RESUMEN

Obesity is a chronic, progressive and relapsing disease, characterized by the presence of abnormal or excess adiposity that impairs health and social well-being. Screening for obesity should be performed regularly by mea­suring body mass index (BMI) and waist circumference. The clinical assessment of obesity should aim to establish the diagnosis and identify the causes and consequences of abnormal or excess adiposity on a patient's physical, mental and functional health. Providers participating in the assessment of obesity should focus on establishing values and goals of treatment, identi­fying which resources and tools may be needed and foster­ing self-efficacy with the patient in order to achieve long-term success. A non-judgmental, stigma-free environment is necessary for an effective assessment of a patient living with obesity.

Asunto(s)

Humanos , Índice de Masa Corporal , Triaje , Obesidad/diagnóstico

RESUMEN

BACKGROUND: Bariatric surgery in Canada is primarily delivered within publicly funded specialty clinics. Previous studies have demonstrated that bariatric surgery is superior to intensive medical management for reduction of weight and obesity-related comorbidities. Our objective was to compare the effectiveness and safety of laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (LSG) and adjustable gastric banding (LAGB) in a publicly funded, population-based bariatric treatment program. METHODS: We followed consecutive bariatric surgery patients for 2 years. The primary outcome was weight change (in kilograms). Between-group changes were analyzed using multivariable regression. Last-observation-carried-forward imputation was used for missing data. RESULTS: We included 150 consecutive patients (51 RYGB; 51 LSG; 48 LAGB) in our study. At baseline, mean age was 43.5 ± 9.5 years, 87.3% of patients were women, and preoperative body mass index (BMI) was 46.2 ± 7.4. Absolute and relative (% of baseline) weight loss at 2 years were 36.6 ± 19.5 kg (26.1 ± 12.2%) for RYGB, 21.4 ± 16.0 kg (16.4 ± 11.6%) for LSG and 7.0 ± 9.7 kg (5.8 ± 7.9%) for LAGB (p < 0.001). Change in BMI was greater for the RYGB (-13.0 ± 6.6) than both the LSG (-7.6 ± 5.7) and the LAGB (-2.6 ± 3.5) groups (p < 0.001). The reduction in diabetes, hypertension and dyslipidemia was greater after RYGB than after LAGB (all p < 0.05). There were no deaths. The anastomotic and staple leakage rate was 1.3%. CONCLUSION: In a publicly funded, population-based bariatric surgery program, RYGB and LSG demonstrated greater weight loss than the LAGB procedure. Bypass resulted in the greatest reduction in obesity-related comorbidities. All procedures were safe.

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BACKGROUND: Au Canada, la chirurgie bariatrique est effectuée principalement dans des cliniques spécialisées financées par le secteur public. Des études ont démontré que les interventions de cette nature sont supérieures à la prise en charge médicale intensive pour la perte de poids et la réduction des affections comorbides liées à l'obésité. L'objectif de notre étude était de comparer l'efficacité et l'innocuité de la dérivation gastrique Roux-en-Y par laparoscopie (DGRY), de la gastrectomie longitudinale (GL) et de la gastroplastie par anneau gastrique modulable (GAGM) dans le cadre d'un programme de traitement bariatrique basé sur la population financé par les deniers publics. METHODS: Nous avons suivi pendant 2 ans des patients ayant subi une chirurgie bariatrique. Le résultat primaire à l'étude était la variation pondérale (en kilogrammes). Nous avons analysé la variation intergroupe au moyen d'une régression multivariable et utilisé la méthode d'imputation des données manquantes par report de la dernière observation. RESULTS: Nous avons retenu 150 patients consécutifs (51 DGRY; 51 GL; 48 GAGM). Au début de l'étude, l'âge moyen était de 43,5 ± 9,5 ans, 87,3 % des patients étaient des femmes, et leur indice de masse corporelle (IMC) avant l'opération était de 46,2 ± 7,4. Après 2 ans, la perte de poids moyenne (pourcentage du poids de départ) était de 36,6 ± 19,5 kg (26,1 ± 12,2 %) pour la DGRY, de 21,4 ± 16,0 kg (16,4 ± 11,6 %) pour la GL, et de 7,0 ± 9,7 kg (5,8 ± 7,9 %) pour la GAGM (p < 0,001). La variation de l'IMC était plus grande pour le groupe DGRY (13,0 ± 6,6) que pour les 2 autres groupes (7,6 ± 5,7 pour la GL et 2,6 ± 3,5 pour la GAGM; p < 0,001). L'incidence sur le diabète, l'hypertension et la dyslipidémie était également plus grande après la DGRY qu'après la GAGM (p < 0,05 pour tous). Il n'y a eu aucun décès. Le taux de fuites anastomotiques et liées aux sutures était de 1,3 %. CONCLUSION: Dans le cadre d'un programme de chirurgie bariatrique basé sur une population et financé par le secteur public, la DGRY et la GL ont entraîné une plus grande perte de poids que la GAGM. La dérivation a donné lieu à la plus forte réduction des affections comorbides liées à l'obésité. Toutes les interventions se sont avérées sécuritaires.

