Proximity to Food Outlets and Diabetes-Related Health Outcomes: A Cross-Sectional Study in Robeson County, NC

Type 2 diabetes is a growing epidemic in the United States, and already affects 25.8 million Americans (8.3%) in 2011. The prevalence of type 2 diabetes has nearly tripled from 1990 to 2010 and is projected to increase. If this pattern continues, the Centers for Disease Control and Prevention (CDC) estimates that one-third of Americans will have type 2 diabetes by 2050. In North Carolina, this problem is particularly acute; the state has the 13th highest prevalence of diabetes at 9.8% of the general population. Robeson County—a rural area with a large American Indian population of Lumbee descent—has shown dramatically higher diabetes prevalence than the rest of the state, at 13.7%. The high prevalence of diabetes in Robeson County raises significant concerns about the long-term health status its residents. Research has shown that lifestyle modifications, including dietary changes, can reduce the development of diabetes, as well as the need for treatment of existing diabetes. Unfortunately, rural areas tend to have a dearth of healthy food retailers, such as supermarkets, while boasting a plethora of fast food options. Due to various barriers—such as distance to, and price of, healthy food options—low-income and minority groups living in rural areas are even less likely to have consistent access to healthy, affordable food. Without a healthy diet, it can be challenging for individuals to achieve optimal control over diabetes risk factors, such as A1c level, blood pressure level, and body mass index (BMI). Over time, poor eating behaviors can heighten one’s risk for developing diabetes, or experiencing diabetes-related complications such as kidney failure, amputation, or blindness. It is important to evaluate access to healthy food options in Robeson County to inform future intervention and policy action to reverse diabetes trends in this area. While many individuals living in rural areas lack access to healthy food options and are subsequently at risk for developing diabetes, low-income and minority groups face even higher risk for diabetes morbidity and mortality. Minority groups are disproportionately represented among the poor, and low socioeconomic status is often associated with limited access to affordable, healthy food. Robeson County, with nearly 30% of individuals in poverty, and nearly 40% of individuals of American Indian descent, has many residents that are particularly vulnerable to the risk factors that cause diabetes. At present, little is known about the specific interaction between geographic access to healthy foods and diabetes in a predominantly rural, low-income, and minority area, such as Robeson County. Researchers have begun using Geographic Information Systems (GIS) mapping technology to explore the food environment, as it offers the benefit of visually determining ‘food activity spaces,’ the geographic locations and variety of food outlets at which individuals shop. The impetus for using GIS in Robeson County came from the CEO of Robeson Health Care Corporation (RHCC), a federally qualified health center with four clinics serving patients in Robeson County. This research aims to use GIS to better understand the relationship between food access and various diabetes-related risk factors in Robeson County, North Carolina in order to ultimately inform community policy changes.Bachelor of Science in Public Healt

Quantitative PCR data indicate TBX3, TBX5, HDAC6, SIRT1, SIRT6 gene expression is suppressed in the lungs of patients with COPD, while mRNA expression of HDAC2 does not change compared to lung tissue from normal smokers.

<p>The extent of the suppression is highly significant between patients with mild and those with severe COPD. Patient diagnosis was based on the National Heart, Lung, and Blood Institute/World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD) <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002597#pcbi.1002597-Pauwels1" target="_blank">[146]</a>. Fifteen normal, nine mild COPD, and six severe COPD samples were used for this analysis. The data is represented as Mean ± S.D. The data was analyzed using student's t-test for comparing mRNA expression in the respective groups. *represents a significance of p-value<0.01.</p

Patients with COPD have suppressed TBX2 and increased CDKN2A, CDKN1A, and caveolin-1 mRNA and protein expression.

<p>A) Quantitative PCR data indicate TBX2 gene expression is suppressed, while senescence factors, CDKN2A, CDKN1A, and caveolin-1 are induced in the lungs of patients with COPD compared to lung tissue from normal smokers. Fifteen normal, nine mild COPD, and six severe COPD samples were used for this analysis. The data is represented as Mean ± S.D. The data was analyzed using student's t-test for comparing mRNA expression in the respective groups. B) Representative Western blots showing suppressed TBX2, HDAC2, SIRT1 proteins and increased expression of CDKN2A, CDKN1A and caveolin-1 proteins in samples from patients with COPD. C) Densitometry analysis of Western blot data. Four normal, four mild COPD, and four severe COPD samples were used for this analysis. Densitometry analysis was carried out using image-J software. The data is represented as Mean ± S.D. The data was analyzed using student's t-test for comparing protein expression in the respective groups. *represents a significance of p-value<0.01.</p

Proportion and list of direct neighbors also asserted in initial networks generated via other mutual information—based algorithm.

