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AIM: This study assessed the impact of dapagliflozin on food intake, eating behaviour, energy expenditure, magnetic resonance imaging (MRI)-determined brain response to food cues and body composition in patients with type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: Patients were given dapagliflozin 10 mg once daily in a randomized, double-blind, placebo-controlled trial with short-term (1 week) and long-term (12 weeks) cross-over periods. The primary outcome was the difference in test meal food intake between long-term dapagliflozin and placebo treatment. Secondary outcomes included short-term differences in test meal food intake, short- and long-term differences in appetite and eating rate, energy expenditure and functional MRI brain activity in relation to food images. We determined differences in glycated haemoglobin, weight, liver fat (by 1 H magnetic resonance spectroscopy) and subcutaneous/visceral adipose tissue volumes (by MRI). RESULTS: In total, 52 patients (43% were women) were randomized; with the analysis of 49 patients: median age 58 years, weight 99.1 kg, body mass index 35 kg/m2 , glycated haemoglobin 49 mmol/mol. Dapagliflozin reduced glycated haemoglobin by 9.7 mmol/mol [95% confidence interval (CI) 3.91-16.27, p = .004], and body weight (-2.84 vs. -0.87 kg) versus placebo. There was no short- or long-term difference in test meal food intake between dapagliflozin and placebo [mean difference 5.7 g (95% CI -127.9 to 139.3, p = .933); 15.8 g (95% CI -147.7 to 116.1, p = .813), respectively] nor in the rate of eating, energy expenditure, appetite, or brain responses to food cues. Liver fat (median reduction -4.7 vs. 1.95%), but not subcutaneous/visceral adipose tissue, decreased significantly with 12 weeks of dapagliflozin. CONCLUSIONS: The reduction in body weight and liver fat with dapagliflozin was not associated with compensatory adaptations in food intake or energy expenditure.
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Diabetes Mellitus Tipo 2 , Humanos , Femenino , Persona de Mediana Edad , Masculino , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Hipoglucemiantes/uso terapéutico , Hemoglobina Glucada , Estudios Cruzados , Compuestos de Bencidrilo/uso terapéutico , Hígado/diagnóstico por imagen , Hígado/metabolismo , Peso Corporal , Metabolismo Energético , Método Doble Ciego , Resultado del Tratamiento , Glucemia/metabolismoRESUMEN
Introduction: Adherence to unsupervised exercise is poor, yet unsupervised exercise interventions are utilised in most healthcare settings. Thus, investigating novel ways to enhance adherence to unsupervised exercise is essential. This study aimed to examine the feasibility of two mobile health (mHealth) technology-supported exercise and physical activity (PA) interventions to increase adherence to unsupervised exercise. Methods: Eighty-six participants were randomised to online resources (n = 44, females n = 29) or MOTIVATE (n = 42, females n = 28). The online resources group had access to booklets and videos to assist in performing a progressive exercise programme. MOTIVATE participants received exercise counselling sessions supported via mHealth biometrics which allowed instant participant feedback on exercise intensity, and communication with an exercise specialist. Heart rate (HR) monitoring, survey-reported exercise behaviour and accelerometer-derived PA were used to quantify adherence. Remote measurement techniques were used to assess anthropometrics, blood pressure, HbA1c and lipid profiles. Results: HR-derived adherence rates were 22 ± 34% and 113 ± 68% in the online resources and MOTIVATE groups, respectively. Self-reported exercise behaviour demonstrated moderate (Cohen's d = 0.63, CI = 0.27 to 0.99) and large effects (Cohen's d = 0.88, CI = 0.49 to 1.26) in favour of online resources and MOTIVATE groups, respectively. When dropouts were included, 84% of remotely gathered data were available, with dropouts removed data availability was 94%. Conclusion: Data suggest both interventions have a positive impact on adherence to unsupervised exercise but MOTIVATE enables participants to meet recommended exercise guidelines. Nevertheless, to maximise adherence to unsupervised exercise, future appropriately powered trials should explore the effectiveness of the MOTIVATE intervention.