Asunto(s)

Gastrectomía/métodos , Derivación Gástrica/métodos , Gastroplastia/métodos , Obesidad/cirugía , Evaluación de Resultado en la Atención de Salud , Pérdida de Peso , Adulto , Canadá , Femenino , Estudios de Seguimiento , Gastrectomía/efectos adversos , Derivación Gástrica/efectos adversos , Gastroplastia/efectos adversos , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

Obesity is a chronic and complex medical condition associated with a large number of complications affecting most organs and systems through multiple pathways. Strategies for weight management include behavioral, pharmacological, and surgical interventions, all of which can result in a reduction in obesity-related comorbidities and improvements in quality of life. However, subsequent weight regain often reduces the durability of these improvements. The objective of this article is to review evidence supporting the long-term effects of intentional weight loss on morbidity, mortality, quality of life, and health-care cost. Overall, considerable evidence suggests that intentional weight loss is associated with clinically relevant benefits for the majority of obesity-related comorbidities. However, the degree of weight loss that must be achieved and sustained to reap these benefits varies widely between comorbidities.

Asunto(s)

Promoción de la Salud , Obesidad/terapia , Pérdida de Peso , Enfermedades Cardiovasculares/prevención & control , Dolor Crónico , Comorbilidad , Diabetes Mellitus Tipo 2/prevención & control , Incontinencia Fecal , Femenino , Fertilidad , Cálculos Biliares , Costos de la Atención en Salud , Humanos , Metabolismo de los Lípidos , Salud Mental , Neoplasias , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Obesidad/complicaciones , Obesidad/mortalidad , Osteoartritis , Embarazo , Calidad de Vida , Enfermedades Respiratorias , Factores de Tiempo , Incontinencia Urinaria

RESUMEN

BACKGROUND: Low socioeconomic status (SES) has been associated with higher risk of cardiometabolic diseases in developed societies, but investigation of SES and cardiometabolic risk in children in less economically developed populations is sparse. We aimed to examine associations among SES and cardiometabolic risk factors in Colombian children. METHODS: We used data from a population-based study of 1282 children aged 6-10 years from Bucaramanga, Colombia. SES was classified according to household wealth, living conditions and access to public utilities. Anthropometric and biochemical parameters were measured at a clinic visit. Cardiometabolic risk factors were analysed continuously using linear regression and as binary outcomes-according to established paediatric cut points-using logistic regression to calculate OR and 95% CIs. RESULTS: Mean age of the children was 8.4 (SD 1.4) and 51.1% of the sample were boys. Odds of overweight/obesity, abdominal obesity and insulin resistance were greater among higher SES. Compared with the lowest SES stratum, children in the highest SES had higher odds of overweight/obesity (OR=3.25, 95% CI 1.89 to 5.57), abdominal obesity (OR=2.74, 95% CI 1.41 to 5.31) and insulin resistance (OR=2.60, 95% CI 1.81 to 3.71). In contrast, children in the highest SES had lower odds of hypertriglyceridaemia (triglycerides ≥90th centile; OR=0.28, 95% CI 0.14 to 0.54) and low (≤10th centile) high-density lipoprotein (HDL) cholesterol (OR=0.35, 95% CI 0.15 to 0.78). CONCLUSIONS: In Colombian children, SES is directly associated with obesity and insulin resistance, but inversely associated with dyslipidaemia (hypertriglyceridaemia and low HDL cholesterol). Our findings highlight the need to analyse cardiometabolic risk factors separately in children and to carefully consider a population's level of economic development when studying their social determinants of cardiometabolic disease.

Asunto(s)

Adiposidad , Enfermedades Cardiovasculares/epidemiología , Dislipidemias/epidemiología , Resistencia a la Insulina , Obesidad Infantil/epidemiología , Clase Social , Determinantes Sociales de la Salud/economía , Análisis de Varianza , Enfermedades Cardiovasculares/economía , Niño , Estudios Transversales , Países en Desarrollo/economía , Países en Desarrollo/estadística & datos numéricos , Dislipidemias/economía , Femenino , Humanos , Entrevistas como Asunto , Modelos Lineales , Modelos Logísticos , Masculino , Obesidad Abdominal/economía , Obesidad Abdominal/epidemiología , Obesidad Infantil/economía , Examen Físico , Factores Protectores , Factores de Riesgo

