Diseases Commons^™

Differences In Health-Related Outcomes And Health Care Resource Utilization In Breast Cancer Survivors With And Without Type 2 Diabetes, Susan Storey, Zuoyi Zhang, Xiao Luo, Megan Metzger, Amrutha Ravali Jakka, Kun Huang, Diane Von Ah

Journal of Patient-Centered Research and Reviews

Purpose: Up to 74% of breast cancer survivors (BCS) have at least one preexisting comorbid condition, with diabetes (type 2) common. The purpose of this study was to examine differences in health-related outcomes (anemia, neutropenia, and infection) and utilization of health care resources (inpatient, outpatient, and emergency visits) in BCS with and without diabetes.

Methods: In this retrospective cohort study, data were leveraged from the electronic health records of a large health network linked to the Indiana State Cancer Registry. BCS diagnosed between January 2007 and December 2017 and who had received chemotherapy were included. Multivariable logistic regression and generalized …

Prevalence Of Endocrine Disorders Among 6078 Individuals With Down Syndrome In The United States, Anne Rivelli, Veronica Fitzpatrick, Danielle Wales, Laura Chicoine, Gengjie Jia, Andrey Rzhetsky, Brian Chicoine

Journal of Patient-Centered Research and Reviews

Findings from a recent study describing prevalence of common disease conditions in the largest documented cohort of individuals with Down syndrome (DS) in the United States strongly suggested significant disparity in endocrine disorders among these individuals when compared with age- and sex-matched individuals without DS. This retrospective, descriptive study is a follow-up report documenting prevalence of 21 endocrine disorder conditions, across 28 years of data, from 6078 individuals with DS and 30,326 age- and sex-matched controls, abstracted from electronic medical records within a large integrated health system. Overall, individuals with DS experienced higher prevalence of adrenal insufficiency and Addison’s disease; …

Glynac (Glycine And N-Acetylcysteine) Supplementation Improves Impaired Mitochondrial Fuel Oxidation And Lowers Insulin Resistance In Patients With Type 2 Diabetes: Results Of A Pilot Study, Rajagopal V Sekhar

Faculty, Staff and Students Publications

Patients with type 2 diabetes (T2D) are known to have mitochondrial dysfunction and increased insulin resistance (IR), but the underlying mechanisms are not well understood. We reported previously that (a) adequacy of the antioxidant glutathione (GSH) is necessary for optimal mitochondrial fatty-acid oxidation (MFO); (b) supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC) in mice corrected GSH deficiency, reversed impaired MFO, and lowered oxidative stress (OxS) and IR; and (c) supplementing GlyNAC in patients with T2D improved GSH synthesis and concentrations, and lowered OxS. However, the effect of GlyNAC on MFO, MGO (mitochondrial glucose oxidation), IR and plasma FFA …

Secretogranin Iii Stringently Regulates Pathological But Not Physiological Angiogenesis In Oxygen-Induced Retinopathy, Chang Dai, Prabuddha Waduge, Liyang Ji, Chengchi Huang, Ye He, Hong Tian, Elizabeth Zuniga-Sanchez, Amit Bhatt, Iok-Hou Pang, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Conventional angiogenic factors, such as vascular endothelial growth factor (VEGF), regulate both pathological and physiological angiogenesis indiscriminately, and their inhibitors may elicit adverse side effects. Secretogranin III (Scg3) was recently reported to be a diabetes-restricted VEGF-independent angiogenic factor, but the disease selectivity of Scg3 in retinopathy of prematurity (ROP), a retinal disease in preterm infants with concurrent pathological and physiological angiogenesis, was not defined. Here, using oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, we quantified an exclusive binding of Scg3 to diseased versus healthy developing neovessels that contrasted sharply with the ubiquitous binding of VEGF. Functional immunohistochemistry visualized …

Trends In Premature Mortality From Acute Myocardial Infarction In The United States, 1999 To 2019, Sourbha S. Dani, Ahmad N. Lone, Zulqarnain Javed, Muhammad S. Khan, Muhammad Zia Khan, Edo Kaluski, Salim S. Virani, Michael D. Shapiro, Miguel Cainzos‐Achirica, Khurram Nasir

Office of the Provost

Pagination are not provided by the author/publisher. This work was published before the author joined Aga Khan University.

Childhood Trauma And Chronic Disease, Breanna Urena

Graduate Research Projects

No abstract provided.

Does Tight Glycemic Control Slow The Progression Of Chronic Kidney Disease?, Elani Dodd

Graduate Research Projects

No abstract provided.

A Quality Improvement Project To Increase Diabetic Retinopathy Screenings, Daniel Joh, Reema George, Brandi Addison

Gulf Coast Division GME Research Day 2022

No abstract provided.

