures in persons with T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1249/MSS.0000000000002776DOI Listing
January 2022

Association of Cycling With All-Cause and Cardiovascular Disease Mortality Among Persons With Diabetes: The European Prospective Investigation Into Cancer and Nutrition (EPIC) Study.

JAMA Intern Med 2021 09;181(9):1196-1205

University of Southern Denmark, Odense, Denmark.

Importance: Premature death from all causes and cardiovascular disease (CVD) causes is higher among persons with diabetes.

Objective: To investigate the association between time spent cycling and all-cause and CVD mortality among persons with diabetes, as well as to evaluate the association between change in time spent cycling and risk of all-cause and CVD mortality.

Design, Setting, And Participants: This prospective cohort study included 7459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition study. Questionnaires regarding medical history, sociodemographic, and lifestyle information were administered in 10 Western European countries from 1992 through 2000 (baseline examination) and at a second examination 5 years after baseline. A total of 5423 participants with diabetes completed both examinations. The final updated primary analysis was conducted on November 13, 2020.

Exposures: The primary exposure was self-reported time spent cycling per week at the baseline examination. The secondary exposure was change in cycling status from baseline to the second examination.

Main Outcomes And Measures: The primary and secondary outcomes were all-cause and CVD mortality, respectively, adjusted for other physical activity modalities, diabetes duration, and sociodemographic and lifestyle factors.

Results: Of the 7459 adults with diabetes included in the analysis, the mean (SD) age was 55.9 (7.7) years, and 3924 (52.6%) were female. During 110 944 person-years of follow-up, 1673 deaths from all causes were registered. Compared with the reference group of people who reported no cycling at baseline (0 min/wk), the multivariable-adjusted hazard ratios for all-cause mortality were 0.78 (95% CI, 0.61-0.99), 0.76 (95% CI, 0.65-0.88), 0.68 (95% CI, 0.57-0.82), and 0.76 (95% CI, 0.63-0.91) for cycling 1 to 59, 60 to 149, 150 to 299, and 300 or more min/wk, respectively. In an analysis of change in time spent cycling with 57 802 person-years of follow-up, a total of 975 deaths from all causes were recorded. Compared with people who reported no cycling at both examinations, the multivariable-adjusted hazard ratios for all-cause mortality were 0.90 (95% CI, 0.71-1.14) in those who cycled and then stopped, 0.65 (95% CI, 0.46-0.92) in initial noncyclists who started cycling, and 0.65 (95% CI, 0.53-0.80) for people who reported cycling at both examinations. Similar results were observed for CVD mortality.

Conclusion And Relevance: In this cohort study, cycling was associated with lower all-cause and CVD mortality risk among people with diabetes independent of practicing other types of physical activity. Participants who took up cycling between the baseline and second examination had a considerably lower risk of both all-cause and CVD mortality compared with consistent noncyclists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamainternmed.2021.3836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290339PMC
September 2021

The effects of different doses of exercise on pancreatic β-cell function in patients with newly diagnosed type 2 diabetes: study protocol for and rationale behind the "DOSE-EX" multi-arm parallel-group randomised clinical trial.

Trials 2021 Apr 1;22(1):244. Epub 2021 Apr 1.

Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Background: Lifestyle intervention, i.e. diet and physical activity, forms the basis for care of type 2 diabetes (T2D). The current physical activity recommendation for T2D is aerobic training for 150 min/week of moderate to vigorous intensity, supplemented with resistance training 2-3 days/week, with no more than two consecutive days without physical activity. The rationale for the recommendations is based on studies showing a reduction in glycated haemoglobin (HbA1c). This reduction is supposed to be caused by increased insulin sensitivity in muscle and adipose tissue, whereas knowledge about effects on abnormalities in the liver and pancreas are scarce, with the majority of evidence stemming from in vitro and animal studies. The aim of this study is to investigate the role of the volume of exercise training as an adjunct to dietary therapy in order to improve the pancreatic β-cell function in T2D patients less than 7 years from diagnosis. The objective of this protocol for the DOSE-EX trial is to describe the scientific rationale in detail and to provide explicit information about study procedures and planned analyses.

Methods/design: In a parallel-group, 4-arm assessor-blinded randomised clinical trial, 80 patients with T2D will be randomly allocated (1:1:1:1, stratified by sex) to 16 weeks in either of the following groups: (1) no intervention (CON), (2) dietary intervention (DCON), (3) dietary intervention and supervised moderate volume exercise (MED), or (4) dietary intervention and supervised high volume exercise (HED). Enrolment was initiated December 15th, 2018, and will continue until N = 80 or December 1st, 2021. Primary outcome is pancreatic beta-cell function assessed as change in late-phase disposition index (DI) from baseline to follow-up assessed by hyperglycaemic clamp. Secondary outcomes include measures of cardiometabolic risk factors and the effect on subsequent complications related to T2D. The study was approved by The Scientific Ethical Committee at the Capital Region of Denmark (H-18038298).

Trial Registration: The Effects of Different Doses of Exercise on Pancreatic β-cell Function in Patients With Newly Diagnosed Type 2 Diabetes (DOSE-EX), NCT03769883, registered 10 December 2018 https://clinicaltrials.gov/ct2/show/NCT03769883 ). Any modification to the protocol, study design, and changes in written participant information will be approved by The Scientific Ethical Committee at the Capital Region of Denmark before effectuation.

Discussion: The data from this study will add knowledge to which volume of exercise training in combination with a dietary intervention is needed to improve β-cell function in T2D. Secondarily, our results will elucidate mechanisms of physical activity mitigating the development of micro- and macrovascular complications correlated with T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-021-05207-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017660PMC
April 2021

A systematic review of adherence to physical activity interventions in individuals with type 2 diabetes.

Diabetes Metab Res Rev 2021 Nov 26;37(8):e3444. Epub 2021 Mar 26.

Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Lifestyle interventions are pivotal for successful management of type 2 diabetes (T2D), however, the proportion of people with T2D adhering to physical activity advice has not been thoroughly studied. The purpose of this systematic review was to summarise the evidence on adherence to exercise or physical activity components in lifestyle interventions in those with T2D. We searched MEDLINE EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus on 12 November 2019. Eligible studies enrolled adults with T2D and reported the proportion of adherence to lifestyle interventions as a primary or secondary outcome. We included 11 studies (nine randomised controlled trials (RCTs) enrolling 1717 patients and two nonrandomised studies enrolling 62 patients). Only one of the studies had low risk of bias. The proportion of participants adhering to physical activity varied from 32% to 100% with a median of 58%. Adherence was higher in interventions using supervised training and lowest in interventions using remote coaching and the adherence rate in observational studies was higher compared to RCTs (92% vs. 55%; p < 0.01). Study duration, risk of bias, or participants' sex, were not associated with adherence to physical activity. The proportion of those with T2D adhering to physical activity interventions for T2D varies widely and most of the included studies had a high risk of bias. These findings have important implications for planning and power analysis of future trials and when counselling patients about lifestyle interventions including physical activity or exercise components.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dmrr.3444DOI Listing
November 2021

One-year intensive lifestyle intervention and improvements in health-related quality of life and mental health in persons with type 2 diabetes: a secondary analysis of the U-TURN randomized controlled trial.

BMJ Open Diabetes Res Care 2021 01;9(1)

Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Introduction: The effects of lifestyle interventions in persons with type 2 diabetes (T2D) on health-related quality of life (HRQoL) and subjective well-being are ambiguous, and no studies have explored the effect of exercise interventions that meet or exceed current recommended exercise levels. We investigated whether a 1-year intensive lifestyle intervention is superior in improving HRQoL compared with standard care in T2D persons.

Research Design And Methods: We performed secondary analyses of a previously conducted randomized controlled trial (April 2015 to August 2016). Persons with non-insulin-dependent T2D (duration ≤10 years) were randomized to 1-year supervised exercise and individualized dietary counseling (ie, 'U-TURN'), or standard care. The primary HRQoL outcome was change in the 36-item Short Form Health Survey (SF-36) physical component score (PCS) from baseline to 12 months of follow-up, and a key secondary outcome was changes in the SF-36 mental component score (MCS).

Results: We included 98 participants (U-TURN group=64, standard care group=34) with a mean age of 54.6 years (SD 8.9). Between-group analyses at 12-month follow-up showed SF-36 PCS change of 0.8 (95% CI -0.7 to 2.3) in the U-TURN group and deterioration of 2.4 (95% CI -4.6 to -0.1) in the standard care group (difference of 3.2, 95% CI 0.5 to 5.9, p=0.02) while no changes were detected in SF-36 MCS. At 12 months, 19 participants (30%) in the U-TURN group and 6 participants (18%) in the standard care group achieved clinically significant improvement in SF-36 PCS score (adjusted risk ratio 2.6, 95% CI 1.0 to 4.5 corresponding to number needed to treat of 4, 95% CI 1.6 to infinite).

Conclusion: In persons with T2D diagnosed for less than 10 years, intensive lifestyle intervention improved the physical component of HRQoL, but not the mental component of HRQoL after 1 year, compared with standard care.

Trial Registration Number: NCT02417012.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjdrc-2020-001840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812095PMC
January 2021

No effects of dapagliflozin, metformin or exercise on plasma glucagon concentrations in individuals with prediabetes: A post hoc analysis from the randomized controlled PRE-D trial.

Diabetes Obes Metab 2021 02 18;23(2):530-539. Epub 2020 Nov 18.

Steno Diabetes Center Copenhagen, Copenhagen, Denmark.

Aim: To assess the effects of dapagliflozin, metformin and exercise treatment on changes in plasma glucagon concentrations in individuals with overweight and HbA1c-defined prediabetes.

Materials And Methods: One-hundred and twenty individuals with overweight (body mass index ≥ 25 kg/m ) and prediabetes (HbA1c of 39-47 mmol/mol) were randomized to a 13-week intervention with dapagliflozin (10 mg once daily), metformin (850 mg twice daily), exercise (30 minutes of interval training 5 days per week) or control (habitual living). A 75-g oral glucose tolerance test (OGTT) (0, 30, 60 and 120 minutes) was administered at baseline, at 13 weeks (end of intervention) and at 26 weeks (end of follow-up). Linear mixed effects models with participant-specific random intercepts were used to investigate associations of the interventions with fasting plasma glucagon concentration, insulin/glucagon ratio and glucagon suppression during the OGTT.

Results: At baseline, the median (Q1; Q3) age was 62 (54; 68) years, median fasting plasma glucagon concentration was 11 (7; 15) pmol/L, mean (SD) HbA1c was 40.9 (2.3) mmol/mol and 56% were women. Compared with the control group, fasting glucagon did not change in any of the groups from baseline to the end of the intervention (dapagliflozin group: -5% [95% CI: -29; 26]; exercise group: -8% [95% CI: -31; 24]; metformin group: -2% [95% CI: -27; 30]). Likewise, there were no differences in insulin/glucagon ratio and glucagon suppression during the OGTT between the groups.

Conclusions: In individuals with prediabetes, 13 weeks of treatment with dapagliflozin, metformin or exercise was not associated with changes in fasting or post-OGTT glucagon concentrations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.14246DOI Listing
February 2021

The effects of dapagliflozin, metformin or exercise on glycaemic variability in overweight or obese individuals with prediabetes (the PRE-D Trial): a multi-arm, randomised, controlled trial.

Diabetologia 2021 01 16;64(1):42-55. Epub 2020 Oct 16.

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Aims/hypothesis: We aimed to investigate the short-term efficacy and safety of three glucose-lowering interventions in overweight or obese individuals with prediabetes defined by HbA.

Methods: The PRE-D Trial was a randomised, controlled, parallel, multi-arm, open-label, non-blinded trial performed at Steno Diabetes Center Copenhagen, Gentofte, Denmark. One hundred and twenty participants with BMI ≥25 kg/m, 30-70 years of age, and prediabetes (HbA 39-47 mmol/mol [5.7-6.4%]) were randomised 1:1:1:1 to dapagliflozin (10 mg once daily), metformin (1700 mg daily), interval-based exercise (5 days/week, 30 min/session) or control (habitual lifestyle). Participants were examined at baseline and at 6, 13 and 26 weeks after randomisation. The primary outcome was the 13 week change in glycaemic variability (calculated as mean amplitude of glycaemic excursions [MAGE]) determined using a continuous glucose monitoring system (pre-specified minimal clinically important difference in MAGE ∼30%).

