RESUMO
Conventionally, women are perceived to feel colder than men, but controlled comparisons are sparse. We measured the response of healthy, lean, young women and men to a range of ambient temperatures typical of the daily environment (17 to 31 °C). The Scholander model of thermoregulation defines the lower critical temperature as threshold of the thermoneutral zone, below which additional heat production is required to defend core body temperature. This parameter can be used to characterize the thermoregulatory phenotypes of endotherms on a spectrum from "arctic" to "tropical." We found that women had a cooler lower critical temperature (mean ± SD: 21.9 ± 1.3 °C vs. 22.9 ± 1.2 °C, P = 0.047), resembling an "arctic" shift compared to men. The more arctic profile of women was predominantly driven by higher insulation associated with more body fat compared to men, countering the lower basal metabolic rate associated with their smaller body size, which typically favors a "tropical" shift. We did not detect sex-based differences in secondary measures of thermoregulation including brown adipose tissue glucose uptake, muscle electrical activity, skin temperatures, cold-induced thermogenesis, or self-reported thermal comfort. In conclusion, the principal contributors to individual differences in human thermoregulation are physical attributes, including body size and composition, which may be partly mediated by sex.
Assuntos
Regulação da Temperatura Corporal , Humanos , Feminino , Masculino , Regulação da Temperatura Corporal/fisiologia , Adulto , Regiões Árticas , Adulto Jovem , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Marrom/metabolismo , Caracteres Sexuais , Fatores Sexuais , Temperatura Corporal/fisiologia , Termogênese/fisiologia , Metabolismo Basal/fisiologiaRESUMO
BACKGROUND & AIMS: Hepatic energy metabolism is a dynamic process modulated by multiple stimuli. In nonalcoholic fatty liver disease (NAFLD), human studies typically focus on the static fasting state. We hypothesized that unique postprandial alterations in hepatic lipid metabolism are present in NAFLD. METHODS: In a prospective clinical study, 37 patients with NAFLD and 10 healthy control subjects ingested a standardized liquid meal with pre- and postprandial blood sampling. Postprandial plasma lipid kinetics were characterized at the molecular lipid species level by untargeted lipidomics, cluster analysis, and lipid particle isolation, then confirmed in a mouse model. RESULTS: There was a specific increase of multiple plasma diacylglycerol (DAG) species at 4 hours postprandially in patients with NAFLD but not in controls. This was replicated in a nonalcoholic steatohepatitis mouse model, where postprandial DAGs increased in plasma and concomitantly decreased in the liver. The increase in plasma DAGs appears early in the disease course, is dissociated from NAFLD severity and obesity, and correlates with postprandial insulin levels. Immunocapture isolation of very low density lipoprotein in human samples and stable isotope tracer studies in mice revealed that elevated postprandial plasma DAGs reflect hepatic secretion of endogenous, rather than meal-derived lipids. CONCLUSIONS: We identified a selective insulin-related increase in hepatic secretion of endogenously derived DAGs after a mixed meal as a unique feature of NAFLD. DAGs are known to be lipotoxic and associated with atherosclerosis. Although it is still unknown whether the increased exposure to hepatic DAGs contributes to extrahepatic manifestations and cardiovascular risk in NAFLD, our study highlights the importance of extending NAFLD research beyond the fasting state.
Assuntos
Insulinas , Hepatopatia Gordurosa não Alcoólica , Animais , Diglicerídeos/metabolismo , Humanos , Insulinas/metabolismo , Lipidômica , Fígado/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estudos ProspectivosRESUMO
Sleep has been shown to affect cognitive function in laboratory studies; however, its association to the academic performance of adolescents has largely been demonstrated using self-reported measures. Studies with objective measures of both sleep and academic performance are limited. The aim of the present study was to determine whether the free-living sleep quantity, quality, and timing of 15-year-old adolescents measured with wrist actiography are associated with their scores on national standardised examinations as an objective measure of academic achievement. We measured sleep with wrist actiography for 1 week in 253 (150 girls) Icelandic adolescents with a mean (SD) age of 15.9 (0.3) years. Multiple linear regression was used to assess associations between sleep parameters and combined standardised examination scores in mathematics, English, and Icelandic obtained from the Icelandic Directorate of Education. We found that students went to bed at 00:49 hours (± 51.8 min) and slept for a mean (SD) of 6.6 (0.7) hr/night, with a median (interquartile range) night-to-night variation in sleep duration of 1.2 (0.7) hr and an efficiency of 88.1 (5.3)%. Combined analyses adjusted for sex, demonstrated that both bedtime and night-to-night variability in total sleep time were negatively associated with the average score across all topics. Sex-specific associations did not indicate clear differences between boys and girls. These findings suggest that, in addition to appropriate sleep duration, public health guidance should also highlight the importance of early and consistent sleep schedules to academic achievement for both boys and girls.
