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1.
Eur J Clin Nutr ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745052

RESUMO

BACKGROUND/OBJECTIVES: Type 1 diabetes (T1D) is associated with an increase in resting metabolic rate (RMR), but the impact of T1D on other components of 24-h energy expenditure (24-h EE) is not known. Also, there is a lack of equations to estimate 24-h EE in patients with T1D. The aims of this analysis were to compare 24-h EE and its components in young adults with T1D and healthy controls across the spectrum of body mass index (BMI) and derive T1D-specific equations from clinical variables. SUBJECTS/METHODS: Thirty-three young adults with T1D diagnosed ≥1 year prior and 33 healthy controls matched for sex, age and BMI were included in this analysis. We measured 24-h EE inside a whole room indirect calorimeter (WRIC) and body composition with dual x-ray absorptiometry. RESULTS: Participants with T1D had significantly higher 24-h EE than healthy controls (T1D = 2047 ± 23 kcal/day vs control= 1908 ± 23 kcal/day; P < 0.01). We derived equations to estimate 24-h EE with both body composition (fat free mass + fat mass) and anthropometric (weight + height) models, which provided high coefficients of determination (R2 = 0.912 for both). A clinical model that did not incorporate spontaneous physical activity yielded high coefficients of determination as well (R2 = 0.897 and R2 = 0.880 for body composition and anthropometric models, respectively). CONCLUSION: These results confirm that young adults with established T1D have increased 24-h EE relative to controls without T1D. The derived equations from clinically available variables can assist clinicians with energy prescriptions for weight management in patients with T1D.

2.
Obesity (Silver Spring) ; 29(9): 1508-1515, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34355521

RESUMO

OBJECTIVE: This analysis aimed to measure the intraparticipant reliability-the intraclass correlation coefficient-of all the components of daily energy expenditure (EE) (24-hour EE, sleep EE, resting EE, basal EE, and thermic effect of food) over a period of 3 consecutive days in 35 study participants. METHODS: The components of daily EE and substrate use (respiratory exchange ratio) were measured over 3 consecutive days before and after a 3-week 1,000-kcal/d caloric restriction/weight-loss intervention. RESULTS: There was a high degree of reliability for sleep EE (96.8%), 24-hour EE (97.8%), basal EE (90.6%), and resting EE (93.2%) during the run-in period. The intraclass correlation coefficient for the follow-up period after weight loss (3.67 ± 1.10 kg) remained high for sleep EE (95.6%), 24-hour EE (100%), basal EE (96.1%), and resting EE (92.5%). The minimal detectable differences in EE were reduced by 30% for both 24-hour EE and sleep EE when comparing 2 days versus 1 day spent in the whole-room indirect calorimeter. CONCLUSIONS: The reliability of the daily components of EE is very high both prior to and after a weight-loss intervention. We here provide instrumental data for investigators to adequately power studies investigating energy metabolism using whole-room indirect calorimetry.


Assuntos
Metabolismo Energético , Sono , Calorimetria , Calorimetria Indireta , Humanos , Oxirredução , Reprodutibilidade dos Testes
3.
Obesity (Silver Spring) ; 29(6): 1003-1013, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34029448

RESUMO

OBJECTIVE: The aim of this study was to determine the effects of prolonged (72 hours) glucagon administration at a low dose (LD) (12.5 ng/kg/min) and high dose (HD) (25 ng/kg/min) on energy expenditure (EE) in healthy individuals with overweight or obesity. METHODS: Thirty-one healthy participants with overweight or obesity (BMI of 27-45 kg/m2 , 26-55 years old, 23 females) were randomized into LD, HD, or placebo groups and underwent 72-hour intravenous infusion of glucagon. Whole-room calorimetry was used to assess EE and substrate use during five overnight stays (2 days at baseline, 3 days of infusion) and during two 24-hour stays (baseline vs. day 3). Blood was sampled at regular intervals throughout the inpatient stay and analyzed for glucagon and biomarkers of metabolism. RESULTS: HD infusion elevated plasma glucagon levels compared with the placebo and LD infusion (P < 0.001). Sleeping, basal, and 24-hour EE was not significantly different among groups at any time point. Those receiving HD had significantly higher basal fat oxidation (Fat Ox) at days 2 and 3 than those receiving the placebo (P < 0.05); however, no differences in 24-hour Fat Ox were observed among groups (baseline vs. day 3). CONCLUSIONS: An HD plasma glucagon infusion over 72 hours does not increase any aspects of EE in healthy individuals with overweight or obesity.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Glucagon/administração & dosagem , Obesidade/metabolismo , Sobrepeso/metabolismo , Adulto , Calorimetria , Esquema de Medicação , Feminino , Glucagon/farmacologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos , Fatores de Tempo
4.
Obesity (Silver Spring) ; 29 Suppl 1: S31-S38, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33759394