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Exercise during pregnancy presents many benefits for the mother and baby. Yet, pregnancy is characterised by a decrease in exercise. Studies have reported barriers to antenatal exercise. The coronavirus (COVID-19) pandemic may have further exacerbated barriers to antenatal exercise as pregnant females faced many challenges. Rich, in-depth exploration into pregnant female's perceived barriers to antenatal exercise during COVID-19 is imperative. Questionnaires reporting physical activity levels were completed by all participants (n = 14). Semi-structured interviews were conducted between November 2020 and May 2021 in the UK. Interviews were analysed using thematic analysis and revealed four main themes: 'Perceptions of being an active person shaping activity levels in pregnancy', 'How do I know what is right? Uncertainty, seeking validation and feeling informed', 'Motivators to antenatal exercise' and 'A process of adaptations and adjustment'. Findings indicate that the COVID-19 pandemic exacerbated barriers to antenatal exercise and highlight the importance of direct psychosocial support and clear, trustworthy information. Findings also support the fundamental need for better education amongst healthcare professionals regarding antenatal exercise.
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COVID-19 , COVID-19/epidemiología , Ejercicio Físico , Femenino , Humanos , Madres , Pandemias , Embarazo , Mujeres Embarazadas/psicología , Investigación CualitativaRESUMEN
Optimisation of lifestyle factors such as smoking and alcohol are encouraged to improve fecundability rates in the fertility setting. Currently, routine fertility consultations do not involve counselling or imparting advice regarding habitual physical activity (PA) and/or structured exercise, despite data showing that vigorous PA can be associated with delayed time to pregnancy. Therefore, this study aimed to determine habitual PA in a sample of women attending the one stop infertility (OSI) clinic. 250 women attending a large tertiary level NHS fertility unit prospectively anonymously completed a questionnaire over a period of 9 months. Participant's (mean age 34±5years, mean BMI 29±7kg/m2) habitual PA levels varied from vigorous exercise on ≥5 days/week (8%, n=17), to no moderate or high intensity activities across the whole week (66%, n=29). The majority of women reported no structured exercise (72%, n=179). No association was identified between any domain of PA and BMI, age, alcohol units, regular periods, or time spent trying to conceive (P > 0.05). Participant's habitual PA levels varied widely and no association between any domain of PA and background of the women was identified. No existing evidence and/or guidelines to explicitly inform women attempting to conceive regarding recommended PA levels are available, despite PA being a modifiable, affordable, and feasible lifestyle choice with the possible potential to improve fertility. A large-scale, clinical trial assessing effects of PA on fecundability is warranted to gain insights into the potential of this lifestyle factor to improve fertility outcomes and to explore the underlying biological mechanisms involved.
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BACKGROUND: Bariatric surgery promotes weight loss and improves co-morbid conditions, with patients who are more physically active having better outcomes. However, levels of physical activity and sedentary behaviour often remain unchanged following surgery. OBJECTIVES: To identify interventions and components thereof that are able to facilitate changes in physical activity and sedentary behaviour. ELIGIBILITY: Physical activity and/or sedentary behaviour must have been measured, pre and post intervention, in patients who have undergone bariatric surgery. STUDY APPRAISAL AND SYNTHESIS METHODS: Four databases were searched with key-words. Two researchers conducted paper screening, data extraction and risk-of-bias assessment. RESULTS: Twelve studies were included; eleven were randomised. Two were delivered presurgery and ten postsurgery; five found positive effect. Moderate to vigorous physical activity increased in three studies, two of which also found a significant increase in step count. The fourth found a significant increase in strenuous activity and the fifth a significant increase in metabolic equivalent of task/day and reduced time spent watching television. LIMITATIONS: Meta-analysis could not be conducted due to heterogeneity of outcomes and the tools used. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: This review has identified interventions and components thereof that were able to provoke positive effect. However, intervention and control conditions were not always well described particularly in terms of behaviour change techniques and the rationale for their use. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (CRD42019121372).
