Abstract Introduction & Background The role of dietary fiber in breast cancer etiology remains unclear. A negative correlation may be due to fiber’s ability to stave off obesity and aid in the extraction of serum estrogen, two known risk factors for the disease. Effects may differ by source, and type, of fiber. Most of the data available is from research with non-Hispanic white women. However, fiber intake may vary significantly across cultures. Purpose Statement & Question The research sought to investigate whether an increased intake of dietary fiber was associated with a corresponding decrease in the incidence of breast cancer. The question posed was: Among post-menopausal women of various cultures, what is the effect of high dietary fiber intake compared to low intake on the risk of developing breast cancer? Literature Review The search was for specific studies examining the effect of dietary fiber on breast cancer development. The university’s scholarly search engine was utilized to find five studies using key terms such as “dietary fiber” and “breast cancer”. Findings Results showed an overall protective effect from high (> 25 grams/day) total dietary fiber intake on developing breast cancer. Findings for soluble versus insoluble fiber were inconsistent, but evidence suggests that fiber from beans, vegetables, and fruit may have a greater effect than fiber from whole grains. Conclusion High total fiber consumption may reduce the risk of developing breast cancer. Future research should investigate whether results hold true across more diverse populations.

Polycystic Ovarian Syndrome (PCOS) is an endocrine disorder that affects women’s menstrual cycles, androgen (male hormones) levels, and cysts on the ovaries. This endocrine disorder has various symptoms, with insulin resistance as a hallmark symptom. Approximately 65-70% of women with PCOS have insulin resistance and hyperinsulinemia, whether or not they are overweight, obese, or lean (Marshall & Dunaif, 2012). Many women with PCOS struggle to lose weight because their excess weight is related to nutrition, lifestyle factors, and imbalanced hormones. Understanding PCOS as a metabolic disorder with nutritional implications led to investigating the potential benefit of having registered dietitian nutritionists (RDN) as part of the healthcare team of women with PCOS. We developed a survey based on the literature on PCOS, diet/nutrition interventions, and the role of RDNs in the healthcare team of PCOS women of childbearing age. Only childbearing-age women (18–44) diagnosed with PCOS were eligible to complete the survey. The survey was designed as a needs assessment to determine if women with PCOS are routinely referred to RDNs for support; whether or not such support is beneficial; and what gaps in knowledge or misconceptions about nutrition and PCOS exist among participants. Most importantly, it was designed to examine if women understand how nutrition relates to managing their PCOS symptoms and future disease risks. The data from this survey shows the need for RDNs on the healthcare team of women with PCOS and gives us an understanding of nutrition education interventions that could be developed for future studies. Understanding how RDNs play a role in symptom management could lead to a better quality of life for women with PCOS.

Dyslipidemia is increasing among U.S. children, and the prevalence is highest among children with diabetes and obesity. Recently, vitamin D deficiency has been suggested as a possible dietary risk factor for dyslipidemia. Despite the high prevalence of vitamin D deficiency amongst children, virtually no studies have evaluated the association between vitamin D and dyslipidemia among children. We evaluated the vitamin D and dyslipidemia relationship among 240 children and adolescents aged 2 through 21 years who were outpatients of a pediatric endocrinology unit at a large tertiary care facility in Western Massachusetts from April 2008 to April 2010. Eligible children were those with either obesity and/or type 1 or 2 diabetes mellitus. A total of 17.4% of children had severe (<15.0 ng/ml) vitamin D deficiency, 19.2% had moderate (15.0-19.9 ng/ml) deficiency, 36.3% were insufficient (20.0-29.9 ng/ml), and 27.1% had normal (≥30.0 ng/ml) levels. A total of 28.8% of children had high total cholesterol (TC ≥180 mg/dL), 19.6% had high triglycerides (TG; <10years: ≥110 mg/dL, ≥10years: ≥130 mg/dL), 21.3% had low high density lipoprotein (HDL <40 mg/dL), and 6.7% had high low density lipoprotein (LDL ≥130 mg/dL). Moderate vitamin D deficiency was associated with increased risk of high TC (adjusted odds ratio [OR adj] = 2.9, 95% confidence interval (CI): 1.0, 8.8) compared to children with normal vitamin D levels. Severe vitamin D deficiency was associated with an increased risk of low HDL (OR adj = 3.5, 95% CI: 1.0-12.3) and high TG (OR adj = 11.7, 95% CI: 1.9, 70.3) compared to children with normal vitamin D levels. Children with moderate vitamin D deficiency had approximately 3-fold increased risk of high TC compared to children with normal vitamin D levels. In comparison to children with normal vitamin D levels, severe vitamin D deficiency was associated with a strong and significant increased risk of low HDL and high TG; with a significant dose-response relationship. Additionally, in linear regression analyses, we found that an increase in vitamin D deficiency was associated with a significant mean increase in all four measures of dyslipidemia. Vitamin D adequacy may reduce the risk of dyslipidemia in children.

