Diseases Commons^™

Adipocyte-Specific Ablation Of Pu1 Promotes Energy Expenditure And Ameliorates Metabolic Syndrome In Aging Mice, Ke Yun Chen, Alejandra De Angulo, Xin Guo, Aditya More, Scott A Ochsner, Eduardo Lopez, David Saul, Weijun Pang, Yuxiang Sun, Neil J Mckenna, Qiang Tong

Faculty, Staff and Students Publications

Objective: Although PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of the age-associated metabolic syndrome.

Methods: We generated mice with adipocyte-specific PU.1 knockout, assessed metabolic changes in young and older adult PU.1^fl/fl (control) and AdipoqCre PU.1^fl/fl (aPU.1KO) mice, including body weight, body composition, energy expenditure, and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice.

Results: aPU.1KO mice have elevated energy …

Endmt Regulation By Small Rnas In Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress, Roberta Giordo, Yusra M A Ahmed, Hilda Allam, Salah Abusnana, Lucia Pappalardo, Gheyath K Nasrallah, Arduino Aleksander Mangoni, Gianfranco Pintus

Faculty, Staff and Student Publications

Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, and increased mortality. A common denominator of these complications is the myofibroblast-driven excessive deposition of extracellular matrix proteins. Although fibroblast appears to be the primary source of myofibroblasts, other cells, including endothelial cells, can generate myofibroblasts through a process known as endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their typical phenotype to acquire mesenchymal features, characterized by the development of invasive and migratory abilities as well as the expression of typical mesenchymal products such as α-smooth …

To Determine The Efficacy Of Bilateral Inferior Petrosal Sinus Sampling In Differentiating Cushing Disease From Ectopic Cushing Syndrome, Muhammad Azeemuddin, Tanveer Ul Haq, Shahmeer Khan, Raza Sayani, Ayesha Shoukat Hussain, Rumaisa Khan

Department of Radiology

Management of endogenous Cushing syndrome is based on its aetiology. Increased Adrenocorticotropic Hormone (ACTH) levels are the most common cause of this disorder and, therefore, it is critical to determine the source of ACTH before further management. Dynamic post contrast MRI is currently the most common investigation implied to diagnose pituitary adenoma; however, it comes with the drawback of low specificity and high false positive results. Inferior petrosal sinus sampling (IPSS) is an established invasive procedure performed to differentiate central versus peripheral source of ACTH which, in turn, results in hypercortesolaemia. This is a series of 14 patients who underwent …

Associations Between Fruit Intake And Risk Of Diabetes In The Ausdiab Cohort: Supplementary Material, Nicola P. Bondonno, Raymond J. Davey, Kevin Murray, Simone Radavelli-Bagatini, Catherine P. Bondonno, Lauren C. Blekkenhorst, Marc Sim, Dianna J. Magliano, Robin M. Daly, Jonathan E. Shaw, Joshua R. Lewis, Jonathan M. Hodgson

Research Datasets

Supplementary Material accompanying manuscript entitled ‘Associations between fruit intake and risk of diabetes in the AusDiab cohort’.

The E3 Ligase Traf4 Promotes Igf Signaling By Mediating Atypical Ubiquitination Of Irs-1, Wenjuan Yu, Ramesh Singh, Zhao Wang, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Insulin-like growth factor (IGF) is a potent mitogen that activates the IGF receptor (IGFR)/insulin receptor substrate (IRS) axis, thus stimulating growth in normal cells and uncontrolled cell proliferation in cancer. Posttranslational modifications of IRS such as ubiquitination tightly control IGF signaling, and we previously identified IRS-1 as a potential substrate for the E3 ubiquitin ligase TRAF4 using an unbiased screen. Here we provide evidence that TRAF4-mediated ubiquitination of IRS-1 is physiologically relevant and crucial for IGF signal transduction. Through site-directed mutagenesis we found that TRAF4 promotes an atypical K29-linked ubiquitination at the C-terminal end of IRS-1. Its depletion abolishes AKT …

