Obesity has reached pandemic proportions worldwide, doubling in developed and developing nations. In the United States, a significant percentage of children and teenagers are classified as obese, with a disproportionate representation of Latino and African American children. This is concerning, considering the associations between childhood overweight and obesity and increased childhood morbidity, including type 2 diabetes mellitus (T2DM), insulin resistance syndrome, hypertension, dyslipidemia, and other serious health issues. While obesity is easily recognized, it has remained difficult to treat, incurring substantial annual costs.
This article delves into the factors influencing weight and health, particularly focusing on a study involving prepubescent Latino children. The study, "Published in final edited form as: J Pediatr Nurs. 2008 Sep 4;24(5):378-388," investigated the contributions of stress and body mass index (BMI) to tumor necrosis factor-α (TNF-α) levels, an inflammatory cytokine, and the modifying effects of sex and family history of T2DM.
The Study: Stress, BMI, and TNF-α in Latino Children
The study involved 112 nondiabetic school-aged Hispanic children in South Florida, with a substantial portion being obese and presenting a family history of T2DM. Stressful life events were assessed through parental reports, and plasma TNF-α levels were determined using enzyme-linked immunosorbent assay. Multiple linear regression analyses were conducted to analyze the relationships between stress, BMI, TNF-α levels, and the potential interaction effects of sex and family history of T2DM.
Key Findings
The study revealed that both stress and BMI independently contributed to a significant proportion of the unique variance associated with TNF-α levels. The association between stress and TNF-α was not modified by sex or family history of T2DM. These findings suggest that BMI and stress are independent determinants of TNF-α among Latino children.
The Role of TNF-α in Obesity-Related Complications
TNF-α, as an inflammatory cytokine, has been implicated in the pathogenesis of medical complications secondary to obesity, including insulin resistance and T2DM. Insulin resistance itself has been characterized as a proinflammatory "condition" involving increased TNF-α and other inflammatory cytokines. However, the molecular mechanisms remain poorly understood, and relatively few studies have examined these effects in children, with inconsistent findings noted. Some research has found increasing levels of TNF-α with increased BMI, while others have found no relationship or even higher TNF-α levels with decreased BMI in child populations.
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Other Factors Influencing TNF-α Levels
Besides obesity, other factors can contribute to increased circulating TNF-α levels, including cachexia, febrile and other infectious illnesses, acute injury and increased pain, growth hormone (GH) levels, and greater psychosocial stress levels. Differential effects have been noted for men versus women with regard to the relationship between greater psychosocial stress and higher circulating levels of TNF-α. However, this relationship has not been studied extensively in children.
The Link Between Stress and Obesity
Research has demonstrated indirect associations between greater psychosocial stress and increased obesity, most commonly via eating behaviors. Stress has been specifically implicated in the pathogenesis of central (or abdominal) obesity and related comorbidities. The mechanism postulated involves the activation of the hypothalamic-pituitary-adrenal (HPA) axis, with increased adrenal hormones associated directly with the centralization of body fat and increased glucocorticoids associated with increased food intake, otherwise defined as “stress eating”.
Study Objectives and Hypotheses
Recognizing that prior work with adults had demonstrated significant associations between stress and TNF-α levels, one of the main objectives was to determine if elevated psychosocial stress would help explain the observed elevations in TNF-α levels among the children. In this regard, it was hypothesized that greater stress would remain associated with increased TNF-α levels in these children.Another main objective was to tease apart the potential independent effects of BMI and stress on TNF-α within this population of Latino children. It was hypothesized that increased stress and decreased BMI would demonstrate independent relative effects on TNF-α levels among these children.A further main objective was to determine if these associations were modified by sex and/or family history of T2DM within these same children.
Study Methodology
The study involved randomly selecting and enrolling school-aged children. Participants underwent a physical examination and a blood test, while their parents were interviewed regarding health habits and history. Children were excluded from the study if they had a chronic disease, a diagnosed endocrine or hormonal cause for obesity, or medications that could affect their glucose tolerance. The construct of psychosocial stress was assessed via parental completion of the Life Events Checklist (LEC) for children, a measure that has been well validated for the assessment of stress among child populations. Body composition was assessed with several measures, including height, weight, and BMI. Fasting plasma TNF-α levels were determined from fasting baseline blood collections from a standardized oral glucose tolerance test (OGTT) administration. Enzyme-linked immunosorbent assay was used to determine fasting plasma TNF-α concentrations. Statistical analyses were performed to examine the relationships between BMI, stress, and TNF-α.