Assuntos
Sono , Estudantes , Adolescente , Cognição , Escolaridade , Feminino , Humanos , Masculino , AutorrelatoRESUMO
BACKGROUND: Metabolic disease risk in youth is influenced by sedentary behaviors. Acute in-lab studies show that, during a single day, interrupting a sedentary period with short bouts of physical activity improves glucometabolic outcomes. OBJECTIVE: To determine if acutely improved glucose metabolism persists after multi-day interruptions of sitting with walking brief bouts. We hypothesized that children who underwent interrupting sitting on multiple days would demonstrate lower insulin area under the curve during an oral glucose tolerance test compared to uninterrupted sitting. METHODS: Healthy, normoglycemic children (N = 109) ages 7-11 years were randomized to one of two conditions: Control (3 h of daily Uninterrupted Sitting) or Interrupted Sitting (3-min of moderate-intensity walking every 30 min for 3 h daily); with dietary intake controlled through provision of foodstuffs for the entire experiment. Participants attended six consecutive daily visits at a research ambulatory unit. The primary outcome was insulin area under the curve during the oral glucose tolerance test on day 6 during interrupted or uninterrupted sitting; secondary outcomes included glucose and c-peptide area under the curve, energy intake at a buffet meal on day 6, and free-living activity. RESULTS: Among 93 children (42 uninterrupted sitting, 51 interrupted sitting), daily interrupted sitting resulted in 21% lower insulin (ß = 0.102 CI:0.032-0.172, p = 0.005) and a 10% lower C-peptide (ß = 0.043, CI:0.001-0.084, p = 0.045) area under the curve. Matsuda and Glucose Effectiveness Indices were also improved (p's < 0.05). There were no group differences in energy intake or expenditure. CONCLUSIONS: Sustained behavioral change by interrupting sedentary behaviors is a promising intervention strategy for improving metabolic risk in children.
Assuntos
Glicemia , Comportamento Sedentário , Humanos , Criança , Adolescente , Glicemia/metabolismo , Peptídeo C/metabolismo , Exercício Físico , Glucose , Insulina/metabolismo , Estudos Cross-Over , Período Pós-PrandialRESUMO
The current obesity pandemic results from a physiological imbalance in which energy intake chronically exceeds energy expenditure (EE), and prevention and treatment strategies remain generally ineffective. Approaches designed to increase EE have been informed by decades of experiments in rodent models designed to stimulate adaptive thermogenesis, a long-term increase in metabolism, primarily induced by chronic cold exposure. At the cellular level, thermogenesis is achieved through increased rates of futile cycling, which are observed in several systems, most notably the regulated uncoupling of oxidative phosphorylation from ATP generation by uncoupling protein 1, a tissue-specific protein present in mitochondria of brown adipose tissue (BAT). Physiological activation of BAT and other organ thermogenesis occurs through ß-adrenergic receptors (AR), and considerable effort over the past 5 decades has been directed toward developing AR agonists capable of safely achieving a net negative energy balance while avoiding unwanted cardiovascular side effects. Recent discoveries of other BAT futile cycles based on creatine and succinate have provided additional targets. Complicating the current and developing pharmacological-, cold-, and exercise-based methods to increase EE is the emerging evidence for strong physiological drives toward restoring lost weight over the long term. Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.