<p>This dissertation takes the format of a "three paper model" (i.e. Sandwich Thesis), and all three articles have been submitted for publication.</p> <p>Article 1 (Chapter 4) - appears in <em>Food, Culture & Society (2014).</em></p> <p>Article 2 (Chapter 5) - appears in <em>Social Science & Medicine (2014).</em></p> <p>Article 3 (Chapter 6) - Revise & Resubmit from <em>Sociology of Health & Illness</em></p> / <p>Food and the various aspects surrounding what we eat, what we <em>should</em> eat, and concerns about how to remain healthy and ward off disease and illness is escalating while our choices are endless. In this competitive food market a new type has emerged: the functional food. Functional foods are those that have an added health benefit beyond the basic nutritional content and display physiological benefits in reducing chronic diseases. A popular category of functional foods are those that purport to lower one's cholesterol. In particular, high cholesterol is marketed as a "disease" rather than a risk factor for various cardiovascular diseases, such as heart disease. Little is known about the sociological diagnosis of high cholesterol and the marketing of functional foods, in particular with women. This dissertation address this gap by asking: (1) How is high cholesterol (HC) identified and marketed as a disease rather than a risk factor for cardiovascular diseases in functional food advertising - specifically addressing the Becel® pro.activ® margarine campaign? (2) How do women understand the issue and <em>causes </em>of high cholesterol; and (3) What do women understand the <em>solution </em>to high cholesterol to be and how do they view Becel's^® high cholesterol solution? --The findings center on 4 key issues: <ol> <li>The construction and marketing of high cholesterol <em>as a disease</em> (i.e. via the sociology of diagnosis), rather than a risk factor for heart disease;</li> <li>The causes of high cholesterol and attribution of blame are placed on women's poor lifestyle choices and seen as an individual responsibility;</li> <li>There are class differences regarding women's knowledge and awareness of the social determinants of health (SDOH); and</li> <li>The solution to high cholesterol is individualized via the 'proactive myopia' repertoire.</li> </ol></p> / Doctor of Philosophy (PhD)

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. The work herein identified several widely used pharmaceutical agents and endocrine disrupting chemicals as PXR-selective agonists such as drugs involved in HIV therapy and phthalates/phthalate substitutes, respectively. We investigated the role of amprenavir, an HIV protease inhibitor, and tributyl citrate, a phthalate substitute, on PXR-dependent alterations in lipoprotein metabolism. Acute exposure with either xenobiotic in mice elicited increases in the proatherogenic LDL-cholesterol levels in a PXR-dependent manner. PXR activation significantly induced expression of genes involved in intestinal lipid metabolism. Further, we went on to identify the intestinal cholesterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), as a direct PXR-target gene. PXR activation also stimulated cholesterol uptake in both murine and human intestinal cells. Moreover, we provide evidence that the microsomal triglyceride transfer protein (MTP) may be a direct PXR-target gene. Taken together, these findings provide critical mechanistic insight into the role of xenobiotic-mediated PXR activation on lipid homeostasis and demonstrate a potential role of PXR in mediating adverse effects of xenobiotics on CVD risk in humans. In addition to PXR signaling, we investigated the role of IκB kinase β (IKKβ), a central coordinator of inflammation, in adipocyte progenitor cells. Targeting IKKβ in adipose progenitor cells resulted in decreased high fat diet (HFD)-elicited adipogenesis, while protecting mice from inflammation and associated insulin resistance. Consistently, we discovered that IKKβ inhibition by antisense oligonucleotides ablated HFD-induced adiposity, while protecting mice against associated metabolic disorders. In conclusion, targeting IKKβ with antisense therapy may present as a novel therapeutic approach to combat obesity and metabolic dysfunctions.