Results: One hundred and twelve participants attended the examination at 13 weeks and 111 attended the follow-up visit at 26 weeks. Compared with the control group, there was a small decrease in MAGE in the dapagliflozin group (17.1% [95% CI 0.7, 30.8], p = 0.042) and a small, non-significant, reduction in the exercise group (15.3% [95% CI -1.2, 29.1], p = 0.067), whereas MAGE was unchanged in the metformin group (0.1% [95% CI -16.1, 19.4], p = 0.991)). Compared with the metformin group, MAGE was 17.2% (95% CI 0.8, 30.9; p = 0.041) lower in the dapagliflozin group and 15.4% (95% CI -1.1, 29.1; p = 0.065) lower in the exercise group after 13 weeks, with no difference between exercise and dapagliflozin (2.2% [95% CI -14.8, 22.5], p = 0.815). One serious adverse event occurred in the control group (lung cancer).

Conclusions/interpretation: Treatment with dapagliflozin and interval-based exercise lead to similar but small improvements in glycaemic variability compared with control and metformin therapy. The clinical importance of these findings in prediabetes is uncertain.

Trial Registration: ClinicalTrials.gov NCT02695810 FUNDING: The study was funded by the Novo Nordisk Foundation, AstraZeneca AB, the Danish Innovation Foundation, the University of Copenhagen and Ascensia Diabetes Care Denmark ApS Graphical abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-020-05306-1DOI Listing
January 2021

The multivariate physical activity signature associated with metabolic health in children and youth: An International Children's Accelerometry Database (ICAD) analysis.

Prev Med 2020 12 3;141:106266. Epub 2020 Oct 3.

Department of Sport, Food and Natural Sciences, Faculty of Education, Arts and Sports, Western Norway University of Applied Sciences, Sogndal, Norway. Electronic address:

There is solid evidence for an association between physical activity and metabolic health outcomes in children and youth, but for methodological reasons most studies describe the intensity spectrum using only a few summary measures. We aimed to determine the multivariate physical activity intensity signature associated with metabolic health in a large and diverse sample of children and youth, by investigating the association pattern for the entire physical intensity spectrum. We used pooled data from 11 studies and 11,853 participants aged 5.8-18.4 years included in the International Children's Accelerometry Database. We derived 14 accelerometry-derived (ActiGraph) physical activity variables covering the intensity spectrum (from 0-99 to ≥8000 counts per minute). To handle the multicollinearity among these variables, we used multivariate pattern analysis to establish the associations with indices of metabolic health (abdominal fatness, insulin sensitivity, lipid metabolism, blood pressure). A composite metabolic health score was used as the main outcome variable. Associations with the composite metabolic health score were weak for sedentary time and light physical activity, but gradually strengthened with increasing time spent in moderate and vigorous intensities (up to 4000-5000 counts per minute). Association patterns were fairly consistent across sex and age groups, but varied across different metabolic health outcomes. This novel analytic approach suggests that vigorous intensity, rather than less intense activities or sedentary behavior, are related to metabolic health in children and youth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ypmed.2020.106266DOI Listing
December 2020

The interaction between metformin and physical activity on postprandial glucose and glucose kinetics: a randomised, clinical trial.

Diabetologia 2021 02 26;64(2):397-409. Epub 2020 Sep 26.

Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Aims/hypothesis: The aim of this parallel-group, double-blinded (study personnel and participants), randomised clinical trial was to assess the interaction between metformin and exercise training on postprandial glucose in glucose-intolerant individuals.

Methods: Glucose-intolerant (2 h OGTT glucose of 7.8-11.0 mmol/l and/or HbA of 39-47 mmol/mol [5.7-6.5%] or glucose-lowering-medication naive type 2 diabetes), overweight/obese (BMI 25-42 kg/m) individuals were randomly allocated to a placebo study group (PLA, n = 15) or a metformin study group (MET, n = 14), and underwent 3 experimental days: BASELINE (before randomisation), MEDICATION (after 3 weeks of metformin [2 g/day] or placebo treatment) and TRAINING (after 12 weeks of exercise training in combination with metformin/placebo treatment). Training consisted of supervised bicycle interval sessions with a mean intensity of 64% of Watt for 45 min, 4 times/week. The primary outcome was postprandial glucose (mean glucose concentration) during a mixed meal tolerance test (MMTT), which was assessed on each experimental day. For within-group differences, a group × time interaction was assessed using two-way repeated measures ANOVA. Between-group changes of the outcomes at different timepoints were compared using unpaired two-tailed Student's t tests.

Results: Postprandial glucose improved from BASELINE to TRAINING in both the PLA group and the MET group (∆PLA: -0.7 [95% CI -1.4, 0.0] mmol/l, p = 0.05 and ∆MET: -0.7 [-1.5, -0.0] mmol/l, p = 0.03), with no between-group difference (p = 0.92). In PLA, the entire reduction was seen from MEDICATION to TRAINING (-0.8 [-1.3, -0.1] mmol/l, p = 0.01). Conversely, in MET, the entire reduction was observed from BASELINE to MEDICATION (-0.9 [-1.6, -0.2] mmol/l, p = 0.01). The reductions in mean glucose concentration during the MMTT from BASELINE to TRAINING were dependent on differential time effects: in the PLA group, a decrease was observed at timepoint (t) = 120 min (p = 0.009), whereas in the MET group, a reduction occurred at t = 30 min (p < 0.001). V̇O increased 15% (4.6 [3.3, 5.9] ml kg min, p < 0.0001) from MEDICATION to TRAINING and body weight decreased (-4.0 [-5.2, -2.7] kg, p < 0.0001) from BASELINE to TRAINING, with no between-group differences (p = 0.7 and p = 0.5, respectively).

Conclusions/interpretation: Metformin plus exercise training was not superior to exercise training alone in improving postprandial glucose. The differential time effects during the MMTT suggest an interaction between the two modalities.