RESUMEN

BACKGROUND: Guidelines and experts describe 5% to 10% reductions in body weight as 'clinically important'; however, it is not clear if 5% to 10% weight reductions correspond to clinically important improvements in health-related quality of life (HRQL). Our objective was to calculate the amount of weight loss required to attain established minimal clinically important differences (MCIDs) in HRQL, measured using three validated instruments. METHODS: Data from the Alberta Population-based Prospective Evaluation of Quality of Life Outcomes and Economic Impact of Bariatric Surgery (APPLES) study, a population-based, prospective Canadian cohort including 150 wait-listed, 200 medically managed and 150 surgically treated patients were examined. Two-year changes in weight and HRQL measures (Short-Form (SF)-12 physical (PCS; MCID = 5) and mental (MCS; MCID = 5) component summary score, EQ-5D Index (MCID = 0.03) and Visual Analog Scale (VAS; MCID = 10), Impact of Weight on Quality of Life (IWQOL)-Lite total score (MCID = 12)) were calculated. Separate multivariable linear regression models were constructed within medically and surgically treated patients to determine if weight changes achieved HRQL MCIDs. Pooled analysis in all 500 patients was performed to estimate the weight reductions required to achieve the pre-defined MCID for each HRQL instrument. RESULTS: Mean age was 43.7 (SD 9.6) years, 88% were women, 92% were white, and mean initial body mass index was 47.9 (SD 8.1) kg/m2. In surgically treated patients (two-year weight loss = 16%), HRQL MCIDs were reached for all instruments except the SF-12 MCS. In medically managed patients (two-year weight loss = 3%), MCIDs were attained in the EQ-index but not the other instruments. In all patients, percent weight reductions to achieve MCIDs were: 23% (95% confidence interval (CI): 17.5, 32.5) for PCS, 25% (17.5, 40.2) for MCS, 9% (6.2, 15.0) for EQ-Index, 23% (17.3, 36.1) for EQ-VAS, and 17% (14.1, 20.4) for IWQOL-Lite total score. CONCLUSIONS: Weight reductions to achieve MCIDs for most HRQL instruments are markedly higher than the conventional threshold of 5% to 10%. Surgical, but not medical treatment, consistently led to clinically important improvements in HRQL over two years. TRIAL REGISTRATION: Clinicaltrials.gov NCT00850356.

Asunto(s)

Estado de Salud , Obesidad/terapia , Calidad de Vida , Pérdida de Peso/fisiología , Adulto , Cirugía Bariátrica , Índice de Masa Corporal , Canadá , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento

RESUMEN

BACKGROUND: Obesity is a pressing public health concern, which frequently presents in primary care. With the explosive obesity epidemic, there is an urgent need to maximize effective management in primary care. The 5As of Obesity Management™ (5As) are a collection of knowledge tools developed by the Canadian Obesity Network. Low rates of obesity management visits in primary care suggest provider behaviour may be an important variable. The goal of the present study is to increase frequency and quality of obesity management in primary care using the 5As Team (5AsT) intervention to change provider behaviour. METHODS/DESIGN: The 5AsT trial is a theoretically informed, pragmatic randomized controlled trial with mixed methods evaluation. Clinic-based multidisciplinary teams (RN/NP, mental health, dietitians) will be randomized to control or the 5AsT intervention group, to participate in biweekly learning collaborative sessions supported by internal and external practice facilitation. The learning collaborative content addresses provider-identified barriers to effective obesity management in primary care. Evidence-based shared decision making tools will be co-developed and iteratively tested by practitioners. Evaluation will be informed by the RE-AIM framework. The primary outcome measure, to which participants are blinded, is number of weight management visits/full-time equivalent (FTE) position. Patient-level outcomes will also be assessed, through a longitudinal cohort study of patients from randomized practices. Patient outcomes include clinical (e.g., body mass index [BMI], blood pressure), health-related quality of life (SF-12, EQ5D), and satisfaction with care. Qualitative data collected from providers and patients will be evaluated using thematic analysis to understand the context, implementation and effectiveness of the 5AsT program. DISCUSSION: The 5AsT trial will provide a wide range of insights into current practices, knowledge gaps and barriers that limit obesity management in primary practice. The use of existing resources, collaborative design, practice facilitation, and integrated feedback loops cultivate an applicable, adaptable and sustainable approach to increasing the quantity and quality of weight management visits in primary care. TRIAL REGISTRATION: NCT01967797.

Asunto(s)

Conducta Cooperativa , Manejo de la Enfermedad , Obesidad/diagnóstico , Obesidad/terapia , Atención Primaria de Salud/organización & administración , Índice de Masa Corporal , Canadá , Protocolos Clínicos , Toma de Decisiones , Femenino , Humanos , Capacitación en Servicio , Masculino , Grupo de Atención al Paciente/organización & administración , Satisfacción del Paciente , Calidad de Vida , Proyectos de Investigación

Asunto(s)

Fármacos Antiobesidad/uso terapéutico , Obesidad Mórbida/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , Adulto , Femenino , Humanos

RESUMEN

OBJECTIVE: To characterize health-related quality of life (HRQL) impairment in severely obese subjects, using several validated instruments. METHODS: A cross-sectional analysis of 500 severely obese subjects was completed. Short-Form (SF)-12 [Physical (PCS) and Mental (MCS) component summary scores], EuroQol (EQ)-5D [Index and Visual Analog Scale (VAS)], and Impact of Weight on Quality of Life (IWQOL)-Lite were administered. Multivariable linear regression models were performed to identify independent predictors of HRQL. RESULTS: Increasing BMI was associated with lower PCS (-1.33 points per 5 kg/m(2) heavier; P < 0.001), EQ-index (-0.02; P < 0.001), EQ-VAS (-1.71; P = 0.003), and IWQOL-Lite (-3.72; P = 0.002), but not MCS (P = 0.69). The strongest predictors (all P < 0.005) for impairment in each instrument were: fibromyalgia for PCS (-5.84 points), depression for MCS (-7.49 points), stroke for EQ-index (-0.17 points), less than full-time employment for EQ-VAS (-7.06 points), and coronary disease for IWQOL-Lite (-10.86 points). Chronic pain, depression, and sleep apnea were associated with reduced HRQL using all instruments. CONCLUSION: The clinical impact of BMI on physical and general HRQL was small, and mental health scores were not associated with BMI. Chronic pain, depression, and sleep apnea were consistently associated with lower HRQL.