L’hypoglycémie est une barrière au traitement du diabète de type 1 (DbT1). La collation au coucher est recommandée pour prévenir l’hypoglycémie nocturne (HN), mais son efficacité n’est pas démontrée. Objectif : Déterminer si une prise alimentaire en soirée est associée à la survenue d’HN. Étude observationnelle : 100 DbT1 ont porté un lecteur de glucose en continu et complété un journal alimentaire pendant 72 heures. L’HN est survenue durant 28 % des nuits. Une prise alimentaire en soirée n’était pas associée à l’HN. Toutefois, dans un modèle ajusté, l’apport en glucides en soirée était positivement associé aux HN (avec injection d’insuline rapide) et l’apport en protéines inversement associé aux HN (sans injection d’insuline rapide). Manger en soirée ne semble pas associé à moins d’HN. Des études contrôlées sont nécessaires pour comprendre l’effet de la collation au coucher sur le contrôle glycémique et le rôle de l’insuline rapide injectée en soirée. / Hypoglycemia remains a limiting factor of type 1 diabetes (T1D) treatment. Bedtime snack is often suggested to reduce nocturnal hypoglycemia (NH), but its effectiveness is not supported by evidence-based data. Objective: To determine the association between post-dinner dietary intake and NH occurrence. This is an observational study during which 100 T1D wore a blinded continuous glucose monitoring system and completed a food diary for 72 hours. NH occurred on 28 % of the 282 nights studied. Post-dinner dietary intake was not associated with NH. However, in multivariate models, carbohydrate intake was positively associated with NH (when rapid insulin was injected) and protein intake was inversely associated with NH (without rapid insulin injected). Post-dinner dietary intake does not seem to be associated with a reduce occurrence of NH. Further studies are needed to better understand the impact of bedtime snack on glycemic control and the role of the injection of rapid insulin in the evening.

Liver disease is now a leading cause of non-AIDS related morbidity and mortality in people living with HIV (PLWH). The present study investigated the interplay between adverse lifestyle factors that are prevalent in PLWH, biological mediators of liver pathogenesis, and a non-invasive measure of liver fibrosis (FIB-4 index) in HIV mono- and HIV/HCV co-infected individuals. The results of this investigation in the Miami Adult Studies of HIV (MASH) cohort show that the odds of liver fibrosis progression significantly increased over two years for HIV mono-infected participants who drank alcohol hazardously (OR 3.038, P=0.048), and had BMI ≥ 28kg/m2 (OR 2.934, P=0.027). Cocaine use reduced the odds of advancing one stage of liver fibrosis (OR 0.228, P=0.038), but an interaction between high BMI and cocaine use slightly raised the odds by 4.8% of liver fibrosis progression (P=0.072). HIV/HCV co-infected participants showed interactions between cocaine use and high BMI with increased FIB-4 stage (OR 4.985, P= 0.034), however no lifestyle factors could independently predict FIB-4 stage in this group. Biological mediators previously associated with liver pathogenesis were associated with higher FIB-4 index over 2 years in a subset of (n=65) HIV mono-infected participants. Plasma measures of oxidative stress (% oxidized glutathione: OR 4.342, P= 0.046), hepatocyte-specific apoptosis (Cytokeratin-18 (CK-18): OR 1.008, P=0.021), and microbial endotoxin (lipopolysaccharide (LPS): OR 1.098, P= 0.097) were associated with having higher odds of progressing at least one stage of FIB-4 over 2 years. The same biological mediators were also associated with liver fibrosis within HIV infected people who also had a harmful lifestyle characteristic. FIB-4 index was significantly associated with % oxidized glutathione in obese subjects (β=0.563, P=0.018), TGF-β1 in cocaine users (β=0.858, P=0.027), and CK-18 in HIV infected individuals without any adverse lifestyle factors (β=0.435, P=0.015). Taken together, the findings of these studies describe interrelationships between HIV disease status, lifestyle, and biological mediators of liver fibrosis. The results show interactions between lifestyle conditions and the mediators of liver fibrosis may account for higher rates of liver disease in HIV infection. Research is warranted to develop personalized therapeutics for PLWH to curb the burden of liver disease.

Current research shows moderate alcohol consumption is associated with decreased risk of diabetes and excessive consumption or binge drinking can cause insulin resistance and diabetes. In 2010, diabetes was the seventh leading cause of death in the United Statesand was responsible for significant health complications: blindness, kidney failure, and limb amputations, and is a large national economic burden. Fasting blood glucose (FBG) is a tool used to help diagnose diabetes. Abnormally high FBG, ≥100 mg/dl, is indicative of diabetes and pre-diabetes. Few studies have observed diabetic prevalence among young adults or college students. Studying young adults can help provide added information about early risk factors for diabetes and pre-diabetes, facilitating public health efforts to stem the rising tide of the diabetes epidemic. This study aimed to research the associations between alcohol consumption (numbers of days alcohol consumed in the past month and binge alcohol consumption in the past month) and FBG in a college population as part of the FLASH cohort study. FBG levels were measured in 141 young adult participants and alcohol consumption was determined by self report. Other individual-level characteristics and potential confounding variables were also collected. The association between alcohol consumption and FBG followed a J-shaped curve whereby students who reported drinking 6-8 days within the last 30 days showed significantly lower FBG levels than those who did not drink and those who consumed alcohol on nine or more days (p=0.04). Binge drinking did not have a significant association with FBG (p=0.4). Sex and body mass index were also significantly associated with FBG. In conclusion, moderate frequency of alcohol consumption is found to have an inverse relationship with FBG and excessive drinking can reverse these effects.