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Cirugía Bariátrica , Conducta Sedentaria , Ejercicio Físico , Promoción de la Salud/métodos , HumanosRESUMEN
INTRODUCTION: Exercise and physical activity (PA) are fundamental to the treatment of type 2 diabetes. Current exercise and PA strategies for newly diagnosed individuals with type 2 diabetes are either clinically effective but unsuitable in routine practice (supervised exercise) or suitable in routine practice but clinically ineffective (PA advice). Mobile health (mHealth) technologies, offering biometric data to patients and healthcare professionals, may bridge the gap between supervised exercise and PA advice, enabling patients to engage in regular long-term physically active lifestyles. This feasibility randomised controlled trial (RCT) will evaluate the use of mHealth technology when incorporated into a structured home-based exercise and PA intervention, in those recently diagnosed with type 2 diabetes. METHODS AND ANALYSIS: This feasibility multicentre, parallel group RCT will recruit 120 individuals with type 2 diabetes (diagnosis within 5-24 months, aged 40-75 years) in the UK (n=60) and Canada (n=60). Participants will undertake a 6-month structured exercise and PA intervention and be supported by an exercise specialist (active control). The intervention group will receive additional support from a smartwatch and phone app, providing real-time feedback and enabling improved communication between the exercise specialist and participant. Primary outcomes are recruitment rate, adherence to exercise and loss to follow-up. Secondary outcomes include a qualitative process evaluation and piloting of potential clinical outcome measures for a future RCT. ETHICS AND DISSEMINATION: The trial was approved in the UK by the South East Scotland Research Ethics Committee 01 (20/SS/0101) and in Canada by the Clinical Research Ethics Board of the University of British Columbia (H20-01936), and is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be published in peer-reviewed journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBERS: ISRCTN14335124; ClinicalTrials.gov: NCT04653532.
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Diabetes Mellitus Tipo 2 , Telemedicina , Biometría , Diabetes Mellitus Tipo 2/terapia , Ejercicio Físico , Estudios de Factibilidad , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: The newer glucose-lowering therapies for type 2 diabetes (T2D), the glucagon-like peptide-1 receptor agonists (GLP1-RAs) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i), have additional clinical benefits beyond improving glycaemic control; promoting weight loss, addressing associated cardiovascular risk factors and reducing macrovascular and microvascular complications. Considering their independent mechanisms of actions, there is a potential for significant synergy with combination therapy, yet limited data exist. This 32-week randomised, double-blind, placebo-controlled trial will gain mechanistic insight into the effects of coadministration of exenatide QW, a weekly subcutaneous GLP1-RA, with dapagliflozin, a once daily oral SGLT2i, on the dynamic, adaptive changes in energy balance, total, regional and organ-specific fat mass and multiorgan insulin sensitivity. METHODS AND ANALYSIS: 110 obese patients with diagnosed T2D (glycated haemoglobin, HbA1c ≥48 mmol/mol) will be treated for 32 weeks with dapagliflozin (10 mg once daily either alone or in combination with exenatide QW (2 mg once weekly); active treatments will be compared with a control group (placebo tablet and sham injection). The primary objective of the study is to compare the adjusted mean reduction in total body fat mass (determined by dual-energy X-ray absorptiometry, DEXA) from baseline following 32 weeks of treatment with exenatide QW and dapagliflozin versus dapagliflozin alone compared with control (placebo). Secondary outcome measures include changes in (1) energy balance (energy intake and energy expenditure measured by indirect calorimetry); (2) appetite (between and within meals) and satiety quotient; (3) body composition including visceral adipose tissue, subcutaneous adipose tissue, liver and pancreatic fat. Exploratory outcome measures include metabolic changes in hepatic and peripheral insulin sensitivity (using a two-stage hyperinsulinaemic, euglycaemic clamp), central nervous system responses to food images using blood oxygen level-dependent (BOLD) functional MRI (fMRI) and changes in cardiovascular function (using transthoracic echocardiography, cardiac MR and duplex ultrasonography). ETHICS AND DISSEMINATION: This study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1147) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice. Results from the study will be published in peer-reviewed scientific and open access journals and/or presented at scientific conferences and summarised for distribution to the participants. TRIAL SPONSOR: University of Liverpool. TRIAL REGISTRATION NUMBER: ISRCTN 52028580; EUDRACT number 2015-005242-60.
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Diabetes Mellitus Tipo 2 , Compuestos de Bencidrilo , Glucemia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Método Doble Ciego , Exenatida , Glucósidos , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVE: This study examined the effects of a short-term reduction in physical activity, and subsequent resumption, on metabolic profiles, body composition and cardiovascular (endothelial) function. DESIGN: Twenty-eight habitually active (≥10,000 steps/day) participants (18 female, 10 male; age 32 ± 11 years; BMI 24.3 ± 2.5 kg/m2) were assessed at baseline, following 14 days of step-reduction and 14 days after resuming habitual activity. METHODS: Physical activity was monitored throughout (SenseWear Armband). Endothelial function (flow mediated dilation; FMD), cardiorespiratory fitness ( V . ⢠O 2 peak) and body composition including liver fat (dual-energy x-ray absorptiometry and magnetic resonance spectroscopy) were determined at each assessment. Statistical analysis was performed using one-way within subject's ANOVA; data presented as mean (95% CI). RESULTS: Participants decreased their step count from baseline by 10,111 steps/day (8949, 11,274; P < 0.001), increasing sedentary time by 103 min/day (29, 177; P < 0.001). Following 14 days of step-reduction, endothelial function was reduced by a 1.8% (0.4, 3.3; P = 0.01) decrease in FMD. Following resumption of habitual activity, FMD increased by 1.4%, comparable to the baseline level 0.4% (-1.8, 2.6; P = 1.00). Total body fat, waist circumference, liver fat, whole body insulin sensitivity and cardiorespiratory fitness were all adversely affected by 14 days step-reduction (P < 0.05) but returned to baseline levels following resumption of activity. CONCLUSION: This data shows for the first time that whilst a decline in endothelial function is observed following short-term physical inactivity, this is reversed on resumption of habitual activity. The findings highlight the need for public health interventions that focus on minimizing time spent in sedentary behavior.
