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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments. PURPOSE/HYPOTHESIS: The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors. STUDY TYPE: Cohort. SUBJECTS: Four community-dwelling adults with obesity. FIELD STRENGTH/SEQUENCE: 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE. ASSESSMENT: Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing. STATISTICAL TESTS: Linear regression in MATLAB, ICC analyses using SAS 9.4, one-sided 95% confidence intervals for the ICC. RESULTS: PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF. CONCLUSIONS: We demonstrated harmonization of PDFF, MRS, and MRE-based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.
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Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Projetos Piloto , Reprodutibilidade dos Testes , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Obesidade/patologiaRESUMO
Recent advancements in immunology and islet biology have unveiled remarkable prospects for the postponement of Type 1 diabetes (T1D) through the strategic modulation of the immune system. In this Perspective, we discuss the pharmaceutical strides achieved, traversing from pre-clinical validation to the execution of impactful clinical trials. We begin with the initial investigations involving cyclosporine and glucocorticoids in rodent models, such as the non-obese diabetic (NOD) mouse, which guided early clinical trials. We then discuss the pre-clinical studies using suitable mouse models that eventually led to contemporary clinical trials targeting immune cell functionality and cytokine signaling pathways. Collectively, these discoveries promote the exciting paradigm of immune system modulation to mitigate autoimmunity, which continues to broaden. Notably, the use of baricitinib, a potent JAK1/2 inhibitor, and teplizumab, an anti-CD3 monoclonal antibody, represent discrete methodologies converging upon a singular outcome: the preservation of islet beta-cell functionality. The latter interventional strategies build on the original idea that tempering specific facets of the immune system will generate therapeutic benefit. Enthusiasm from these discoveries stems from efficacy with reduced side effects when compared with past approaches. The success of therapeutic intervention(s) in pre-clinical studies, combined with knowledge about stages of progression to clinical T1D, have ultimately encouraged the design of more successful clinical trials targeting highly specific populations at risk. Collectively, these findings instill a profound sense of optimism, suggesting that the prevention and even reversal of T1D may soon be within reach.
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BACKGROUND: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS: We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS: A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.).
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Colecalciferol/uso terapêutico , Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais , Estado Pré-Diabético/tratamento farmacológico , Vitaminas/uso terapêutico , Administração Oral , Idoso , Colecalciferol/administração & dosagem , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Fatores de Risco , Falha de Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitaminas/administração & dosagemRESUMO
BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.
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Antibacterianos , Estatura , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Prescrições , Aumento de PesoRESUMO
OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.
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COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Criança , Adolescente , Humanos , Feminino , Masculino , Pandemias , COVID-19/epidemiologia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos Retrospectivos , Cetoacidose Diabética/complicaçõesRESUMO
The limitations of self-report measures of dietary intake are well-known. Novel, technology-based measures of dietary intake may provide a more accurate, less burdensome alternative to existing tools. The first objective of this study was to compare participant burden for two technology-based measures of dietary intake among school-age children: the Automated-Self-Administered 24-hour Dietary Assessment Tool-2018 (ASA24-2018) and the Remote Food Photography Method (RFPM). The second objective was to compare reported energy intake for each method to the Estimated Energy Requirement for each child, as a benchmark for actual intake. Forty parent-child dyads participated in two, 3-d dietary assessments: a parent proxy-reported version of the ASA24 and the RFPM. A parent survey was subsequently administered to compare satisfaction, ease of use and burden with each method. A linear mixed model examined differences in total daily energy intake between assessments, and between each assessment method and the Estimated Energy Requirement (EER). Reported energy intake was 379 kcal higher with the ASA24 than the RFPM (P = 0·0002). Reported energy intake with the ASA24 was 231 kcal higher than the EER (P = 0·008). Reported energy intake with the RFPM did not differ significantly from the EER (difference in predicted means = -148 kcal, P = 0·09). Median satisfaction and ease of use scores were five out of six for both methods. A higher proportion of parents reported that the ASA24 was more time-consuming than the RFPM (74·4 % v. 25·6 %, P = 0·002). Utilisation of both methods is warranted given their high satisfaction among parents.
