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Whilst the exercise-induced myokine interleukin-6 (IL-6) plays a beneficial role in cardiac structural adaptations, its influence on exercise-induced functional cardiac outcomes remains unknown. We hypothesised that IL-6 activity is required for exercise-induced improvements in left ventricular global longitudinal strain (LV GLS). In an exploratory study 52 individuals with abdominal obesity were randomised to 12 weeks' high-intensity exercise or no exercise in combination with IL-6 receptor inhibition (IL-6i) or placebo. LV strain and volume measurements were assessed by cardiac magnetic resonance. Exercise improved LV GLS by -5.4% [95% CI: -9.1% to -1.6%] (P = 0.007). Comparing the change from baseline in LV GLS in the exercise + placebo group (-4.8% [95% CI: -7.4% to -2.2%]; P < 0.0004) to the exercise + IL-6i group (-1.1% [95% CI: -3.8% to 1.6%]; P = 0.42), the exercise + placebo group changed -3.7% [95% CI: -7.4% to -0.02%] (P = 0.049) more than the exercise + IL6i group. However, the interaction effect between exercise and IL-6i was insignificant (4.5% [95% CI: -0.8% to 9.9%]; P = 0.09). Similarly, the exercise + placebo group improved LV global circumferential strain by -3.1% [95% CI: -6.0% to -0.1%] (P = 0.04) more compared to the exercise + IL-6i group, yet we found an insignificant interaction between exercise and IL-6i (4.2% [95% CI: -1.8% to 10.3%]; P = 0.16). There was no effect of IL-6i on exercise-induced changes to volume rates. This study underscores the importance of IL-6 in improving LV GLS in individuals with abdominal obesity suggesting a role for IL-6 in cardiac functional exercise adaptations.
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Exercício Físico , Interleucina-6 , Obesidade Abdominal , Função Ventricular Esquerda , Humanos , Obesidade Abdominal/fisiopatologia , Obesidade Abdominal/metabolismo , Obesidade Abdominal/terapia , Interleucina-6/metabolismo , Masculino , Feminino , Exercício Físico/fisiologia , Função Ventricular Esquerda/fisiologia , Pessoa de Meia-Idade , Adulto , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Receptores de Interleucina-6 , Imageamento por Ressonância MagnéticaRESUMO
The Scandinavian winter-swimming culture combines brief dips in cold water with hot sauna sessions, with conceivable effects on body temperature. We study thermogenic brown adipose tissue (BAT) in experienced winter-swimming men performing this activity 2-3 times per week. Our data suggest a lower thermal comfort state in the winter swimmers compared with controls, with a lower core temperature and absence of BAT activity. In response to cold, we observe greater increases in cold-induced thermogenesis and supraclavicular skin temperature in the winter swimmers, whereas BAT glucose uptake and muscle activity increase similarly to those of the controls. All subjects demonstrate nocturnal reduction in supraclavicular skin temperature, whereas a distinct peak occurs at 4:30-5:30 a.m. in the winter swimmers. Our data leverage understanding of BAT in adult human thermoregulation, suggest both heat and cold acclimation in winter swimmers, and propose winter swimming as a potential strategy for increasing energy expenditure.