Study Results
The study included 55 girls and 57 boys, of whom 43.8% (n = 49) were found to meet criteria for obesity at the 95th percentile (adjusted for age and sex; Hammer, Kraemer, Wilson, Ritter, & Dornbusch, 1991), 52.7% (n = 59) presented with a family history of T2DM (for both first- and second-degree relatives), as determined by physician interview (Mitchell et al., 1993), and 25% (n = 28) were obese and had a positive family history of T2DM. As expected, obese children demonstrated greater insulin resistance, higher diastolic and systolic blood pressures, higher fasting glucose, triglyceride, and very-low-density lipoprotein cholesterol levels, and lower high-density lipoprotein cholesterol levels compared with nonobese children. Higher circulating TNF-α levels were associated with nonobese status, female sex, and decreased insulin resistance (Dixon et al., 2004). Higher plasma TNF-α levels were associated with lower BMI and greater stress in the sample. BMI and stress were positively correlated, but the relationship did not reach statistical significance.
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Implications and Future Directions
The findings implicate BMI and stress as independent determinants of TNF-α (an inflammatory cytokine and adipocytokine) among Latino children. This highlights the importance of addressing both obesity and stress in interventions aimed at reducing inflammation and preventing related health complications in this population. Further research is needed to fully understand the complex interplay between BMI, stress, TNF-α, and other factors in the development of obesity-related health issues in children.
Broader Context: Health Disparities and Interventions
The study on Denise Valdez's weight loss journey and related factors is part of a broader effort to understand and address health disparities and improve health outcomes for diverse populations. Other research initiatives and studies are also contributing to this goal:
The Health Care Systems Research Network (HCSRN): This network comprises learning health systems with integrated care delivery and embedded research units. The network's annual conference serves as a forum for research teams from member institutions to disseminate project findings, explore scientific collaborations, and share insights about population-based research practices that can measurably improve health and health care for all.
Maternal Anemia Interventions: Studies have shown that maternal anemia interventions significantly improved serum hemoglobin levels. Although parenteral maternal anemia interventions marginally improved serum hemoglobin levels, multifaceted randomized controlled trials (RCTs) are essential to validate these findings.
Molecular Data Harmonization: The Kaiser Permanente (KP) Center for Effectiveness and Safety Research (CESR) is working to secure discrete result data from outside testing vendors and create a Virtual Data Warehouse (VDW) molecular marker result database at each KP region to facilitate future genetic research. Molecular data harmonization enables population-level analyses to improve diagnostic yield by disambiguating conflicting clinical interpretations and variants of uncertain significance.
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COVID-19 Treatment in Pregnant Women: Research has shown that a significant proportion of pregnant patients with COVID-19 are not receiving recommended antiviral medications, highlighting the need for targeted work to increase access to recommended COVID-19 therapeutics during pregnancy.
Ambulatory Care Sensitive Conditions in People with HIV: Studies have found that people with HIV (PWH) have a moderately higher prevalence of both acute and chronic ambulatory care sensitive conditions (ACSCs) compared with people without HIV (PWoH). However, the attenuation or reversal of the association in fully adjusted models suggests PWH receive high quality care, with differences in prevalence of ACSC events attributable to underlying patient factors.
Knee Osteoarthritis and Neighborhood Characteristics: Spatial analysis has demonstrated variations in knee osteoarthritis (KOA) prevalence by census tract among veterans living in the St. Louis Metropolitan Census Area. Follow-up spatial regression analysis will incorporate individual and neighborhood characteristics to identify what neighborhood attributes, such as walkability, may contribute to clustering.
Type 2 Diabetes and the COVID-19 Pandemic: The COVID-19 pandemic onset was followed by an increase in type 2 diabetes (T2D) incidence overall and with sharper increases among Hispanic adults.
Racial Segregation and Health Outcomes: The Jenks natural breaks method identifies statistically distinct, meaningful neighborhood segregation categories and should be preferred in future studies examining associations between segregation and health outcomes.
Corporate Social Responsibility in Healthcare: Clinician volunteerism through Corporate Social Responsibility (CSR) initiatives boosts job satisfaction, workplace connectedness, and well-being, while addressing burnout.