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1.
Int J Obes (Lond) ; 41(11): 1669-1675, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28736441

RESUMEN

BACKGROUND/OBJECTIVES: Resistance and reactance collected by bioelectrical impedance (BIA) can be used in equations to estimate percent body fat at relatively low cost and subject burden. To our knowledge, no such equations have been developed in a nationally representative sample. SUBJECTS/METHODS: Dual-energy X-ray absorptiometry assessed percent body fat from the 1999 to 2004 National Health and Nutrition Survey was the criterion method for development of sex-specific percent body fat equations using up to 6467 males or 4888 females 8-49 years of age. Candidate variables were studied in multiple mathematical forms and interactions using the Least Absolute Shrinkage and Selection Operator. Models were fit in 2/3's of the data and validated in 1/3 of the data selected at random. Final coefficients, R2 values and root mean square error (RMSE) were estimated in the full data set. RESULTS: Models that included age, ethnicity, height, weight, BMI and BIA assessments (resistance, reactance and height2/resistance) had R2 values of 0.831 in men and 0.864 in women in the full data set. RMSE measurements were between 2 and 3 body fat percentage points, and all equations showed low bias across groups formed by age, race/ethnicity or body mass index category. The addition of triceps skinfold and waist circumference increased the R2 to 0.905 in males and 0.883 in females. Adding other anthropometrics (plus menses in females) had little impact on performance. Reactance and resistance alone (in multiple mathematical forms) performed poorly with R2~0.2. CONCLUSIONS: Equations that included BIA assessments along with demographic and anthropometric variables provided percent body fat assessments that had high generalizability, strong predictive ability and low bias.


Asunto(s)
Absorciometría de Fotón , Tejido Adiposo/patología , Composición Corporal/fisiología , Impedancia Eléctrica , Obesidad/patología , Adolescente , Adulto , Distribución de la Grasa Corporal , Índice de Masa Corporal , Niño , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Obesidad/diagnóstico por imagen , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Factores Sexuales , Grosor de los Pliegues Cutáneos , Estados Unidos/epidemiología , Circunferencia de la Cintura , Adulto Joven
2.
Int J Obes (Lond) ; 40(4): 587-94, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26538187

RESUMEN

BACKGROUND/OBJECTIVES: Although numerous equations to predict percent body fat have been published, few have broad generalizability. The objective of this study was to develop sets of equations that are generalizable to the American population 8 years of age and older. SUBJECTS/METHODS: Dual-emission X-ray absorptiometry (DXA) assessed percent body fat from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) was used as the response variable for development of 14 equations for each gender that included between 2 and 10 anthropometrics. Other candidate variables included demographics and menses. Models were developed using the Least Absolute Shrinkage and Selection Operator (LAASO) and validated in a » withheld sample randomly selected from 11 884 males or 9215 females. RESULTS: In the final models, R(2) ranged from 0.664 to 0.845 in males and from 0.748 to 0.809 in females. R(2) was not notably improved by development of equations within, rather than across, age and ethnic groups. Systematic over or under estimation of percent body fat by age and ethnic groups was within 1 percentage point. Seven of the fourteen gender-specific models had R(2) values above 0.80 in males and 0.795 in females and exhibited low bias by age, race/ethnicity and body mass index (BMI). CONCLUSIONS: To our knowledge, these are the first equations that have been shown to be valid and unbiased in both youth and adults in estimating DXA assessed body fat. The equations developed here are appropriate for use in multiple ethnic groups, are generalizable to the US population and provide a useful method for assessment of percent body fat in settings where methods such as DXA are not feasible.


Asunto(s)
Tejido Adiposo/patología , Composición Corporal/fisiología , Obesidad Infantil/epidemiología , Absorciometría de Fotón , Adolescente , Índice de Masa Corporal , Niño , Femenino , Humanos , Masculino , Encuestas Nutricionales , Obesidad Infantil/diagnóstico , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Factores Sexuales , Grosor de los Pliegues Cutáneos , Estados Unidos/epidemiología , Circunferencia de la Cintura
3.
Int J Obes (Lond) ; 39(7): 1109-13, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25394308

RESUMEN

Energy intake (EI) and physical activity energy expenditure (PAEE) are key modifiable determinants of energy balance, traditionally assessed by self-report despite its repeated demonstration of considerable inaccuracies. We argue here that it is time to move from the common view that self-reports of EI and PAEE are imperfect, but nevertheless deserving of use, to a view commensurate with the evidence that self-reports of EI and PAEE are so poor that they are wholly unacceptable for scientific research on EI and PAEE. While new strategies for objectively determining energy balance are in their infancy, it is unacceptable to use decidedly inaccurate instruments, which may misguide health-care policies, future research and clinical judgment. The scientific and medical communities should discontinue reliance on self-reported EI and PAEE. Researchers and sponsors should develop objective measures of energy balance.