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OBJECTIVES: To summarize existing evidence and quantify the effects of physical activity on vascular function and structure in autoimmune rheumatic diseases (ARDs). METHODS: Databases were searched (through March 2020) for clinical trials evaluating the effects of physical activity interventions on markers of micro- and macrovascular function and macrovascular structure in ARDs. Studies were combined using random effects meta-analysis, which was conducted using Hedges' g. Meta-analyses were performed on each of the following outcomes: microvascular function [i.e. skin blood flow or vascular conductance responses to acetylcholine (ACh) or sodium nitropusside (SNP) administration]; macrovascular function [i.e. brachial flow-mediated dilation (FMD%) or brachial responses to glyceryl trinitrate (GTN%); and macrovascular structure [i.e. aortic pulse wave velocity (PWV)]. RESULTS: Ten studies (11 trials) with a total of 355 participants were included in this review. Physical activity promoted significant improvements in microvascular [skin blood flow responses to ACh, g = 0.92 (95% CI 0.42, 1.42)] and macrovascular function [FMD%, g = 0.94 (95% CI 0.56, 1.02); GTN%, g = 0.53 (95% CI 0.09, 0.98)]. Conversely, there was no evidence for beneficial effects of physical activity on macrovascular structure [PWV, g = -0.41 (95% CI -1.13, 0.32)]. CONCLUSIONS: Overall, the available clinical trials demonstrated a beneficial effect of physical activity on markers of micro- and macrovascular function but not on macrovascular structure in patients with ARDs. The broad beneficial impact of physical activity across the vasculature identified in this review support its role as an effective non-pharmacological management strategy for patients with ARDs.
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Enfermedades Autoinmunes/fisiopatología , Endotelio Vascular/fisiopatología , Ejercicio Físico/fisiología , Microvasos/fisiopatología , Enfermedades Reumáticas/fisiopatología , Humanos , Microcirculación , Análisis de la Onda del Pulso , Flujo Sanguíneo Regional , Vasodilatación/fisiología , VasodilatadoresRESUMEN
INTRODUCTION: Obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) often occur concurrently, and untreated OSA may potentially amplify the high risk of cardiovascular disease in T2DM. Compliance with continuous positive airway pressure (CPAP), the conventional treatment for OSA, can be poor and considering weight loss is the most effective treatment for OSA. This trial examines whether the glucagon-like peptide-1 receptor agonist liraglutide, a glucose-lowering therapy associated with significant weight loss used in T2DM, can improve the severity and symptoms of OSA. METHODS AND ANALYSIS: This is an outpatient, single-centred, open-labelled, prospective, phase IV randomised controlled trial in a two-by-two factorial design. One hundred and thirty-two patients with newly diagnosed OSA (apnoea-hypopnoea index (AHI) ≥15 events/hour), and existing obesity and T2DM (glycated haemoglobin (HbA1c) ≥47 mmol/mol), will be recruited from diabetes and sleep medicine outpatient clinics in primary and secondary care settings across Liverpool. Patients will be allocated equally, using computer-generated random, permuted blocks of unequal sizes, to each of the four treatment arms for 26 weeks: (i) liraglutide (1.8 mg once per day) alone, (ii) liraglutide 1.8 mg once per day with CPAP, (iii) CPAP alone (conventional care) or (iv) no treatment (control). The primary outcome measure is change in OSA severity, determined by AHI. Secondary outcome measures include effects on glycaemic control (glycated haemoglobin (HbA1c)), body weight and quality of life measures. Exploratory measures include measures of physical activity, MRI-derived measures of regional body composition including fat mass (abdominal subcutaneous, visceral, neck and liver fat) and skeletal muscle mass (cross-sectional analysis of thigh), indices of cardiac function (using transthoracic echocardiography) and endothelial function. ETHICAL APPROVAL: The study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1019) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBERS: ISRCTN16250774. EUDRACT No. 2014-000988-41. UTN U1111-1139-0677.