Funding: The Beckett foundation, A.P Møller Foundation, DDA, the Research Foundation of Rigshospitalet and Trygfonden.

Trial Registration: ClinicalTrials.gov (NCT03316690). Graphical abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-020-05282-6DOI Listing
February 2021

Health Technology Readiness Profiles Among Danish Individuals With Type 2 Diabetes: Cross-Sectional Study.

J Med Internet Res 2020 09 15;22(9):e21195. Epub 2020 Sep 15.

Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Background: Information technologies (IT) are increasingly implemented in type 2 diabetes (T2D) treatment as a resource for remotely supported health care. However, possible pitfalls of introducing IT in health care are generally overlooked. Specifically, the effectiveness of IT to improve health care may depend on the user's readiness for health technology.

Objective: We aim to investigate readiness for health technology in relation to mental well-being, sociodemographic, and disease-related characteristics among individuals with T2D.

Methods: Individuals with T2D (aged ≥18 years) who had been referred to self-management education, exercise, diet counseling, smoking cessation, or alcohol counseling completed a questionnaire survey covering (1) background information, (2) the 5-item World Health Organization Well-Being Index (WHO-5), (3) receptiveness to IT use in physical activity, and (4) the Readiness and Enablement Index for Health Technology (READHY), constituted by dimensions related to self-management, social support, and eHealth literacy. Individuals were divided into profiles using cluster analysis based on their READHY scores. Outcomes included differences across profiles in mental well-being, sociodemographic, and disease-related characteristics.

Results: Participants in the study were 155 individuals with T2D with a mean age of 60.2 (SD 10.7) years, 55.5% (86/155) of which were men and 44.5% (69/155) of which were women. Participants were stratified into 5 health technology readiness profiles based on the cluster analysis: Profile 1, high health technology readiness; Profile 2, medium health technology readiness; Profile 3, medium health technology readiness and high level of emotional distress; Profile 4, medium health technology readiness and low-to-medium eHealth literacy; Profile 5, low health technology readiness. No differences in sociodemographic and disease-related characteristics were observed across profiles; however, we identified 3 vulnerable subgroups of individuals: Profile 3 (21/155, 13.5%), younger individuals (mean age of 53.4 years, SD 8.9 years) with low mental well-being (mean 42.7, SD 14.7) and emotional distress (mean 1.69, SD 0.38); Profile 4 (20/155, 12.9%), older individuals (mean age 66.3 years, SD 9.0 years) with less IT use (50.0% used IT for communication) and low-to-medium eHealth literacy; and Profile 5 (36/155, 23.2%) with low mental well-being (mean 43.4, SD 20.1) and low readiness for health technology.

Conclusions: Implementation of IT in health care of individuals with T2D should be based on comprehensive consideration of mental well-being, emotional distress, and readiness for health technology rather than sociodemographic and disease-related characteristics to identify the individuals in need of social support, self-management education, and extensive IT support. A one-size-fits-all approach to IT implementation in health care will potentially increase the risk of treatment failure among the most vulnerable individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/21195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525399PMC
September 2020

The Impact of Physical Activity on Glycemic Variability Assessed by Continuous Glucose Monitoring in Patients With Type 2 Diabetes Mellitus: A Systematic Review.

Front Endocrinol (Lausanne) 2020 31;11:486. Epub 2020 Jul 31.

Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Patients with Type 2 Diabetes Mellitus (T2DM) have increased risk of developing vascular complications due to chronic hyperglycemia. Glycemic variability (GV) has been suggested to play an even more important role in the risk of developing diabetic complications than sustained hyperglycemia. Physical activity (PA) has shown reducing effects on mean plasma glucose; however, the effect on GV in T2DM needs further description. The objective of this review is to evaluate the effect of PA on GV, assessed by continuous glucose monitoring (CGM) in people with T2DM. A systematic literature search was conducted on MEDLINE and Embase to find randomized controlled trials (RCTs) covering the aspects T2DM, PA, and CGM. Following eligibility screening, variables of population characteristics, PA interventions, and GV outcomes were extracted and processed through qualitative synthesis. Risk of bias (ROB) was assessed using Cochrane ROB tool v2.0. Of 1,825 identified articles, 40 full texts were screened. In the ten included RCTs matching the eligibility criteria, sample sizes ranged from nine to 63, mean age from 51 (SD 11) to 65 (SD 2) years and mean T2DM duration from four (SD 3) to ten (SD 6) years. Eight RCTs examined GV following single bouts of exercise, while two RCTs examined GV following training interventions. One RCT applied parallel group design, while nine RCTs applied crossover design. Numeric reductions in GV following acute exercise were seen, with four RCTs reaching statistical significance. Numeric reductions in GV were seen following training interventions, with one RCT reaching statistical significance. Numeric reductions of GV after PA appeared independently of intensity and T2DM progression but higher in participants with high baseline HbA1c and GV than with low. 80% of the trials were evaluated as ROB. The systematic literature search revealed limited and biased evidence showing that acute PA numerically reduced GV in patients with T2DM. PA reduced GV independently of PA intensity and T2DM progression. Prolonged RCTs with low ROB are needed to confirm reducing effects of PA on GV and to assess the influence of patient- and intervention characteristics on the effect of PA on GV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438766PMC
June 2021

Effects of an intensive lifestyle intervention on the underlying mechanisms of improved glycaemic control in individuals with type 2 diabetes: a secondary analysis of a randomised clinical trial.

Diabetologia 2020 11 20;63(11):2410-2422. Epub 2020 Aug 20.

The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.

Aims/hypothesis: The aim was to investigate whether an intensive lifestyle intervention, with high volumes of exercise, improves beta cell function and to explore the role of low-grade inflammation and body weight.

