Nutritional and Metabolic Diseases Commons^™

Evaluating The Feasibility And Preliminary Effectiveness Of A Tailored Diabetes Education Program For Rural Residents, Brittany L. Smalls, Oluwatosin Leshi, Suraksha Khanal, Grejika E. Abram-Erby

Journal of Appalachian Health

Introduction: Diabetes is a top ten Rural Healthy People 2030 priority for health improvement among rural Americans. Socioeconomic, environmental, geographic and political barriers contribute to the type 2 diabetes (T2D) prevalence and its disparate impact in rural communities. However, promoting proper self-care behaviors via self-management education can help people with diabetes better manage their condition.

Purpose: To account for the social environmental factors that affect rural residents, a tailored diabetes education program was developed, and the program’s effectiveness in improving diabetes knowledge and T2D-related health outcomes was assessed.

Methods: Using data collected from Appalachian Kentucky residents enrolled in a six-week, …

Metabolism As A Regulator Of Sleep And Cortical Activity In Health And Alzheimer’S Disease, Nicholas J. Constantino

Theses and Dissertations--Neuroscience

Metabolic flexibility is essential for maintaining normal physiological function, enabling an organism to sense, flux, utilize, and switch fuel sources in response to changing energetic availability, demand, and cellular needs. Energetic demands are state-dependent, with wake and sleep exhibiting distinct metabolic profiles. Sleep is highly sensitive to changes in metabolism and requires metabolic flexibility to both transition into and maintain sleep stability. Alzheimer’s disease (AD) is increasingly recognized as a disease of altered metabolism yet is often framed as a disease of energetic failure. We instead define AD as a disease of metabolic inflexibility, characterized not by insufficient energy availability, …

A Tale Of Two Serpins: Pathologic And Protective Roles Of Agt And Pai-1 In Metabolic And Cardiovascular Disease, Alex C. Pettey

Theses and Dissertations--Physiology

Metabolic and cardiovascular diseases are leading causes of morbidity and mortality worldwide. Conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), aortic aneurysm, and cardiac fibrosis have limited pharmacological therapies, underscoring the need for deeper mechanistic investigations. Serine protease inhibitors (serpins) have been implicated in these pathologies and represent potential therapeutic targets. Despite structural homology, serpins regulate diverse physiological processes through both protease inhibition and non-inhibitory mechanisms. This dissertation examines the roles of two serpins, angiotensinogen (AGT) and plasminogen activator inhibitor-1 (PAI-1), in preclinical models of metabolic and cardiovascular disease to identify novel mechanisms that may inform future therapeutic strategies. …

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

The Effect Of Fructose Metabolism On Hepatic De Novo Lipogenesis And Adipose Tissue Insulin Resistance, Taghreed Ibrahim Fadhul

Theses and Dissertations--Nutritional Sciences

There is a worldwide epidemic of obesity and metabolic dysfunction. The root cause of obesity is driven by a positive energy balance, which is a consequence of increased caloric intake and decreased energy expenditure. Energy intake is the more dominant force, as increasing energy expenditure is a time-consuming and labor-intensive process. The caloric surplus can be mainly accounted for by increased consumption of high-fat and high-sugar diets. While the risks associated with fat consumption are well-documented, the impact of sugar intake is less understood.

Fructose is a simple sugar widely consumed in modern diets. Its intake has been associated with …

Sex-Specific Roles Of The Adipocyte Mineralocorticoid Receptor In Obesity And Early Life Stress, Meghan B. Turner

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a burgeoning health epidemic caused by chronic overnutrition and exacerbated by genetic, environmental and developmental factors. The adipocyte mineralocorticoid receptor (MR), a transcriptionally active nuclear receptor, is speculated to contribute to metabolic dysfunction in the obese state. MR expression is increased in obese adipose tissue, and MR modulates the expression of fat-derived hormones such as leptin and adiponectin. In women, obesity can be exacerbated by early life stress, such as adverse childhood experiences (ACEs). Studies show that women display a positive association between cumulative ACE exposures and increased body mass index. Previously, we demonstrated that maternal separation and …

Long-Term Cardiometabolic Effects Of Preconceptional And Prenatal Opioid Exposure In The Adult Offspring, Nermin Hassan Mohamed Selim Ahmed

Theses and Dissertations--Pharmacology and Nutritional Sciences

Opioid use disorder (OUD), one of the greatest public health threats in the US, requires urgent attention. In 2022, the CDC reported 107,941 overdose deaths, over 70% attributed to synthetic opioids such as fentanyl (FEN). An alarming increase in opioid use disorder (OUD) diagnoses in pregnant people resulted in a 5-fold rise in cases of neonatal opioid withdrawal syndrome (NOWS). This condition elicits sympathetic overactivity, neural hyperexcitability, and a stress reaction characterized by tachycardia and hypertension. Whether prenatal exposure to fentanyl induces cardiovascular dysfunction in the offspring remains undetermined, impeding the timely development of strategies to mitigate OUD-related health risks …