Asunto(s)

Obesidad/epidemiología , Calidad de Vida , Adulto , Índice de Masa Corporal , Comorbilidad , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/psicología , Estudios Prospectivos , Factores Socioeconómicos

RESUMEN

BACKGROUND: Multidisciplinary bariatric care is increasingly being delivered in Canada within publicly funded regional programs. Demand is high, wait lists are long, and clinical effectiveness is unknown. OBJECTIVE: To examine the "real-world" outcomes associated with a publicly funded, population-based regional bariatric (medical and surgical) program. RESEARCH DESIGN: Prospective observational cohort. SUBJECTS: Five hundred consecutive patients (150 wait-listed, 200 medically treated, 150 surgically treated) from the Edmonton Weight Wise program were enrolled. MEASURES: The primary outcome was weight change (kg). Between-group changes were analyzed using multivariable regression adjusted for age, sex, and baseline weight and "last-observation-carried-forward" was used for missing data. Subjects transitioning between groups (wait-list to medical or medical to surgery) were censored when crossing over. RESULTS: At baseline, mean age was 43.7 ± 9.6 years, mean body mass index was 47.9 ± 8.1 kg/m, and 88% were female. A total of 412 subjects (82%) completed 2-year follow-up and 143 (29%) subjects crossed over to the next treatment phase. Absolute and relative (% of baseline) mean weight reductions were 1.5 ± 8.5 kg (0.9 ± 6.1%) for wait-listed, 4.1 ± 11.6 kg (2.8 ± 8.1%) for medically treated, and 22.0 ± 19.7 kg (16.3 ± 13.5%) for surgically treated (P<0.001) subjects. For surgery, weight reductions were 7.0 ± 9.7 kg (5.8 ± 7.9%) with banding, 21.4 ± 16.0 kg (16.4 ± 11.6%) with sleeve gastrectomy, and 36.6 ± 19.5 kg (26.1 ± 12.2%) with gastric bypass (P<0.001). Rates of hypertension, diabetes, and dyslipidemia decreased to a significantly greater degree with surgery than medical management (P<0.001) and stayed the same or increased in wait-listed subjects. CONCLUSIONS: Population-based bariatric care, particularly bariatric surgery, was clinically effective. Weight and cardiometabolic risk was relatively stable wait-listed patients receiving "usual care."

Asunto(s)

Cirugía Bariátrica/estadística & datos numéricos , Obesidad Mórbida/terapia , Listas de Espera , Pérdida de Peso , Adolescente , Adulto , Índice de Masa Corporal , Canadá/epidemiología , Terapia Cognitivo-Conductual , Diabetes Mellitus/epidemiología , Dieta , Dislipidemias/epidemiología , Ejercicio Físico , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven

RESUMEN

BACKGROUND: Sexual abuse may be associated with poorer weight loss outcomes following bariatric treatment. Identifying predictors of abuse would enable focused screening and may increase weight management success. METHODS: We analyzed data from 500 consecutively recruited obese subjects from a population-based, regional bariatric program. The prevalence of self-reported sexual abuse was ascertained using a single interview question. Health status was measured using a visual analogue scale (VAS). Multivariable logistic regression was performed to identify sexual abuse predictors. RESULTS: The mean age was 43.7 y (SD 9.6), 441 (88.2%) were females, 458 (91.8%) were white, and the mean body mass index (BMI) was 47.9 kg/m(2) (SD 8.1). The self-reported prevalence of past abuse was 21.8% (95% CI 18.4-25.4%). Abused subjects had worse health status (VAS score 53.1 (SD 21.2) versus 58.0 (SD 20.1), P = 0.03). BMI was not associated with abuse (P > 0.5). Age, sex, BMI, and covariate-adjusted independent predictors of abuse included alcohol addiction (adjusted odds ratio 15.8; 95% CI 4.0-62.8), posttraumatic stress disorder (4.9; 2.5-9.5), borderline personality (3.8; 1.0-13.8), depression (2.4; 1.3-4.3), and lower household income (3.4; 1.6-7.0). CONCLUSIONS: Abuse was common amongst obese patients managed in a population-based bariatric program; alcohol addiction, psychiatric comorbidities, and low-income status were highly associated with sexual abuse.