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Rememoração Mental , Avaliação Nutricional , Dieta , Registros de Dieta , Ingestão de Alimentos , Ingestão de Energia , Humanos , Fotografação , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: The aim of this study was to investigate the pharmacokinetic, pharmacodynamic and safety profile of the glucagon-like peptide-1 receptor agonist, lixisenatide, for the treatment of type 2 diabetes (T2D) in pediatric individuals. MATERIALS AND METHODS: In this Phase 1, multicenter, randomized, double-blind, placebo-controlled, parallel-group, ascending repeated dose study (NCT02803918), participants aged ≥10 and < 18 years were randomized 3:1 to receive once-daily lixisenatide in 2-week increments of 5, 10, and 20 µg (n = 18) or placebo (n = 5) for 6 weeks. RESULTS: Mean lixisenatide concentrations generally increased with increasing doses irrespective of anti-drug antibody (ADA) status; however, mean lixisenatide concentrations and inter-subject variability were higher for participants with positive ADA status. Improvements in fasting plasma glucose, post-prandial glucose, AUC0-4.5 , HbA1c , and body weight were observed with lixisenatide. Overall, the safety profile was consistent with the known profile in adults, with no unexpected side effects and no treatment-emergent adverse events resulting in death or discontinuation. The most common events in the lixisenatide group were vomiting (11.1%) and nausea (11.1%). No symptomatic hypoglycemia was reported in either group. No clinically significant hematologic, biochemical or vital sign abnormalities were observed. CONCLUSIONS: Mean lixisenatide concentrations generally increased with increasing dose, irrespective of ADA status. Lixisenatide was associated with improved glycemic control and a trend in body weight reduction compared with placebo. The safety and tolerability profile of repeated lixisenatide doses of up to 20 µg per day in children and adolescents with T2D was reflective of the established safety profile of lixisenatide in adults.
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Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Peptídeos , Adolescente , Glicemia , Peso Corporal , Criança , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Peptídeos/farmacocinética , Peptídeos/uso terapêutico , Resultado do TratamentoRESUMO
AIMS: To assess the pharmacokinetic (PK) and pharmacodynamic characteristics of VI-0521, a fixed-dose combination of immediate-release phentermine (PHEN) and extended-release topiramate (TPM) in adolescents aged 12 to 17 years with obesity, and to report weight loss and adverse events using this drug combination. MATERIALS AND METHODS: This was a multicentre, randomized, double-blind, parallel-design, placebo-controlled study in adolescents with obesity. A total of 42 adolescents were randomly assigned in a 1:1:1 ratio to placebo, or to a mid-dose (PHEN/TPM 7.5 mg/46 mg), or a top-dose (PHEN/TPM 15 mg/92 mg) of VI-0521. A total of 26 adolescents were included in the PK analysis (14 from the mid-dose group and 12 from the top-dose group). RESULTS: On day 56, arithmetic means of terminal elimination half-life, apparent clearance (CL/F) and apparent central volume of distribution (Vc/F) were consistent across dose levels for both PHEN and TPM. Arithmetic means of CL/F and Vc/F for PHEN and TPM administered as a combination in adolescents with obesity were within 10% to 30% of those previously assessed in adults with obesity enrolled in phase II and III studies. A higher proportion of adolescents in both the mid- and top-dose groups (13.3% and 50.0%, respectively) compared with placebo (0.0%) reached ≥5% weight loss at day 56. The least squares (LS) mean change in systolic blood pressure from baseline to day 56 was -5.2 mmHg for the placebo group, -2.5 mmHg for the mid-dose group, and - 5.5 mmHg for the top-dose group. The LS mean change in diastolic blood pressure from baseline to day 56 was -2.4 mmHg for the placebo group, +3.8 mmHg for the mid-dose group, and + 2.0 mmHg for the top-dose group. Participants in the top-dose group had increases in heart rate from baseline of 4.1 bpm, while participants in the mid-dose group experienced a mean decrease in heart rate of 4.5 bpm at day 56. Both PHEN/TPM dose combinations were safe and well tolerated. CONCLUSIONS: Treatment of adolescents with obesity using a fixed-dose combination of PHEN/TPM for 8 weeks resulted in exposure to PHEN and TPM that was comparable to that observed in adults, statistically significant weight loss, and a tolerable safety profile. These data indicate that both mid- and top-dose levels are appropriate for longer-term safety and efficacy studies in adolescents.