RESUMO

Although many individuals achieve weight loss of 10% or more, the ability to maintain a reduced body mass over months and years is much rarer. Unfortunately, our understanding of the adverse consequences of having overweight and obesity argues that long-term maintenance of a reduced weight provides the greatest health benefit. However, to achieve long-term weight reduction requires overcoming neuroendocrine systems that favor restoration of one's initial weight. Identifying and characterizing the components of these systems will be important if we are to develop therapies and strategies to reduce the rates of obesity and its complications in our modern society. During this session, Eric Ravussin and Steven R. Smith, respectively, discussed the physiology of the weight-reduced state that favors weight regain and a molecular component that contributes to this response.


Assuntos
Metabolismo Energético/fisiologia , Redução de Peso/fisiologia , Humanos , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)/organização & administração , Obesidade/metabolismo , Obesidade/fisiopatologia , Obesidade/terapia , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia , Sobrepeso/terapia , Estados Unidos
5.
Am J Clin Nutr ; 110(4): 805-813, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31204775

RESUMO

BACKGROUND: A metabolic adaptation, defined as an increase in energy expenditure (EE) beyond what is expected with weight gain during overfeeding (OF), has been reported but also refuted. Much of the inconsistency stems from the difficulty in conducting large, well-controlled OF studies in humans. OBJECTIVES: The primary aim of this study was to determine whether a metabolic adaptation to OF exists and if so, attenuates weight gain. METHODS: Thirty-five young adults consumed 40% above their baseline energy requirements for 8 wk, and sleeping metabolic rate (SMR) and 24-h sedentary energy expenditure (24h-EE) were measured before and after OF. Subjects were asked to return for a 6-mo post-OF follow-up visit to measure body weight, body composition, and physical activity. RESULTS: After adjusting for gains in fat-free mass and fat mass, SMR increased by 43 ± 123 kcal/d more than expected (P = 0.05) and 24h-EE by 23 ± 139 kcal/d (P = 0.34), indicating an overall lack of metabolic adaptation during OF despite a wide variability in the response. Among the 30 subjects who returned for the 6-mo follow-up visit, those who had a lower-than-predicted SMR (basal EE) retained more of the fat gained during OF. Likewise, subjects displaying a higher-than-predicted sedentary 24h-EE lost significantly more fat during the 6-mo follow-up. CONCLUSIONS: Metabolic adaptation to OF was on average very small but variable between subjects, revealing "thrifty" or "spendthrift" metabolic phenotypes related to body weight loss 6 mo later. This trial was registered at clinicaltrials.gov as NCT01672632.


Assuntos
Adaptação Fisiológica/fisiologia , Peso Corporal/efeitos dos fármacos , Ingestão de Energia , Metabolismo Energético/fisiologia , Adulto , Peso Corporal/fisiologia , Dieta , Exercício Físico , Feminino , Humanos , Masculino , Mitocôndrias/metabolismo , Fatores de Tempo , Adulto Jovem
6.
Am J Clin Nutr ; 109(5): 1328-1334, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31028699

RESUMO

BACKGROUND: Low-carbohydrate diets have been reported to significantly increase human energy expenditure when measured using doubly labeled water (DLW) but not by respiratory chambers. Although DLW may reveal true physiological differences undetected by respiratory chambers, an alternative possibility is that the expenditure differences resulted from failure to correctly estimate the respiratory quotient (RQ) used in the DLW calculations. OBJECTIVE: To examine energy expenditure differences between isocaloric diets varying widely in carbohydrate and to quantitatively compare DLW data with respiratory chamber and body composition measurements within an energy balance framework. DESIGN: DLW measurements were obtained during the final 2 wk of month-long baseline (BD; 50% carbohydrate, 35% fat, 15% protein) and isocaloric ketogenic diets (KD; 5% carbohydrate, 80% fat, 15% protein) in 17 men with a BMI of 25-35 kg/m2. Subjects resided 2 d/wk in respiratory chambers to measure energy expenditure (EEchamber). DLW expenditure was calculated using chamber-determined RQ either unadjusted (EEDLW) or adjusted (EEDLWΔRQ) for net energy imbalance using diet-specific coefficients. Accelerometers measured physical activity. Body composition changes were measured by dual-energy X-ray absorptiometry (DXA) which were combined with energy intake measurements to calculate energy expenditure by balance (EEbal). RESULTS: After transitioning from BD to KD, neither EEchamber nor EEbal were significantly changed (∆EEchamber = 24 ± 30 kcal/d; P = 0.43 and ∆EEbal = -141 ± 118 kcal/d; P = 0.25). Similarly, physical activity (-5.1 ± 4.8%; P = 0.3) and exercise efficiency (-1.6 ± 2.4%; P = 0.52) were not significantly changed. However, EEDLW was 209 ± 83 kcal/d higher during the KD (P = 0.023) but was not significantly increased when adjusted for energy balance (EEDLWΔRQ = 139 ± 89 kcal/d; P = 0.14). After removing 2 outliers whose EEDLW were incompatible with other data, EEDLW was marginally increased during the KD by 126 ± 62 kcal/d (P = 0.063) and EEDLW∆RQ was only 46 ± 65 kcal/d higher (P = 0.49). CONCLUSIONS: DLW calculations failing to account for diet-specific energy imbalance effects on RQ erroneously suggest that low-carbohydrate diets substantially increase energy expenditure. This trial was registered at clinicaltrials.gov as NCT01967563.