Severe Metformin-Associated Lactic Acidosis In The Setting Of Diabetic Nephropathy, Steven Nevers, Jared Lewis, Omer Farooq

Gulf Coast Division GME Research Day 2022

No abstract provided.

Trends In Stunting, Underweight And Overweight Among Children Aged < 5 Years In Kuwait: Findings From Kuwait Nutritional Surveillance System (2007-2019), Nawal Alqaoud, Abdullah Al-Taiar

Community & Environmental Health Faculty Publications

Background: There is a paucity of data on the secular trends of stunting and overweight among children aged < 5 years in oil-rich countries in the Middle East.

Aims: To examine the secular trends of stunting, underweight and overweight in children aged < 5 years in Kuwait between 2007 and 2019.

Methods: We used large individual data records (n=48 108) from the Kuwait Nutritional Surveillance System (KNSS) to calculate height/length-for-age z score (HAZ), weight-for-age z score and body mass index (BMI)-for-age z score using World Health Organization growth references. Stunting and underweight were defined as less than -2 standard deviation (SD) and overweight (including obesity) as ≥ 2 SD. Trends of stunting, underweight and overweight were …

The Role Of Glis3 In Zebrafish Endocrine Development And Regeneration, Tasha Swenney

Murray State Theses and Dissertations

Maintenance of proper blood glucose homeostasis is governed by the endocrine cells of the pancreas. Dysregulation of blood glucose is characteristic of the disease, diabetes mellitus. Relatively little is known about the molecular mechanisms that underlie diabetes. The genes associated with more common forms of diabetes remain more enigmatic and likely have less direct roles in blood glucose homeostasis such as glucose sensing, insulin secretion, and β cell maintenance. GLIS3, a transcription factor involved in pancreatic development as well as the transcriptional regulation of insulin has been identified as a risk locus for type 1 and type 2 diabetes …

Severe Mixed Mitral Valve Disease Due To Massive Mitral Annular Calcification: A Case Report And Literature Review, Fateh Ali Tipoo Sultan, Sheema Saadia

Section of Cardiology

We present an unusual case of massive mitral annular calcification (MAC) leading to severe mixed mitral valve disease, viz severe mitral regurgitation and severe mitral stenosis. To our knowledge, severe mixed mitral valve disease secondary to MAC is extremely rare. The patient (a 65-year-old lady) presented with worsening shortness of breath and signs of congestive heart failure. Echocardiographic examination revealed massive mitral annular calcification. Despite the massive annular calcification, she had experienced neither embolism nor endocarditis in the past. Because of severe symptomatic mitral regurgitation and mitral stenosis, surgery was advised; however, the patient declined it.

A Sudden Fall: Hypokalemic Familial Thyrotoxic Periodic Paralysis, Haroutiun Hamzoian, Aswin Srinivasan, Reuben Plasencia, Branden Wilson, Rajeev Raghavan

Gulf Coast Division GME Research Day 2022

No abstract provided.

Ambiguous Genitalia: A Medical, Surgical, Psychiatric And Ethical Concern, Saachi M. Khanna, Anoush Sardesai Sadat, Ranjani Rammohan, Sundeep Payyanur Thotan

Manipal Journal of Medical Sciences

Disorders of Sexual Differentiation or DSDs are congenital anomalies which lead to the abnormal development of the internal and external genitalia. Our main objective in this review was to bring to light the psychiatric side of healthcare for a patient with ambiguous genitalia and DSD and create more awareness of the ethical aspects of the condition. The most important step in the management of DSD is the avoidance of prematurely designating sex or using gendered pronouns, as well as reassuring the family. Treatment is not singular, but a multidisciplinary approach. It involves medical management and surgical correction of the genitalia. …

Patient And Provider Perspectives On Medication Non-Adherence Among Patients With Depression And/Or Diabetes In Diverse Community Settings – A Qualitative Analysis, Jane E Hamilton, Eduardo Blanco, Salih Selek, Kelly L Wirfel, Elmer V Bernstam, Dawn Velligan, Meghana Gudala, Kirk Roberts

Faculty, Staff and Student Publications

BACKGROUND: Diabetes and depression affect a significant percentage of the world's total population, and the management of these conditions is critical for reducing the global burden of disease. Medication adherence is crucial for improving diabetes and depression outcomes, and research is needed to elucidate barriers to medication adherence, including the intentionality of non-adherence, to intervene effectively. The purpose of this study was to explore the perspectives of patients and health care providers on intentional and unintentional medication adherence among patients with depression and diabetes through a series of focus groups conducted across clinical settings in a large urban area.

