RESUMO
Intercellular communication via gap junctions has a fundamental role in regulating cell growth and tissue homeostasis, and its dysregulation may be involved in cancer development and radio- and chemotherapy resistance. Connexin43 (Cx43) is the most ubiquitously expressed gap junction channel protein in human tissues. Emerging evidence indicates that dysregulation of the sorting of Cx43 to lysosomes is important in mediating the loss of Cx43-based gap junctions in cancer cells. However, the molecular basis underlying this process is currently poorly understood. Here, we identified the E3 ubiquitin ligase ITCH as a novel regulator of intercellular communication via gap junctions. We demonstrate that ITCH promotes loss of gap junctions in cervical cancer cells, which is associated with increased degradation of Cx43 in lysosomes. The data further indicate that ITCH interacts with and regulates Cx43 ubiquitination and that the ITCH-induced loss of Cx43-based gap junctions requires its catalytic HECT (homologous to E6-AP C-terminus) domain. The data also suggest that the ability of ITCH to efficiently promote loss of Cx43-based gap junctions and degradation of Cx43 depends on a functional PY (PPXY) motif in the C-terminal tail of Cx43. Together, these data provide new insights into the molecular basis underlying the degradation of Cx43 and have implications for the understanding of how intercellular communication via gap junctions is lost during cancer development.
Assuntos
Conexina 43 , Ubiquitina-Proteína Ligases , Humanos , Comunicação Celular , Conexina 43/genética , Conexinas , Junções Comunicantes , Lisossomos , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: Rapid gastric emptying is associated with obesity and overeating, whereas delayed gastric emptying is associated with anorexia. Acute effects of exercise on gastric emptying have been investigated extensively, but the influence of habitual physical activity on gastric emptying and transit time in other regions of the gastrointestinal tract is poorly understood. OBJECTIVE: The objective was to investigate associations between objectively measured habitual physical activity and gastrointestinal transit times in adults with varying degrees of adiposity. METHODS: 50 adults (58% women) were included in this cross-sectional study. Physical activity was measured by an accelerometer placed on the lower back for 7 d. Gastric emptying time, small bowel transit time, colonic transit time, and whole gut transit time were simultaneously evaluated by a wireless motility capsule, which was ingested together with a standardized mixed meal. Linear regression models were applied to assess the associations of total activity counts and time spent at different intensities-sedentary activity (0-100 counts/min), low light activity (101-759 counts/min), high light activity (760-1951 counts/min); moderate and vigorous activity (≥1952 counts/min)) with gastrointestinal transit times. RESULTS: Median [Q1; Q3] age was 56.5 [46.6-65.5] y, and body mass index (BMI) was 32.1 [28.5-35.1] kg/m2. For every additional hour spent performing high light intensity physical activity, colonic transit time was 25.5 % [95% CI: 3.10, 42.7] more rapid (P = 0.028), and whole gut transit time was 16.2 % [95% CI: 1.84, 28.4] more rapid (P = 0.028) when adjusted for sex, age, and body fat. No other associations were observed. CONCLUSIONS: More time spent on physical activity at high light intensity was associated with more rapid colonic and whole gut transit time, independent of age, sex, and body fat, whereas other intensities of physical activity and gastrointestinal transit times were not associated. TRIAL REGISTRATION: Clinicaltrials.gov IDs (NCT03894670, NCT03854656).
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Trânsito Gastrointestinal , Sobrepeso , Adulto , Humanos , Feminino , Masculino , Estudos Transversais , Obesidade , Exercício Físico , Esvaziamento GástricoRESUMO
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.
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Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/psicologia , Microbioma Gastrointestinal , Estilo de Vida , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Dieta , Exercício Físico , Fezes/microbiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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 110â¯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 57â¯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.
Assuntos
Ciclismo/fisiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/reabilitação , Exercício Físico/fisiologia , Neoplasias/complicações , Avaliação Nutricional , Doenças Cardiovasculares/mortalidade , Causas de Morte/tendências , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
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 HbA1c. 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/m2, 30-70 years of age, and prediabetes (HbA1c 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 â¼30%). 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.