Asunto(s)
Ingestión de Energía , Metabolismo Energético , Actividad Motora , Autoinforme , Exactitud de los Datos , Conocimientos, Actitudes y Práctica en Salud , Política de Salud , Humanos , Estudios Observacionales como Asunto , Formulación de Políticas , Reproducibilidad de los Resultados
4.
Int J Obes (Lond) ; 37(8): 1154-60, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23207404

RESUMEN

BACKGROUND: Body mass index (BMI; weight (Wt)/height (Ht) (in kg m(-2)) and waist circumference (WC) are widely used as proxy anthropometric measures for total adiposity. Little is known about what scaling power of 'x' in both Wt(kg)/Ht(m)(x) and WC(m)/Ht(m)(x) is maximally associated with measured total body fat mass (TBFM). Establishing values for x would provide the information needed to create optimum anthropometric surrogate measures of adiposity. OBJECTIVE: To estimate the value of 'x' that renders Wt/Ht(x) and WC/Ht(x) maximally associated with DXA-measured TBFM. SUBJECTS: Participants of the NHANES 1999-2004 surveys, stratified by sex (men, women), race/ethnicity (non-Hispanic whites, non-Hispanic blacks, Mexican-Americans), and age(18-29, 30-49, 50-84 years). METHODS: We apply a grid search by increasing x from 0.0-3.0 by increments of 0.1 to the simple regression models, TBFM=b0+b1*(Wt/Ht(x)) and TBFM=b0+b1*(WC/Ht(x)) to obtain an estimate of x that results in the greatest R(2), taking into account complex survey design features and multiply imputed data. RESULTS: R(2)'s for BMI are 0.86 for men (N=6544) and 0.92 for women (N=6362). The optimal powers x for weight are 1.0 (R(2)=0.90) for men and 0.8 (R(2)=0.96) for women. The optimal power x for WC is 0, that is, no scaling of WC to height, for men (R(2)=0.90) or women (R(2)=0.82). The optimal powers for weight across nine combinations of race/ethnicity and age groups for each sex vary slightly (x=0.8-1.3) whereas the optimal scaling powers for WC are all 0 for both sexes except for non-Hispanic black men aged 18-29y (x=0.1). Although the weight-for-height indices with optimal powers are not independent of height, they yield more accurate TBFM estimates than BMI. CONCLUSION: In reference to TBFM, Wt/Ht and Wt/Ht(0.8) are the optimal weight-for-height indices for men and women, respectively, whereas WC alone, without Ht adjustment, is the optimal WC-for-height index for both sexes. Thus, BMI, an index independent of height, may be less useful when predicting TBFM.


Asunto(s)
Tejido Adiposo , Negro o Afroamericano , Peso Corporal , Hispánicos o Latinos , Encuestas Nutricionales , Obesidad/epidemiología , Circunferencia de la Cintura , Población Blanca , Grasa Abdominal/patología , Absorciometría de Fotón , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estatura , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/etnología , Obesidad/patología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Factores de Riesgo , Estados Unidos
5.
Int J Obes (Lond) ; 37(12): 1611-3, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23628852

RESUMEN

Despite theoretical evidence that the model commonly referred to as the 3500-kcal rule grossly overestimates actual weight loss, widespread application of the 3500-kcal formula continues to appear in textbooks, on respected government- and health-related websites, and scientific research publications. Here we demonstrate the risk of applying the 3500-kcal rule even as a convenient estimate by comparing predicted against actual weight loss in seven weight loss experiments conducted in confinement under total supervision or objectively measured energy intake. We offer three newly developed, downloadable applications housed in Microsoft Excel and Java, which simulates a rigorously validated, dynamic model of weight change. The first two tools available at http://www.pbrc.edu/sswcp, provide a convenient alternative method for providing patients with projected weight loss/gain estimates in response to changes in dietary intake. The second tool, which can be downloaded from the URL http://www.pbrc.edu/mswcp, projects estimated weight loss simultaneously for multiple subjects. This tool was developed to inform weight change experimental design and analysis. While complex dynamic models may not be directly tractable, the newly developed tools offer the opportunity to deliver dynamic model predictions as a convenient and significantly more accurate alternative to the 3500-kcal rule.


