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UNLABELLED - What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index.
BACKGROUND - Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children.
OBJECTIVE - To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance.
METHODS - Sixty-nine healthy subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a prospective longitudinal cohort for 18 months (n = 17 with complete data).
RESULTS - Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P = 0.046).
CONCLUSIONS - Elevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance.
© 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.
Intrauterine environmental pertubations have been linked to the development of adult hypertension. We sought to evaluate the interrelated roles of sex, nitric oxide, and reactive oxygen species (ROS) in programmed cardiovascular disease. Programming was induced in mice by maternal dietary intervention (DI; partial substitution of protein with carbohydrates and fat) or carbenoxolone administration (CX, to increase fetal glucocorticoid exposure). Adult blood pressure and locomotor activity were recorded by radiotelemetry at baseline, after a week of high salt, and after a week of high salt plus nitric oxide synthase inhibition (by l-NAME). In male offspring, DI or CX programmed an elevation in blood pressure that was exacerbated by N(omega)-nitro-l-arginine methyl ester administration, but not high salt alone. Mesenteric resistance vessels from DI male offspring displayed impaired vasorelaxation to ACh and nitroprusside, which was blocked by catalase and superoxide dismutase. CX-exposed females were normotensive, while DI females had nitric oxide synthase-dependent hypotension and enhanced mesenteric dilation. Despite the disparate cardiovascular phenotypes, both male and female DI offspring displayed increases in locomotor activity and aortic superoxide production. Despite dissimilar blood pressures, DI and CX-exposed females had reductions in cardiac baroreflex sensitivity. In conclusion, both maternal malnutrition and fetal glucocorticoid exposure program increases in arterial pressure in male but not female offspring. While maternal DI increased both superoxide-mediated vasoconstriction and nitric oxide mediated vasodilation, the balance of these factors favored the development of hypertension in males and hypotension in females.
As food intake declines with aging, older adults develop energy and nutrient inadequacies. It is important to design practical approaches to combat insufficient dietary intakes to decrease risk for acute and chronic diseases, illness, and injury. Manipulating the energy density of meals has improved energy intakes in institutional settings, but the effects on community-residing older adults who are at nutrition risk have not been investigated. The aim of this study was to determine whether enhancing the energy density of food items regularly served in a home-delivered meals program would increase lunch and 24-hour energy and nutrient intakes. In a randomized crossover counterbalanced design, 45 older adult Older American Act Nutrition Program participants received a regular and enhanced version of a lunch meal on alternate weeks. The types of foods, portion sizes (gram weight), and appearance of the lunch meal was held constant. Consumption of the enhanced meal increased average lunch energy intakes by 86% (P<0.001) and 24-hour energy intakes by 453 kcal (from 1,423.1+/-62.2 to 1,876.2+/-78.3 kcal, P<0.001). The 24-hour intakes of several key macronutrients and micronutrients also improved. These data suggest that altering the energy density of regularly served menu items is an effective strategy to improve dietary intakes of free-living older adults.
Metabolic bone disease is often silent, often undiagnosed, and occurs frequently in patients with chronic gastrointestinal illnesses. Potentially modifiable risk factors, such as malnutrition, malabsorption, prolonged use of glucocorticoids, and a sedentary lifestyle, can lead to low bone mass, an increased rate of bone loss, and debilitating bone disease. This article explores common gastrointestinal illnesses that place patients at risk for developing metabolic bone disease. Concepts are presented to assist the practitioner in identifying patients at risk; clinical evaluation and diagnostic test selection are discussed, and therapeutic options for the prevention and treatment of metabolic bone disease in gastrointestinal illness are presented.