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Tecido Adiposo Marrom/fisiologia , Temperatura Baixa , Estações do Ano , Natação/fisiologia , Termogênese/fisiologia , Tecido Adiposo Marrom/diagnóstico por imagem , Adulto , Ritmo Circadiano/fisiologia , Hormônios/sangue , Humanos , Imageamento por Ressonância Magnética , Masculino , Percepção , Tomografia por Emissão de Pósitrons , Temperatura Cutânea/fisiologia , Termografia , Adulto JovemRESUMO
NEW FINDINGS: What is the central question of this study? Does blockade of the IL-6 receptor by tocilizumab inhibit immune cell mobilization to the blood stream in humans during an acute bout of exercise? What is the main finding and its importance? Blockade of IL-6 receptor signalling by tocilizumab attenuates mobilization of NK cells and dendritic cells to the blood stream during exercise. This implies an inhibitory effect of tocilizumab on the innate immune response to physical stress, which could be considered in clinical settings. ABSTRACT: Immune cells are recruited from their storage organs and the endothelial walls to the blood stream in response to physiological stress. This is essential for the recognition and clearing of infected, transformed or damaged cells. One of the most potent stimuli to recruit immune cells to the circulation is exercise. Accordingly, exercise has proven beneficial in disease settings, such as cancer and diabetes. Interleukin-6 (IL-6) is released from contracting skeletal muscle in response to exercise, and rodent studies have established a link between exercise-induced IL-6 and recruitment of natural killer (NK) cells. Whether exercise-induced IL-6 is involved in regulating NK cell mobilization in humans is unclear. This study explored the effect of IL-6 receptor blockade on immune cell mobilization during an acute bout of exercise in humans. In a randomized, placebo-controlled clinical study, abdominally obese humans receiving placebo infusions or tocilizumab infusions performed an acute bout of exercise before and after the intervention. Immune cell recruitment was measured by flow cytometry. IL-6 receptor blockade attenuated the increase of NK cells by 53% (mean difference -0.49 (95% CI: -0.89 to -0.08) × 109 cells L-1 , P < 0.001) and dendritic cells by 66% (mean difference -0.14 (95% CI: -0.28 to 0.010) × 109 cells L-1 , P < 0.001) induced by an acute bout of exercises. No changes were observed for T cells, monocytes and neutrophils. Treatments which interact with the exercise-mediated immune surveillance provide relevant clinical information in pursuing the 'exercise as medicine' concept.
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Células Dendríticas/efeitos dos fármacos , Exercício Físico/fisiologia , Células Matadoras Naturais/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Receptores de Interleucina-6/antagonistas & inibidores , Linfócitos T/efeitos dos fármacos , Adolescente , Anticorpos Monoclonais Humanizados/farmacologia , Células Dendríticas/imunologia , Método Duplo-Cego , Feminino , Humanos , Células Matadoras Naturais/imunologia , Masculino , Monócitos/imunologia , Linfócitos T/imunologiaRESUMO
CONTEXT: Interleukin 6 (IL-6) contributes to bone remodeling in preclinical studies. Clinical trials investigating the role of IL-6 in bone remodeling are limited. OBJECTIVE: To investigate if IL-6 regulates bone remodeling in humans. DESIGN: Plasma concentrations of the bone resorption marker carboxy-terminal type I collagen crosslinks (CTX) and of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) were measured during a mixed-meal tolerance test (MMTT) in 3 placebo-controlled human studies. PARTICIPANTS: Five healthy individuals participated in study 1; 52 obese individuals, in study 2; and 10 healthy individuals, in study 3. INTERVENTIONS: Study 1 was a single-blinded crossover study consisting of a 1-h infusion of saline (placebo) or the IL-6 receptor antibody tocilizumab followed by an exercise bout. Study 2 was a randomized, double-blinded 12-week exercise training intervention study. Participants received infusions of saline or tocilizumab. Study 3 was a randomized, double-blinded, crossover study consisting of 30 min infusion of saline or IL-6. MAIN OUTCOMES MEASURES: Effect of IL-6 on CTX levels. RESULTS: CTX was significantly (P < 0.01) decreased during MMTTs in all 3 studies. Treatment with tocilizumab did not affect exercise or meal induced changes in plasma CTX or P1NP concentrations acutely (study 1) or after a 12-week treatment period (study 2). Exogenous IL-6 had no effect on CTX or P1NP plasma concentrations (study 3). CONCLUSIONS: IL-6 may not regulate bone remodeling in humans.
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Tecido Adiposo/metabolismo , Adiposidade , Terapia por Exercício , Miocárdio/metabolismo , Obesidade Abdominal/terapia , Receptores de Interleucina-6/metabolismo , Tecido Adiposo/fisiopatologia , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/metabolismo , Obesidade Abdominal/fisiopatologia , Receptores de Interleucina-6/antagonistas & inibidores , Transdução de Sinais , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
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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.