Assuntos
Metabolismo Energético , Mitocôndrias/metabolismo , Obesidade/terapia , Termogênese , Tecido Adiposo Marrom/metabolismo , Peso Corporal , Gerenciamento Clínico , Ingestão de Energia/fisiologia , Humanos , Obesidade/metabolismo , Obesidade/fisiopatologia , Fosforilação Oxidativa , Receptores Adrenérgicos beta/metabolismoRESUMO
Gluconeogenesis (GNG), the formation of glucose from noncarbohydrate precursors, requires adenosine triphosphate (ATP). Previous studies have estimated the energetic cost of GNG in humans based on theoretical calculations of rates of GNG, moles of oxygen consumption by GNG, and average oxygen consumption. Few human studies have measured the energy expenditure (EE) due to GNG. We estimated EE attributable to GNG in patients with three insulin resistance conditions and high GNG rates (insulin receptor pathogenic variants, lipodystrophy, and type 2 diabetes) and obesity without diabetes. Fractional GNG was measured by incorporation of deuterium from body water into newly formed glucose, endogenous glucose production (EGP) as glucose appearance following administration of [6,6-2H2]glucose, and total GNG as fractional GNG × EGP. EE was measured by indirect calorimetry and compared with predicted EE from the Mifflin St. Jeor equation. EE attributable to GNG was estimated using linear regression after accounting for age and fat-free mass (FFM). EE in patients with insulin resistance was significantly higher than predicted by the Mifflin St. Jeor equation. GNG correlated with resting EE (REE). EE attributable to GNG in patients with insulin resistance was almost one-third of REE, substantially higher than theorized in healthy subjects. Our findings demonstrate that GNG is a significant contributor to EE in insulin-resistant states. Prediction equations may underestimate caloric needs in patients with insulin resistance. Therefore, targeting caloric needs to account for higher EE due to increased GNG should be considered in energy balance studies in patients with insulin resistance.NEW & NOTEWORTHY Gluconeogenesis is an energy-requiring process that is upregulated in diabetes, contributing to hyperglycemia. Previous studies have estimated that gluconeogenesis accounts for less than 10% of resting energy expenditure. This study estimates the energy expenditure attributable to gluconeogenesis in uncommon and severe forms of insulin resistance and common, milder forms of insulin resistance. In these populations, gluconeogenesis accounts for almost one-third of resting energy expenditure, substantially higher than previously theorized in the literature.
Assuntos
Metabolismo Energético/fisiologia , Gluconeogênese/fisiologia , Resistência à Insulina , Adolescente , Adulto , Calorimetria Indireta , Criança , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Lipodistrofia/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Adulto JovemRESUMO
Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m2; 8 obese, BMI 34.8 ± 3.3 kg/m2] after 5 h of tolerable cold exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1-71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT-cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal-with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.
Assuntos
Tecido Adiposo Marrom/diagnóstico por imagem , Adiposidade , Índice de Massa Corporal , Obesidade/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Tecido Adiposo Marrom/metabolismo , Adulto , Glucose-6-Fosfato/administração & dosagem , Glucose-6-Fosfato/análogos & derivados , Humanos , Masculino , Obesidade/metabolismoRESUMO
PURPOSE: Sedentary time relates to higher anxiety and more negative affect in children. This study assessed whether interrupting sitting over 3 hours is sufficient to influence state anxiety, positive affect, or negative affect, and tested weight status as a moderator. METHODS: Analyses were the second (preplanned) purpose of a larger study. Children (N = 61; age: mean [SD] = 9.5 [1.3]; 43% healthy weight) completed 2 experimental conditions: continuous sitting for 3 hours and sitting for 3 hours interrupted with walking for 3 minutes in every 30 minutes. State anxiety, positive affect, and negative affect were reported at pretest and posttest. Multilevel models for repeated measures assessed whether experimental condition predicted posttest scores. RESULTS: Experimental condition was unrelated to posttest state anxiety or positive affect. Weight status moderated how experimental condition influenced posttest negative affect (P = .003). Negative affect was lower in the children of healthy weight after interrupted sitting (vs continuous sitting; ß = -0.8; 95% confidence interval, -1.5 to 0.0, P = .05), but it was higher in the children with overweight/obesity after interrupted sitting (vs continuous sitting; ß = 0.6; 95% confidence interval, 0.0 to 1.2, P = .06). CONCLUSIONS: Interrupting sitting acutely reduced negative affect in children of healthy weight, but not in children with overweight. Further research is needed to better understand the potential emotional benefits of sitting interruptions in youth.