Assuntos
Calorimetria Indireta/métodos , Dieta com Restrição de Carboidratos , Dieta Cetogênica , Carboidratos da Dieta/administração & dosagem , Metabolismo Energético , Comportamento Alimentar , Absorciometria de Fóton , Acelerometria , Adulto , Composição Corporal , Índice de Massa Corporal , Carboidratos da Dieta/metabolismo , Ingestão de Energia , Exercício Físico/fisiologia , Humanos , Masculino , Obesidade/metabolismo , Esforço Físico/fisiologia , Reprodutibilidade dos Testes , Projetos de Pesquisa , Respiração , Água
7.
Metabolism ; 83: 1-10, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29374510

RESUMO

OBJECTIVE: Overfeeding is a strategy for evaluating the effects of excess energy intake. In this secondary analysis we tested the possibility that different levels of dietary protein might differentially modify the response of fatty acyl-carnitines to overfeeding. METHODS: Twenty-three healthy adult men and women were overfed by 40% for 8 weeks while in-patients with diets containing 5% (LPD), 15% (NPD) or 25% (HPD) protein. Plasma fatty acyl-carnitines were measured by gas chromatography/mass spectrometry (GC/MS) at baseline and after 8 weeks of overfeeding. Measurements included: body composition by DXA, energy expenditure by ventilated hood and doubly-labeled water, fat cell size from subcutaneous fat biopsies, and fat distribution by CT scan. RESULTS: Analysis was done on 5 groups of fatty acyl-carnitines identified by principal components analysis and 6 individual short-chain fatty acyl carnitines. Higher protein intake was associated with significantly lower 8 week levels of medium chain fatty acids and C2, C4-OH and C 6:1, but higher values of C3 and C5:1 acyl-carnitines derived from essential amino acids. In contrast energy and fat intake were only weakly related to changes in fatty acyl-carnitines. A decease or smaller rise in 8 week medium chain acyl-carnitines was associated with an increase in sleeping energy expenditure (P = 0.0004), and fat free mass (P < 0.0001) and a decrease in free fatty acid concentrations (FFA) (P = 0.0067). In contrast changes in short-chain fatty acyl-carnitines were related to changes in resting energy expenditure (P = 0.0026), and fat free mass (P = 0.0007), and C4-OH was positively related to FFA (P = 0006). CONCLUSION: Protein intake was the major factor influencing changes in fatty acyl carnitines during overfeeding with higher values of most acyl-fatty acids on the low protein diet. The association of dietary protein and fat intake may explain the changes in energy expenditure and metabolic variables resulting in the observed patterns of fatty acyl carnitines.


Assuntos
Composição Corporal/fisiologia , Carnitina/análogos & derivados , Carnitina/sangue , Metabolismo Energético/fisiologia , Ácidos Graxos/sangue , Hiperfagia/sangue , Hiperfagia/metabolismo , Adolescente , Adulto , Dieta , Ingestão de Energia , Feminino , Humanos , Masculino , Adulto Jovem
8.
Diabetes ; 66(1): 36-44, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27999106

RESUMO

Glucagon (GCG) acutely stimulates energy expenditure (EE) and hepatic glucose production (HGP) in humans, but whether these effects persist during hyperglucagonemia of longer duration is unclear. Using a prospective, randomized, single-blind, crossover study design, we therefore measured EE and rates of glucose appearance (glucose RA) during three separate infusion protocols in healthy lean males: A) 10-h overnight GCG infusion (6 ng/[kg × min]) followed by 3-h infusion of GCG, octreotide (OCT), and insulin (INS) for basal replacement; B) overnight saline (SAL) infusion followed by GCG/OCT/INS infusion; and C) overnight SAL infusion followed by SAL/OCT/INS infusion. Sleep EE, measured at 6 to 7 h of the overnight infusion, was increased 65-70 kcal/24 h in A compared with B and C. During the 3-h infusion, mean resting EE remained significantly increased in A versus C by ∼50 kcal/24 h; in B, resting EE increased with a statistical trend but was not significantly greater than in C. Glucose RA increased to comparable levels in A and B. We conclude that in healthy lean males, stimulation of EE and HGP is sustained during hyperglucagonemia of longer duration when insulin secretion is inhibited. The increase in EE at the present GCG dose was of marginal clinical significance.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Glucagon/farmacologia , Glucose/metabolismo , Fígado/metabolismo , Adulto , Glicemia/metabolismo , Estudos Cross-Over , Glucagon/administração & dosagem , Humanos , Insulina/metabolismo , Fígado/efeitos dos fármacos , Masculino , Método Simples-Cego
9.
Am J Clin Nutr ; 104(2): 324-33, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27385608