The Function Of The Insulin Receptor In Liver Subcell Types And Its Dichotomous Role In Hepatic Dysfunction, Wang-Hsin Lee

Theses and Dissertations--Pharmacology and Nutritional Sciences

Insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD) have become significant health issues worldwide. Increased prevalence of hepatic insulin resistance and MASLD worsens the threat of its progressive complications, such as liver fibrosis, which can lead to cirrhosis and death if left untreated. Treatments for MASLD-induced liver fibrosis are mainly insulin sensitizers. However, activating insulin signaling leads to a higher death rate in end-stage liver fibrosis. This dissertation discusses the emerging insights into hepatic insulin resistance and potential treatment targets in the heme degradation pathway for reversal. We also investigated the mechanisms that the insulin receptor (INSR) regulates in …

Exenatide As Chronopharmacotherapy For T2dm Associated Complications: Targeting Nondipping Blood Pressure And Sleep Insufficiency, Aaron Chacon

Theses and Dissertations--Pharmacology and Nutritional Sciences

Although largely impacted by age, race and ethnicity, and socioeconomic factors, Type 2 Diabetes Mellitus (T2DM) is primarily driven by obesity, currently affecting ~30 million in the U.S and ~463 million globally. T2DM carries numerous complications, including high prevalence of hypertension and nondipping blood pressure (BP), sleep insufficiency and fragmentation. Nondipping BP is an inadequate drop in BP (≤ 10%) during sleeping hours compared with waking hours. Lending to this, sleep disturbance acts as both precursor and consequence of metabolic dysregulation, greatly impacting circadian rhythmicity. To model these conditions, we utilized diabetic (db/db) mice. These mice carry a point mutation …

Investigation Of Lower Extremity Neuromuscular Function In Individuals With And Without Diabetes, Roya Hoveizavi

Theses and Dissertations--Kinesiology and Health Promotion

Background: Diabetes mellitus is associated with notable neuromuscular and motor dysfunctions that could lead to an increased risk of plantar ulcers and amputations. Several contributing factors, including increased muscle-tendon stiffness and abnormal muscle activation pattern may influence the kinematics and kinetics of walking in people with diabetes and promote formation of plantar ulcers. Hyperglycemia and the resultant accelerated rate of glycation have been recognized as the leading cause of muscle and tendon degeneration, yet the precise mechanisms by which diabetes affects the biomechanical properties of the muscle-tendon unit remains unclear. Altered muscle activity during gait is observed in people with …

Maximal Strength Training Increases Metabolic Energy Expenditure In Sedentary Adults Classified As Obese, Robert E. Anderson Iii

Theses and Dissertations--Nutrition and Food Systems

Background: Metabolic adaptations reduce resting and non-resting energy expenditure to account for approximately 120 kcal/day. Weight loss promotes greater skeletal muscle efficiency, reducing the energy cost of physical activity and is correlated with declines in skeletal muscle glucose oxidation. Maximal Strength Training (MST) has the potential to upregulate glucose utilization and may offset these metabolic adaptations. Objective: To determine if MST offsets markers of metabolic adaptation by increasing resting and non-resting energy expenditure in sedentary individuals classified as obese. Methods: Five (5) participants (2 females, 3 males), ages 18-35 years, with obesity (BMI 30–45 kg/m2) were enrolled in an 8-week …

The Relative Contribution Of Liver And Intestine In Reverse Cholesterol Transport, Rupinder Kaur

Theses and Dissertations--Pharmacy

Despite decades of advances in research, death due to cardiometabolic disease remains the largest contributor to mortality in the US. While present therapies oppose “forward cholesterol transport,” and atherosclerotic plaque progression, they do not remove cholesterol from established atherosclerotic plaques. Reverse cholesterol transport (RCT) is the active process of mobilizing peripheral cholesterol for excretion through the hepatobiliary (transhepatic cholesterol elimination, THCE) or intestinal (transintestinal cholesterol elimination, TICE) pathways. Currently, there are no clinically approved therapeutics that target RCT. Elucidation of the mechanisms that govern RCT and TICE, and the subsequent identification of novel targets is of importance. The present work …

Factors Associated With Lifestyle Modification For Type 2 Diabetes Self-Management And Prevention, Leigh Anne Koonmen

Theses and Dissertations--Nursing

Diabetes is the seventh leading cause of death in the United States, affecting roughly 13% of U.S. adults aged 18 years or older. Type 2 diabetes accounts for 90-95% of all diabetes cases and is characterized by the progressive development of insulin resistance leading to sustained elevated blood glucose levels. Management of type 2 diabetes includes risk-reduction strategies and continuous medical care to prevent the development of complications.

