Accumulating evidence links cardiometabolic health with social and environmental neighborhood exposures, which may contribute to health inequities. We examined whether environmental characteristics were individually or jointly associated with insulin resistance, hypertension, obesity, type 2 diabetes, and metabolic syndrome in San Diego County, CA. As part of the Community of Mine Study, cardiometabolic outcomes of insulin resistance, hypertension, BMI, diabetes, and metabolic syndrome were collected in 570 participants. Seven census tract level characteristics of participants' residential environment were assessed and grouped as follows: economic, education, health care access, neighborhood conditions, social environment, transportation, and clean environment. Generalized estimating equation models were performed, to take into account the clustered nature of the data and to estimate β or relative risk (RR) and 95 % confidence intervals (CIs) between each of the seven environmental characteristics and cardiometabolic outcomes. Quantile g-computation was used to examine the association between the joint effect of a simultaneous increase in all environmental characteristics and cardiometabolic outcomes. Among 570 participants (mean age 58.8 ± 11 years), environmental economic, educational and health characteristics were individually associated with insulin resistance, diabetes, obesity, and metabolic syndrome. In the mixture analyses, a joint quartile increase in all environmental characteristics (i.e., improvement) was associated with decreasing insulin resistance (β, 95 %CI: -0.09, -0.18-0.01)), risk of diabetes (RR, 95 %CI: 0.59, 0.36-0.98) and obesity (RR, 95 %CI: 0.81, 0.64-1.02). Environmental characteristics synergistically contribute to cardiometabolic health and independent analysis of these determinants may not fully capture the potential health impact of social and environmental determinants of health.

We examined diabetes self-management class utilization in a study sample of adult BRFSS 2012 participants with diabetes (n=34,665).  This study assessed demographic variables that might be associated with class utilization, specifically sex, age, income, having health insurance (yes or no), and ethnicity (Hispanic and non-Hispanic) on diabetes self-management class utilization. Participation in diabetes self-management class was 53.8% overall.  Male sex, age greater than 49 years, income <$25,000 per year, and lack of health insurance were each significantly associated with decreased class utilization.  Hispanics (n=2,962) were 43% less likely to have taken a class compared to non-Hispanics (n=31,703) (OR 0.57, CI:0.53-0.62, p<0.001) with 41.2% of Hispanics and 55% of non-Hispanics reporting that they had taken a diabetes self-management class.  This disparity remained after adjusting for sex, age, income, and health insurance (OR 0.60, CI:0.55-0.65, p<0.001). Efforts to enhance participation in diabetes self-management education are needed, particularly in Hispanic communities.

Introduction: Children and adolescents with cancer report increased fatigue and decreased physical activity, introducing risk factors for chronic disease and suppressed quality of life. Research suggests an inverse relationship between fatigue and physical activity, but the biological explanation is not well understood. The purpose of this study was to 1) explore metabolites associated with fatigue or physical activity and 2) to identify any shared metabolomic elements. Methods: Children, ages 8-17 years, attending a pediatric oncology summer camp provided Patient-Reported Outcome Measurement System® (PROMIS) Pediatric Fatigue assessments, physical activity data (steps/day), and urine samples pre- and post-camp. Differences in PROMIS Pediatric Fatigue scores and average daily steps were calculated using paired t-tests. Liquid chromatography-tandem mass spectrometry was conducted using a targeted metabolomic approach. Results: Thirty-two enrolled children had complete data. Fatigue scores decreased (pre-camp 45.1; post-camp 42.1; p = 0.04) while steps-per-day increased (pre-camp 6699; post-camp 16,021; p < 0.001). Twenty-seven metabolites significantly differentiated (false discovery rate <0.20) between low, medium, or high physical activity, while 8 metabolites discriminated between high and low fatigue. Indole-3-lactic acid, a tryptophan metabolite, was significantly associated with both physical activity and fatigue. Conclusion: This study provides evidence of metabolome associations with fatigue and physical activity in children with cancer. Overlapping metabolomic elements provide evidence of biological inter-connectivity and suggest areas for future research. Given the known evidence regarding the benefits of physical activity, and the potential interaction with fatigue, nurses should routinely assess patient reports of these elements and provide patient/family education related to fatigue management and physical activity goals.