<p>Proportion and list of direct neighbors also asserted in initial networks generated via other mutual information—based algorithm.</p

Suppressed Expression of T-Box Transcription Factors Is Involved in Senescence in Chronic Obstructive Pulmonary Disease

<div><p>Chronic obstructive pulmonary disease (COPD) is a major global health problem. The etiology of COPD has been associated with apoptosis, oxidative stress, and inflammation. However, understanding of the molecular interactions that modulate COPD pathogenesis remains only partly resolved. We conducted an exploratory study on COPD etiology to identify the key molecular participants. We used information-theoretic algorithms including Context Likelihood of Relatedness (CLR), Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE), and Inferelator. We captured direct functional associations among genes, given a compendium of gene expression profiles of human lung epithelial cells. A set of genes differentially expressed in COPD, as reported in a previous study were superposed with the resulting transcriptional regulatory networks. After factoring in the properties of the networks, an established COPD susceptibility locus and domain-domain interactions involving protein products of genes in the generated networks, several molecular candidates were predicted to be involved in the etiology of COPD. These include COL4A3, CFLAR, GULP1, PDCD1, CASP10, PAX3, BOK, HSPD1, PITX2, and PML. Furthermore, T-box (TBX) genes and cyclin-dependent kinase inhibitor 2A (CDKN2A), which are in a direct transcriptional regulatory relationship, emerged as preeminent participants in the etiology of COPD by means of senescence. Contrary to observations in neoplasms, our study reveals that the expression of genes and proteins in the lung samples from patients with COPD indicate an increased tendency towards cellular senescence. The expression of the anti-senescence mediators TBX transcription factors, chromatin modifiers histone deacetylases, and sirtuins was suppressed; while the expression of TBX-regulated cellular senescence markers such as CDKN2A, CDKN1A, and CAV1 was elevated in the peripheral lung tissue samples from patients with COPD. The critical balance between senescence and anti-senescence factors is disrupted towards senescence in COPD lungs.</p> </div

Inferelator predictions of regulators of twenty Biclusters generated using FABIA.

<p>Inferelator predictions of regulators of twenty Biclusters generated using FABIA.</p

Patient characteristics.

<p>FEV₁ = Forced expiratory volume at 1 sec; FVC = Function vital capacity; SD = Standard deviation; COPD = Chronic obstructive pulmonary disease.</p><p>GOLD (Global Initiative for Chronic Obstructive Lung Disease) Stages:</p><p>1 – mild COPD: FEV₁≥80% predicted, FEV₁:FVC<70%.</p><p>2 – moderate COPD: 50%≤FEV₁≤80% predicted, FEV₁:FVC<70%.</p><p>3 – severe COPD: 30%≤FEV₁≤50% predicted, FEV₁:FVC<70%.</p><p>4 – very severe COPD: FEV1<30%predicted or FEV₁<50% predicted with chronic respiratory failure, FEV₁:FVC<70%.</p><p>Pack years: (Packs smoked per day)×(years as a smoker).</p

Several aging-related genes are statistically linked to the expressions of TBX2, CDKN2A, and TGFB1.

<p>Several aging-related genes are statistically linked to the expressions of TBX2, CDKN2A, and TGFB1.</p

Figure 4

<p>A) The state of the Type IV collagen alpha 3 subunit, COL4A3, depends on the states of both TBX2 and CDKN2A in human lung epithelial cells. Following Robust Multi-Array Analysis of a compendium of 109 Affymetrix arrays on the U133A platform, the Context Likelihood of Relatedness (CLR) algorithm was used to generate a transcriptional regulatory network involving all available probe sets (at a CLR likelihood estimate cut-off of 2.5). Olive-green nodes represent genes whose median probe set expressions are suppressed in COPD. White nodes represent genes whose median probe set expressions are elevated in COPD. COL4A3, whose expression is suppressed in the COPD lung, is thus statistically dependent on both TBX2 and CDKN2A. B) Evolutionarily conserved probable protein domain-domain interactions corresponding to the predictions of <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002597#pcbi-1002597-t005" target="_blank">Table 5</a>. The thickness of each edge is commensurate with the corresponding computed probabilities. The COL4A3 protein has the Collagen domain (Collagen in Pfam database; InterPro Database Accession IPR008160) and probably engages PML via its zf-C3HC4 domain (zf-C3HC4 in Pfam database; InterPro Database Accession IPR001841). By way of its Collagen domain, COL4A3 interacts with PITX2 via its Homeobox domain (Homeobox in Pfam database; InterPro Database Accession IPR001356). Among others, there is also a probable interaction between the zf-C3HC4 of PML and the Ankyrin repeat (Ank in Pfam database; InterPro Database Accession IPR002110) domain of CDKN2A that could impact the COPD etiology.</p

Maximum likelihood estimation indicating probabilities of protein-protein interactions based on evolutionarily conserved domain-domain interactions.

<p>MLE = Maximum likelihood estimation.</p><p>Probable interactions involving COL4A3, which is in the susceptibility locus, are in bold character.</p