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Diabetes Mellitus Tipo 2 , Apnea Obstructiva del Sueño , Presión de las Vías Aéreas Positiva Contínua , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón , Humanos , Liraglutida/uso terapéutico , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/terapia , Resultado del Tratamiento , Pérdida de PesoRESUMEN
BACKGROUND: Data suggest that metabolic health status, incorporating components of metabolic syndrome (MetS), predicts cardiovascular disease (CVD) risk better than BMI. This study explored the association of MetS and obesity with endothelial function, a prognostic risk factor for incident CVD. METHODS: Forty-four participants were phenotyped according to BMI as non-obese vs obese (<30 or >30 kg/m2) and according to the International Diabetes Federation criteria of MetS: ≤2 criteria MetS (MetS-) vs ≥3 criteria MetS (MetS+); (1.)non-obese MetS- vs (2.) non-obese MetS+ and (3.) obese MetS- vs (4.) obese MetS+. Flow-mediated dilation (FMD), body composition including liver fat (MRI and spectroscopy), dietary intake, intensities of habitual physical activity and cardio-respiratory fitness were determined. Variables were analysed using a one-factor between-groups ANOVA and linear regression; mean (95% CI) are presented. RESULTS: Individuals with MetS+ displayed lower FMD than those with MetS-. For non-obese individuals mean difference between MetS+ and MetS- was 4.1% ((1.0, 7.3); P = 0.004) and obese individuals had a mean difference between MetS+ and MetS- of 6.2% ((3.1, 9.2); P < 0.001). Although there was no association between BMI and FMD (P = 0.27), an increased number of MetS components was associated with a lower FMD (P = 0.005), and after adjustment for age and sex, 19.7% of the variance of FMD was explained by MetS, whereas only 1.1% was explained by BMI. CONCLUSIONS: In this study cohort, components of MetS, rather than obesity per se, contribute to reduced FMD, which suggests a reduced bioavailability of nitric oxide and thus increased risk of CVD.
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Síndrome Metabólico/fisiopatología , Obesidad/fisiopatología , Vasodilatación , Adiposidad , Adulto , Composición Corporal , Índice de Masa Corporal , Arteria Braquial/fisiopatología , Enfermedades Cardiovasculares/fisiopatología , Estudios de Cohortes , Ingestión de Alimentos , Endotelio Vascular/fisiopatología , Ejercicio Físico , Femenino , Humanos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Aptitud Física , Factores de RiesgoRESUMEN
BACKGROUND: Although the health benefits of regular physical activity and exercise are well established and have been incorporated into national public health recommendations, there is a relative lack of understanding pertaining to the harmful effects of physical inactivity. Experimental paradigms including complete immobilization and bed rest are not physiologically representative of sedentary living. A useful 'real-world' approach to contextualize the physiology of societal downward shifts in physical activity patterns is that of short-term daily step reduction. RESULTS: Step-reduction studies have largely focused on musculoskeletal and metabolic health parameters, providing relevant disease models for metabolic syndrome, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), sarcopenia and osteopenia/osteoporosis. In untrained individuals, even a short-term reduction in physical activity has a significant impact on skeletal muscle protein and carbohydrate metabolism, causing anabolic resistance and peripheral insulin resistance, respectively. From a metabolic perspective, short-term inactivity-induced peripheral insulin resistance in skeletal muscle and adipose tissue, with consequent liver triglyceride accumulation, leads to hepatic insulin resistance and a characteristic dyslipidaemia. Concomitantly, various inactivity-related factors contribute to a decline in function; a reduction in cardiorespiratory fitness, muscle mass and muscle strength. CONCLUSIONS: Physical inactivity maybe particularly deleterious in certain patient populations, such as those at high risk of T2D or in the elderly, considering concomitant sarcopenia or osteoporosis. The effects of short-term physical inactivity (with step reduction) are reversible on resumption of habitual physical activity in younger people, but less so in older adults. Nutritional interventions and resistance training offer potential strategies to prevent these deleterious metabolic and musculoskeletal effects. IMPACT: Individuals at high risk of/with cardiometabolic disease and older adults may be more prone to these acute periods of inactivity due to acute illness or hospitalization. Understanding the risks is paramount to implementing countermeasures.