Asunto(s)
Dieta Reductora , Ingestión de Energía , Pérdida de Peso , Algoritmos , Metabolismo Energético , Femenino , Objetivos , Humanos , Difusión de la Información , Masculino
6.
Int J Obes (Lond) ; 36(7): 931-7, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22249227

RESUMEN

OBJECTIVE: Children differ greatly in their ability to self-regulate food intake for reasons that are poorly understood. This laboratory-based twin study tested the genetic and environmental contributions to self-regulatory eating and body fat in early childhood. METHODS: A total of 69 4-7 year-old same-sex twin pairs, including 40 monozygotic and 29 dizygotic pairs, were studied. Self-regulatory eating was operationalized as the percentage compensation index (COMPX%), assessed by a 'preload' challenge in which lunch intake was measured following a low- (3 kcal) or high-calorie (159 kcal) drink. Body fat indexes also were measured. The familial association for COMPX% was estimated by an intraclass correlation, and biometric analyses estimated heritability. RESULTS: Children ate more at lunch following the low- compared with high-energy preload (P<0.001), although variability in COMPX% was considerable. Compensation was significantly poorer among African American and Hispanic compared with European American children, and among girls compared with boys. There was a familial association for self-regulatory eating (ρ = 0.23, P = 0.03) but no significant genetic component. In all, 22% of the variance in COMPX% was due to shared environmental 'household' factors, with the remaining variance attributable to child-specific 'unique' or 'random' environments. Poorer self-regulatory eating was associated with greater percent body fat (r = -0.21, P = 0.04). CONCLUSIONS: Self-regulatory eating was influenced by environmental factors, especially those differing among siblings. The absence of a significant genetic effect may reflect the age of the sample or could be artifactual due to measurement issues that need to be considered in future studies.


Asunto(s)
Regulación del Apetito/fisiología , Fenómenos Fisiológicos Nutricionales Infantiles/fisiología , Ingestión de Alimentos/fisiología , Conducta Alimentaria , Regulación del Apetito/genética , Bebidas , Índice de Masa Corporal , Niño , Fenómenos Fisiológicos Nutricionales Infantiles/genética , Preescolar , Estudios de Cohortes , Ingestión de Energía , Femenino , Humanos , Masculino , Factores Sexuales , Gemelos Dicigóticos , Gemelos Monocigóticos , Circunferencia de la Cintura
7.
Osteoporos Int ; 23(9): 2293-301, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22173789

RESUMEN

UNLABELLED: The relationship between bone marrow adipose tissue and bone mineral density is different between African Americans and Caucasians as well as between men and women. This suggests that the mechanisms that regulate the differentiation and proliferation of bone marrow stromal cells may differ in these populations. INTRODUCTION: It has long been established that there are ethnic and sex differences in bone mineral density (BMD) and fracture risk. Recent studies suggest that bone marrow adipose tissue (BMAT) may play a role in the pathogenesis of osteoporosis. It is unknown whether ethnic and sex differences exist in the relationship between BMAT and BMD. METHODS: Pelvic BMAT was evaluated in 455 healthy African American and Caucasian men and women (age 18-88 years) using whole-body T1-weighted magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. RESULTS: A negative correlation was observed between pelvic BMAT and total body BMD or pelvic BMD (r = -0.533, -0.576, respectively; P < 0.001). In multiple regression analyses with BMD as the dependent variable, ethnicity significantly entered the regression models as either an individual term or an interaction with BMAT. Menopausal status significantly entered the regression model with total body BMD as the dependent variable. African Americans had higher total body BMD than Caucasians for the same amount of BMAT, and the ethnic difference for pelvic BMD was greater in those participants with a higher BMAT. Men and premenopausal women had higher total body BMD levels than postmenopausal women for the same amount of BMAT. CONCLUSIONS: An inverse relationship exists between BMAT and BMD in African American and Caucasian men and women. The observed ethnic and sex differences between BMAT and BMD in the present study suggest the possibility that the mechanisms regulating the differentiation and proliferation of bone marrow stromal cells may differ in these populations.


Asunto(s)
Tejido Adiposo/anatomía & histología , Densidad Ósea/fisiología , Médula Ósea/anatomía & histología , Huesos Pélvicos/anatomía & histología , Absorciometría de Fotón , Tejido Adiposo/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Huesos Pélvicos/diagnóstico por imagen , Factores Sexuales , Adulto Joven
8.
Sci Rep ; 12(1): 12375, 2022 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-35858946

RESUMEN

The limitations of BMI as a measure of adiposity and health risks have prompted the introduction of many alternative biomarkers. However, ranking diverse biomarkers from best to worse remains challenging. This study aimed to address this issue by introducing three new approaches: (1) a calculus-derived, normalized sensitivity score (NORSE) is used to compare the predictive power of diverse adiposity biomarkers; (2) multiple biomarkers are combined into multi-dimensional models, for increased sensitivity and risk discrimination; and (3) new visualizations are introduced that convey complex statistical trends in a compact and intuitive manner. Our approach was evaluated on 23 popular biomarkers and 6 common medical conditions using a large database (National Health and Nutrition Survey, NHANES, N ~ 100,000). Our analysis established novel findings: (1) regional composition biomarkers were more predictive of risk than global ones; (2) fat-derived biomarkers had stronger predictive power than weight-related ones; (3) waist and hip are always elements of the strongest risk predictors; (4) our new, multi-dimensional biomarker models yield higher sensitivity, personalization, and separation of the negative effects of fat from the positive effects of lean mass. Our approach provides a new way to evaluate adiposity biomarkers, brings forth new important clinical insights and sets a path for future biomarker research.