Introduction

Many breast cancer survivors experience problems with cognitive functioning that can persist years after treatment. Increasing physical activity has been shown to improve cognitive functioning in healthy and cognitively impaired adults, but has not yet been tested in cancer survivors. The primary aim of this randomized controlled trial is to examine the effects of a 3-month physical activity intervention compared to a waitlist Control arm on neuropsychological outcomes and subjective cognitive concerns in breast cancer survivors.

Methods

Eighty sedentary breast cancer survivors, self-reporting difficulties with cognition, will be randomized into an Exercise arm or Control arm. The Exercise arm includes an activity tracker (i.e., a Fitbit), phone calls, plus tailored and non-tailored email content. The Control arm will receive emails on women's health topics on the same schedule as the Exercise arm. Assessments conducted at baseline and 3 months include: neuropsychological testing, cognitive concerns and other aspects of quality of life, and 7 days of a hip-worn accelerometer. Participants will also provide fasting blood draws to assess brain-derived neurotropic factor, Insulin-like growth factor 1, insulin resistance, and C-reactive protein. Primary and secondary outcomes are changes in neuropsychological testing and cognitive concerns. Biomarkers will be examined to further understand the underlying relationship between physical activity and cognition.

Conclusion

The Memory & Motion study is designed to test whether increasing physical activity can improve cognitive functioning in breast cancer survivors. Results from this study could be used to guide development of interventions to improve cognitive functioning in breast cancer survivors.

Purpose of review

Disparities in obesity rates in the US continue to increase. Here we review progress and highlight gaps in understanding disparities in obesity with a focus on the Hispanic/Latino population from a systems epidemiology framework. We review seven domains: environment, behavior, biomarkers, nutrition, microbiome, genomics, and epigenomics/transcriptomics. We focus on recent advances that include at least two or more of these domains, and then provide a real world example of data collection efforts that reflect these domains.

Recent findings

Research into DNA methylation related to discrimination and microbiome relating to eating behaviors and food content is furthering understanding of why disparities in obesity persist. Environmental and neighborhood level research is uncovering the importance of exposures such as air and noise pollution and systematic or structural racism for obesity and related outcomes through behaviors such as sleep.

Individual sleep dimensions have been linked to cardiovascular disease (CVD) risk and cardiometabolic health (CMH), but sleep health is multifaceted. We investigated associations of a multidimensional sleep health (MDSH) score, enabling the assessment of sleep health gradients, with CVD and CMH. Participants were 4555 adults aged ≥20 years from the 2017-2018 National Health and Nutrition Examination Survey. A MDSH score, capturing poor, moderate, and ideal sleep was computed from self-reported sleep duration, sleep regularity, difficulty falling asleep, symptoms of sleep disorders, and daytime sleepiness. Survey-weighted multivariable linear and logistic models examined associations of MDSH with CVD and CMH. Ideal and moderate vs. poor MDSH were related to lower odds of hypertension (62% and 41%), obesity (73% and 56%), and central adiposity (68% and 55%), respectively; a statistically significant linear trend was observed across gradients of MDSH (p-trend < 0.001). Ideal vs. moderate/poor MDSH was associated with 32% and 40% lower odds of prevalent CVD and type 2 diabetes, respectively. More favorable MDSH was associated with lower blood pressure, BMI, waist circumference, and fasting glucose. In sex-stratified analyses, ideal vs. moderate/poor MDSH was associated with lower CVD odds and blood pressure in women only. The MDSH framework may be more than just the sum of its parts and could better capture information regarding CVD risk.