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BACKGROUND: Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC could improve endothelial and cerebrovascular function. The aim of this pilot study was to obtain estimates for the change in conduit artery and cerebrovascular function following a 7-day rIPC intervention. METHODS: Twenty-one patients with T2DM were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 220 mmHg, interspaced by 5-min reperfusion) or control. We examined peripheral endothelial function using flow mediated dilation (FMD) before and after ischemia-reperfusion injury (IRI, 20 min forearm ischaemic-20 min reperfusion) and cerebrovascular function, assessed by dynamic cerebral autoregulation (dCA) at three time points; pre, post and 8 days post intervention. RESULTS: For exploratory purposes, we performed statistical analysis on our primary comparison (pre-to-post) to provide an estimate of the change in the primary and secondary outcome variables. Using pre-intervention data as a covariate, the change from pre-post in FMD was 1.3% (95% CI: 0.69 to 3.80; P = 0.09) and 0.23 %cm/s %/mmHg mmHg/% (-0.12, 0.59; P = 0.18) in dCA normalised gain with rIPC versus control. Based upon this, a sample size of 20 and 50 for FMD and normalised gain, respectively, in each group would provide 90% power to detect statistically significant (P < 0.05) between-group difference in a randomised controlled trial. CONCLUSION: We provide estimates of sample size for a randomised control trial exploring the impact of daily rIPC for 7 days on peripheral endothelial and cerebrovascular function. The directional changes outline from our pilot study suggest peripheral endothelial function can be enhanced by daily rIPC in patients with T2DM.
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Diabetes Mellitus Tipo 2/terapia , Precondicionamiento Isquémico/métodos , Daño por Reperfusión/terapia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Factores de TiempoRESUMEN
Background Premenopausal women have a lower incidence of cardiovascular disease, which may partly be due to a protective effect of estrogen on endothelial function. Animal studies suggest that estrogen may also improve the relationship between shear rate ( SR ) and endothelial function. We aimed to explore the relationship between endothelial function (ie, flow-mediated dilation [ FMD ]) and SR (ie, SR area under the curve [ SRAUC ]) in women versus men, and between pre- versus postmenopausal women. Methods and Results Brachial artery FMD and SRAUC were measured in accordance with expert-consensus guidelines in 932 healthy participants who were stratified into young adults (18-40 years, 389 men, 144 women) and older adults (>40 years, 260 men, 139 women). Second, we compared premenopausal (n=173) and postmenopausal women (n=110). There was evidence of a weak correlation between SRAUC and FMD in all groups but older men, although there was variation in strength of outcomes. Further exploration using interaction terms (age-sex× SRAUC ) in linear regression revealed differential relationships with FMD (young women versus young men [ß=-5.8-4, P=0.017] and older women [ß=-5.9-4, P=0.049]). The correlation between SRAUC and FMD in premenopausal women ( r2=0.097) was not statistically different from that in postmenopausal women ( r2=0.025; Fisher P=0.30). Subgroup analysis using stringent inclusion criteria for health markers (n=505) confirmed a stronger FMD - SRAUC correlation in young women compared with young men and older women. Conclusions Evidence for a stronger relationship between endothelial function and the eliciting SR stimulus is present in young women compared with men. Estrogen may contribute to this finding, but larger healthy cohorts are required for conclusive outcomes.