Methods: This was a randomised, assessor-blinded, controlled trial. Ninety-eight individuals with type 2 diabetes (duration <10 years), BMI of 25-40 kg/m, no use of insulin and taking fewer than three glucose-lowering medications were randomised (2:1) to either the standard care plus intensive lifestyle group or the standard care alone group. Standard care consisted of individual guidance on disease management, lifestyle advice and blinded regulation of medication following a pre-specified algorithm. The intensive lifestyle intervention consisted of aerobic exercise sessions that took place 5-6 times per week, combined with resistance exercise sessions 2-3 times per week, with a concomitant dietary intervention aiming for a BMI of 25 kg/m. In this secondary analysis beta cell function was assessed from the 2 h OGTT-derived disposition index, which is defined as the product of the Matsuda and the insulinogenic indices.

Results: At baseline, individuals were 54.8 years (SD 8.9), 47% women, type 2 diabetes duration 5 years (IQR 3-8) and HbA was 49.3 mmol/mol (SD 9.2); 6.7% (SD 0.8). The intensive lifestyle group showed 40% greater improvement in the disposition index compared with the standard care group (ratio of geometric mean change [RGM] 1.40 [95% CI 1.01, 1.94]) from baseline to 12 months' follow-up. Plasma concentration of IL-1 receptor antagonist (IL-1ra) decreased 30% more in the intensive lifestyle group compared with the standard care group (RGM 0.70 [95% CI 0.58, 0.85]). Statistical single mediation analysis estimated that the intervention effect on the change in IL-1ra and the change in body weight explained to a similar extent (59%) the variance in the intervention effect on the disposition index.

Conclusions/interpretation: Our findings show that incorporating an intensive lifestyle intervention, with high volumes of exercise, in individuals with type 2 diabetes has the potential to improve beta cell function, associated with a decrease in low-grade inflammation and/or body weight.

Trial Registration: ClinicalTrials.gov NCT02417012 Graphical abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-020-05249-7DOI Listing
November 2020

Cancer Survivors' Receptiveness to Digital Technology-Supported Physical Rehabilitation and the Implications for Design: Qualitative Study.

J Med Internet Res 2020 08 5;22(8):e15335. Epub 2020 Aug 5.

Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark.

Background: Physical activity is associated with a positive prognosis in cancer survivors and may decrease the risk of adverse effects of treatment. Accordingly, physical activity programs are recommended as a part of cancer rehabilitation services. Digital technology may support cancer survivors in increasing their level of physical activity and increase the reach or efficiency of cancer rehabilitation services, yet it also comes with a range of challenges.

Objective: The aim of this qualitative study was to explore cancer survivors' receptiveness to using digital technology as a mode of support to increase their physical activity in a municipality-based cancer rehabilitation setting.

Methods: Semistructured interviews were conducted with 11 cancer survivors (3 males, 8 females, age range 32-82 years) who were referred for cancer rehabilitation and had participated in a questionnaire survey using the Readiness and Enablement Index for Health Technology (READHY) questionnaire. Data analysis was based on the content analysis method.

Results: Two themes were identified as important for the interviewees' receptiveness to using digital technology services in connection with their physical activity during rehabilitation: their attitude toward physical activity and their attitude toward digital technology-assisted physical activity. Our results indicated that it is important to address the cancer survivors' motivation for using technology for physical activity and their individual preferences in terms of the following: (1) incidental or structured (eg, cardiovascular and strength exercises or disease-specific rehabilitative exercises) physical activity; (2) social or individual context; and (3) instruction (know-how) or information (know-why).

Conclusions: The identified preferences provide new insight that complements the cancer survivors' readiness level and can likely help designers, service providers, and caregivers provide solutions that increase patient receptiveness toward technology-assisted physical activity. Combining digital technology informed by cancer survivors' needs, preferences, and readiness with the capacity building of the workforce can aid in tailoring digital solutions to suit not only individuals who are receptive to using such technologies but also those reluctant to do so.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/15335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439140PMC
August 2020

Birth weight, cardiometabolic risk factors and effect modification of physical activity in children and adolescents: pooled data from 12 international studies.

Int J Obes (Lond) 2020 10 3;44(10):2052-2063. Epub 2020 Jun 3.

Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway.

Objectives: Low and high birth weight is associated with higher levels of cardiometabolic risk factors and adiposity in children and adolescents, and increases the risk of cardiovascular diseases, obesity, and early mortality later in life. Moderate-to-vigorous physical activity (MVPA) is associated with lower cardiometabolic risk factors and may mitigate the detrimental consequences of high or low birth weight. Thus, we examined whether MVPA modified the associations between birth weight and cardiometabolic risk factors in children and adolescents.

Methods: We used pooled individual data from 12 cohort- or cross-sectional studies including 9,100 children and adolescents. Birth weight was measured at birth or maternally reported retrospectively. Device-measured physical activity (PA) and cardiometabolic risk factors were measured in childhood or adolescence. We tested for associations between birth weight, MVPA, and cardiometabolic risk factors using multilevel linear regression, including study as a random factor. We tested for interaction between birth weight and MVPA by introducing the interaction term in the models (birth weight x MVPA).

Results: Most of the associations between birth weight (kg) and cardiometabolic risk factors were not modified by MVPA (min/day), except between birth weight and waist circumference (cm) in children (p = 0.005) and HDL-cholesterol (mmol/l) in adolescents (p = 0.040). Sensitivity analyses suggested that some of the associations were modified by VPA, i.e., the associations between birth weight and diastolic blood pressure (mmHg) in children (p = 0.009) and LDL- cholesterol (mmol/l) (p = 0.009) and triglycerides (mmol/l) in adolescents (p = 0.028).

Conclusion: MVPA appears not to consistently modify the associations between low birth weight and cardiometabolic risk. In contrast, MVPA may mitigate the association between higher birth weight and higher waist circumference in children. MVPA is consistently associated with a lower cardiometabolic risk across the birth weight spectrum. Optimal prenatal growth and subsequent PA are both important in relation to cardiometabolic health in children and adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41366-020-0612-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508671PMC
October 2020

Dose-Response Effects of Exercise on Glucose-Lowering Medications for Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

Mayo Clin Proc 2020 03 30;95(3):488-503. Epub 2020 Jan 30.

Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Objective: To investigate whether a dose-response relationship exists between volume of exercise and discontinuation of glucose-lowering medication treatment in patients with type 2 diabetes.