Asunto(s)
Adiposidad , Composición Corporal , Biomarcadores , Índice de Masa Corporal , Humanos , Encuestas Nutricionales , Obesidad
9.
Int J Obes (Lond) ; 35(11): 1363-76, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21343903

RESUMEN

OBJECTIVE: Obesity is related to increased risk of several health complications, including depression. Many studies have reported improvements in mood with weight loss, but results have been equivocal. The present meta-analysis examined changes in symptoms of depression that were reported in trials of weight loss interventions. Between-groups comparisons of different weight loss methods (for example, lifestyle modification, diet-alone and pharmacotherapy) were examined, as were within-group changes for each treatment type. METHOD: MEDLINE was searched for articles published between 1950 and January 2009. Several obesity-related terms were intersected with terms related to depression. Results were filtered to return only studies of human subjects, published in English. Of 5971 articles, 394 were randomized controlled trials. Articles were excluded if they did not report mean changes in weight or symptoms of depression, included children or persons with psychiatric disorders (other than depression), or provided insufficient data for analysis. Thirty-one studies (n=7937) were included. Two authors independently extracted a description of each study treatment, sample characteristics, assessment methods and changes in weight and symptoms of depression. Treatments were categorized as lifestyle modification, non-dieting, dietary counseling, diet-alone, exercise-alone, pharmacotherapy, placebo or control interventions. RESULTS: Random effects models found that lifestyle modification was superior to control and non-dieting interventions for reducing symptoms of depression, and marginally better than dietary counseling and exercise-alone programs. Exercise-alone programs were superior to controls. No differences were found for comparisons of pharmacologic agents and placebos. Within-group analyses found significant reductions in symptoms of depression for nearly all active interventions. A meta-regression found no relationship between changes in weight and changes in symptoms of depression in lifestyle modification interventions. CONCLUSIONS: On average, obese individuals in weight loss trials experienced reductions in symptoms of depression. Future studies should examine incidence and resolution of clinically significant depressive disorders with weight loss interventions.


Asunto(s)
Depresión/etiología , Obesidad/psicología , Obesidad/terapia , Pérdida de Peso , Terapia Combinada , Depresión/diagnóstico , Depresión/prevención & control , Femenino , Humanos , Intención , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Conducta de Reducción del Riesgo
10.
Int J Obes (Lond) ; 35(9): 1216-24, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21224830

RESUMEN

BACKGROUND: Obesity and motor vehicle crash (MVC) injuries are two parallel epidemics in the United States. An important unanswered question is whether there are sex differences in the associations between the presence of obesity and non-fatal MVC injuries. OBJECTIVES: To further understand the association between obesity and non-fatal MVC injuries, particularly the sex differences in these relations. METHODS: We examined this question by analyzing data from the 2003 to 2007 National Automotive Sampling System Crashworthiness Data System (NASS CDS). A total of 10,962 drivers who were aged 18 years or older and who survived frontal collision crashes were eligible for the study. RESULTS: Male drivers experienced a lower rate of overall non-fatal MVC injuries than did female drivers (38.1 versus 52.2%), but experienced a higher rate of severe injuries (0.7 versus 0.2%). After adjusting for change in velocity (ΔV) during the crashes, obese male drivers showed a much higher risk (logistic coefficients of body mass index (BMI) for moderate, serious and severe injury are 0.0766, 0.1470 and 0.1792, respectively; all P<0.05) of non-fatal injuries than did non-obese male drivers and these risks increased with injury severity. Non-fatal injury risks were not found to be increased in obese female drivers. The association between obesity and risk of non-fatal injury was much stronger for male drivers than for female drivers. CONCLUSION: The higher risk of non-fatal MVC injuries in obese male drivers might result from their different body shape and fat distribution compared with obese female drivers. Our findings should be considered for obesity reduction, traffic safety evaluation and vehicle design for obese male drivers and provide testable hypotheses for future studies.