RESUMO

BACKGROUND: The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat. OBJECTIVE: We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition. DESIGN: Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW). RESULTS: Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 ± 13 kcal/d, P = 0.0004) and SEE (89 ± 14 kcal/d, P < 0.0001) and decreased RQ (-0.111 ± 0.003, P < 0.0001). EEDLW increased by 151 ± 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass. CONCLUSION: The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. This trial was registered at clinicaltrials.gov as NCT01967563.


Assuntos
Composição Corporal/efeitos dos fármacos , Dieta com Restrição de Carboidratos , Dieta Cetogênica , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Obesidade/dietoterapia , Tecido Adiposo/metabolismo , Adulto , Carboidratos da Dieta/metabolismo , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/metabolismo , Gorduras na Dieta/farmacologia , Ingestão de Energia , Humanos , Masculino , Obesidade/metabolismo , Sobrepeso , Redução de Peso
10.
Am J Clin Nutr ; 101(3): 496-505, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25733634

RESUMO

BACKGROUND: Energy expenditure (EE) increases with overfeeding, but it is unclear how rapidly this is related to changes in body composition, increased body weight, or diet. OBJECTIVE: The objective was to quantify the effects of excess energy from fat or protein on energy expenditure of men and women living in a metabolic chamber. DESIGN: We conducted a randomized controlled trial in 25 participants who ate ∼40% excess energy for 56 d from 5%, 15%, or 25% protein diets. Twenty-four-hour EE (24EE) and sleeping EE (SleepEE) were measured on days 1, 14, and 56 of overfeeding and on day 57 while consuming the baseline diet (usually day 57). Metabolic and molecular markers of muscle metabolism were measured in skeletal muscle biopsy specimens. RESULTS: In the low-protein diet group whose excess energy was fat, the 24EE and SleepEE did not increase during the first day of overfeeding. When extra energy contained protein, both 24EE and SleepEE increased in relation to protein intake (r = 0.50, P = 0.02). The 24EE over 8 wk in all 3 groups was correlated with protein intake (r = 0.60, P = 0.004) but not energy intake (r = 0.16; P = 0.70). SleepEE was unchanged by overfeeding in the low-protein diet group, and baseline surface area predicted increased 24EE in this group. Protein and fat oxidation were reciprocally related during overfeeding. Observed 24EE was higher than predicted on days 1 (P ≤ 0.05), 14 (P = 0.0001), and 56 (P = 0.0007). There was no relation between change in fat mass and change in EE. CONCLUSIONS: Excess energy, as fat, does not acutely increase 24EE, which rises slowly as body weight increases. Excess energy as protein acutely stimulates 24EE and SleepEE. The strongest relation with change in 24EE was the change in energy expenditure in tissue other than muscle or fat-free mass.


Assuntos
Dieta com Restrição de Gorduras/efeitos adversos , Proteínas Alimentares/administração & dosagem , Metabolismo Energético , Hiperfagia/metabolismo , Músculo Quadríceps/metabolismo , Regulação para Cima , Adaptação Fisiológica , Adolescente , Adulto , Biomarcadores/metabolismo , Dieta Hiperlipídica/efeitos adversos , Dieta com Restrição de Proteínas/efeitos adversos , Proteínas Alimentares/efeitos adversos , Proteínas Alimentares/metabolismo , Ingestão de Energia , Feminino , Humanos , Masculino , Comportamento Sedentário , Método Simples-Cego , Termogênese , Aumento de Peso , Adulto Jovem
11.
J Pers Assess ; 97(3): 261-70, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25257898

RESUMO

This pragmatic study evaluated the effectiveness of a collaborative assessment intervention as an approach to midtherapy consultation, which has yet to be empirically tested. Ten adult participants in ongoing psychotherapy with a variety of presenting concerns, primarily consisting of general mood and adjustment issues, received a brief assessment-based intervention based on Finn's (2007) Therapeutic Assessment model. Following the collection of assessment questions and the administration of a multimethod assessment battery, clients and therapists participated in a joint feedback session with the assessor. Clients were then followed as their psychotherapy continued. The results of idiographic and aggregate analytic approaches revealed significant reductions in client-reported symptomatic distress, as evidenced by a medium effect size (d = -.50) and a significant change in the trajectory of distress. Client reports of the process of psychotherapy revealed a significant increase in the clients' ratings of the working alliance. The findings suggest that a midtherapy consultation using collaborative/therapeutic assessment methods is beneficial but that further rigorous investigation is needed.