Assuntos
Afeto , Ansiedade/diagnóstico , Sobrepeso/psicologia , Obesidade Infantil/psicologia , Comportamento Sedentário , Peso Corporal , Criança , Estudos Cross-Over , Feminino , Humanos , Masculino , Maryland , Postura Sentada , Fatores de Tempo , CaminhadaRESUMO
Accurate estimation of energy expenditure (EE) from accelerometer outputs remains a challenge in older adults. The aim of this study was to validate different ActiGraph (AG) equations for predicting EE in older adults. Forty older adults (age = 77.4 ± 8.1 yrs) completed a set of household/gardening activities in their residence, while wearing an AG at the hip (GT3X+) and a portable calorimeter (MetaMax 3B - criterion). Predicted EEs from AG were calculated using five equations (Freedson, refined Crouter, Sasaki and Santos-Lozano (vertical-axis, vectormagnitude)). Accuracy of equations was assessed using root-mean-square error (RMSE) and mean bias. The Sasaki equation showed the lowest RMSE for all activities (0.47 METs) and across physical activity intensities (PAIs) (range 0.18-0.48 METs). The Freedson and Santos-Lozano equations tended to overestimate EE for sedentary activities (range: 0.48 to 0.97 METs), while EEs for moderate-to-vigorous activities (MVPA) were underestimated (range: -1.02 to -0.64 METs). The refined Crouter and Sasaki equations showed no systematic bias, but they respectively overestimated and underestimated EE across PAIs. In conclusion, none of the equations was completely accurate for predicting EE across the range of PAIs. However, the refined Crouter and Sasaki equations showed better overall accuracy and precision when compared with the other methods.
Assuntos
Actigrafia/métodos , Actigrafia/estatística & dados numéricos , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Atividades Cotidianas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Calorimetria Indireta , Feminino , Monitores de Aptidão Física , Humanos , Masculino , Reprodutibilidade dos Testes , Comportamento SedentárioRESUMO
Dynamic sitting, such as fidgeting and desk work, might be associated with health, but remains difficult to identify out of accelerometry data. We examined, in a laboratory study, whether dynamic sitting can be identified out of triaxial activity counts. Among 18 participants (56% men, 27.3 ± 6.5 years), up to 236 counts per minute were recorded in the anteroposterior and mediolateral axes during dynamic sitting using a hip-worn accelerometer. Subsequently, we examined in 621 participants (38% men, 80.0 ± 4.7 years) from the AGES-Reykjavik Study whether dynamic sitting was associated with cardio-metabolic health. Compared to participants who recorded the fewest dynamic sitting minutes (Q1), those with more dynamic sitting minutes had a lower BMI (Q2 = -1.39 (95%CI = -2.33;-0.46); Q3 = -1.87 (-2.82;-0.92); Q4 = -3.38 (-4.32;-2.45)), a smaller waist circumference (Q2 = -2.95 (-5.44;-0.46); Q3 = -3.47 (-6.01;-0.93); Q4 = -8.21 (-10.72;-5.71)), and a lower odds for the metabolic syndrome (Q2 = 0.74 [0.45;1.20] Q3 = 0.58 [0.36;0.95]; Q4 = 0.36 [0.22;0.59]). Our findings suggest that dynamic sitting might be identified using accelerometry and that this behaviour was associated with health. This might be important given the large amounts of time people spend sitting. Future studies with a focus on validation, causation and physiological pathways are needed to further examine the possible relevance of dynamic sitting.
Assuntos
Acelerometria/instrumentação , Metabolismo Energético , Exercício Físico/fisiologia , Comportamento Sedentário , Postura Sentada , Adolescente , Adulto , Índice de Massa Corporal , Feminino , Monitores de Aptidão Física , Humanos , Masculino , Síndrome Metabólica , Pessoa de Meia-Idade , Fatores de Risco , Circunferência da Cintura , Adulto JovemRESUMO
Bombesin-like receptor 3 (BRS-3) is an orphan G protein-coupled receptor that regulates energy expenditure, food intake, and body weight. We examined the effects of BRS-3 deletion and activation on blood pressure and heart rate. In free-living, telemetered Brs3 null mice the resting heart rate was 10% lower than wild-type controls, while the resting mean arterial pressure was unchanged. During physical activity, the heart rate and blood pressure increased more in Brs3 null mice, reaching a similar heart rate and higher mean arterial pressure than control mice. When sympathetic input was blocked with propranolol, the heart rate of Brs3 null mice was unchanged, while the heart rate in control mice was reduced to the level of the null mice. The intrinsic heart rate, measured after both sympathetic and parasympathetic blockade, was similar in Brs3 null and control mice. Intravenous infusion of the BRS-3 agonist MK-5046 increased mean arterial pressure and heart rate in wild-type but not in Brs3 null mice, and this increase was blocked by pretreatment with clonidine, a sympatholytic, centrally acting α2-adrenergic agonist. In anesthetized mice, hypothalamic infusion of MK-5046 also increased both mean arterial pressure and heart rate. Taken together, these data demonstrate that BRS-3 contributes to resting cardiac sympathetic tone, but is not required for activity-induced increases in heart rate and blood pressure. The data suggest that BRS-3 activation increases heart rate and blood pressure via a central sympathetic mechanism.