Asunto(s)

Cirugía Bariátrica , Obesidad Mórbida/epidemiología , Obesidad Mórbida/cirugía , Autoinforme , Delitos Sexuales/estadística & datos numéricos , Adulto , Alberta/epidemiología , Alcoholismo/epidemiología , Índice de Masa Corporal , Distribución de Chi-Cuadrado , Comorbilidad , Estudios Transversales , Femenino , Estado de Salud , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad Mórbida/diagnóstico , Obesidad Mórbida/psicología , Oportunidad Relativa , Pobreza/estadística & datos numéricos , Prevalencia , Factores de Riesgo , Delitos Sexuales/psicología , Resultado del Tratamiento , Pérdida de Peso

RESUMEN

Obesity, which results from an imbalance between calorie intake and expenditure, now affects over 500 million individuals worldwide. Lifestyle and behavioural interventions aimed at reducing calorie intake and/or increasing energy expenditure have limited long-term effectiveness due to complex and persistent hormonal, metabolic and neurochemical adaptations that defend against weight loss and promote weight regain. Surgical treatments for obesity, although highly effective, are unavailable or unsuitable for the majority of individuals with excess adiposity. Accordingly, few effective treatment options are available to most individuals with obesity. In the past, the use of antiobesity drugs, seemingly the logical choice to fill this therapeutic gap, has been limited because of a lack of efficacy, poor long-term adherence rates and serious adverse effects. In 2012, the FDA approved two new medications-lorcaserin and phentermine-topiramate controlled release-and is currently reviewing the resubmission of naltrexone sustained release-bupropion sustained release. This Review presents the available data on the efficacy and safety of these three medications and discusses future perspectives and challenges related to pharmacological weight management.

Asunto(s)

Obesidad/tratamiento farmacológico , Depresores del Apetito/uso terapéutico , Benzazepinas/uso terapéutico , Combinación de Medicamentos , Fructosa/análogos & derivados , Fructosa/uso terapéutico , Humanos , Estilo de Vida , Fentermina/uso terapéutico , Topiramato

RESUMEN

Preeclampsia (PE) and fetal growth restriction (FGR) contribute significantly to fetal and maternal morbidity and mortality. Although the causes of PE and FGR are not fully understood, both conditions are known to be associated with impaired uterine artery blood flow. Resveratrol, a polyphenol found in a number of plants, has been shown to induce relaxation of uterine arteries in vitro as well as improve many pathological conditions associated with PE and FGR. We hypothesized that treatment of endothelial nitric oxide synthase knockout mice (eNOS⁻/⁻) and catechol-O-methyltransferase knockout mice (COMT⁻/⁻) with resveratrol during pregnancy would improve uterine artery blood flow and therefore ameliorate the PE-like phenotype and FGR in these murine models. Pregnant C57BL/6J, eNOS⁻/⁻ and COMT⁻/⁻ mice received either resveratrol supplemented diet (4 g/kg diet) or control diet between gestational day (GD) 0.5 and GD 18.5. Resveratrol supplementation significantly increased uterine artery blood flow velocity and fetal weight in COMT⁻/⁻ but not in eNOS⁻/⁻ mice. There were no effects of resveratrol on litter size and placental weight among the groups. In conclusion, resveratrol increased uterine artery blood flow velocity and fetal weight in COMT⁻/⁻ mice, suggesting potential as a therapeutic strategy for PE and FGR.

Asunto(s)

Retardo del Crecimiento Fetal/tratamiento farmacológico , Preeclampsia/tratamiento farmacológico , Flujo Sanguíneo Regional/fisiología , Estilbenos/farmacología , Útero/irrigación sanguínea , Análisis de Varianza , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Catecol O-Metiltransferasa/genética , Femenino , Peso Fetal/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Acústica , Óxido Nítrico Sintasa de Tipo III/genética , Embarazo , Proteinuria , Flujo Sanguíneo Regional/efectos de los fármacos , Resveratrol , Estilbenos/uso terapéutico

RESUMEN

OBJECTIVE: To compare BMI with abdominal skinfold thickness (ASF), waist circumference and waist-to-height ratio in the prediction of insulin resistance (IR) in prepubertal Colombian children. DESIGN: We calculated age- and sex-specific Z-scores for BMI, ASF, waist circumference, waist-to-height ratio and three other skinfold-thickness sites. Logistic regression with stepwise selection (P = 0·80 for entry and P = 0·05 for retention) was performed to identify predictors of IR and extreme IR, which were determined by age- and sex-specific Z-scores to identify the ≥ 90th and ≥ 95th percentile of homeostasis model assessment (HOMAIR), respectively. We used receiver operating characteristic curves to compare the area under the curve between models. SETTING: Bucaramanga, Colombia. SUBJECTS: Children (n 1261) aged 6-10 years in Tanner stage 1 from a population-based study. RESULTS: A total of 127 children (seventy girls and fifty-seven boys) were classified with IR, including sixty-three children (thirty-three girls and thirty boys) classified with extreme IR. Only ASF and BMI Z-scores were retained as predictors of IR by stepwise selection. Adding ASF Z-score to BMI Z-score improved the area under the curve from 0·794 (95 % CI 0·752, 0·837) to 0·811 (95 % CI 0·770, 0·851; P for contrast = 0·01). In predicting extreme IR, the addition of ASF Z-score to BMI Z-score improved the area under the curve from 0·837 (95 % CI 0·790, 0·884) to 0·864 (95 % CI 0·823, 0·905; P for contrast = 0·01). CONCLUSIONS: ASF Z-score predicted IR independent of BMI Z-score in our population of prepubertal children. ASF and BMI Z-scores together improved IR risk stratification compared with BMI Z-score alone, opening new perspectives in the prediction of cardiometabolic risk in prepubertal children.