Asunto(s)
Accidentes de Tránsito/estadística & datos numéricos , Obesidad/epidemiología , Adulto , Índice de Masa Corporal , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Modelos Logísticos , Masculino , Oportunidad Relativa , Factores de Riesgo , Factores Sexuales , Estados Unidos/epidemiología
11.
Int J Obes (Lond) ; 35(1): 121-7, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20531353

RESUMEN

OBJECTIVE: Nutritional status is assessed by measuring BMI or percent body fat (%fat). BMI can misclassify persons who carry more weight as fat-free mass and %fat can be misleading in cases of malnutrition or in disease states characterized by wasting of lean tissue. The fat-free mass index (FFMI) is proposed to assess body composition in individuals who have a similar body composition but differ in height allowing identification of those suffering from malnutrition, wasting or those that possess a relatively high muscle mass. The purpose was to determine whether the FFMI differs in a group of racially/ethnically diverse adults. DESIGN: Cross-sectional. SUBJECTS: Subjects were a multi-ethnic sample (Caucasian, CA; African American, AA; Hispanic, HIS and Asian, AS) of 1339 healthy males (n = 480) and females (n = 859) ranging in age from 18-110 years. Total body fat, total fat-free mass and bone mineral density were estimated using dual energy X-ray absorptiometry. RESULTS: FFMI differed among the four ethnic groups (P ≤ 0.05) for both genders. A curvilinear relationship was found between age and FFMI for both genders although the coefficients in the quadratic model differed between genders (P ≤ 0.001) indicating the rate of change in FFMI differed between genders. The estimated turning point where FFMI started to decline was in the mid 20s for male and mid 40s for female participants. An age × gender interaction was found such that the rate of decline was greater in male than female participants (P ≤ 0.001). For both genders, FFMI was greatest in AA and the least in AS (P ≤ 0.001). There was no significant interaction between race and age or age(2) (P = 0.06). However, male participants consistently had a greater FFMI than female participants (P ≤ 0.001). CONCLUSIONS: These findings have clinical implications for identifying individuals who may not be recognized as being malnourished based on their BMI or %fat but whose fat-free mass corrected for height is relatively low.


Asunto(s)
Tejido Adiposo/patología , Asiático/estadística & datos numéricos , Negro o Afroamericano/estadística & datos numéricos , Composición Corporal , Índice de Masa Corporal , Hispánicos o Latinos/estadística & datos numéricos , Desnutrición/etnología , Población Blanca/estadística & datos numéricos , Absorciometría de Fotón/métodos , Tejido Adiposo/anatomía & histología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estatura/etnología , Peso Corporal/etnología , Densidad Ósea , Estudios Transversales , Femenino , Humanos , Masculino , Desnutrición/patología , Persona de Mediana Edad , New York/epidemiología , Estado Nutricional/etnología , Adulto Joven
12.
Osteoporos Int ; 22(12): 3029-35, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21243336

RESUMEN

UNLABELLED: We examined ethnic difference in the association of body fat and trunk fat with bone mineral density (BMD) among Chinese, white, and black subjects. We found that, with greater body and trunk fat, both white and black subjects were more likely to have a low BMD than Chinese subjects. INTRODUCTION: Ethnic differences in body fat, abdominal fat distribution, and BMD have been found in previous studies between Chinese and white subjects. However, the associations of body fat and abdominal fat distribution with BMD have not been studied, and whether the ethnic differences have an effect on these associations is unclear. METHODS: We evaluated 1,147 subjects aged ≥ 18 years (805 Chinese, 193 whites, and 149 blacks). Percent body fat (%BF), percent trunk fat (%TF), and total and regional BMD including that of head, arm, leg, trunk, rib, spine, and pelvis were measured by dual-energy X-ray absorptiometry. Linear regression models were developed to test the association of ethnicity, %BF, and interaction between ethnicity and %BF with BMD. The models were repeated again, replacing %BF with %TF. RESULTS: Chinese subjects showed lower BMD in total and most regions compared with black and white subjects; however, these differences were eliminated between Chinese and whites within both sexes and between Chinese and black men when age, weight, height, and %BF were added. %BF and %TF were negatively associated with most regional body BMD. The interactions between %BF, %TF, and ethnicity were found in most regional body BMD among Chinese, white, and black subjects for both men and women. CONCLUSION: Both %BF and %TF have negative associations with BMD. With greater accumulation of %BF and %TF, both white and black subjects may experience a higher risk of low BMD than Chinese subjects.