Assuntos
Pressão Sanguínea , Frequência Cardíaca , Receptores da Bombesina/metabolismo , Sistema Nervoso Simpático/fisiologia , Adrenérgicos/farmacologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Receptores da Bombesina/genética , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismoRESUMO
The technology and application of current accelerometer-based devices in physical activity (PA) research allow the capture and storage or transmission of large volumes of raw acceleration signal data. These rich data not only provide opportunities to improve PA characterisation, but also bring logistical and analytic challenges. We discuss how researchers and developers from multiple disciplines are responding to the analytic challenges and how advances in data storage, transmission and big data computing will minimise logistical challenges. These new approaches also bring the need for several paradigm shifts for PA researchers, including a shift from count-based approaches and regression calibrations for PA energy expenditure (PAEE) estimation to activity characterisation and EE estimation based on features extracted from raw acceleration signals. Furthermore, a collaborative approach towards analytic methods is proposed to facilitate PA research, which requires a shift away from multiple independent calibration studies. Finally, we make the case for a distinction between PA represented by accelerometer-based devices and PA assessed by self-report.
Assuntos
Acelerometria/métodos , Exercício Físico/fisiologia , Acelerometria/tendências , Consenso , Difusão de Inovações , Humanos , Monitorização Ambulatorial/métodos , Monitorização Ambulatorial/tendências , Inquéritos Nutricionais , AutorrelatoRESUMO
We aimed to compare self-reported adherence to the physical activity recommendation with accelerometry in older adults and to identify determinants of misperception. The sample included 138 adults age 65-75 yr old participating in the Longitudinal Aging Study Amsterdam. Participants completed a lifestyle questionnaire and wore an accelerometer for one week. More than half (56.8%) of the participants reported to adhere to the physical activity recommendation (in 5-min bouts), however, based on accelerometry, this percentage was only 24.6%. Of those who reported to adhere, 65.3% did not do so based on accelerometry. The misperceivers were older (p < .009), more often female (p = .007), had a poorer walking performance (p = .02), reported a lower social support (p = .04), and tended to have a lower self-efficacy (p = .09) compared with those who correctly perceived their adherence to the recommendation. These results suggest that misperception of adherence to the physical activity recommendation is highly prevalent among specific subgroups of older adults.
Assuntos
Exercício Físico , Conhecimentos, Atitudes e Prática em Saúde , Atividade Motora/fisiologia , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Comportamento de Redução do Risco , Autorrelato/classificação , Acelerometria , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/classificação , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
PURPOSE: Accelerometers are used to objectively measure physical behaviors in free-living environments, typically for seven consecutive days or more. We examined whether participants experience "wear fatigue," a decline in wear time day over day, during typical assessment period acquired in a nationally representative sample of 6- to 80-yr-olds in the United States. METHODS: Participants were instructed to wear an ActiGraph GT3X+ on their nondominant wrist continuously for seven consecutive days. Participants with seven complete days of recorded data, regardless of wear status, were included in the analyses ( N = 13,649). Wear was scored with the sleep, wake, and nonwear algorithm. RESULTS: Participants averaged 1248 ± 3.6 min·d -1 (mean ± SE) of wear over the assessment, but wear time linearly decreased from day 1 (1295 ± 3.2 min) to day 7 (1170 ± 5.3 min), resulting in a wear fatigue of -18.1 ± 0.7 min·d -1 ( ß ± SE). Wear fatigue did not differ by sex but varied by age-group-highest in adolescents (-26.8 ± 2.4 min·d -1 ) and lowest in older adults (-9.3 ± 0.9 min·d -1 ). Wear was lower in evening (1800-2359 h) and early morning (0000-0559 h) compared with the middle of the day and on weekend days compared with weekdays. We verified similar wear fatigue (-23.5 ± 0.7 min·d -1 ) in a separate sample ( N = 14,631) with hip-worn devices and different wear scoring. Applying minimum wear criteria of ≥10 h·d -1 for ≥4 d reduced wear fatigue to -5.3 and -18.7 min·d -1 for the wrist and hip, respectively. CONCLUSIONS: Patterns of wear suggest noncompliance may disproportionately affect estimates of sleep and sedentary behavior, particularly for adolescents. Further study is needed to determine the effect of wear fatigue on longer assessments.