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Fármacos Antiobesidade , Adolescente , Fármacos Antiobesidade/efeitos adversos , Criança , Método Duplo-Cego , Frutose/efeitos adversos , Humanos , Obesidade/complicações , Obesidade/tratamento farmacológico , Fentermina/efeitos adversos , TopiramatoRESUMO
BACKGROUND: High levels of sedentary behavior and low physical activity are associated with poor health, and the cognitive determinants of these behaviors in children and adolescents are not well understood. To address this gap, we developed a novel, non-verbal, computer-based assessment to quantify the degree to which youth prefer to be sedentary relative to physically active in their leisure time. METHODS: The Activity Preference Assessment (APA) uses a forced-choice paradigm to understand implicit decision-making processes when presented with common sedentary and physical activities. The APA bias score ranges from - 100 to + 100, with positive scores indicating a relative preference for sedentary activities, and negative scores representing a preference for physical activities. In 60 children ages 8-17 years, we assessed the validity of this behavioral task against a free-choice play observation, accelerometry-measured activity, anthropometrics and body composition, and cardiorespiratory fitness. We explored neighborhood, family, and individual-level factors that may influence implicit activity preferences. Test-retest reliability was assessed over one week. RESULTS: The majority of children (67%) preferred sedentary relative to physical activities. APA bias scores were positively associated with sedentary time during free-choice play. In girls, bias scores were negatively associated with average daily MVPA. APA bias scores were positively associated with body fat and negatively associated with cardiorespiratory fitness. These findings were independent of age, sex, and race/ethnicity. Neighborhood access to physical activity spaces, the number of people in the home, perceived physical self-competence (e.g., coordination, strength), and self-reported depressive symptoms were associated with activity preferences. The intra-class correlation for test-retest reliability was r = 0.59. CONCLUSIONS: The APA shows promise as a novel tool for quantifying children's relative preference for sedentary versus physical activities. Implicit bias scores from the APA are clinically meaningful, as shown by significant associations with adiposity and cardiorespiratory fitness. Future longitudinal studies should examine the directionality of the association between preferences and health markers, and the degree to which implicit activity preferences are modifiable. Importantly, the task only takes an average of 10 min to complete, highlighting a potential role as an efficient screening tool for the propensity to be sedentary versus physically active. TRIAL REGISTRATION: ClinicalTrials.gov NCT03624582 .
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Comportamento do Adolescente , Comportamento Infantil , Tomada de Decisões , Exercício Físico , Atividades de Lazer , Comportamento Sedentário , Inquéritos e Questionários , Acelerometria , Adiposidade , Adolescente , Composição Corporal , Aptidão Cardiorrespiratória , Criança , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Obesidade , Psicometria , Reprodutibilidade dos Testes , Características de Residência , AutorrelatoRESUMO
PURPOSE OF REVIEW: To discuss selected endocrine causes of hypertension and to provide practical clinical recommendations regarding the evaluation and treatment of these disorders. RECENT FINDINGS: More than 15 endocrine disorders with varying rates of prevalence can cause hypertension. For example, primary aldosteronism may exist in up to 20% of patients with resistant hypertension. Recognition of these important secondary causes of hypertension is essential to provide contemporary targeted therapies in order to improve long-term disease outcomes. Clinicians must have a broad understanding of the prevalence, clinical presentation, and current diagnostic modalities for endocrine causes of hypertension to facilitate prompt referral, identification, and optimal management of these disorders. Endocrine causes of hypertension are multifactorial and, in some cases, widely prevalent. It is important for clinicians considering secondary causes of hypertension to be knowledgeable about the underlying pathophysiology of these disorders and to understand when additional evaluation and treatment may be needed.