Asunto(s)
Tejido Adiposo/fisiología , Distribución de la Grasa Corporal/estadística & datos numéricos , Densidad Ósea/fisiología , Absorciometría de Fotón , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Población Negra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Población Blanca , Adulto Joven
13.
Int J Obes (Lond) ; 34(8): 1243-54, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20212496

RESUMEN

OBJECTIVE: To evaluate the weight loss efficacy, safety and tolerability of taranabant, a CB1R inverse agonist, in obese and overweight patients. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. SUBJECTS: Patients >or=18 years old, BMI 27-43 kg m(-2), were randomized to placebo (n=209) or taranabant 0.5 mg (n=207), 1 mg (n=208) or 2 mg given orally once daily (n=417) for 52 weeks. MEASUREMENTS: Key efficacy measurements included body weight (BW), waist circumference (WC), lipid endpoints and glycemic endpoints. RESULTS: Based on a last observation carried forward analysis of the all-patients-treated population, mean change in BW for taranabant 0.5, 1, and 2 mg and placebo was -5.4, -5.3, -6.7 and -1.7 kg, respectively (P<0.001 for all doses vs placebo). The proportions of patients who lost at least 5 and 10% of their baseline BW at week 52 were significantly higher for all taranabant doses vs placebo (P<0.001 for all doses). Reductions in WC, percentage of body fat, and triglycerides were significant for taranabant 2 mg and in triglycerides for taranabant 1 mg vs placebo. There was no effect of taranabant vs placebo on other lipid or glucose-related endpoints. Incidences of adverse experiences classified in the gastrointestinal (diarrhea and nausea), nervous system (dizziness/dizziness postural), psychiatric-related (irritability and anger/aggression) and vascular (flushing/hot flush) organ systems were higher and statistically significant in the taranabant 2-mg group compared with the placebo group. Irritability was higher and statistically significant in all taranabant groups compared with the placebo group. CONCLUSION: All three doses of taranabant-induced clinically meaningful and statistically significant weight loss. Incidences of adverse experiences in organ systems known to express CB1R were higher in taranabant groups.


Asunto(s)
Amidas/administración & dosificación , Fármacos Antiobesidad/administración & dosificación , Obesidad/tratamiento farmacológico , Piridinas/administración & dosificación , Receptor Cannabinoide CB1/antagonistas & inhibidores , Pérdida de Peso , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
14.
Int J Obes (Lond) ; 34(5): 919-35, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20157323

RESUMEN

OBJECTIVE: To evaluate the efficacy, safety and tolerability of taranabant in obese and overweight patients. DESIGN: Double-blind, randomized, placebo-controlled study. SUBJECTS: Patients were >or=18 years old, with body mass index of 27-43 kg m(-2), and 51% with metabolic syndrome (MS) randomized to placebo (N=417) or taranabant 2 mg (N=414), 4 mg (N=415) or 6 mg (N=1256) for 104 weeks. MEASUREMENTS: Key efficacy measurements included body weight, waist circumference (WC), lipid and glycemic end points. RESULTS: On the basis of risk/benefit assessments, the 6-mg dose was discontinued during year 1 (patients on 6 mg were down-dosed to 2 mg or placebo) and the 4-mg dose was discontinued during year 2 (patients on 4 mg were down-dosed to 2 mg). Changes from baseline in body weight at week 52 (all-patients-treated population, last observation carried forward analysis) were -2.6, -6.6 and -8.1 kg, respectively, for placebo and taranabant 2 and 4 mg (both doses P<0.001 vs placebo). For patients who completed year 1, changes from baseline in body weight at week 104 were -1.4, -6.4 and -7.6 kg for placebo and taranabant 2 and 4 mg, respectively (both doses P<0.001 vs placebo). The proportions of patients at weeks 52 and 104 who lost at least 5 and 10% of their baseline body weight were significantly higher and the proportions of patients who met criteria for MS were significantly lower for taranabant 2 and 4 mg vs placebo. The incidence of adverse experiences classified in the gastrointestinal, nervous, psychiatric, cutaneous and vascular organ systems were generally observed to be dose related with taranabant vs placebo. CONCLUSION: Taranabant at the 2- and 4-mg dose was effective in achieving clinically significant weight loss over 2 years and was associated with dose-related increases in adverse experiences. On the basis of these and other data, an assessment was made that the overall safety and efficacy profile of taranabant did not support its further development for the treatment of obesity.


Asunto(s)
Amidas/administración & dosificación , Fármacos Antiobesidad/administración & dosificación , Peso Corporal/efectos de los fármacos , Síndrome Metabólico/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Piridinas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Amidas/efectos adversos , Fármacos Antiobesidad/efectos adversos , Índice de Masa Corporal , Peso Corporal/fisiología , Dieta Reductora , Método Doble Ciego , Femenino , Humanos , Masculino , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Obesidad/fisiopatología , Piridinas/efectos adversos , Receptor Cannabinoide CB1/agonistas , Medición de Riesgo , Resultado del Tratamiento , Adulto Joven
16.
Diabetes Obes Metab ; 12(6): 517-31, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20518807