Assuntos
Transtornos do Humor/terapia , Relações Profissional-Paciente , Psicoterapia/métodos , Encaminhamento e Consulta , Adulto , Comportamento Cooperativo , Retroalimentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/psicologia , Adulto Jovem
12.
Am J Clin Nutr ; 99(4): 834-42, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24500151

RESUMO

BACKGROUND: Achieving energy balance is critical for the interpretation of results obtained in respiratory chambers. However, 24-h energy expenditure (24EE) predictions based on estimated resting metabolic rate and physical activity level are often inaccurate and imprecise. OBJECTIVE: We aimed to develop and validate equations to better achieve energy balance in a respiratory chamber by adding or subtracting food items. DESIGN: By using a randomized data set with measures of 24EE (n = 241) performed at the Pennington Biomedical Research Center, we developed equations to predict 24EE from anthropometric, demographic, and body composition variables before and at 3 and 7 h into the chamber measurement. The equations were tested on an independent data set (n = 240) and compared with published predictive equations. RESULTS: By using anthropometric and demographic variables, the equation was as follows: 24EE (kcal/d) = 11.6 [weight (kg)] + 8.03 [height (cm)] - 3.45 [age (y)] + 217 (male) - 52 (African American) - 235. The mean prediction error was -9 ± 155 kcal/d (2046 ± 305 compared with 2055 ± 343 kcal/d for measured 24EE; P = 0.36). The prediction achieved a precision of ±10% of measured 24EE in 83% of the participants. Energy prescription was then refined by equations with the use of energy expenditure values after 3 h, 7 h, or both into the chamber study. These later equations improved the precision (±10% of measured 24EE) to 92% (P = 0.003) and 96% (P < 0.0001) of the participants at 3 and 7 h, respectively. Body composition did not improve 24EE predictions. CONCLUSIONS: We showed the use of a set of equations to prescribe and adjust energy intake to achieve energy balance in respiratory chambers over 24 h. These equations may be used in most respiratory chambers and modified to accommodate exercise or specific feeding protocols.


Assuntos
Ingestão de Energia , Metabolismo Energético , Modelos Biológicos , Avaliação Nutricional , Necessidades Nutricionais , Adulto , Negro ou Afro-Americano , Metabolismo Basal , Composição Corporal , Índice de Massa Corporal , Ingestão de Energia/etnologia , Estudos de Viabilidade , Feminino , Humanos , Louisiana , Masculino , Pessoa de Meia-Idade , Necessidades Nutricionais/etnologia , Sobrepeso/etnologia , Sobrepeso/metabolismo , Comportamento Sedentário , População Branca , Adulto Jovem
13.
Circ Cardiovasc Imaging ; 6(4): 560-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23661689

RESUMO

BACKGROUND: Lorcaserin is a selective 5-HT2C agonist evaluated for weight management in clinical trials. Echocardiographic monitoring was conducted to test the hypothesis that selective 5-HT2C agonism would avoid valvular heart disease. METHODS AND RESULTS: Echocardiographic and weight change data from 5249 obese and overweight patients in 3 phase 3 trials were integrated. Treatment duration with 10 mg lorcaserin twice daily or placebo was 52 weeks. The proportions of patients who developed Food and Drug Administration-defined valvulopathy (≥ mild aortic or ≥ moderate mitral regurgitation) and changes in regurgitant grade at each heart valve were evaluated. Possible associations between weight or body mass index change and valvulopathy were explored. New valvulopathy was present in 2.04% of placebo and 2.37% of lorcaserin recipients at 52 weeks (risk difference, 0.33%; 95% confidence interval, -0.46 to 1.13; risk ratio, 1.16 [all patients with sufficient echocardiographic data, last-observation-carried-forward imputation] or 1.03 [patients who completed 52 weeks]). Changes in weight and body mass index were negatively associated with presence of valvulopathy at week 52 (P=0.02 and P=0.04, respectively); a 5% decrease in weight was associated with an odds ratio of 1.15 for Food and Drug Administration-defined valvulopathy. Most changes in regurgitation were ±1 grade in both treatment groups at all heart valves. CONCLUSIONS: In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo. Point estimates for risk ratios ranged from 1.03 to 1.16 and may be at least partially influenced by greater weight loss in the lorcaserin group than in the placebo group. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00395135, NCT00603291, NCT00603902.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/prevenção & controle , Benzazepinas/uso terapêutico , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/prevenção & controle , Obesidade/tratamento farmacológico , Receptor 5-HT2C de Serotonina/efeitos dos fármacos , Agonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Adolescente , Adulto , Idoso , Fármacos Antiobesidade/efeitos adversos , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/metabolismo , Benzazepinas/efeitos adversos , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/metabolismo , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/metabolismo , Razão de Chances , Estudos Prospectivos , Receptor 5-HT2C de Serotonina/metabolismo , Fatores de Risco , Agonistas do Receptor 5-HT2 de Serotonina/efeitos adversos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia , Redução de Peso/efeitos dos fármacos , Adulto Jovem
14.
Cell Metab ; 17(4): 534-48, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23562077