Nutritional status is an important predictor of clinical outcome in end-stage renal disease (ESRD) patients, especially in patients on chronic hemodialysis. Uremic malnutrition is strongly associated with increased risk of death and hospitalization events in this patient population, and decreased muscle mass is the most significant predictor of these outcomes. Several factors that influence protein metabolism predispose chronic hemodialysis patients to increased catabolism and loss of lean body mass. The available evidence suggests that low protein and energy intake associated with advanced uremia along with catabolic consequences of dialytic therapies can lead to the development of uremic malnutrition. Recent studies show that the hemodialysis procedure induces a net protein catabolic state at the whole-body level as well as skeletal muscle. There is evidence to suggest that these undesirable effects are due to decreased protein synthesis and increased proteolysis. Provision of nutrients, either in the form of intradialytic parenteral nutrition or oral feeding during hemodialysis, can adequately compensate for the catabolic effects of the hemodialysis procedure. While the mechanisms of these effects are not studied in detail, changes in extracellular amino acid concentrations, along with certain anabolic hormones such as insulin, are important mediators of these actions.
OBJECTIVES - We used stress process theory to identify family caregiving variables that are salient to the experience of managing older adults' home enteral nutrition. In this article, we describe the specific tasks family caregivers performed and their unique training needs in the context of caregiver preparedness, competence, effectiveness, and health care use.
DESIGN - Hospital billing lists from two university-affiliated institutions in Miami, FL, were used to identify older adults who had enteral tubes placed over a 6-month period. Consent was obtained from those older adults discharged for the first time on home enteral nutrition and their family caregivers at the first scheduled outpatient visit.
SUBJECTS/SETTING - In-home interviews were conducted with a diverse sample of 30 family caregivers (14 white, 8 Hispanic, 7 African-American, 1 Asian) during their first 3 months (mean=1.83+/-0.69 months) of home enteral nutrition caregiving.
STATISTICAL ANALYSES PERFORMED - Descriptive statistics were used to summarize data for all variables; chi(2) analysis was conducted to analyze differences in categorical variables. One-way analysis of variance was used to analyze mean differences among caregivers grouped by ethnicity for total number of hours and tasks performed. Post hoc comparisons were conducted using the Tukey HSD test. The Spearman rho correlations were calculated to assess bivariate associations between quantitative variables.
RESULTS - Caregivers reported providing from 6 to 168 hours of care weekly (mean=61.87+/-49.67 hours), in which they performed an average of 19.73+/-8.09 caregiving tasks daily. Training needs identified were greatest for technical and nutrition-related tasks. Preparedness for caregiving scores were low (mean=1.72, maximum=4.0) and positively correlated with caregiver competence (P<.001) and self-rated caregiver effectiveness (P=.004). Preparedness negatively correlated with health care use (P=.03).
CONCLUSIONS - Caregivers of older adults on home enteral nutrition need training for multiple nutrition-related and caregiving tasks. Multidisciplinary interventions, involving dietitian expertise, are needed to better prepare caregivers to improve both caregiver effectiveness and enteral nutrition outcomes.
Uremic malnutrition is highly prevalent and is associated with poor clinical outcomes in end-stage renal disease (ESRD) patients. Inadequate diet and a state of persistent catabolism play major roles in predisposing these patients to uremic malnutrition and appear to have an additive effect on overall outcome. Recent studies highlight the existence of a complex syndrome involving chronic inflammation, metabolic abnormalities, and hormonal derangements contributing to the increased morbidity and mortality observed in ESRD patients. Novel strategies such as appetite stimulants, anti-inflammatory drugs, and anabolic hormones along with conventional nutritional supplementation may provide potential interventions to improve clinical outcome in ESRD patients.
Uremic malnutrition and chronic inflammation are important comorbid conditions that predict poor clinical outcome in end-stage renal disease (ESRD) patients. These conditions are also closely associated with cardiovascular disease, the major cause of death in ESRD patients. A pathophysiologic link between malnutrition, inflammation, and atherosclerosis has been proposed in this patient population. Indeed, multiple lines of evidence suggest that chronic inflammation can predispose ESRD patients to a catabolic and atherogenic state. Malnutrition can also result from chronic inflammation and can accelerate the progression of cardiovascular disease. Whereas a single common etiology has not been identified in this complex process, nutritional and anti-inflammatory interventions provide potential treatment options to counter the high mortality and morbidity in ESRD patients.