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Doenças do Sistema Endócrino , Hiperaldosteronismo , Hipertensão , Doenças do Sistema Endócrino/complicações , Humanos , Hiperaldosteronismo/complicações , Hipertensão/etiologiaRESUMO
Cranberries are high in polyphenols, and epidemiological studies have shown that a high-polyphenol diet may reduce risk factors for diabetes and CVD. The present study aimed to determine if short-term cranberry beverage consumption would improve insulin sensitivity and other cardiovascular risk factors. Thirty-five individuals with obesity and with elevated fasting glucose or impaired glucose tolerance participated in a randomised, double-blind, placebo-controlled, parallel-designed pilot trial. Participants consumed 450 ml of low-energy cranberry beverage or placebo daily for 8 weeks. Changes in insulin sensitivity and cardiovascular risk factors including vascular reactivity, blood pressure, RMR, glucose tolerance, lipid profiles and oxidative stress biomarkers were evaluated. Change in insulin sensitivity via hyperinsulinaemic-euglycaemic clamp was not different between the two groups. Levels of 8-isoprostane (biomarker of lipid peroxidation) decreased in the cranberry group but increased in the placebo group (-2·18 v. +20·81 pg/ml; P = 0·02). When stratified by baseline C-reactive protein (CRP) levels, participants with high CRP levels (>4 mg/l) benefited more from cranberry consumption. In this group, significant differences in the mean change from baseline between the cranberry (n 10) and the placebo groups (n 7) in levels of TAG (-13·75 v. +10·32 %; P = 0·04), nitrate (+3·26 v. -6·28 µmol/l; P = 0·02) and 8-isoprostane (+0·32 v. +30·8 pg/ml; P = 0·05) were observed. These findings indicate that 8 weeks of daily cranberry beverage consumption may not impact insulin sensitivity but may be helpful in lowering TAG and changing certain oxidative stress biomarkers in individuals with obesity and a proinflammatory state.
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Bebidas , Doenças Cardiovasculares/prevenção & controle , Resistência à Insulina , Obesidade/complicações , Vaccinium macrocarpon , Adulto , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Método Duplo-Cego , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Placebos , Fatores de RiscoRESUMO
OBJECTIVE: To conduct a preliminary assessment of the relationships between cardiorespiratory fitness, adiposity, and cardiometabolic health using gold standard measures in diverse youth ranging from overweight to severe obesity. METHODS: Twenty of 30 participants (mean [SD]; age 13.2 [1.8] y, 55% female, 45% African American) met the criteria for VO2peak during a graded cycle ergometer test to volitional fatigue. The body composition was measured by dual-energy X-ray absorptiometry (percentage of body fat, fat mass index, and fat-free mass) and magnetic resonance imaging (abdominal visceral and subcutaneous [SAT] adipose tissue). The VO2peak was expressed relative to fat-free mass. Fasting lipid levels, glycemic biomarkers, and vital signs were examined individually and used in a composite cardiometabolic risk score. Accelerometer-measured physical activity and sedentary time were included as covariates. RESULTS: VO2peak was negatively associated with abdominal SAT (r = -.49, P < .05), but not visceral adipose tissue or markers of cardiometabolic health. The association between SAT and VO2peak was partly explained by habitual sedentary time. CONCLUSIONS: We demonstrated a significant negative association between cardiorespiratory fitness and SAT in a diverse group of high-risk youth. The inclusion of rigorous, laboratory-based measures and youth with severe obesity extends the previous work in pediatric populations.
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Adiposidade , Aptidão Cardiorrespiratória , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Adolescente , Criança , Exercício Físico , Feminino , Humanos , Gordura Intra-Abdominal , Masculino , Comportamento SedentárioRESUMO
PURPOSE: Heart rate recovery (HRR) after exercise is an independent risk factor for cardiovascular disease and mortality. Regular aerobic exercise can improve HRR, yet little is known regarding the dose necessary to promote increases. The aim was to assess the impact of different doses of vigorous-intensity aerobic exercise on HRR in individuals with overweight/obesity. METHODS: Data from 137 sedentary adults with overweight/obesity from E-MECHANIC were analyzed. Participants were randomized to either a moderate-dose exercise group (8 kcal/kg body weight/week; KKW), a high-dose exercise group (20 KKW), or a non-exercise control group. HRR was defined as the difference between peak heart rate (HR) during a graded exercise test and the HR after exactly 1 min of active recovery at 1.5 mph and level grade. RESULTS: Change in HRR did not differ significantly by exercise group; therefore, the data from both exercise groups were combined. The combined exercise group showed an improvement in HRR of 2.7 bpm (95% CI 0.1, 5.4; p = 0.04) compared to the control group. Those participants who lost more weight during the intervention (non-compensators) increased HRR by 6.2 bpm (95% CI 2.8, 9.5; p < 0.01) compared to those who lost less weight (compensators). Multiple linear regression models indicated that improvements in HRR are independently associated with increases in VO2peak (ß = 0.4; 95% CI 0.1, 0.7; p = 0.04) but also influenced by concomitant weight loss (ß = 0.6; 95% CI 0.2, 1.1; p = 0.01). CONCLUSION: Exercise-induced improvements in 1-min HRR are likely due to increases in cardiorespiratory fitness as well as concomitant weight loss.