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Velocidad del Flujo Sanguíneo/fisiología , Arteria Braquial/fisiopatología , Enfermedades Cardiovasculares/fisiopatología , Endotelio Vascular/fisiopatología , Longevidad/fisiología , Estrés Fisiológico/fisiología , Vasodilatación/fisiología , Adolescente , Adulto , Progresión de la Enfermedad , Ejercicio Físico/fisiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION/PURPOSE: To investigate whether (a) lower levels of daily physical activity (PA) and greater sedentary time accounted for contrasting metabolic phenotypes (higher liver fat/presence of metabolic syndrome [METS+] vs lower liver fat/absence of metabolic syndrome [METS-]) in individuals of similar body mass index and (b) the association of sedentary time on metabolic health and liver fat. METHODS: Ninety-eight habitually active participants (53 female, 45 male; age, 39 ± 13 yr; body mass index 26.9 ± 5.1 kg·m), underwent assessments of PA (SenseWear armband; wear time ~98%), cardiorespiratory fitness (VËO2 peak), body composition (magnetic resonance imaging and magnetic resonance spectroscopy) and multiorgan insulin sensitivity (oral glucose tolerance test). We undertook a) cross-sectional analysis comparing four groups: nonobese or obese, with and without metabolic syndrome (METS+ vs METS-) and b) univariate and multivariate regression for sedentary time and other levels of PA in relation to liver fat. RESULTS: Light, moderate, and vigorous PA did not account for differences in metabolic health between individuals, whether nonobese or obese, although METS+ individuals were more sedentary, with a higher number, and prolonged bouts (~1-2 h). Overall, sedentary time, average daily METS and VËO2 peak were each independently associated with liver fat percentage. Each additional hour of daily sedentary time was associated with a 1.15% (95% confidence interval, 1.14%-1.50%) higher liver fat content. CONCLUSIONS: Greater sedentary time, independent of other levels of PA, is associated with being metabolically unhealthy; even in habitually active people, lesser sedentary time, and higher cardiorespiratory fitness and average daily METS is associated with lower liver fat.
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Ejercicio Físico , Hígado Graso/metabolismo , Síndrome Metabólico/metabolismo , Conducta Sedentaria , Adulto , Glucemia/metabolismo , Composición Corporal , Índice de Masa Corporal , Capacidad Cardiovascular , Estudios Transversales , Femenino , Humanos , Insulina/sangre , Hígado/diagnóstico por imagen , Hígado/metabolismo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/metabolismoRESUMEN
AIMS/HYPOTHESIS: Low physical activity levels and sedentary behaviour are associated with obesity, insulin resistance and type 2 diabetes. We investigated the effects of a short-term reduction in physical activity with increased sedentary behaviour on metabolic profiles and body composition, comparing the effects in individuals with first-degree relatives with type 2 diabetes (FDR+ve) vs those without (FDR-ve). METHODS: Forty-five habitually active participants (16 FDR+ve [10 female, 6 male] and 29 FDR-ve [18 female, 11 male]; age 36 ± 14 years) were assessed at baseline, after 14 days of step reduction and 14 days after resuming normal activity. We determined physical activity (using a SenseWear armband), cardiorespiratory fitness ([Formula: see text]), body composition (dual-energy x-ray absorptiometry/magnetic resonance spectroscopy) and multi-organ insulin sensitivity (OGTT) at each time point. Statistical analysis was performed using a two-factor between-groups ANCOVA, with data presented as mean ± SD or (95% CI). RESULTS: There were no significant between-group differences in physical activity either at baseline or following step reduction. During the step-reduction phase, average daily step count decreased by 10,285 steps (95% CI 9389, 11,182; p < 0.001), a reduction of 81 ± 8%, increasing sedentary time by 223 min/day (151, 295; p < 0.001). Pooling data from both groups, following step reduction there was a significant decrease in whole-body insulin sensitivity (Matsuda index) (p < 0.001), muscle insulin sensitivity index (p < 0.001), cardiorespiratory fitness (p = 0.002) and lower limb lean mass (p = 0.004). Further, there was a significant increase in total body fat (p < 0.001), liver fat (p = 0.001) and LDL-cholesterol (p = 0.013), with a borderline significant increase in NEFA AUC during the OGTT (p = 0.050). Four significant between-group differences were apparent: following step reduction, FDR+ve participants accumulated 1.5% more android fat (0.4, 2.6; p = 0.008) and increased triacylglycerol by 0.3 mmol/l (0.1, 0.6; p = 0.044). After resuming normal activity, FDR+ve participants engaged in lower amounts of vigorous activity (p = 0.006) and had lower muscle insulin sensitivity (p = 0.023). All other changes were reversed with no significant between-group differences. CONCLUSIONS/INTERPRETATION: A short-term reduction in physical activity with increased sedentary behaviour leads to a reversible reduction in multi-organ insulin sensitivity and cardiorespiratory fitness, with concomitant increases in central and liver fat and dyslipidaemia. The effects are broadly similar in FDR+ve and FDR-ve individuals. Public health recommendations promoting physical activity should incorporate advice to avoid periods of sedentary behaviour.