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Tecido Adiposo/patologia , Exercício Físico , Obesidade Abdominal/terapia , Pericárdio , Treinamento Resistido , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Método Simples-Cego , Resultado do TratamentoRESUMO
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
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: Exercise reduces the amount of visceral adipose tissue (VAT) and the risk of cardiometabolic diseases. The underlying mechanisms responsible for these exercise-induced adaptations are unclear, but they may involve lipolytic actions of interleukin-6 (IL-6). Contracting skeletal muscles secrete IL-6, leading to increased circulating IL-6 levels in response to exercise. The aim of this study is to investigate whether IL-6 is involved in mediating the effects of exercise on visceral and epicardial adipose tissue volume and glycaemic control. METHODS/DESIGN: Seventy-five physically inactive males and females aged > 18 years with a waist-to-height ratio > 0.5 and/or waist circumference ≥ 88 cm (females) or ≥ 102 cm (males) are being recruited to participate in a 12-week intervention study. Participants are randomly allocated to one of five groups (1:1:1:1:1). Two groups consist of supervised endurance exercise training combined with the IL-6 blocker tocilizumab (ET) or saline used as placebo (EP), two groups consist of no exercise combined with tocilizumab (NT) or placebo (NP), and one group consists of resistance exercise and placebo (RP). Although the study is an exploratory trial, the primary outcome is change in VAT volume from before to after intervention, with secondary outcomes being changes in (1) epicardial adipose tissue, (2) pericardial adipose tissue and (3) gastric emptying. Depots of adipose tissue are quantitated by magnetic resonance imaging Gastric emptying and glucose metabolism are assessed using mixed-meal tolerance tests. DISCUSSION: Understanding the role of IL-6 in mediating the effects of exercise on visceral and epicardial adipose tissue and glycaemic control may lead to novel therapeutic approaches in the prevention of cardiometabolic diseases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02901496 . Registered on 1 August 2016 and posted retrospectively on 15 September 2016.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Esvaziamento Gástrico/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Gordura Intra-Abdominal/efeitos dos fármacos , Obesidade Abdominal/terapia , Receptores de Interleucina-6/antagonistas & inibidores , Treinamento Resistido , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/metabolismo , Dinamarca , Feminino , Humanos , Interleucina-6/metabolismo , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/fisiopatologia , Resistência Física , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Interleucina-6/metabolismo , Fatores de Tempo , Resultado do Tratamento , Circunferência da Cintura , Razão Cintura-Estatura , Adulto JovemRESUMO
OBJECTIVE: Individuals with metabolic syndrome have increased risk of type 2 diabetes and cardiovascular disease. We aimed to test the hypothesis that a high level of cardiorespiratory fitness (CR-fitness), counteracts accumulation of visceral fat, decreases inflammation and lowers risk factors of the metabolic syndrome. METHOD: The study sample included 1,293 Danes (age 49-52 years) who from 2009 to 2011 participated in the Copenhagen Aging and Midlife Biobank, including a questionnaire, physical tests, and blood samples. Multiple linear regression models were performed with CR-fitness as exposure and plasma levels of cytokines and high sensitive C-reactive protein as outcomes and measures of abdominal obesity were added to test if they explained the potential association. Similarly, multiple linear regression models were performed with CR-fitness as exposure and factors of the metabolic syndrome as outcomes and the potential explanation by inflammatory biomarkers were tested. All models were adjusted for the effect of age, sex, smoking, alcohol consumption, socio-economic status, and acute inflammatory events within the preceding two weeks. RESULTS: CR-fitness was inversely associated with high sensitive C-reactive protein, Interleukin (IL)-6, and IL-18, and directly associated with the anti-inflammatory cytokine IL-10, but not associated with tumor necrosis factor alpha, interferon gamma or IL-1ß. Abdominal obesity could partly explain the significant associations. Moreover, CR-fitness was inversely associated with an overall metabolic syndrome score, as well as triglycerides, glycated haemoglobin A1c, systolic blood pressure, diastolic blood pressure and directly associated with high-density lipoprotein. Single inflammatory biomarkers and a combined inflammatory score partly explained these associations. CONCLUSION: Data suggest that CR-fitness has anti-inflammatory effects that are partly explained by a reduction in abdominal obesity and a decrease in the metabolic syndrome risk profile. The overall inflammatory load was mainly driven by high sensitive C-reactive protein and IL-6.