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Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Adulto , Peso Corporal/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Comportamento Sedentário , Redução de Peso/fisiologiaRESUMO
BACKGROUND: Steps/day is widely utilized to estimate the total volume of ambulatory activity, but it does not directly reflect intensity, a central tenet of public health guidelines. Cadence (steps/min) represents an overlooked opportunity to describe the intensity of ambulatory activity. We sought to establish thresholds linking directly observed cadence with objectively measured intensity in 6-20 year olds. METHODS: One hundred twenty participants completed multiple 5-min bouts on a treadmill, from 13.4 m/min (0.80 km/h) to 134.0 m/min (8.04 km/h). The protocol was terminated when participants naturally transitioned to running, or if they chose to not continue. Steps were visually counted and intensity was objectively measured using a portable metabolic system. Youth metabolic equivalents (METy) were calculated for 6-17 year olds, with moderate intensity defined as ≥4 and < 6 METy, and vigorous intensity as ≥6 METy. Traditional METs were calculated for 18-20 year olds, with moderate intensity defined as ≥3 and < 6 METs, and vigorous intensity defined as ≥6 METs. Optimal cadence thresholds for moderate and vigorous intensity were identified using segmented random coefficients models and receiver operating characteristic (ROC) curves. RESULT: Participants were on average (± SD) aged 13.1 ± 4.3 years, weighed 55.8 ± 22.3 kg, and had a BMI z-score of 0.58 ± 1.21. Moderate intensity thresholds (from regression and ROC analyses) ranged from 128.4 steps/min among 6-8 year olds to 87.3 steps/min among 18-20 year olds. Comparable values for vigorous intensity ranged from 157.7 steps/min among 6-8 year olds to 119.3 steps/min among 18-20 year olds. Considering both regression and ROC approaches, heuristic cadence thresholds (i.e., evidence-based, practical, rounded) ranged from 125 to 90 steps/min for moderate intensity, and 155 to 125 steps/min for vigorous intensity, with higher cadences for younger age groups. Sensitivities and specificities for these heuristic thresholds ranged from 77.8 to 99.0%, indicating fair to excellent classification accuracy. CONCLUSIONS: These heuristic cadence thresholds may be used to prescribe physical activity intensity in public health recommendations. In the research and clinical context, these heuristic cadence thresholds have apparent value for accelerometer-based analytical approaches to determine the intensity of ambulatory activity.
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Equivalente Metabólico , Esforço Físico , Caminhada , Adolescente , Adulto , Fatores Etários , Criança , Exercício Físico , Teste de Esforço , Feminino , Humanos , Masculino , Saúde Pública , Curva ROC , Corrida , Adulto JovemRESUMO
BACKGROUND: African American adults experience a high prevalence of obesity and its associated comorbidities, including diabetes. Church-based interventions have been shown to be effective in decreasing weight in this population. mHealth interventions can address two needs for obesity treatment in this community, including enhancing weight loss and providing wide dissemination. OBJECTIVE: This study aimed to assess the feasibility and efficacy of a church-based weight loss intervention that incorporates mHealth technology. METHODS: In this study, 8 churches (n=97) were randomly assigned to the intervention or delayed intervention condition (control group). We recruited participants through their respective church. Volunteer church members were trained by study staff to deliver the 10-session, 6-month intervention. Participants in the intervention group attended group sessions and received automated short message service (SMS) text messages designed to reinforce behavioral strategies. Conversely, participants in the delayed intervention condition received SMS text messages related to health conditions relevant for African American adults. We obtained measures of body composition, blood pressure, blood glucose, and cholesterol. RESULTS: We successfully recruited 97 African American adults, with a mean age of 56.0 (SE 10.3) years and a mean body mass index of 38.6 (SE 6.4) kg/m2 (89/97, 91.8% females), who attended the churches that were randomized to the intervention (n=68) or control (n=29) condition. Of these, 74.2% (72/97) of the participants (47/68, 69.1% intervention; 25/29, 86.2% delayed intervention) completed the 6-month assessment. The average intervention group attendance was 55%. There was a significant difference in weight loss (P=.04) between participants in the intervention (-1.5 (SE 0.5) kg) and control (0.11 (SE 0.6) kg) groups. Among participants in the intervention group, the correlation between the number of SMS text messages sent and the percent body fat loss was r=.3 with P=.04. The participants reported high satisfaction with the automated SMS text messages. CONCLUSIONS: Automated SMS text messages were well-received by participants, suggesting that more enhanced mHealth technologies are a viable option for interventions targeting African American adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT02863887; https://clinicaltrials.gov/ct2/show/NCT02863887 (Archived by WebCite at http://www.webcitation.org/71JiYzizO).