Lifestyle is a major contributing factor to morbidity and mortality rates in the United States. Preventative health behaviors, such as engaging in physical activity, maintaining a healthy weight, and following a healthy …

Dietary Assessments And Their Association With Psychological Factors, Inflammation, And Cardiovascular Health Outcomes, Junghee Kang

Theses and Dissertations--Nursing

Cardiovascular diseases (CVDs), a group of disorders of the heart and blood vessels, are the leading cause of death worldwide, causing one-third of deaths each year. Diet is one of the most important behavioral risk factors for CVD. The effects of behavioral risk factors, such as diet, may lead to increased blood pressure, increased blood glucose, raised blood lipids, and overweight and obesity. Inflammation contributes to the development of CVD and can be influenced by diet. Dietary assessment indices can measure diet quality from an individual's dietary intake by scoring food and nutrient intakes. However, the mediation effects of diet …

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

The Gestation Of Health: Environmental Insults, Behavioral Interventions, And Protective Mechanisms, Brittany Breon Rice

Theses and Dissertations--Pharmacology and Nutritional Sciences

Diabetes remains a leading cause of death nationwide despite pharmacological advances. Recent etiological investigations of the disease detail the role of perinatal exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), in enhancing disease susceptibility. Polychlorinated biphenyl 126, a coplanar PCB, elicits its toxic effects through the aryl-hydrocarbon receptor and the disruption of endocrine signaling. The goal of this dissertation was to focus on delineating the differences in the developmental windows of diabetes susceptibility respective to the timing of PCB126 exposure and to understand the influence of maternal exercise and nuclear-factor erythroid-2-related factor 2 (Nrf2) expression in combating the negative …

Pre-Clinical Advancements In Biomarkers, Tools, And Therapeutics For A Metabolic Neurodegenerative Disease, Zoë Simmons

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the storage form of glucose and a highly important substrate for cellular metabolism. Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis. Multiple labs demonstrated that laforin is a glycogen phosphatase and mutations in the gene encoding laforin cause the formation of aberrant glycogen-like aggregates called Lafora bodies (LBs). LBs are cytoplasmic, water-insoluble aggregates that drive neurodegeneration and early death in Lafora disease (LD) patients. The direct relationship between mutated laforin, …

Identification Of Infant Feeding Practices In Eastern Kentucky And Southern West Virginia That Correlate With High Weight-For-Length, Havilah R. Adkins

DNP Projects

Background: Approximately 20% of children in the United States are obese. West Virginia and Kentucky rank in the top 10 for obesity rates in children as young as 2-4 years old. Obesity increases the risk for numerous short-term health problems and impacts long-term health, development, quality of life, and life expectancy. Research indicates that obesogenic behaviors can be addressed prior to the development of obesity or significant health problems to prevent, rather than treat. Interventions targeting caregivers of infants younger than 2-years can promote early development of healthy feeding habits that persist through the developmental stages of nutrition. Before a …

Role Of Pancreatic Amylin In Alzheimer’S And Brain Microvascular Pathologies, Han Gia Ly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer disease (AD) and cerebral vascular disease (CVD) are common causes of impaired cognition and behavior in humans. Epidemiological studies have shown that AD and CVD development and progression associated with metabolic risk factors including type 2 diabetes (T2D). However, the underlying molecular mechanisms remain elusive, which hampers the development of treatment and prevention strategies. Research results from our laboratory and others have shown that amylin, a hormone secreted by the pancreas and involved in glucose homeostasis, induces small-vessel-type pathologies and modulates amyloid composition in both familial (genetically predisposed) and sporadic forms of AD. The results indicate amylin as a …

Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II …

Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …

Current Assessment And Intervention Strategies For Childhood Obesity Used By Pediatric Care Providers, Jennifer Bivins

DNP Projects

Childhood obesity rates in the United States have tripled since the 1970s in the U.S. (CDC, 2018). Due to the persistent rise in obesity rate sin children and the possible health risks associated with obesity, it is important for pediatric providers to appropriately assess and treat childhood obesity. There is limited data on what pediatric providers in the primary care setting are doing to address this growing health problem. PURPOSE: The purpose of this study was to determine current assessment and intervention strategies for childhood obesity used by pediatric health care providers at the University of Kentucky, General Pediatric clinic. …