RESUMEN

AIM: To evaluate the efficacy and safety of taranabant in overweight and obese patients with type 2 diabetes mellitus (T2DM). METHODS: This was a multicenter, double-blind, randomized, placebo-controlled study in overweight and obese patients with T2DM (ages > or = 18 and < or = 75 years) with a BMI > or = 27 kg/m(2) and < or = 43 kg/m(2) and HbA1c > or =7.0 and < or = 10.0%, who were either not on an antihyperglycaemic agent or on a stable dose of metformin (> or = 1500 mg/day). After a 2-week placebo run-in, patients were randomized to placebo (N = 156) or taranabant 0.5-mg (N = 155), 1-mg (N = 157), or 2-mg (N = 155) once daily for 52 weeks. Primary efficacy endpoints were changes from baseline in body weight (BW) and HbA1c at Week 36, with results at Week 52 being key secondary endpoints. RESULTS: In the all-patients-treated population, using a last-observation-carried-forward analysis, reductions in BW were -2.5, -3.7, -4.5 and -5.1 kg at Week 36 and -2.4, -4.0, -4.6 and -5.3 kg at Week 52 in the placebo, 0.5-, 1- and 2-mg groups, respectively (all doses significant vs. placebo at both time points). The proportion of patients who lost > or = 5 and > or = 10% of their baseline BW was significantly greater in the 1- and 2-mg groups vs. placebo at Week 36 and all taranabant groups vs. placebo at Week 52. Reductions in HbA1c were -0.40, -0.47, -0.68 and -0.71% at Week 36 and -0.30, -0.43, -0.65 and -0.64% at Week 52, in the placebo, 0.5-, 1- and 2-mg groups, respectively (1- and 2-mg doses significant vs. placebo at both time points). After 52 weeks, the incidences of adverse experiences classified in the gastrointestinal (diarrhoea, nausea, vomiting), nervous system-related (dizziness, sensory-related), and psychiatric (irritability, depression-related) organ systems were numerically higher or statistically significantly higher in all taranabant groups compared with the placebo group. CONCLUSIONS: After 36 and 52 weeks, treatment with taranabant at the 1- and 2-mg doses led to clinically significant weight loss and improvement in glycaemic parameters in overweight and obese patients with T2DM that was associated with dose-related increases in adverse experiences. Based on these data and data from other Phase III clinical studies, it was determined that the overall safety and efficacy profile of taranabant did not support further development for the treatment of obesity.


Asunto(s)
Amidas/administración & dosificación , Fármacos Antiobesidad/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Piridinas/administración & dosificación , Receptor Cannabinoide CB1/agonistas , Adolescente , Adulto , Anciano , Amidas/efectos adversos , Fármacos Antiobesidad/efectos adversos , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Dieta Reductora , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/dietoterapia , Piridinas/efectos adversos , Pérdida de Peso/efectos de los fármacos , Adulto Joven
17.
Int J Sports Med ; 31(10): 737-41, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20645233

RESUMEN

The purpose of this study was to analyse the association between body composition changes, from a weight stable period to prior competition, on upper-body power in judo athletes. 27 top-level male athletes were evaluated at baseline (weight stable period) and 1-3 days before competition, with a time difference of approximately 1 month. Total body and extracellular water were estimated by dilution techniques (deuterium and bromide, respectively) and intracellular water was calculated as the difference. Body composition was assessed by DXA. A power-load spectrum was used to assess upper-body power output in a bench-press position. Comparison of means, bivariate, and partial correlations were used. Results indicate that though no significant mean changes were found in body composition and upper-body power, individual variability was large. Among all body composition changes, only total-body water (r=0.672; p<0.001) and intracellular water (r=0.596; p=0.001) were related to upper-body power variation. These associations remained significant after controlling for weight and arm lean-soft tissue changes (r=0.594, p=0.002 for total-body water; r=0.524, p=0.007 for intracellular water). These findings highlight the need for tracking total-body water, specifically the intracellular compartment in elite judo athletes in order to avoid reductions in upper-body power when a target body weight is desired prior to competition.


Asunto(s)
Composición Corporal/fisiología , Agua Corporal/fisiología , Artes Marciales/fisiología , Absorciometría de Fotón , Adulto , Atletas , Peso Corporal/fisiología , Bromuros , Deuterio , Humanos , Masculino , Fuerza Muscular/fisiología , Compuestos de Sodio , Adulto Joven
18.
Int J Obes (Lond) ; 33(9): 947-55, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19597516

RESUMEN

Rimonabant and taranabant are two extensively studied cannabinoid-1 receptor (CB1R) inverse agonists. Their effects on in vivo peripheral tissue metabolism are generally well replicated. The central nervous system site of action of taranabant or rimonabant is firmly established based on brain receptor occupancy studies. At the whole-body level, the mechanism of action of CB1R inverse agonists includes a reduction in food intake and an increase in energy expenditure. At the tissue level, fat mass reduction, liver lipid reduction and improved insulin sensitivity have been shown. These effects on tissue metabolism are readily explained by CB1R inverse agonist acting on brain CB1R and indirectly influencing the tissue metabolism through the autonomic nervous system. It has also been hypothesized that rimonabant acts directly on adipocytes, hepatocytes, pancreatic islets or skeletal muscle in addition to acting on brain CB1R, although strong support for the contribution of peripherally located CB1R to in vivo efficacy is still lacking. This review will carefully examine the published literature and provide a perspective on what new tools and studies are required to address the peripheral site of action hypothesis.