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Compostos Benzidrílicos/uso terapêutico , Glicemia/análise , Exercício Físico , Glucosídeos/uso terapêutico , Metformina/uso terapêutico , Sobrepeso/sangue , Estado Pré-Diabético/terapia , Adulto , Idoso , Índice de Massa Corporal , Dinamarca , Hemoglobinas Glicadas/análise , Controle Glicêmico/métodos , Humanos , Hipoglicemiantes/uso terapêutico , Pessoa de Meia-Idade , Obesidade/sangue , Estado Pré-Diabético/tratamento farmacológico , Resultado do TratamentoRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Informática Médica/métodos , Telemedicina/métodos , Estudos Transversais , Dinamarca , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Sobreviventes de Câncer/psicologia , Tecnologia Digital/métodos , Neoplasias/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Projetos de PesquisaRESUMO
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.
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Exercício Físico , Mortalidade , Doenças Cardiovasculares/mortalidade , Causas de Morte , Doença das Coronárias/mortalidade , Metabolismo Energético , Humanos , Neoplasias/mortalidade , Fatores de RiscoRESUMO
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/m2 . 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.
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Diabetes Mellitus Tipo 2/terapia , Dieta/métodos , Terapia por Exercício/métodos , Estilo de Vida , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Redução de Peso/fisiologiaRESUMO
BACKGROUND: The increasing digitization of health care services with enhanced access to fast internet connections, along with wide use of smartphones, offers the opportunity to get health advice or treatment remotely. For service providers, it is important to consider how consumers can take full advantage of available services and how this can create an enabling environment. However, it is important to consider the digital context and the attributes of current and future users, such as their readiness (ie, knowledge, skills, and attitudes, including trust and motivation). OBJECTIVE: The objective of this study was to evaluate how the eHealth Literacy Questionnaire (eHLQ) combined with selected dimensions from the Health Education Impact Questionnaire (heiQ) and the Health Literacy Questionnaire (HLQ) can be used together as an instrument to characterize an individual's level of health technology readiness and explore how the generated data can be used to create health technology readiness profiles of potential users of health technologies and digital health services. METHODS: We administered the instrument and sociodemographic questions to a population of 305 patients with a recent cancer diagnosis referred to rehabilitation in a setting that plans to introduce various technologies to assist the individuals. We evaluated properties of the Readiness and Enablement Index for Health Technology (READHY) instrument using confirmatory factor analysis, convergent and discriminant validity analysis, and exploratory factor analysis. To identify different health technology readiness profiles in the population, we further analyzed the data using hierarchical and k-means cluster analysis. RESULTS: The confirmatory factor analysis found a suitable fit for the 13 factors with only 1 cross-loading of 1 item between 2 dimensions. The convergent and discriminant validity analysis revealed many factor correlations, suggesting that, in this population, a more parsimonious model might be achieved. Exploratory factor analysis pointed to 5 to 6 constructs based on aggregates of the existing dimensions. The results were not satisfactory, so we performed an 8-factor confirmatory factor analysis, resulting in a good fit with only 1 item cross-loading between 2 dimensions. Cluster analysis showed that data from the READHY instrument can be clustered to create meaningful health technology readiness profiles of users. CONCLUSIONS: The 13 dimensions from heiQ, HLQ, and eHLQ can be used in combination to describe a user's health technology readiness level and degree of enablement. Further studies in other populations are needed to understand whether the associations between dimensions are consistent and the number of dimensions can be reduced.