Asunto(s)

Adiposidad , Índice de Masa Corporal , Resistencia a la Insulina , Grasa Intraabdominal , Obesidad/complicaciones , Grosor de los Pliegues Cutáneos , Abdomen , Área Bajo la Curva , Niño , Colombia/epidemiología , Femenino , Trastornos del Metabolismo de la Glucosa/epidemiología , Trastornos del Metabolismo de la Glucosa/etiología , Humanos , Modelos Logísticos , Masculino , Pubertad , Curva ROC

RESUMEN

We have previously shown that adult offspring exposed to a prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) are more susceptible to cardiovascular pathologies. Our objectives were to evaluate the interaction between hypoxia-induced IUGR and postnatal diet in the early development of cardiovascular pathologies. Furthermore, we sought to determine whether the postnatal administration of resveratrol could prevent the development of cardiovascular disorders associated with hypoxia-induced IUGR. On day 15 of pregnancy, Sprague-Dawley rats were randomly assigned to hypoxia (11.5% oxygen), to induce IUGR, or normal oxygen (control) groups. For study A, male offspring (3 wk of age) were randomly assigned a low-fat (LF, <10% fat) or a high-fat (HF, 45% fat) diet. For study B, offspring were randomized to either HF or HF+resveratrol diets. After 9 wk, cardiac and vascular functions were evaluated. Prenatal hypoxia and HF diet were associated with an increased myocardial susceptibility to ischemia. Blood pressure, in vivo cardiac function, and ex vivo vascular function were not different among experimental groups; however, hypoxia-induced IUGR offspring had lower resting heart rates. Our results suggest that prenatal insults can enhance the susceptibility to a second hit such as myocardial ischemia, and that this phenomenon is exacerbated, in the early stages of life by nutritional stressors such as a HF diet. Supplementing HF diets with resveratrol improved cardiac tolerance to ischemia in offspring born IUGR but not in controls. Thus we conclude that the additive effect of prenatal (hypoxia-induced IUGR) and postnatal (HF diet) factors can lead to the earlier development of cardiovascular pathology in rats, and postnatal resveratrol supplementation prevented the deleterious cardiovascular effects of HF diet in offspring exposed to prenatal hypoxia.

Asunto(s)

Dieta Alta en Grasa , Corazón/fisiopatología , Hipoxia/fisiopatología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Femenino , Retardo del Crecimiento Fetal/patología , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Resveratrol , Estilbenos/farmacología

RESUMEN

Preeclampsia and fetal growth restriction are responsible for the majority of maternal and perinatal morbidity and mortality associated with complicated pregnancies. Although their etiologies are complex and multifactorial, both are associated with increased uterine artery resistance. Sildenafil citrate is able to rescue the dysfunction observed ex vivo in uterine arteries of women with preeclampsia. The ability of sildenafil citrate to increase uterine artery vasodilation, thereby decreasing uterine artery resistance and, hence, ameliorated preeclampsia and fetal growth restriction, was tested in a mouse model of preeclampsia, the catechol-O-methyl transferase knockout mouse (COMT(-/-)). COMT(-/-) and C57BL/6J mice were treated (0.2 mg/mL in drinking water, n=6-12) from gestational day 12.5 to 18.5. Measures of pup growth, including body weight, crown/rump length, and abdominal circumference, were reduced in COMT(-/-) mice; this was normalized after treatment with Sildenafil. COMT(-/-) mice also demonstrated abnormal umbilical Doppler waveforms, including reverse arterial blood flow velocity. This was normalized after treatment with Sildenafil. Abnormal uterine artery Doppler waveforms were not demonstrated in COMT(-/-) mice, although ex vivo responses of uterine arteries to phenylephrine were increased; moreover, treatment with Sildenafil did improve ex vivo sensitivity to an endothelium-dependent vasodilator. The data presented here demonstrate that Sildenafil can rescue pup growth and improve abnormal umbilical Doppler waveforms, providing support for a potential new therapeutic strategy targeting fetal growth restriction.

Asunto(s)

Catecol O-Metiltransferasa/metabolismo , Retardo del Crecimiento Fetal/prevención & control , Retardo del Crecimiento Fetal/fisiopatología , Miometrio/irrigación sanguínea , Piperazinas/administración & dosificación , Preeclampsia/tratamiento farmacológico , Sulfonas/administración & dosificación , Arterias Umbilicales/efectos de los fármacos , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Retardo del Crecimiento Fetal/diagnóstico por imagen , Hipertensión/complicaciones , Hipertensión/diagnóstico , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Preeclampsia/fisiopatología , Embarazo , Proteinuria/complicaciones , Proteinuria/diagnóstico , Purinas/administración & dosificación , Citrato de Sildenafil , Ultrasonografía Doppler , Arterias Umbilicales/diagnóstico por imagen , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificación