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Biomarcadores/metabolismo , Aptidão Cardiorrespiratória , Terapia por Exercício , Mediadores da Inflamação/metabolismo , Inflamação/reabilitação , Síndrome Metabólica/prevenção & controle , Obesidade Abdominal/reabilitação , Composição Corporal , Feminino , Humanos , Inflamação/complicações , Inflamação/metabolismo , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Obesidade Abdominal/metabolismo , Fatores de RiscoRESUMO
OBJECTIVE: Up to 30% of obese individuals are metabolically healthy. Metabolically healthy obese (MHO) individuals are characterized by having low abdominal adiposity, low inflammation level and low risk of developing metabolic comorbidity. In this study, we hypothesize that cardiorespiratory fitness (fitness) is a determinant factor for the MHO individuals and aim to investigate the associations between fitness, abdominal adiposity and low-grade inflammation within different BMI categories. METHOD: Data from 10,976 individuals from the general population, DANHES 2007-2008, on waist circumference, fitness and C-reactive protein (hsCRP) were analysed using multiple linear and median quantile regressions. RESULTS: In men, an inverse association between fitness (+5 mL min-1 kg-1) and waist circumference (-1.45 cm; 95% CI: -1.55 to -1.35 cm; p<0.001), and an inverse association between fitness (+5 mL min-1 kg-1) and hsCRP (-0.22 mg/L; 95% CI: -0.255 to -0.185 mg/L; p<0.001) was found, all independent of BMI. Similarly in women, an inverse association between fitness (+5 mL min-1 kg-1) and waist circumference (-1.15 cm; 95% CI: -1.25 to -1.0 cm; p<0.001), and an inverse association between fitness (+5 mL min-1 kg-1) and hsCRP (-0.26 mg/L; 95% CI: -0.3 to -0.22 mg/L; p<0.001) was found, all independent of BMI. Additionally, significant positive associations between waist circumference and hsCRP were found for both men and women, independently of BMI. CONCLUSION: Fitness was found to be inversely associated with both abdominal adiposity and low-grade inflammation independent of BMI. These data suggest that, in spite of BMI, high fitness levels lead to a reduction in abdominal fat mass and low-grade inflammation.
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Índice de Massa Corporal , Inflamação/fisiopatologia , Obesidade Abdominal , Aptidão Física , Adulto , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Circunferência da CinturaRESUMO
In healthy subjects, it has been suggested that exercise may acutely suppress energy-intake and appetite, with peak intensity being an important determinant for this effect. In subjects with type 2 diabetes (T2D), the effect of exercise on appetite-related variables is, however, virtually unknown. We aimed to assess the effects of two exercise interventions, differing with regards to peak intensity, on energy-intake, satiety and appetite-related hormones in subjects with T2D. Thirteen subjects with T2D completed three 60-min interventions with continuous measurement of oxygen consumption in a randomized and counterbalanced order: (1) Control, (2) Continuous walking (CW; intended 73% of VO2peak), (3) Interval-walking (IW; repeated cycles of 3 min slow [54% of VO2peak] and 3 min fast walking [89% of VO2peak]). Forty-five minutes after completion of the intervention, a 3-h liquid mixed meal tolerance test (MMTT, 450 kcal) with regular satiety assessments and blood samples for appetite-related hormones commenced. An ad libitum meal was served after the MMTT, with subsequent calculation of energy-intake. Moreover, free-living diet records were completed for the following ~32 h. Exercise interventions were well-matched for mean oxygen consumption (CW = 77 ± 2% of VO2peak; IW = 76 ± 1% of VO2peak, P > 0.05). No differences in appetite-related hormones or energy-intake were found (P > 0.05 for all comparisons). IW increased fullness compared to Control shortly after the intervention (P < 0.05) and tended to reduce hunger 2 h into the MMTT compared to CW and Control (P < 0.10). In conclusion, a single exercise session does not affect energy-intake during the following ~4-36 h in subjects with T2D. However, satiety may be affected up to ~3 h after the exercise session, dependent on peak intensity.