Assuntos
Educação em Saúde/métodos , Letramento em Saúde/métodos , Acessibilidade aos Serviços de Saúde/normas , Telemedicina/métodos , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
Background: During recent years, there has been an increased focus on technology within cancer survivorship and physical activity rehabilitation. Failure to acknowledge the individuals wishes and/or limitations in the use of technology introduces risk of neglecting or excluding low-resource individuals, thus adding to an already existing inequity within cancer management. It is important to identify vulnerable sub-populations with particular needs when introducing health technology to offer appropriate rehabilitation and support individuals in taking advantage of technology in their physical activity rehabilitation. We report how a population of cancer survivors referred to municipality-based rehabilitation can be segmented, according to their receptiveness and readiness for health technology utilization, to understand their potential barriers towards using technology. Methods: We used a cross-sectional design with convenience sampling among Danish cancer survivors (n = 305) referred to rehabilitation. Participants completed a questionnaire survey covering background information and a new tool to assess self-reported health technology readiness. Demographic, disease and behavioral factors were described in relation to the participants' receptiveness to use technology in physical activity rehabilitation. Participants were stratified according to their health technology readiness and the resulting groups described with regards to the above-mentioned factors. Results: Almost 30% of the participants were un-receptive to use technology in relation to physical activity rehabilitation and were characterized by being more vulnerable with regards to sociodemographic characteristics and scoring lower on dimensions related to eHealth literacy. Stratification of the participants according to their health technology readiness profile revealed four distinct profiles that were significantly different in sociodemographic, disease and behavioral factors. Conclusion: To reduce the risk of alienating low-resource individuals when introducing health technology, evaluation of the individuals' receptiveness to use technology in a rehabilitation context and their readiness for health technology may help tailor the extent to which technology should be offered to assist the cancer survivors.
Assuntos
Terapia por Exercício , Neoplasias/reabilitação , Aceitação pelo Paciente de Cuidados de Saúde , Telemedicina/métodos , Idoso , Sobreviventes de Câncer , Estudos Transversais , Dinamarca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Fatores SocioeconômicosRESUMO
Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.
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Exercício Físico/fisiologia , Interleucina-6/metabolismo , Gordura Intra-Abdominal/anatomia & histologia , Gordura Intra-Abdominal/metabolismo , Transdução de Sinais , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
BACKGROUND: Low physical activity level is associated with poor prognosis in patients with colorectal cancer (CRC). To increase physical activity, technology-based platforms are emerging and provide intriguing opportunities to prescribe and monitor active lifestyle interventions. The "Interval Walking in Colorectal Cancer"(I-WALK-CRC) study explores the feasibility and efficacy a home-based interval-walking intervention delivered by a smart-phone application in order to improve cardio-metabolic health profile among CRC survivors. The aim of the present report is to describe the design, methods and recruitment results of the I-WALK-CRC study.Methods/Results: The I-WALK-CRC study is a randomized controlled trial designed to evaluate the feasibility and efficacy of a home-based interval walking intervention compared to a waiting-list control group for physiological and patient-reported outcomes. Patients who had completed surgery for local stage disease and patients who had completed surgery and any adjuvant chemotherapy for locally advanced stage disease were eligible for inclusion. Between October 1st, 2015, and February 1st, 2017, 136 inquiries were recorded; 83 patients were eligible for enrollment, and 42 patients accepted participation. Age and employment status were associated with participation, as participants were significantly younger (60.5 vs 70.8 years, Pâ¯<â¯0.001) and more likely to be working (OR 5.04; 95%CI 1.96-12.98, Pâ¯<â¯0.001) than non-participants. CONCLUSION: In the present study, recruitment of CRC survivors was feasible but we aim to better the recruitment rate in future studies. Further, the study clearly favored younger participants. The I-WALK-CRC study will provide important information regarding feasibility and efficacy of a home-based walking exercise program in CRC survivors.