Abstract Obesity is a risk factor for postmenopausal breast cancer. Inflammation, hyperinsulinemia, insulin resistance and altered levels of adipokines have been proposed as possible links between obesity and tumor progression. Furthermore, the composition of fats in the diet can influence inflammation and epidemiological studies have shown that an increase in fish oil (omega-3 fatty acids; ω-3 FAs) intake is associated with a reduction in breast cancer incidence in humans. Several mechanisms have been proposed for the anticancer effect of ω-3 FAs such as suppression of neoplastic transformation, cell proliferation or angiogenesis, or an increase in apoptosis. To study the effects of ω-3 FA on mammary tumor growth in a mouse model of postmenopausal obesity, ovariectomized C57BL/6 mice were fed either a high fat diet (HFD, 60% kcal from fat) or an isocaloric HFD containing 30% ω-3 FA replacement [wt/wt, 24% docosahexaenoic acid (DHA), 6% eicosapentaneoic acid (EPA)]. Fourteen weeks after starting HFDs, mice received orthotopic mammary fat pad injections of Py230 cells derived from a spontaneous polyomavirus middle T antigen (PyVmT) mammary tumor. Mammary tumor growth, inflammatory cytokine expression in perigonadal fat and the mammary fat pads and tumors, and apoptosis and cell proliferation in the tumors were determined at 22 weeks following initiation of the HFDs. There was no difference in body weights between mice fed a HFD with or without ω-3 FA, but ω-3 FA-fed mice had a significantly reduced mammary tumor burden (33%) compared to counterpart HFD-fed mice. The ω-3 FA-fed mice showed decreased expression of macrophages and inflammatory cytokines such as CD11c, TNF-α and iNOS in perigonadal fat. However, surprisingly the ω-3 FA-fed mice showed increased macrophage and inflammatory cytokine expression: CD11c, TNF-α, IL-1β and IL-6 in the mammary fat pads implanted with tumor cells, suggesting that the anti-inflammatory effect of ω-3 FAs may be modulated by implanted tumor cells. No difference was observed in the expression of macrophage marker and inflammatory cytokines in mammary tumors between mice fed a HFD with or without ω-3 FA. Immunohistochemical staining of mammary tumors revealed a high degree of variability in cell proliferation and apoptosis between tumors and no significant differences were observed. To examine whether ω-3 FAs may act directly on Py230 tumor cells to reduce mammary tumor growth, we tested the effects of ω-3 FA on cell growth, apoptosis and signaling in Py230 cells in vitro. DHA significantly inhibited Py230 cell growth in a dose-dependent manner. In addition, DHA inhibited TNF-α-induced cell growth and blocked NF-κB signaling activated by TNF-α in Py230 cells. Furthermore, DHA increased the activities of caspases 3 and 7 and induced apoptosis in Py230 cells. Our results suggest that ω-3 FAs may suppress mammary tumor growth by directly inhibiting the growth of mammary tumor cells via induction of apoptosis. Further analysis of the signaling pathways involved may identify new therapeutic targets for postmenopausal women with breast cancer. Citation Format: Heekyung Chung, Dorothy D. Sears, Nicholas J. Webster, Jerrold M. Olefsky, Lesley G. Ellies. Omega-3 fatty acids reduce mammary tumor growth in a mouse model of postmenopausal breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A123.

Background

Menopause is associated with significant hormonal changes that result in increased total body fat and abdominal fat, amplifying the risk for metabolic syndrome and diseases such as diabetes, cardiovascular disease and cancer in postmenopausal women. Intermittent fasting regimens hold significant health benefit promise for obese humans, however, regimens that include extreme daytime calorie restriction or daytime fasting are generally associated with hunger and irritability, hampering long-term compliance and adoption in the clinical setting. Time-restricted feeding (TRF), a regimen allowing eating only during a specific period in the normal circadian feeding cycle, without calorie restriction, may increase compliance and provide a more clinically viable method for reducing the detrimental metabolic consequences associated with obesity.

Methods

We tested TRF as an intervention in a mouse model of postmenopausal obesity. Metabolic parameters were measured using Clinical Laboratory Animal Monitoring System (CLAMS) and we carried out glucose tolerance tests. We also stained liver sections with oil red O to examine steatosis and measured gene expression related to gluconeogenesis.

Results

Preexisting metabolic disease was significantly attenuated during 7 weeks of TRF. Despite having access to the same high fat diet (HFD) as ad libitum fed (ALF) mice, TRF mice experienced rapid weight loss followed by a delayed improvement in insulin resistance and a reduced severity of hepatic steatosis by having access to the HFD for only 8h during their normal nocturnal feeding period. The lower respiratory exchange ratio in the TRF group compared with the ALF group early in the dark phase suggested that fat was the predominant fuel source in the TRF group and correlated with gene expression analyses that suggested a switch from gluconeogenesis to ketogenesis. In addition, TRF mice were more physically active than ALF fed mice.

Conclusions

Our data support further analysis of TRF as a clinically viable form of intermittent fasting to improve metabolic health due to obesity.