RESUMO

The molecular mechanisms involved in the development of obesity and related complications remain unclear. Here, we report that obese mice and human subjects have increased activity of neutrophil elastase (NE) and decreased serum levels of the NE inhibitor α1-antitrypsin (A1AT, SerpinA1). NE null (Ela2(-/-)) mice and A1AT transgenic mice were resistant to high-fat diet (HFD)-induced body weight gain, insulin resistance, inflammation, and fatty liver. NE inhibitor GW311616A reversed insulin resistance and body weight gain in HFD-fed mice. Ela2(-/-) mice also augmented circulating high molecular weight (HMW) adiponectin levels, phosphorylation of AMP-activated protein kinase (AMPK), and fatty acid oxidation (FAO) in the liver and brown adipose tissue (BAT) and uncoupling protein (UCP1) levels in the BAT. These data suggest that the A1AT-NE system regulates AMPK signaling, FAO, and energy expenditure. The imbalance between A1AT and NE contributes to the development of obesity and related inflammation, insulin resistance, and liver steatosis.


Assuntos
Metabolismo Energético , Resistência à Insulina , Elastase de Leucócito/metabolismo , Obesidade/metabolismo , alfa 1-Antitripsina/sangue , Quinases Proteína-Quinases Ativadas por AMP , Adiponectina/sangue , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Fígado Gorduroso/complicações , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Células Hep G2 , Humanos , Inflamação , Canais Iônicos/metabolismo , Leptina/metabolismo , Elastase de Leucócito/antagonistas & inibidores , Elastase de Leucócito/sangue , Fígado/metabolismo , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Camundongos Transgênicos , Proteínas Mitocondriais/metabolismo , Obesidade/complicações , Obesidade/patologia , Oxirredução , Fosforilação , Piperidinas/farmacologia , Proteínas Quinases/metabolismo , Proteína Desacopladora 1 , Aumento de Peso/efeitos dos fármacos , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo
15.
Obesity (Silver Spring) ; 20(12): 2384-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22627912

RESUMO

Weight loss reduces energy expenditure, but it is unclear whether dietary macronutrient composition affects this reduction. We hypothesized that energy expenditure might be modulated by macronutrient composition of the diet. The Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST study, a prospective, randomized controlled trial in 811 overweight/obese people who were randomized in a 2 × 2 design to diets containing 20en% or 40en% fat and 15en% or 25en% protein (diets with 65%, 55%, 45%, and 35% carbohydrate) provided the data to test this hypothesis. Resting energy expenditure (REE) was measured at baseline, 6, and 24 months using a ventilated hood. REE declined at 6 months by 99.5 ± 8.0 kcal/day in men and 55.2 ± 10.6 kcal/day in women during the first 6 months. This decline was related to the weight loss, and there was no difference between the diets. REE had returned to baseline by 24 months, but body weight was still 60% below baseline. Measured REE at 6 months was significantly lower than the predicted (-18.2 ± 6.7 kcal/day) and was the result of significant reductions from baseline in the low-fat diets (65% or 55% carbohydrate), but not in the high fat diet groups. By 24 months the difference had reversed with measured REE being slightly but significantly higher than predicted (21.8 ± 10.1 kcal/day). In conclusion, we found that REE fell significantly after weight loss but was not related to diet composition. Adaptive thermogenesis was evident at 6 months, but not at 24 months.