RESUMO
Importance: It is unclear whether a lifestyle intervention can maintain glycemic control in patients with type 2 diabetes. Objective: To test whether an intensive lifestyle intervention results in equivalent glycemic control compared with standard care and, secondarily, leads to a reduction in glucose-lowering medication in participants with type 2 diabetes. Design, Setting, and Participants: Randomized, assessor-blinded, single-center study within Region Zealand and the Capital Region of Denmark (April 2015-August 2016). Ninety-eight adult participants with non-insulin-dependent type 2 diabetes who were diagnosed for less than 10 years were included. Participants were randomly assigned (2:1; stratified by sex) to the lifestyle group (n = 64) or the standard care group (n = 34). Interventions: All participants received standard care with individual counseling and standardized, blinded, target-driven medical therapy. Additionally, the lifestyle intervention included 5 to 6 weekly aerobic training sessions (duration 30-60 minutes), of which 2 to 3 sessions were combined with resistance training. The lifestyle participants received dietary plans aiming for a body mass index of 25 or less. Participants were followed up for 12 months. Main Outcomes and Measures: Primary outcome was change in hemoglobin A1c (HbA1c) from baseline to 12-month follow-up, and equivalence was prespecified by a CI margin of ±0.4% based on the intention-to-treat population. Superiority analysis was performed on the secondary outcome reductions in glucose-lowering medication. Results: Among 98 randomized participants (mean age, 54.6 years [SD, 8.9]; women, 47 [48%]; mean baseline HbA1c, 6.7%), 93 participants completed the trial. From baseline to 12-month follow-up, the mean HbA1c level changed from 6.65% to 6.34% in the lifestyle group and from 6.74% to 6.66% in the standard care group (mean between-group difference in change of -0.26% [95% CI, -0.52% to -0.01%]), not meeting the criteria for equivalence (P = .15). Reduction in glucose-lowering medications occurred in 47 participants (73.5%) in the lifestyle group and 9 participants (26.4%) in the standard care group (difference, 47.1 percentage points [95% CI, 28.6-65.3]). There were 32 adverse events (most commonly musculoskeletal pain or discomfort and mild hypoglycemia) in the lifestyle group and 5 in the standard care group. Conclusions and Relevance: Among adults with type 2 diabetes diagnosed for less than 10 years, a lifestyle intervention compared with standard care resulted in a change in glycemic control that did not reach the criterion for equivalence, but was in a direction consistent with benefit. Further research is needed to assess superiority, as well as generalizability and durability of findings. Trial Registration: clinicaltrials.gov Identifier: NCT02417012.
Assuntos
Restrição Calórica , Diabetes Mellitus Tipo 2/terapia , Exercício Físico , Hipoglicemiantes/administração & dosagem , Estilo de Vida , Adulto , Idoso , Aconselhamento , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Redução de PesoRESUMO
INTRODUCTION: Current pharmacological therapies in patients with type 2 diabetes (T2D) are challenged by lack of sustainability and borderline firm evidence of real long-term health benefits. Accordingly, lifestyle intervention remains the corner stone in the management of T2D. However, there is a lack of knowledge regarding the optimal intervention programmes in T2D ensuring both compliance as well as long-term health outcomes. Our objective is to assess the effects of an intensive lifestyle intervention (the U-TURN intervention) on glycaemic control in patients with T2D. Our hypothesis is that intensive lifestyle changes are equally effective as standard diabetes care, including pharmacological treatment in maintaining glycaemic control (ie, glycated haemoglobin (HbA1c)) in patients with T2D. Furthermore, we expect that intensive lifestyle changes will decrease the need for antidiabetic medications. METHODS AND ANALYSIS: The study is an assessor-blinded, parallel group and a 1-year randomised trial. The primary outcome is change in glycaemic control (HbA1c), with the key secondary outcome being reductions in antidiabetic medication. Participants will be patients with T2D (T2D duration <10 years) without complications who are randomised into an intensive lifestyle intervention (U-TURN) or a standard care intervention in a 2:1 fashion. Both groups will be exposed to the same standardised, blinded, target-driven pharmacological treatment and can thus maintain, increase, reduce or discontinue the pharmacological treatment. The decision is based on the standardised algorithm. The U-TURN intervention consists of increased training and basal physical activity level, and an antidiabetic diet including an intended weight loss. The standard care group as well as the U-TURN group is offered individual diabetes management counselling on top of the pharmacological treatment. ETHICS AND DISSEMINATION: This study has been approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-1-2014-114). Positive, negative or inconclusive findings will be disseminated in peer-reviewed journals, at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02417012.