METHODS: …

Treatment Of Hypothyroidism: Desiccated Thyroid Extract, Aimee Fong

Capstone Showcase

The treatment of hypothyroidism with Levothyroxine (T4) has been well studied and FDA approved. However, many patients continue to have signs and symptoms of hypothyroidism while on Levothyroxine treatment despite reaching appropriate thyroid levels. An additional thyroid treatment known as desiccated thyroid extract (DTE) is made from dried pig thyroid glands and is advertised as a “natural” alternative to Levothyroxine. Despite lack of FDA approval and studies surrounding DTE, clinicians have prescribed DTE to patients, many of whom reported relief of their symptoms. The following poster highlights the approach to the treatment of hypothyroidism with Levothyroxine and DTE and outlines …

Management Of Adult Growth Hormone Deficiency Related To Hypopituitarism, Kellie Jamin

Capstone Showcase

The treatment of growth hormone deficiency (GHD) is well-established in childhood but less understood in adults, given the more complex role that growth hormone (GH) assumes in this population. Decreased functionality of the pituitary gland, otherwise known as hypopituitarism, can present with an isolated GHD in adulthood, which may result from a number of factors including neoplasm, ischemia, infection, traumatic injury, or systemic disease. Adult GHD may be definitively diagnosed with a stimulation test, the insulin tolerance test (ITT) being the study of choice. With a positive ITT, the disorder can be treated with growth hormone replacement therapy (GHRT), which …

Paraventricular Vitamin D Receptors Are Required For Glucose Tolerance In Males But Not Females, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Gabrielle Phillips, Yanlin He, Stephanie Sisley

Faculty, Staff and Students Publications

When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice's paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental to glucose homeostasis, an effect that may be more prominent in men. However, it is unknown if vitamin D action in the brain is required for normal glucose regulation in female mice. This study shows that in both viral and genetic models, male mice with obesity and PVH VDR loss have impaired glucose tolerance …

"It Just Kind Of Feels Like A Different World Now:" Stress And Resilience For Adolescents With Type 1 Diabetes In The Era Of Covid-19, Maeve B O'Donnell, Marisa E Hilliard, Viena T Cao, Miranda C Bradford, Krysta S Barton, Samantha Hurtado, Brenda Duran, Samantha Garcia Perez, Kiswa S Rahman, Samantha Scott, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Chuan Zhou, Abby R Rosenberg, Joyce P Yi-Frazier

Faculty, Staff and Students Publications

PURPOSE: The COVID-19 pandemic has been a major stressor for adolescents. Given the unique implications of the pandemic for youth with type 1 diabetes (T1D), who already navigate multiple stressors as a function of their chronic condition, we aimed to describe the impact of the pandemic on adolescents with T1D and describe their coping strategies and resilience resources.

RESEARCH METHOD: In a 2-site (Seattle WA, Houston TX) clinical trial of a psychosocial intervention targeting stress/resilience, adolescents 13-18 years old with T1D ≥ 1 year and elevated diabetes distress were enrolled August 2020 - June 2021. Participants completed a baseline survey …

Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, …

Metastatic Insulinoma Presenting With Postprandial Hypoglycemia, Monique Debrah Maher, Dimpi Nitin Desai, Mandeep Bajaj

Faculty, Staff and Students Publications

BACKGROUND/OBJECTIVE: Patients with an insulinoma, a type of pancreatic neuroendocrine tumor, typically present with fasting hypoglycemia but can rarely present exclusively with postprandial hypoglycemia.

CASE REPORT: A 69-year-old man presented with episodes of postprandial blurry vision, sweating, and confusion for the last 2 years that were becoming more frequent over the last several weeks. Home blood glucose measurements revealed postprandial hypoglycemia (glucose level, 45-70 mg/dL), and symptoms were consistent with the Whipple triad. Continuous glucose monitoring revealed only postprandial hypoglycemia within 2 hours following meals. An outpatient fast was conducted with detectable insulin (6 μIU/mL) and C-peptide (2.0 ng/mL) levels …

A Steroid Receptor Coactivator Small Molecule "Stimulator" Attenuates Post-Stroke Ischemic Brain Injury, Lisa K Mcclendon, Roberto L Garcia, Tyler Lazaro, Ariadna Robledo, Viren Vasandani, Zean Aaron Evan Luna, Abhijit S Rao, Aditya Srivatsan, David M Lonard, Clifford C Dacso, Peter Kan, Bert W O'Malley

Faculty, Staff and Students Publications

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion.