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Apetite , Diabetes Mellitus Tipo 2/fisiopatologia , Ingestão de Energia , Terapia por Exercício/métodos , Caminhada , Idoso , Diabetes Mellitus Tipo 2/terapia , Feminino , Esvaziamento Gástrico , Hormônios Gastrointestinais/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de OxigênioRESUMO
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.
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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
Physical activity and alternate-day fasting/caloric restriction may both ameliorate aspects of the metabolic syndrome, such as insulin resistance, visceral fat mass accumulation, and cognitive impairment by overlapping mechanisms. The purpose of this study was to test the hypothesis that alternate-day caloric restriction (ADCR) with overall energy balance would reduce insulin resistance and accumulation of visceral fat, in addition to improving cognitive functions, after 8 consecutive days in bed. Healthy, lean men (n = 20) were randomized to 1) 8 days of bed rest with three daily isoenergetic meals (control group, n = 10); and 2) 8 days of bed rest with 25% of total energy requirements every other day and 175% of total energy requirements every other day (ADCR group). Oral glucose tolerance testing, dual-energy X-ray absorptiometry (DXA) scans, magnetic resonance imaging of the abdomen and brain, VÌo2max, and tests for cognitive function were performed before and after bed rest. In addition, daily fasting blood samples and 24-h glucose profiles by continuous glucose monitoring system were assessed during the 8 days of bed rest period. Bed rest induced insulin resistance, visceral fat accumulation, and worsening of mood. No positive effects emerged from ADCR on these negative health outcomes. Compared with the control group, ADCR was associated with improved and steadier glycemic control on fasting days and higher glycemic fluctuation and indexes of insulin resistance on overeating days. In contrast to our hypothesis, the metabolic impairment induced by 8 days of bed rest was not counteracted by ADCR with overall energy balance. NEW & NOTEWORTHY: Alternate-day caloric restriction without overall energy reduction does not ameliorate the metabolic impairment induced in lean men by 8 days of bed rest.
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Repouso em Cama/efeitos adversos , Síndrome Metabólica/fisiopatologia , Adulto , Afeto/fisiologia , Glicemia/metabolismo , Restrição Calórica/métodos , Cognição/fisiologia , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Jejum/fisiologia , Glucose/metabolismo , Teste de Tolerância a Glucose/métodos , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/metabolismo , Masculino , Síndrome Metabólica/metabolismo , Adulto JovemRESUMO
Bed rest and physical inactivity are the consequences of hospital admission for many patients. Physical inactivity induces changes in glucose metabolism, but its effect on the incretin effect, which is reduced in, e.g., Type 2 diabetes, is unknown. To investigate how 8 days of strict bed rest affects the incretin effect, 10 healthy nonobese male volunteers underwent 8 days of strict bed rest. Before and after the intervention, all volunteers underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the following day to mimic the blood glucose profile from the OGTT. Blood glucose, serum insulin, serum C-peptide, plasma incretin hormones [glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP)], and serum glucagon were measured serially during both the OGTT and the IVGI. The incretin effect is calculated as the relative difference between the area under the curve for the insulin response during the OGTT and that of the corresponding IVGI, respectively. Concentrations of glucose, insulin, C-peptide, and GIP measured during the OGTT were higher after the bed rest intervention (all P < 0.05), whereas there was no difference in the levels of GLP-1 and Glucagon. Bed rest led to a mean loss of 2.4 kg of fat-free mass, and induced insulin resistance evaluated by the Matsuda index, but did not affect the incretin effect (P = 0.6). In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated change in the incretin effect.