Asunto(s)
Composición Corporal , Diabetes Mellitus Tipo 2/metabolismo , Ejercicio Físico , Conducta Sedentaria , Tejido Adiposo/fisiología , Adulto , Antropometría , Salud de la Familia , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Estilo de Vida , Lípidos/sangre , Hígado/fisiología , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiología , Aptitud Física/fisiología , Adulto JovenRESUMEN
INTRODUCTION: Sodium glucose cotransporter 2 (SGLT2) inhibitors are effective blood-glucose-lowering medications with beneficial effects on body weight in patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is less than that predicted from quantified glycosuria, suggesting a compensatory increase in energy intake or a decrease in energy expenditure. Studies using dual-energy X-ray absorptiometry (DEXA) have suggested most body weight change is due to loss of adipose tissue, but organ-specific changes in fat content (eg, liver, skeletal muscle) have not been determined. In this randomised, double-blind, placebo-controlled crossover study, we aim to study the compensatory changes in energy intake, eating behaviour and energy expenditure accompanying use of the SGLT2 inhibitor, dapagliflozin. Additionally, we aim to quantify changes in fat distribution using MRI, in liver fat using proton magnetic resonance spectroscopy (1H-MRS) and in central nervous system (CNS) responses to food images using blood oxygen level dependent (BOLD) functional MRI (fMRI). METHODS AND ANALYSIS: This outpatient study will evaluate the effect of dapagliflozin (10â mg), compared with placebo, on food intake and energy expenditure at 7â days and 12â weeks. 52 patients with T2DM will be randomised to dapagliflozin or placebo for short-term and long-term trial interventions in a within participants, crossover design. The primary outcome is the difference in energy intake during a test meal between dapagliflozin and placebo. Intake data are collected automatically using a customised programme operating a universal eating monitor (UEM). Secondary outcomes include (1) measures of appetite regulation including rate of eating, satiety quotient, appetite ratings (between and within meals), changes in CNS responses to food images measured using BOLD-fMRI, (2) measures of energy expenditure and (3) changes in body composition including changes in liver fat and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). ETHICAL APPROVAL: This study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/0340) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice (GCP). TRIAL REGISTRATION NUMBER: ISRCTN14818531. EUDRACT number 2013-004264-60.
Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Encéfalo/diagnóstico por imagen , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metabolismo Energético , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Grasa Intraabdominal/metabolismo , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/patología , Composición Corporal , Distribución de la Grasa Corporal , Encéfalo/fisiopatología , Calorimetría Indirecta , Estudios Cruzados , Señales (Psicología) , Diabetes Mellitus Tipo 2/metabolismo , Método Doble Ciego , Ingestión de Alimentos , Conducta Alimentaria , Alimentos , Neuroimagen Funcional , Humanos , Hígado , Imagen por Resonancia Magnética , Tamaño de los Órganos , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
OBJECTIVE: Postmenopausal hot flushes occur due to a reduction in estrogen production causing thermoregulatory and vascular dysfunction. Exercise training enhances thermoregulatory control of sweating, skin and brain blood flow. We aimed to determine if improving thermoregulatory control and vascular function with exercise training alleviated hot flushes. METHODS: Twenty-one symptomatic women completed a 7-day hot flush questionnaire and underwent brachial artery flow-mediated dilation and a cardiorespiratory fitness test. Sweat rate and skin blood flow temperature thresholds and sensitivities, and middle cerebral artery velocity (MCAv) were measured during passive heating. Women performed 16 weeks of supervised exercise training or control, and measurements were repeated. RESULTS: There was a greater improvement in cardiorespiratory fitness (4.45âmL/kg/min [95% CI: 1.87, 8.16]; Pâ=â0.04) and reduced hot flush frequency (48 hot flushes/wk [39, 56]; Pâ<â0.001) after exercise compared with control. Exercise reduced basal core temperature (0.14°C [0.01, 0.27]; Pâ=â0.03) and increased basal MCAv (2.8âcm/s [1.0, 5.2]; Pâ=â0.04) compared with control. Sweat rate and skin blood flow thresholds occurred approximately 0.19°C and 0.17°C earlier, alongside improved sweating sensitivity with exercise. MCAv decreased during heating (Pâ<â0.005), but was maintained 4.5âcm/s (3.6, 5.5; Pâ<â0.005) higher during heating after exercise compared with control (0.6âcm/s [-0.4, 1.4]). CONCLUSIONS: Exercise training that improves cardiorespiratory fitness reduces self-reported hot flushes. Improvements are likely mediated through greater thermoregulatory control in response to increases in core temperature and enhanced vascular function in the cutaneous and cerebral circulations.