RESUMEN

OBJECTIVE: A prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) increases the susceptibility to develop metabolic syndrome (MetS) later in life. Since resveratrol (Resv), the polyphenol produced by plants, exerts insulin-sensitizing effects, we tested whether Resv could prevent deleterious metabolic effects of being born IUGR. RESEARCH DESIGN AND METHODS: Pregnant rats were exposed to either a normoxic (control; 21% O(2)) or a hypoxic (IUGR; 11.5% O(2)) environment during the last third of gestation. After weaning, male offspring were randomly assigned to receive either a high-fat (HF; 45% fat) diet or an HF diet with Resv (4 g/kg diet) for 9 weeks when various parameters of the MetS were measured. RESULTS: Relative to normoxic controls, hypoxia-induced IUGR offspring developed a more severe MetS, including glucose intolerance and insulin resistance, increased intra-abdominal fat deposition and intra-abdominal adipocyte size, and increased plasma triacylglycerol (TG) and free fatty acids, as well as peripheral accumulation of TG, diacylglycerol, and ceramides. In only IUGR offspring, the administration of Resv reduced intra-abdominal fat deposition to levels comparable with controls, improved the plasma lipid profile, and reduced accumulation of TG and ceramides in the tissues. Moreover, Resv ameliorated insulin resistance and glucose intolerance as well as impaired Akt signaling in the liver and skeletal muscle of IUGR offspring and activated AMP-activated protein kinase, which likely contributed to improved metabolic parameters in Resv-treated IUGR rats. CONCLUSIONS: Our results suggest that early, postnatal administration of Resv can improve the metabolic profile of HF-fed offspring born from pregnancies complicated by IUGR.

Asunto(s)

Antioxidantes/farmacología , Retardo del Crecimiento Fetal/metabolismo , Síndrome Metabólico/prevención & control , Efectos Tardíos de la Exposición Prenatal/prevención & control , Estilbenos/farmacología , Animales , Peso Corporal/fisiología , Calorimetría Indirecta , Grasas de la Dieta/efectos adversos , Grasas de la Dieta/metabolismo , Ingestión de Energía/fisiología , Femenino , Retardo del Crecimiento Fetal/etiología , Hipoxia/complicaciones , Hipoxia/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Actividad Motora/fisiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Resveratrol

RESUMEN

Almost 30 years ago, a series of epidemiological studies popularized the early programming theory that had resulted from observed associations between low birthweight and increased cardiovascular morbidity and mortality later in life. Since then, several clinical and experimental models have been created to understand the principles and mechanisms of this fascinating phenomenon and describe its relevance to the pathophysiology of cardiovascular and many other chronic diseases. Despite the growing body of published evidence, the specific mechanisms mediating early programming effects are still elusive. Moreover, many controversial issues have arisen regarding the characteristics of the most commonly used clinical and experimental models, the existence of potential windows of susceptibility for different organs, and the presence of sex differences in its pathophysiology. Therefore, this review synthesizes some of the antecedents behind the early programming theory and discusses some of the controversial issues surrounding it. Early programming has been extensively linked to several chronic diseases; however, for the purposes of this review we have concentrated on the potential role of this entity in the pathophysiology of chronic cardiovascular diseases.

Asunto(s)

Enfermedades Cardiovasculares/etiología , Sistema Cardiovascular/embriología , Desarrollo Fetal , Efectos Tardíos de la Exposición Prenatal , Adulto , Animales , Enfermedades Cardiovasculares/fisiopatología , Sistema Cardiovascular/fisiopatología , Susceptibilidad a Enfermedades , Femenino , Humanos , Masculino , Modelos Biológicos , Embarazo , Caracteres Sexuales

RESUMEN

OBJECTIVE: It is recognized that there is a remarkable variability in the systemic response to high-fat (HF) diets that cannot be completely explained by genetic factors. In addition, pregnancy complications leading to intrauterine growth restriction (IUGR) have been associated with an increased risk of developing metabolic syndrome (MetS) later in life. Thus, we hypothesized that offspring born with IUGR exhibit permanent metabolic changes that make them more susceptible to HF diet-induced MetS. RESEARCH DESIGN AND METHODS: SD rats born normal (control) or with hypoxia-induced IUGR were randomized to low-fat (10% fat) or HF (45% fat) diets. After 9 weeks of feeding, physiological and molecular pathways involved in the MetS were evaluated. RESULTS: IUGR offspring exhibited decreased energy intake and physical activity relative to controls. In offspring fed a HF diet, IUGR was associated with decreased total body fat content, a relative increase in intra-abdominal fat deposition and adipocyte size, an increase in fasting plasma concentrations of leptin, triglyceride and free fatty acids, and an increased concentration of triglycerides and ceramides in both liver and skeletal muscle. These changes in lipid homeostasis were accompanied by in vivo insulin resistance and impaired glucose tolerance and associated with increased phosphorylation of protein kinase C , inhibition of insulin receptor substrate 1, and a decreased activation of protein kinase B (PKB; also known as Akt) in liver and skeletal muscle in response to insulin. CONCLUSIONS: IUGR enhances specific deleterious metabolic responses to a HF diet. Our results suggest that offspring born with IUGR may require special attention and follow-up to prevent the early onset of MetS.