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Cristianismo , Telemedicina/métodos , Envio de Mensagens de Texto , Redução de Peso/fisiologia , Programas de Redução de Peso/métodos , Negro ou Afro-Americano , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
There is a large body of evidence indicating that bariatric surgery provides durable weight loss and health benefits to patients who are obese and have comorbidities such as type 2 diabetes (T2D). However, there are still many questions related to mechanisms of metabolic improvement, predictors of success/failure, and long term consequences, which need to be answered. More recently, there has been a particular interest in the modulation of taste and food preferences that occurs after bariatric surgery and how this affects weight loss in different individuals. Animal models as well as human studies have shed some light on the role of taste in changing food preferences and how these changes may affect weight loss after surgery. The goal of this review is to discuss the physiological and behavioral consequences of bariatric surgery as a treatment for obesity and T2D, with particular emphasis on recent studies describing bariatric surgery-induced modifications in taste perception and food preferences.
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Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/cirurgia , Preferências Alimentares/fisiologia , Obesidade/cirurgia , Paladar/fisiologia , Animais , HumanosRESUMO
OBJECTIVE: Mindfulness is theorized to affect the eating behavior and weight of pregnant women, yet no measure has been validated during pregnancy. METHODS: This study qualitatively and quantitatively evaluated the reliability and validity of the Mindful Eating Questionnaire (MEQ) in overweight and obese pregnant women. Participants completed focus groups and cognitive interviews. The MEQ was administered twice to measure test-retest reliability. The Eating Inventory (EI) and Mindful Attention Awareness Scale (MAAS) were administered to assess convergent validity, and the Neighborhood Environment Walkability Scale (NEWS) assessed discriminant validity. RESULTS: Participants were 20 ± 8 weeks gestation (mean ± SD), 30 ± 2 years old, and 55% were obese. The MEQ total score had good test-retest reliability (r = .85). The total score internal consistency reliability was poor (Cronbach's α = .56). The external cues subscale (ECS) was not internally consistent (α = .31). Other subscales ranged from α = .59-.68. When the ECS was excluded, the MEQ total score internal consistency was acceptable (α = .62). Convergent validity was supported by the MEQ total score (with and without ECS) correlating significantly with the MAAS and the EI disinhibition and hunger subscales. Discriminant validity of the MEQ was supported by the MEQ and NEWS total scores and subscales not being significantly correlated. The quantitative results were supported by the qualitative context and content analysis. CONCLUSION: With the exception of the ECS, the MEQ's reliability and validity was supported in pregnant women, and most of the subscales were more robust in pregnant women than in the original sample of healthy adults. The MEQ's use with overweight and obese pregnant women is supported.