Methods: Neurologic impairment and tissue damage responses were evaluated on day …

The Prevalence And Spectrum Of Reported Incidental Adrenal Abnormalities In Abdominal Computed Tomography Of Cancer Patients: The Experience Of A Comprehensive Cancer Center, Aiham Qdaisat, Sara Bedrose, Obadah Ezzeldin, Ahmed W Moawad, Sai-Ching J Yeung, Khaled M Elsayes, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: The increasing use of computed tomography (CT) has identified many patients with incidental adrenal lesions. Further evaluation of these lesions is often dependent on the language used in the radiology report. Compared to the general population, patients with cancer have a higher risk for adrenal abnormalities, yet data on the prevalence and type of incidental adrenal lesions reported on radiologic reports in cancer patients is limited. In this study, we aimed to determine the prevalence and nature of adrenal abnormalities as an incidental finding reported on radiology reports of cancer patients evaluated for reasons other than suspected adrenal pathology. …

In Silico Integrative Analysis Of Multi-Omics Reveals Regulatory Layers For Diurnal Gene Expression In Mouse Liver, Chunjie Jiang, Panpan Liu, Cam Mong La, Dongyin Guan

Faculty, Staff and Students Publications

Diurnal oscillation persists throughout the body and plays an essential role in maintaining physiological homeostasis. Disruption of diurnal rhythm contributes to many diseases including type 2 diabetes. The regulatory mechanism of the transcription-translation feedback loop (TTFL) of core clock genes is well-established, while a systematic study across all regulatory layers of gene expression, including gene transcription, RNA translation, and DNA binding protein (DBP) activities, is still lacking. We comprehensively bioinformatics analyzed the rhythmicity of gene transcription, mature RNA abundance, protein abundance and DBP activity using publicly available omic-datasets from mouse livers. We found that the core clock genes,

Plasma Diaphanous Related Formin 1 Levels Are Associated With Altered Glucose Metabolism And Insulin Resistance In Patients With Polycystic Ovary Syndrome: A Case Control Study, Xing Li, Mingyu Liao, Jiaqing Shao, Weixin Li, Liu Shi, Dong Wang, Juan Ni, Qiuyue Shen, Fan Yang, Guiliang Peng, Ling Zhou, Yuling Zhang, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

BACKGROUND: Diaphanous related formin 1 (DIAPH1) is a novel component of advanced glycation end product (AGE) signal transduction that was recently found to participate in diabetes-related disorders, obesity, and androgen hormones. We investigated whether plasma DIAPH1 levels were a potential prognostic predictor for polycystic ovary syndrome (PCOS).

METHODS: The levels of circulating plasma DIAPH1 and indicators of glucose, insulin, lipid metabolism, liver enzymes, kidney function, sex hormones, and inflammation were measured in 75 patients with PCOS and 77 healthy participants. All of the participants were divided into normal-weight (NW) and overweight/obese (OW) subgroups. Statistical analyses were performed with R studio. …

Steroid Receptor Coactivators – Their Role In Immunity, Yosi Gilad, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid Receptor Coactivators (SRCs) are essential regulators of transcription with a wide range of impact on human physiology and pathology. In immunology, SRCs play multiple roles; they are involved in the regulation of nuclear factor-κB (NF-κB), macrophage (MΦ) activity, lymphoid cells proliferation, development and function, to name just a few. The three SRC family members, SRC-1, SRC-2 and SRC-3, can exert their immunological function either in an independent manner or act in synergy with each other. In certain biological contexts, one SRC family member can compensate for lack of activity of another member, while in other cases one SRC can …

De Novo Glycine Synthesis Is Reduced In Adults With Morbid Obesity And Increases Following Bariatric Surgery, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Chun Fan Lee, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance.

OBJECTIVE: Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m

METHODS: [1,2-

RESULTS: Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced

CONCLUSION: Hypoglycinemia …

Evaluation Of A Comprehensive Diabetes Mellitus Protocol At A Rural, Federally Qualified Health Center In Southern West Virginia, Hannah D. Davis

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: Diabetes mellitus is a chronic disease that affects nearly 34 million Americans. In rural Appalachia, the population is affected disproportionately at a rate of 14% compared to the national average of 10%. Diabetes is a lifelong, chronic condition managed best by a multidisciplinary team-based approach to achieve optimal disease control. Best practices in the care of diabetes support the use of evidenced based care protocols and leveraging technology to decrease the burden of disease. Type 2 diabetes mellitus (T2DM) is the most common type, making it the focal population for evaluation.

Purpose: The purpose of this project was to …

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …

Rev-Erb Is Essential In Cardiac Fibroblasts Homeostasis, Xiaokang Luo, Shiyang Song, Lei Qi, Chih-Liang Tien, Hui Li, Weiyi Xu, Theodore Lemuel Mathuram, Thomas Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

REV-ERB agonists have shown antifibrotic effects in the heart and other organs. The function of REV-ERB in the cardiac fibroblasts remains unstudied. Here, we characterize the functional difference of REV-ERB in mouse embryonic fibroblasts and cardiac fibroblasts using genetic deletion of REV-ERBα and ß in vitro. We show that REV-ERB α/β double deleted cardiac fibroblasts have reduced viability and proliferation, but increased migration and myofibroblasts activation. Thus, REV-ERB α/β has essential cell-autonomous role in cardiac fibroblasts in maintaining them in a healthy, quiescent state. We also show that existing REV-ERB agonist SR9009 strongly suppresses cardiac fibroblasts activation but in …