Patients And Methods: Secondary analyses of a randomized controlled exercise-based lifestyle intervention trial (April 29, 2015 to August 17, 2016). Patients with non-insulin-dependent type 2 diabetes were randomly assigned to an intensive lifestyle intervention (U-TURN) or standard-care group. Both groups received lifestyle advice and objective target-driven medical regulation. Additionally, the U-TURN group received supervised exercise and individualized dietary counseling. Of the 98 randomly assigned participants, 92 were included in the analysis (U-TURN, n=61, standard care, n=31). Participants in the U-TURN group were stratified into tertiles based on accumulated volumes of exercise completed during the 1-year intervention.

Results: Median exercise levels of 178 (interquartile range [IQR], 121-213; lower tertile), 296 (IQR, 261-310; intermediate tertile), and 380 minutes per week (IQR, 355-446; upper tertile) were associated with higher odds of discontinuing treatment with glucose-lowering medication, with corresponding odds ratios of 12.1 (95% CI, 1.2-119; number needed to treat: 4), 30.2 (95% CI, 2.9-318.5; 3), and 34.4 (95% CI, 4.1-290.1; 2), respectively, when comparing with standard care. Cardiovascular risk factors such as glycated hemoglobin A levels, fitness, 2-hour glucose levels, and triglyceride levels were improved significantly in the intermediate and upper tertiles, but not the lower tertile, compared with the standard-care group.

Conclusion: Exercise volume is associated with discontinuation of glucose-lowering medication treatment in a dose-dependent manner, as are important cardiovascular risk factors in well-treated participants with type 2 diabetes and disease duration less than 10 years. Further studies are needed to support these findings.

Study Registration: ClinicalTrials.gov registration (NCT02417012).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mayocp.2019.09.005DOI Listing
March 2020

Substituting prolonged sedentary time and cardiovascular risk in children and youth: a meta-analysis within the International Children's Accelerometry database (ICAD).

Int J Behav Nutr Phys Act 2019 10 31;16(1):96. Epub 2019 Oct 31.

Department of Sport Medicine, Norwegian School of Sport Sciences, Oslo, Norway.

Background: Evidence on the association between sitting for extended periods (i.e. prolonged sedentary time (PST)) and cardio-metabolic health is inconsistent in children. We aimed to estimate the differences in cardio-metabolic health associated with substituting PST with non-prolonged sedentary time (non-PST), light (LIPA) or moderate-to-vigorous physical activity (MVPA) in children.

Methods: Cross-sectional data from 14 studies (7 countries) in the International Children's Accelerometry Database (ICAD, 1998-2009) was included. Accelerometry in 19,502 participants aged 3-18 years, together with covariate and outcome data, was pooled and harmonized. Iso-temporal substitution in linear regression models provided beta coefficients (95%CI) for substitution of 1 h/day PST (sedentary time accumulated in bouts > 15 min) with non-PST, LIPA or MVPA, for each study, which were meta-analysed.

Results: Modelling substitution of 1 h/day of PST with non-PST suggested reductions in standardized BMI, but estimates were > 7-fold greater for substitution with MVPA (- 0.44 (- 0.62; - 0.26) SD units). Only reallocation by MVPA was beneficial for waist circumference (- 3.07 (- 4.47; - 1.68) cm), systolic blood pressure (- 1.53 (- 2.42; - 0.65) mmHg) and clustered cardio-metabolic risk (- 0.18 (- 0.3; - 0.1) SD units). For HDL-cholesterol and diastolic blood pressure, substitution with LIPA was beneficial; however, substitution with MVPA showed 5-fold stronger effect estimates (HDL-cholesterol: 0.05 (0.01; 0.10) mmol/l); diastolic blood pressure: - 0.81 (- 1.38; - 0.24) mmHg).

Conclusions: Replacement of PST with MVPA may be the preferred scenario for behaviour change, given beneficial associations with a wide range of cardio-metabolic risk factors (including adiposity, HDL-cholesterol, blood pressure and clustered cardio-metabolic risk). Effect estimates are clinically relevant (e.g. an estimated reduction in waist circumference of ≈1.5 cm for 30 min/day replacement). Replacement with LIPA could be beneficial for some of these risk factors, however with substantially lower effect estimates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12966-019-0858-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822444PMC
October 2019

Effects of Exercise Training and IL-6 Receptor Blockade on Gastric Emptying and GLP-1 Secretion in Obese Humans: Secondary Analyses From a Double Blind Randomized Clinical Trial.

Front Physiol 2019 4;10:1249. Epub 2019 Oct 4.

Centre of Inflammation and Metabolism, Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Interleukin-6 (IL-6) is released from skeletal muscle during exercise and systemic IL-6 levels therefore increase acutely in response to a single bout of exercise. We recently showed that an acute increase in IL-6 delayed gastric emptying rate and improved postprandial glycemia. Here we investigate whether repeated increases in IL-6, induced by exercise training, influence gastric emptying rate and moreover if IL-6 is required for exercise-induced adaptations in glycemic control including secretion of glucagon and glucagon-like peptide-1 (GLP-1).

Methods: A total of 52 abdominally obese non-diabetic men and women were randomly assigned into four groups performing 12 weeks of endurance exercise or no exercise with or without IL-6 receptor blockade (tocilizumab). The primary endpoint was change in gastric emptying rate in response to the intervention and other endpoints included changes in glycemic control, glucagon, and GLP-1 secretion.

Results: There was no change in gastric emptying rate in any of the four groups following the intervention and comparing differences in change between groups also revealed no difference. Postprandial glucose remained unchanged in all groups but the exercise + tocilizumab group, which improved postprandial glucose in response to the intervention. The area under the curve for meal-stimulated glucagon, active and total GLP-1 increased in response to IL-6 receptor blockade, this effect was independent of exercise.

Conclusion: Exercise training and long-term IL-6 receptor blockade did not change gastric emptying rates in obese humans. IL-6 receptor blockade increased glucagon and GLP-1 secretion and implicate IL-6 in the regulation of the human alpha and L cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2019.01249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787899PMC
October 2019

Plasma proatrial natriuretic peptide associates with lipid oxidation during exercise and cardiorespiratory fitness in healthy young adults.

Peptides 2019 12 21;122:170156. Epub 2019 Sep 21.