Assuntos
Dieta Saudável , Fenômenos Fisiológicos da Nutrição Materna , Atenção Plena , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Cooperação do Paciente , Complicações na Gravidez/epidemiologia , Adulto , Índice de Massa Corporal , Comportamento Alimentar , Feminino , Humanos , Internet , Louisiana/epidemiologia , Programas de Rastreamento/métodos , Comportamento Materno , Avaliação Nutricional , Gravidez , Pesquisa Qualitativa , Reprodutibilidade dos TestesRESUMO
AIMS/HYPOTHESIS: The role of increased gluconeogenesis as an important contributor to fasting hyperglycaemia at diabetes onset is not known. We evaluated the contribution of gluconeogenesis and glycogenolysis to fasting hyperglycaemia in newly diagnosed youths with type 2 diabetes following an overnight fast. METHODS: Basal rates (µmol kg(FFM) (-1) min(-1)) of gluconeogenesis ((2)H2O), glycogenolysis and glycerol production ([(2)H5] glycerol) were measured in 18 adolescents (nine treatment naive diabetic and nine normal-glucose-tolerant obese adolescents). RESULTS: Type 2 diabetes was associated with higher gluconeogenesis (9.2 ± 0.6 vs 7.0 ± 0.3 µmol kg(FFM) (-1) min(-1), p < 0.01), plasma fasting glucose (7.0 ± 0.6 vs 5.0 ± 0.2 mmol/l, p = 0.004) and insulin (300 ± 30 vs 126 ± 31 pmol/l, p = 0.001). Glucose production and glycogenolysis were similar between the groups (15.4 ± 0.3 vs 12.4 ± 1.4 µmol kg(FFM) (-1) min(-1), p = 0.06; and 6.2 ± 0.8 vs 5.3 ± 0.7 µmol kg(FFM) (-1) min(-1), p = 0.5, respectively). After controlling for differences in adiposity, gluconeogenesis, glycogenolysis and glucose production were higher in diabetic youth (p ≤ 0.02). Glycerol concentration (84 ± 6 vs 57 ± 6 µmol/l, p = 0.01) and glycerol production (5.0 ± 0.3 vs 3.6 ± 0.5 µmol kg(FFM) (-1) min(-1), p = 0.03) were 40% higher in youth with diabetes. The increased glycerol production could account for only ~1/3 of substrate needed for the increased gluconeogenesis in diabetic youth. CONCLUSION/INTERPRETATIONS: Increased gluconeogenesis was a major contributor to fasting hyperglycaemia and hepatic insulin resistance in newly diagnosed untreated adolescents and was an early pathological feature of type 2 diabetes. Increased glycerol availability may represent a significant source of new carbon substrates for increased gluconeogenesis but would not account for all the carbons required to sustain the increased rates.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Gluconeogênese/fisiologia , Glucose/metabolismo , Hiperglicemia/metabolismo , Adolescente , Criança , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Hiperglicemia/sangue , Resistência à Insulina/fisiologia , MasculinoRESUMO
OBJECTIVE: To compare outcomes of diabetic ketoacidosis (DKA) 6 yrs before and 6 yrs after changing rehydration fluids from ½ normal saline to Lactated Ringer's and decreasing the total intended fluid volume administered in the first 24 hrs from 3500 mL/m(2) /d to ≤ 2500 mL/m(2) /d at Texas Children's Hospital (TCH) in response to recommendations by the ESPE, LWPES, and ISPAD in 2004. SUBJECTS/METHODS: A retrospective cohort study was conducted in which 1868 admissions for DKA were identified and reviewed. The cohort was divided into two groups: Group A, 1998-2004, and Group B, 2004-2010. Subjects with suspected clinical cerebral edema and adverse outcomes were identified. RESULTS: Although not statistically significant, there was an equal number (n = 3) of adverse outcomes (death or neurological damage) in each group despite more than double the admissions in Group B (1264) compared with those in Group A (604). Overall, the incidence of suspected clinical cerebral edema was more than double for those admissions in which fluid resuscitation was initiated at an outside hospital (OSH) vs. at TCH (13.6 vs. 5.3%, p < 0.001). CONCLUSIONS: Decreasing the intended fluid rate during the initial 24 hrs to 2500 mL/m(2) /d and increasing the IV fluid sodium content did not significantly decrease the incidence of adverse outcomes in children with DKA. However, children transferred from an OSH had a higher incidence of suspected clinical cerebral edema. Thus, we need to more readily share our management protocols with the emergency rooms of local referring hospitals to potentially decrease the incidence of suspected clinical cerebral edema and adverse outcomes in children transferred with DKA.
Assuntos
Edema Encefálico/epidemiologia , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/terapia , Hidratação/métodos , Adolescente , Edema Encefálico/etiologia , Criança , Cetoacidose Diabética/complicações , Feminino , Hidratação/estatística & dados numéricos , Humanos , Incidência , Soluções Isotônicas/uso terapêutico , Masculino , Estudos Retrospectivos , Lactato de Ringer , Cloreto de Sódio/uso terapêutico , Resultado do TratamentoRESUMO
Based on self-report in the GRADE diabetes study, cumulative incidence of retinopathy was low over 5 years (3.7 %; 184 of 4098 participants) and did not differ among the 4 treatment groups (glargine 4.0 %, glimepiride 3.2 %, liraglutide 3.7 %, sitagliptin 3.8 %). There were no differences in retinopathy with specific therapies in GRADE. Clinicaltrials.gov identifier: NCT01794143.