Asunto(s)

Grasas de la Dieta/metabolismo , Susceptibilidad a Enfermedades/metabolismo , Retardo del Crecimiento Fetal/metabolismo , Hipoxia/complicaciones , Síndrome Metabólico/metabolismo , Análisis de Varianza , Animales , Glucemia/metabolismo , Western Blotting , Composición Corporal , Citocinas/sangre , Susceptibilidad a Enfermedades/etiología , Femenino , Retardo del Crecimiento Fetal/etiología , Intolerancia a la Glucosa/metabolismo , Hipoxia/metabolismo , Insulina/metabolismo , Lípidos/sangre , Masculino , Síndrome Metabólico/etiología , Embarazo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley

RESUMEN

AIMS: Adult offspring who are born intrauterine growth restricted (IUGR) are at risk of developing cardiovascular diseases during adulthood. Additionally, several cardiac diseases are associated with changes in myocardial energy metabolism. However, the potential long-term effects of being born IUGR on cardiac energetics are unknown. The aim of this study was to assess the long-term effect of IUGR on cardiac performance and energy metabolism under aerobic conditions and after ischaemia/reperfusion (IR) injury. METHODS AND RESULTS: To induce IUGR, pregnant Sprague-Dawley rats were randomly assigned to hypoxic (11.5% O(2)) or control (21% O(2)) environments from day 15 to 21 of pregnancy. Cardiac susceptibility to IR was evaluated in male and female offspring at 4 (young-adult) or 12 (ageing) months of age using isolated working hearts. Cardiac production of energy was evaluated using radiolabelled substrates. Both male and female IUGR offspring exhibited an increased susceptibility to IR injury compared with controls (P< 0.05) as well as an increased post-ischaemic production of protons (P< 0.001) secondary to a mismatch between myocardial glycolysis and glucose oxidation rates. Moreover, offspring born IUGR exhibited an increased myocardial production of acetyl-CoA during reperfusion. The mismatch between energy production and cardiac performance indicates that in IUGR offspring, cardiac efficiency during reperfusion was decreased relative to controls. CONCLUSION: Our results suggest that hypoxia-induced IUGR has long-term effects on cardiac susceptibility to IR injury that are independent of sex and age. Moreover, we identified a mismatch in glucose metabolism, leading to proton accumulation in the post-ischaemic myocardium of offspring born IUGR as a potential mechanism involved.

Asunto(s)

Retardo del Crecimiento Fetal/metabolismo , Retardo del Crecimiento Fetal/fisiopatología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Factores de Edad , Animales , Modelos Animales de Enfermedad , Metabolismo Energético/fisiología , Femenino , Glucólisis/fisiología , Corazón/embriología , Corazón/fisiología , Hipoxia/metabolismo , Hipoxia/fisiopatología , Masculino , Miocardio/metabolismo , Oxígeno/administración & dosificación , Embarazo , Ratas , Ratas Sprague-Dawley

RESUMEN

OBJECTIVE: Ovarian deficiency is known to undermine vasoprotective mechanisms and accelerate cardiovascular disease in postmenopausal women. In a rat model of menopause (aged ovariectomized [Ovx] rats), we recently revealed a vasoconstrictor pathway mediated by matrix metalloproteinases (MMPs) via cleavage of big endothelin-1 (ET-1). However, the specific impact of aging and/or Ovx on this pathway remains unknown. We hypothesized that aging exacerbates MMP-mediated vasoconstriction in an ovary-deficient state. METHODS: Young and aged female Sprague-Dawley rats, either intact or Ovx, were assessed for MMP-dependent vasoreactivity. Dose responses to big ET-1 in the absence or presence of an MMP inhibitor (GM6001) were tested on small mesenteric arteries using a pressure myograph system. MMP levels in the vascular tissue were measured by gelatin zymography. RESULTS: Both young Ovx and aged Ovx animals demonstrated a similar increase in the vasoconstriction to big ET-1 compared with the age-matched intact groups. MMP inhibition attenuated big ET-1 response in both Ovx groups and aged controls, but this effect was more pronounced in aged Ovx arteries (area under the curve reduction, 3.8 +/- 0.6 units in aged Ovx rats vs 1.5 +/- 0.5 units in young Ovx rats or 1.8 +/- 0.6 units in aged intact rats; P < 0.05). MMP-2 activity in the vascular tissue increased with age and was further augmented by Ovx. CONCLUSIONS: Regardless of age, ovarian loss increases vascular reactivity to big ET-1, which is mediated, in part, by MMP. Superimposed with advancing age, ovarian deficiency further increases the proconstrictor role of MMP, which corresponds with higher MMP-2 levels in the aging vessel wall. MMP-mediated vasoconstriction may be a mechanism contributing to vascular dysfunction in postmenopausal women.

Asunto(s)

Envejecimiento/fisiología , Endotelina-1/metabolismo , Metaloproteinasas de la Matriz/fisiología , Arterias Mesentéricas/metabolismo , Vasoconstricción/fisiología , Factores de Edad , Animales , Femenino , Menopausia/fisiología , Modelos Animales , Ovariectomía/efectos adversos , Ratas , Ratas Sprague-Dawley