Department of Medicine, Amager Hvidovre Hospital in Glostrup, University of Copenhagen, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Atrial natriuretic peptide (ANP) is known for its natriuretic, diuretic, and vasodilatory properties. However, ANP also has metabolic effects stimulating lipolysis and lipid oxidation. Overweight individuals have decreased circulating ANP concentrations. It has been proposed that this potential ANP deficiency could have biological consequences in overweight-related disorders, including decreased lipolysis and lipid oxidation. The purpose of this study was to investigate the relationships between ANP, exercise-induced lipid oxidation, and cardiorespiratory fitness in 562 20-28-year-old healthy community-based women and men. We measured fasting plasma concentrations of mid-regional proANP (MR-proANP), a stable marker of ANP secretion, the respiratory exchange ratio (RER) during sub-maximal exercise, which provides an estimate of lipid oxidation, and maximal oxygen consumption (VO-max) at the end of a maximal exercise test, which is a measure of cardiorespiratory fitness. An increase of 10 pmol/L in fasting plasma MR-proANP concentrations was related to an increase in relative VO-max of 0.78 (95% CI 0.36-1.09) ml O/min/kg and a decrease in RER of -0.0094 (-0.014 to -0.0045) in age- and sex-adjusted analysis (P < 0.001). Further adjusted for body mass index, a rise of 10 pmol/L in fasting plasma MR-proANP concentrations was associated with a rise in relative VO-max of 0.60 (0.28-0.92) ml O/min/kg and a fall in RER of -0.0096 (-0.015 to -0.0048) (P < 0.001). Fasting plasma MR-proANP concentrations associate with lipid oxidation during exercise and cardiorespiratory fitness in healthy young adults. The data support the existence of important connections between the endocrine heart, hemodynamics, and metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.peptides.2019.170156DOI Listing
December 2019

Association of high amounts of physical activity with mortality risk: a systematic review and meta-analysis.

Br J Sports Med 2020 Oct 12;54(20):1195-1201. Epub 2019 Aug 12.

Research Unit for Exercise Epidemiology, Centre of Research in Childhood Health, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.

Objectives: To systematically review and analyse studies of high amounts of physical activity and mortality risk in the general population.

Eligibility Criteria: Inclusion criteria related to follow-up (minimum 2 years), outcome (mortality from all causes, cancer, cardiovascular disease (CVD) or coronary heart disease), exposure (eg, a category of >1000 metabolic equivalent of task (MET) min/week), study design (prospective cohort, nested case control or case-cohort) and reports of cases and person years of exposure categories.

Information Sources: Systematic searches were conducted in Embase and Pubmed from database inception to 2 March 2019.

Risk Of Bias: The quality of the studies was assessed with the Newcastle-Ottawa scale.

Included Studies: From 31 368 studies identified, 48 were included. Two authors independently extracted outcome estimates and assessed study quality.

Synthesis Of Results: We estimated hazard ratios (HRs) using random effect restricted cubic spline dose-response meta-analyses. Compared with the recommended level of physical activity (750 MET min/week), mortality risk was lower at physical activity levels exceeding the recommendations, at least until 5000 MET min/week for all cause mortality (HR=0.86, 95% CI 0.78 to 0.94) and for CVD mortality (HR=0.73, 95% CI 0.56 to 0.95).

Strengths And Limitations Of Evidence: The strengths of this study include the detailed dose-response analyses, inclusion of 48 studies and examination of sources of heterogeneity. The limitations include the observational nature of the included studies and the inaccurate estimations of amount of physical activity.

Interpretation: Compared with the recommended level, mortality risk was lower at physical activity levels well above the recommended target range. Further, there was no threshold beyond which lifespan was compromised.

Registration: PROSPERO CRD42017055727.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjsports-2018-100393DOI Listing
October 2020

Effect of Aerobic and Resistance Exercise on Cardiac Adipose Tissues: Secondary Analyses From a Randomized Clinical Trial.

JAMA Cardiol 2019 08;4(8):778-787

The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Importance: Epicardial and pericardial adipose tissues are emerging as important risk factors for cardiovascular disease, and there is a growing interest in discovering strategies to reduce the accumulation of fat in these depots.

Objective: To investigate whether a 12-week endurance or resistance training intervention regulates epicardial and pericardial adipose tissue mass.

Design, Setting, And Participants: Secondary analysis of a randomized, assessor-blinded clinical trial initiated on August 2016 and completed April 2018. This single-center, community-based study included 50 physically inactive participants with abdominal obesity.

Interventions: Participants were randomized to a supervised high-intensity interval endurance training (3 times a week for 45 minutes), resistance training (3 times a week for 45 minutes), or no exercise (control group).

Main Outcomes And Measures: Change in epicardial and pericardial adipose tissue mass assessed by magnetic resonance imaging, based on a prespecified secondary analysis plan including 3 of 5 parallel groups.

Results: Of 50 participants (mean [SD] age, 41 [14] years, 10 men [26%]; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 32 [5]), 39 [78%] completed the study. Endurance training and resistance training reduced epicardial adipose tissue mass by 32% (95% CI, 10%-53%) and 24% (95% CI, 1%-46%), respectively, compared with the no exercise control group (56% [95% CI, 24%-88%]; P = .001 and 48% [95% CI, 15%-81%]; P < .001, respectively). While there was a nonsignificant reduction in pericardial adipose tissue mass after endurance training (11% [95% CI, -5% to 27%]; P = .17), resistance training significantly reduced pericardial adipose tissue mass by 31% (95% CI, 16%-47%; P < .001) when compared with the no exercise control group. Compared with the no exercise control group, there was an increase in left ventricular mass by endurance (20 g [95% CI, 11%-30%]; P < .001) and resistance training (18 g [95% CI, 8%-28%]; P < .001). Other cardiometabolic outcomes remained unchanged after the 12-week trial period.

Conclusions And Relevance: In individuals with abdominal obesity, both endurance and resistance training reduced epicardial adipose tissue mass, while only resistance training reduced pericardial adipose tissue mass. These data highlight the potential preventive importance of different exercise modalities as means to reduce cardiac fat in individuals with abdominal obesity.