Assuntos
Metabolismo Basal , Dieta Redutora , Gorduras na Dieta/metabolismo , Proteínas Alimentares/metabolismo , Obesidade/dietoterapia , Obesidade/metabolismo , Redução de Peso , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/fisiopatologia , Estudos Prospectivos , Descanso
16.
JAMA ; 307(1): 47-55, 2012 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-22215165

RESUMO

CONTEXT: The role of diet composition in response to overeating and energy dissipation in humans is unclear. OBJECTIVE: To evaluate the effects of overconsumption of low, normal, and high protein diets on weight gain, energy expenditure, and body composition. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, randomized controlled trial of 25 US healthy, weight-stable male and female volunteers, aged 18 to 35 years with a body mass index between 19 and 30. The first participant was admitted to the inpatient metabolic unit in June 2005 and the last in October 2007. INTERVENTION: After consuming a weight-stabilizing diet for 13 to 25 days, participants were randomized to diets containing 5% of energy from protein (low protein), 15% (normal protein), or 25% (high protein), which they were overfed during the last 8 weeks of their 10- to 12-week stay in the inpatient metabolic unit. Compared with energy intake during the weight stabilization period, the protein diets provided approximately 40% more energy intake, which corresponds to 954 kcal/d (95% CI, 884-1022 kcal/d). MAIN OUTCOME MEASURES: Body composition was measured by dual-energy x-ray absorptiometry biweekly, resting energy expenditure was measured weekly by ventilated hood, and total energy expenditure by doubly labeled water prior to the overeating and weight stabilization periods and at weeks 7 to 8. RESULTS: Overeating produced significantly less weight gain in the low protein diet group (3.16 kg; 95% CI, 1.88-4.44 kg) compared with the normal protein diet group (6.05 kg; 95% CI, 4.84-7.26 kg) or the high protein diet group (6.51 kg; 95% CI, 5.23-7.79 kg) (P = .002). Body fat increased similarly in all 3 protein diet groups and represented 50% to more than 90% of the excess stored calories. Resting energy expenditure, total energy expenditure, and body protein did not increase during overfeeding with the low protein diet. In contrast, resting energy expenditure (normal protein diet: 160 kcal/d [95% CI, 102-218 kcal/d]; high protein diet: 227 kcal/d [95% CI, 165-289 kcal/d]) and body protein (lean body mass) (normal protein diet: 2.87 kg [95% CI, 2.11-3.62 kg]; high protein diet: 3.18 kg [95% CI, 2.37-3.98 kg]) increased significantly with the normal and high protein diets. CONCLUSIONS: Among persons living in a controlled setting, calories alone account for the increase in fat; protein affected energy expenditure and storage of lean body mass, but not body fat storage. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00565149.


Assuntos
Composição Corporal/fisiologia , Proteínas Alimentares/farmacologia , Metabolismo Energético/fisiologia , Hiperfagia/fisiopatologia , Aumento de Peso/fisiologia , Tecido Adiposo , Adolescente , Adulto , Proteínas Alimentares/administração & dosagem , Feminino , Humanos , Masculino , Método Simples-Cego , Adulto Jovem
17.
J Clin Endocrinol Metab ; 96(3): 837-45, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21190985

RESUMO

CONTEXT: Lorcaserin, a selective 5-hydroxytryptamine (5-HT)(2C) receptor agonist, reduces body weight. It is unclear whether weight loss is due to reduced energy intake (EI) or also to enhanced energy expenditure (EE). OBJECTIVE: This study tested the effect of lorcaserin on EI and EE. DESIGN, PARTICIPANTS, AND INTERVENTION: In a double-blind, randomized, placebo-controlled trial, 57 (39 women) overweight and obese (body mass index, 27-45 kg/m(2)) adults were randomized to placebo (n = 28) or 10 mg twice daily lorcaserin (n = 29) for 56 d. Weight maintenance was imposed during d 1-7. Beginning on d 8, participants followed a diet and exercise plan targeting a 600 kcal/d deficit. OUTCOMES: At baseline and after 7 and 56 d of treatment, we measured body weight, body composition (dual x-ray absorptiometry), blood pressure, heart rate, EI at lunch and dinner, subjective appetite ratings, and 24-h EE and 24-h-respiratory quotient (RQ), measured by indirect calorimetry in a respiratory chamber. RESULTS: After 7 d of weight maintenance, EI was significantly (P < 0.01) reduced with lorcaserin but not placebo (mean ± sem for lorcaserin, -286 ± 86 kcal; placebo, -147 ± 89 kcal). After 56 d, lorcaserin resulted in significantly larger reductions in body weight (lorcaserin, -3.8 ± 0.4 kg; placebo, -2.2 ± 0.5 kg; P < 0.01), EI (lorcaserin, -470 ± 87 kcal; placebo, -205 ± 91 kcal; P < .05), and appetite ratings than in placebo. Changes in 24-h EE and 24-h RQ did not differ between groups, even after 24-h EE was adjusted for body weight and composition. Compared with placebo, lorcaserin had no effect on systolic or diastolic blood pressure or heart rate after 56 d. CONCLUSIONS: Lorcaserin reduces body weight through reduced EI, not altered EE or RQ.