Asunto(s)
Amidas/farmacología , Fármacos Antiobesidad/farmacología , Obesidad/tratamiento farmacológico , Piperidinas/farmacología , Pirazoles/farmacología , Piridinas/farmacología , Receptor Cannabinoide CB1/metabolismo , Anciano , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Femenino , Humanos , Masculino , Obesidad/metabolismo , Receptor Cannabinoide CB1/antagonistas & inhibidores , Rimonabant
19.
Int J Obes (Lond) ; 33(12): 1363-73, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19773739

RESUMEN

OBJECTIVE: Although widely applied as a phenotypic expression of adiposity in population and gene-search studies, body mass index (BMI) is also acknowledged to reflect muscularity even though relevant studies directly measuring skeletal muscle (SM) mass are lacking. The current study aimed to fill this important gap by applying advanced imaging methods to test the hypothesis that, after controlling first for adiposity, SM mass is also a significant determinant of BMI in a population-based sample. DESIGN: Whole-body magnetic resonance imaging scans were completed in Coronary Artery Risk Development in Young Adults study subjects aged 33-45 years. Physical activity (PA) levels, alcohol intake and adequacy of food intake were assessed by standardized questionnaires. SUBJECTS: The study included 58 African-American (AA) and 78 Caucasian (C) men; and 63 AA and 64 C women. MEASUREMENTS: Whole-body adipose tissue (AT) and SM volumes. RESULTS: AT was significantly predicted by not only BMI, but also PA and alcohol intake with total model R (2)'s of 0.68 (P<0.0001) for men and 0.89 (P<0.0001) for women. Men had more SM than AT at all levels of BMI whereas SM predominated in women at lower BMIs (C<26 kg/m(2); AA<28 kg/m(2)). In men, both AT and SM contributed a similar proportion of between-subject variation in BMI. In contrast, in women AT contributed approximately 30% more than SM to the variation in BMI. Developed allometric models indicated SM associations with AT, PA and race after adjusting for height. There was little association of age, lifestyle factors or race with BMI after controlling for both AT and SM. CONCLUSION: Variation in muscularity provides a mechanistic basis for the previously observed nonspecificity of BMI as a phenotypic expression of adiposity. These quantitative observations have important implications when choosing adiposity measures in population and gene-search studies.


Asunto(s)
Adiposidad , Índice de Masa Corporal , Músculo Esquelético/anatomía & histología , Adiposidad/etnología , Adiposidad/genética , Adulto , Negro o Afroamericano , Algoritmos , Composición Corporal/genética , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Actividad Motora/genética , Actividad Motora/fisiología , Fenotipo , Encuestas y Cuestionarios , Población Blanca , Imagen de Cuerpo Entero
20.
Blood Purif ; 27(4): 330-7, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19270452

RESUMEN

This study used multi-frequency bioimpedance spectroscopy (BIS) of the arm and whole body to estimate muscle mass (MM) and subcutaneous adipose tissue (SAT) in 31 hemodialysis (HD) patients comparing these results with magnetic resonance imaging (MRI) and body potassium ((40)K) as gold standards. Total body and arm MM (MM(MRI)) and SAT (SAT(MRI)) were measured by MRI. All measurements were made before dialysis treatment. Regression models with the arm (aBIS) and whole body (wBIS) resistances were established. Correlations between gold standards and the BIS model were high for the arm SAT (r(2) = 0.93, standard error of estimate (SEE) = 3.6 kg), and whole body SAT (r(2) = 0.92, SEE = 3.5 kg), and for arm MM (r(2) = 0.84, SEE = 2.28 kg) and whole body MM (r(2) = 0.86, SEE = 2.28 kg). Total body MM and SAT can be accurately predicted by arm BIS models with advantages of convenience and portability, and it should be useful to assess nutritional status in HD patients.


Asunto(s)
Tejido Adiposo , Composición Corporal , Impedancia Eléctrica , Músculos , Diálisis Renal , Negro o Afroamericano , Brazo , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estado Nutricional , Potasio/análisis , Estándares de Referencia , Reproducibilidad de los Resultados
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