Assuntos
Acelerometria , Punho , Adolescente , Humanos , Idoso , Inquéritos Nutricionais , Comportamento Sedentário , Cooperação do PacienteRESUMO
OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and ß-cell function after therapy in AA Y-T2D. METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9â kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. ß-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test. RESULTS: At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (-2.0 ± 1.3 vs -0.6 ± 0.9â mmol/L, P = .008) and a greater increase in sigma (0.72 ± 0.68 vs -0.05 ± 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: -0.36 ± 9.4 vs Met: 0.04 ± 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI. CONCLUSION: Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance ß-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.
RESUMO
Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
Assuntos
Doenças Transmissíveis , Síndrome de Fadiga Crônica , Humanos , Síndrome de Fadiga Crônica/metabolismo , Leucócitos Mononucleares/metabolismo , Doenças Transmissíveis/metabolismo , Biomarcadores/metabolismo , FenótipoRESUMO
BACKGROUND: objectively measured population physical activity (PA) data from older persons is lacking. The aim of this study was to describe free-living PA patterns and sedentary behaviours in Icelandic older men and women using accelerometer. METHODS: from April 2009 to June 2010, 579 AGESII-study participants aged 73-98 years wore an accelerometer (Actigraph GT3X) at the right hip for one complete week in the free-living settings. RESULTS: in all subjects, sedentary time was the largest component of the total wear time, 75%, followed by low-light PA, 21%. Moderate-vigorous PA (MVPA) was <1%. Men had slightly higher average total PA (counts × day(-1)) than women. The women spent more time in low-light PA but less time in sedentary PA and MVPA compared with men (P < 0.001). In persons <75 years of age, 60% of men and 34% of women had at least one bout ≥10 min of MVPA, which decreased with age, with only 25% of men and 9% of women 85 years and older reaching this. CONCLUSION: sedentary time is high in this Icelandic cohort, which has high life-expectancy and is living north of 60° northern latitude.
Assuntos
Atividades Cotidianas , Envelhecimento , Atividade Motora , Comportamento Sedentário , Actigrafia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Índice de Massa Corporal , Feminino , Interação Gene-Ambiente , Humanos , Islândia , Vida Independente , Longevidade , Masculino , Fatores Sexuais , Natação , Fatores de TempoRESUMO
Studies of adolescent body image and screen use are mostly limited to girls, and longitudinal data are scarce. We examined cross-sectional and longitudinal associations between these variables in mid-adolescent boys and girls. Data was collected when participants were at age 15 and 17, by questionnaire and objective measurements (n = 152 had complete data). Sex-specific linear regression was used to explore cross-sectional and longitudinal associations of self-reported screen use (total use, and time spent in gaming, TV/DVD/internet-based watching and internet use for communication) and body image, adjusting for vigorous physical activity, symptoms of depression, and body composition. Screen time was negatively associated with body image at both time points, although more strongly at age 15, and for girls only. Gaming and TV/DVD/internet watching was more strongly associated with body image than internet use for communication. Girls with above median screen time at both ages had 14% lower body image score at age 17 than girls with below median screen time at both time points. Our results suggest that screen use is likely to play a role in the development of body dissatisfaction among adolescent females. Limiting screen time may, therefore, help to mitigate body dissatisfaction in adolescent girls.
Assuntos
Imagem Corporal , Tempo de Tela , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e Questionários , TelevisãoRESUMO
An appealing strategy for treatment of metabolic disease in humans is activation of brown adipose tissue (BAT), a thermogenic organ best visualized through 18F-FDG PET/CT. BAT has been activated to varying degrees by mild cold exposure. However, this approach can cause undesirable stress, and there remains no consensus protocol. Here, we describe standardized methods for both acute and chronic activation of BAT using the orally administered ß3-adrenergic receptor (AR) agonist, mirabegron. Acute pharmacological stimulation has enabled quantification of whole-body BAT volume and metabolic activity using PET/CT imaging, and chronic stimulation increases these properties of BAT over time.