Apoe And Alzheimer’S Disease: Neuroimaging Of Metabolic And Cerebrovascular Dysfunction, Jason A. Brandon, Brandon C. Farmer, Holden C. Williams, Lance A. Johnson

Physiology Faculty Publications

Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for late onset Alzheimer’s Disease (AD), and is associated with impairments in cerebral metabolism and cerebrovascular function. A substantial body of literature now points to E4 as a driver of multiple impairments seen in AD, including blunted brain insulin signaling, mismanagement of brain cholesterol and fatty acids, reductions in blood brain barrier (BBB) integrity, and decreased cerebral glucose uptake. Various neuroimaging techniques, in particular positron emission topography (PET) and magnetic resonance imaging (MRI), have been instrumental in characterizing these metabolic and vascular deficits associated with this important AD risk factor. In …

Assessing Malnutrition In Liver Disease Patients Being Evaluated For Transplant Using The Nutrition Focused Physical Exam, Madison Hilgendorf

Theses and Dissertations--Nutrition and Food Systems

Patients with liver disease have an increased risk for malnutrition because of side effects of the disease. The Nutrition Focused Physical Exam (NFPE) was developed for nutrition professionals to aid physicians in a nutrition-based diagnosis of malnutrition. The purpose of this study was to examine the NFPE for its validity in liver disease patients being evaluated for transplant. In addition, the NFPE was used to assess incidence and severity of malnutrition in end stage liver disease patients and compare these results to already developed malnutrition tools such as the Patient Generated-Subjective Global Assessment (PG-SGA), Triceps Skinfolds (TSF), Mid-Arm Circumference (MAC), …

Stories Of Strength: Chicago Latin@S' Navigation Of Health, Well-Being, And Chronic Disease, Lilian L. Milanés

Theses and Dissertations--Anthropology

Health inequalities take many forms related to race, gender, socioeconomic status, ethnic, language and many other axes throughout communities around the world. Type two diabetes, high blood pressure, and high cholesterol are examples of conditions (among many others) that disproportionately affect Latino@s in the U.S.. The research of this dissertation is based on fieldwork conducted throughout several predominantly Latin@ neighborhoods in Chicago, IL. This dissertation examines how Latin@s in Chicago navigate health and well-being, and how they engage in agentive strategies in the face of chronic disease. I recorded individual life histories and semi-structured interviews, focus groups, and participant observation …

Mechanisms And Potential Therapy On Disrupted Blood Pressure Circadian Rhythm In Diabetes, Tianfei Hou

Theses and Dissertations--Pharmacology and Nutritional Sciences

Arterial blood pressure (BP) undergoes a 24-hour oscillation that peaks in the active day and reaches a nadir at night during sleep in humans. Reduced nocturnal BP fall (also known as non-dipper) is the most common disruption of BP circadian rhythm and is associated with increased risk of untoward cardiovascular events and target organ injury. Up to 75% of diabetic patients are non-dippers. However, the mechanisms underlying diabetes associated non-dipping BP are largely unknown. To address this important question, we generated a novel diabetic db/db-mPer2^Luc mouse model (db/db-mPer2^Luc) that allows quantitatively measuring of mPER2 protein oscillation …

Emerging Roles Of Xenobiotic Detoxification Enzymes In Metabolic Diseases, Michael C. Petriello, Jessie B. Hoffman, Andrew J. Morris, Bernhard Hennig

Superfund Research Center Faculty Publications

Mammalian systems have developed extensive molecular mechanisms to protect against the toxicity of many exogenous xenobiotic compounds. Interestingly, many detoxification enzymes, including cytochrome P450s and flavin-containing monooxygenases, and their associated transcriptional activators [e.g. the aryl hydrocarbon receptor (AhR)], have now been shown to have endogenous roles in normal physiology and the pathology of metabolic diseases. This mini-review will focus on two such instances: the role of flavin-containing monooxygenase 3 (FMO3) in the formation of the cardiometabolic disease biomarker trimethylamine-N-oxide (TMAO) and the role of AhR as a sensor of endogenous ligands such as those generated by the gut microbiota. Understanding …

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Evaluation Of A Primary Care Based Diabetes Education Program, Claire Pfister

DNP Projects

The improved management of diabetes is a critical clinical and economic challenge facing our healthcare system. Educating patients with diabetes to self-manage their disease is a vital component of diabetes care. The purpose of this DNP practice improvement project was to evaluate an innovative health care delivery method of individualized diabetes self-management education (DSME) in primary care. The approach combined individual DSME with a registered dietician and routine diabetes care with the primary care provider into one patient appointment. System data was reviewed to compare referral and attendance patterns of group and individual methods. Changes in clinical indicators of A1C, …