Assuntos
Benzazepinas/farmacologia , Peso Corporal/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Receptor 5-HT2C de Serotonina/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Adolescente , Adulto , Idoso , Apetite/efeitos dos fármacos , Benzazepinas/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Composição Corporal/efeitos dos fármacos , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Obesidade/tratamento farmacológico , Obesidade/psicologia , Sobrepeso/tratamento farmacológico , Sobrepeso/psicologia , Oxirredução , Agonistas do Receptor de Serotonina/efeitos adversos , Inquéritos e Questionários , Adulto Jovem
18.
J Pers Assess ; 92(3): 222-31, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20408022

RESUMO

Wagner's (2001) Logical Rorschach (LR) was designed to be a simple but reliable and valid system for assessing psychological distress and cognitive slippage using the Rorschach Inkblot Method (Exner, 2003). In this investigation, we administered the Rorschach to 50 adults with and without trauma histories. Scoring of the test followed both the Comprehensive System (CS; Exner, 2003) and the LR guidelines. Results indicate that the Perceptual Thinking Index (Exner, 2000, 2003), the CS-derived Trauma Content Index (Armstrong & Loewenstein, 1990) and Aggressive Past (Gacono & Meloy, 1994), and the LR Perceptual Accuracy Score (Wagner, 2001) scores were able to differentiate the 2 groups. Despite largely equivocal findings, it appears that some aspects of the LR may have some validity in the assessment of trauma-related phenomena.


Assuntos
Teste de Rorschach/normas , Estresse Psicológico/diagnóstico , Amnésia/diagnóstico , Amnésia/psicologia , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica/normas , Testes Psicológicos/normas , Reprodutibilidade dos Testes , Estresse Psicológico/psicologia , Adulto Jovem
19.
Obesity (Silver Spring) ; 18(8): 1646-51, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20134408

RESUMO

Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and increase the risk of diabetes in patients with schizophrenia. The goal of this study was to assess potential mechanisms of OLZ-induced weight gain and accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and placebo (PBO) in a randomized, double-blind, crossover study. In periods 1 and 2, subjects received OLZ (5 mg for 3 days then OLZ 10 mg for 12 days) or matching PBO separated by a minimum 12-day washout. Twenty-four hour food intake (FI), resting energy expenditure (REE), activity level, metabolic markers, and insulin sensitivity (IS) were assessed. In total, 30 subjects were enrolled and 21 completed both periods. Mean age and BMI were 27 years (range: 18-49 years) and 22.6 +/- 2.2 kg/m(2), respectively. Relative to PBO, OLZ resulted in a 2.62 vs. 0.08 kg increase in body weight (P < 0.001) and 18% (P = 0.052 or 345 kcal) increase in FI. Excluding one subject with nausea and dizziness on the day of OLZ FI measurement, the increase in FI was 547 kcal, (P < 0.05). OLZ increased REE relative to PBO (113 kcal/day, P = 0.003). Significant increases in triglycerides, plasminogen activator inhibitor-I (PAI-I), leptin, and tumor necrosis factor-alpha (TNF-alpha) were observed. No significant differences in activity level or IS were observed. This study provides evidence that OLZ pharmacology drives the early increase in weight through increased FI, without evidence of decreased energy expenditure (EE), activity level, or short-term perturbations in IS.


Assuntos
Antipsicóticos/efeitos adversos , Metabolismo Basal/efeitos dos fármacos , Benzodiazepinas/efeitos adversos , Biomarcadores/sangue , Ingestão de Energia/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos , Adolescente , Adulto , Método Duplo-Cego , Exercício Físico , Humanos , Resistência à Insulina , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Olanzapina , Inibidor 1 de Ativador de Plasminogênio/sangue , Valores de Referência , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
20.
Assessment ; 14(3): 310-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17690386

RESUMO

There have been no previous studies on how often psychologists conduct feedback and whether they view this practice as a useful component of assessment. To explore psychologists' feedback practices and their perception of the effects of feedback on their clients, the authors examined survey data from 719 psychologist members of the International Neuropsychological Society, the National Academy of Neuropsychology, and the Society for Personality Assessment who regularly conducted assessments as part of their professional activities. The results indicated that the majority of respondents (71%) frequently provided in-person assessment feedback to their clients and/or their clients' families. Furthermore, most respondents (72%) indicated that clients found this information to be helpful and positive. Factors contributing to perceived positive feedback effects, including graduate training and feedback session length, were also examined. Last, differences in the feedback practices of psychologists predominantly practicing neuropsychology versus those predominantly practicing personality assessment were sampled and discussed.


Assuntos
Retroalimentação , Transtornos Mentais/diagnóstico , Neuropsicologia/métodos , Determinação da Personalidade , Transtornos da Personalidade/diagnóstico , Padrões de Prática Médica/estatística & dados numéricos , Psicologia Clínica/métodos , Adulto , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Conhecimento Psicológico de Resultados , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Percepção , Inquéritos e Questionários
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