Trial Registration: ClinicalTrials.gov identifier: NCT02901496.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2019.2074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613292PMC
August 2019

Type 2 diabetes remission 1 year after an intensive lifestyle intervention: A secondary analysis of a randomized clinical trial.

Diabetes Obes Metab 2019 10 30;21(10):2257-2266. Epub 2019 Jun 30.

Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Aim: To investigate whether an intensive lifestyle intervention induces partial or complete type 2 diabetes (T2D) remission.

Materials And Methods: In a secondary analysis of a randomized, assessor-blinded, single-centre trial, people with non-insulin-dependent T2D (duration <10 years), were randomly assigned (2:1, stratified by sex, from April 2015 to August 2016) to a lifestyle intervention group (n = 64) or a standard care group (n = 34). The primary outcome was partial or complete T2D remission, defined as non-diabetic glycaemia with no glucose-lowering medication at the outcome assessments at both 12 and 24 months from baseline. All participants received standard care, with standardized, blinded, target-driven medical therapy during the initial 12 months. The lifestyle intervention included 5- to 6-weekly aerobic and combined aerobic and strength training sessions (30-60 minutes) and individual dietary plans aiming for body mass index ≤25 kg/m . No intervention was provided during the 12-month follow-up period.

Results: Of the 98 randomized participants, 93 completed follow-up (mean [SD] age 54.6 [8.9] years; 46 women [43%], mean [SD] baseline glycated haemoglobin 49.3 [9.3] mmol/mol). At follow-up, 23% of participants (n = 14) in the intervention and 7% (n = 2) in the standard care group met the criteria for any T2D remission (odds ratio [OR] 4.4, 95% confidence interval [CI] 0.8-21.4]; P = 0.08). Assuming participants lost to follow-up (n = 5) had relapsed, the OR for T2D remission was 4.4 (95% CI 1.0-19.8; P = 0.048).

Conclusions: The statistically nonsignificant threefold increased remission rate of T2D in the lifestyle intervention group calls for further large-scale studies to understand how to implement sustainable lifestyle interventions among people with T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.13802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772176PMC
October 2019

The effect of frequency of activity interruptions in prolonged sitting on postprandial glucose metabolism: A randomized crossover trial.

Metabolism 2019 07 4;96:1-7. Epub 2019 Apr 4.

The Centre of Inflammation and Metabolism (CIM) and the Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Denmark.

Objective: The primary objective was to test the hypothesis that increased frequency of interruptions in prolonged sitting reduces postprandial glycemia independent of energy intake and expenditure.

Materials/methods: Healthy, sedentary, centrally obese men (n = 14; age*, 28.2 (23.4; 38.3) years; BMI, 31.9 ± 6.7 kg/m; VOmax*, 39.5 (38.8; 40.9) ml/min/kg; HbA1c, 5.3 ± 0.4% (34.1 ± 4.2 mmol/mol); mean ± SD (*median (25th; 75th percentile)) completed four 8-h interventions in randomized order: 1) uninterrupted sitting (SIT), 2) sitting interrupted by 2 min of walking (~30% of VO) every 20th minute (INT20), 3) sitting interrupted by 6 min of walking every hour (INT60), and 4) sitting interrupted by 12 min of walking every second hour (INT120). A standardized test drink was served at the beginning of and 4 h into the intervention (total of 2310 ± 247 kcal; 50% energy from carbohydrate, 50% energy from fat). Outcomes included the difference in the 8-h total area under the curve (tAUC) for primarily plasma glucose, and secondarily plasma insulin and C-peptide during INT20, INT60, and INT120 compared to SIT.

Results: No difference [95% CI] was observed in the primary outcome, the 8-h tAUC for the plasma glucose, during INT20, INT60, and INT120 compared to SIT (-65.3 mmol/l∗min [-256.3; 125.7], +53.8 mmol/l∗min [-143.1; 250.8], and +18.6 mmol/l∗min [-172.4; 209.6], respectively).

Conclusions: Interrupting sitting with increasing frequency did not reduce the postprandial plasma glucose response to prolonged sitting in healthy, sedentary, centrally obese men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2019.04.003DOI Listing
July 2019

Association of copeptin, a surrogate marker for arginine vasopressin secretion, with insulin resistance: Influence of adolescence and psychological stress.

Peptides 2019 05 16;115:8-14. Epub 2019 Feb 16.

Department of Medicine, Amager and Hvidovre Hospital in Glostrup, University of Copenhagen, Glostrup, Denmark; Department of Medicine O, Endocrine Unit, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.

In middle-aged and elderly individuals, circulating copeptin concentrations, a surrogate marker for arginine vasopressin (AVP) secretion, associates with insulin resistance (IR). Whether this association is present in adolescents and young adults is unclear. Because psychological stress associates with higher circulating copeptin concentrations and IR, it has been speculated that increased AVP secretion could be a link between psychological stress and IR. We measured plasma copeptin concentrations in 351 14-16-year-old adolescents and 617 20-28-year-old young adults from the Danish site of the European Youth Heart Study, a population-based cardiovascular risk factor study in adolescents and young adults. IR was determined by the homeostatic model assessment method. Among the young adults, we used symptoms of depression, evaluated by means of the Major Depression Inventory (MDI) scale, as a measure of psychological stress. We applied linear regressions to examine associations, expressed as unstandardized regression coefficients (B) with 95% confidence intervals (CIs), between variables of interest, stratified by age group and adjusting for age, sex and Tanner stages. Copeptin and IR were log-transformed. Among the young adults, copeptin associated with IR (B (95%CI) = 0.19 (0.11 to 0.27), P < 0.001). This association was not found among the adolescents (B=-0.01 (-0.12 to 0.09), P = 0.78). MDI score associated with IR (B = 0.010 (0.004 to 0.016), P < 0.001) and copeptin (B=0.010 (0.004 to 0.015); P<0.002) in the young adults. Adjusted for copeptin, the strength of the association between MDI score and IR somewhat diminished (to B=0.008). In conclusion, adolescence and psychological stress appear to influence the association between copeptin and IR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.peptides.2019.02.005DOI Listing
May 2019
-->