Using Preliminary Data And Prospective Power Analyses For Mid-Stream Revision Of Projected Group And Subgroup Sizes In Pragmatic Patient-Centered Outcomes Research, Elizabeth A. Tolley Md, Satya Surbhi Md, James E. Bailey Md

Faculty Publications and Presentations

Pragmatic clinical trials are commonly used in patient-centered outcomes research to assess heterogeneity of treatment effects. Patient-Centered Outcomes Research Institute (PCORI) methodology standards for assessing heterogeneity of treatment effects are extremely rigorous, but their implementation in real-world settings can be difficult. Predicting recruitment effectiveness and subgroup characteristics is often challenging and may require mid-stream revision of projected group and subgroup sizes. Yet, little real-world data are available to demonstrate methodologically valid approaches to address situations where such revisions are necessary. These data were used for mid-stream revision of group and subgroup sizes in the Management of Diabetes in Everyday Life …

Response To Comments On Aisha Sheikh Et Al (J Pak Med Assoc. 70: 1477, 2020) Changing Prevalence Of Gestational Diabetes Mellitus During Pregnancy Over More Than A Decade, Aisha Sheikh, Lumaan Sheikh

Section of Diabetes, Endocrinology and Metabolism

No abstract provided.

Patient-Centered Implementation Of Statin Therapy In Patients With Type 2 Diabetes, Giovanna P. Favarato

Doctor of Nursing Practice

Heart disease is the leading cause of morbidity and mortality in Americans with type 2 diabetes mellitus. The American Diabetes Association recommends statins and lifestyle modifications for all patients with type 2 diabetes mellitus for the prevention of atherosclerotic cardiovascular events. A patient-centered approach to primary prevention is encouraged, yet there are no specific instructions regarding implementation. The Statin Choice Decision Aid is a tool designed to facilitate shared decision-making between the patient and the provider in the clinical setting. The 2018 American College of Cardiology/American Heart Association guidelines for the primary prevention of atherosclerotic cardiovascular disease for patients with …

Implementation Of Comprehensive Foot Exams In Primary Care: A Quality Improvement Project, Dora Elia Trevino

Doctor of Nursing Practice

The purpose of this quality improvement project was to increase performance and documentation of provider comprehensive foot exams (CFEs) by 50% among patients with Type 2 diabetes (T2DM) in a small clinic in the southwestern United States.

The project leader assessed clinic systems including the electronic health record (EHR) to identify means to increase CFE completion and documentation rate for patients with T2DM being seen for a chronic disease management (CDM) appointment. A process was created to incorporate a hardcopy CFE documentation form into the EHR and create a pop-up care reminder notification system. Staff and the provider were educated …

Stat1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity In Obesity, Aaron R Cox, Natasha Chernis, David A Bader, Pradip K Saha, Peter M Masschelin, Jessica B Felix, Robert Sharp, Zeqin Lian, Vasanta Putluri, Kimal Rajapakshe, Kang Ho Kim, Dennis T Villareal, Reina Armamento-Villareal, Huaizhu Wu, Cristian Coarfa, Nagireddy Putluri, Sean M Hartig

Faculty, Staff and Students Publications

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes. However, the causal relationship of these events remains unclear. The established dominance of STAT1 function in the immune response suggests an obligate link between inflammation and the comorbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1a-KO) enhanced mitochondrial function …

Lifetime Risk Of Diabetes In Metropolitan Cities In India, Shammi Luhar, Dimple Kondal, Rebecca Jones, Ranjit M. Anjana, Shivani A. Patel, Sanjay Kinra, Lynda Clarke, Mohammed K. Ali, Dorairaj Prabhakaran, Muhammad Masood Kadir

Community Health Sciences

Aims/hypothesis: We aimed to estimate the lifetime risk of diabetes and diabetes-free life expectancy in metropolitan cities in India among the population aged 20 years or more, and their variation by sex, age and BMI.
Methods: A Markov simulation model was adopted to estimate age-, sex- and BMI-specific lifetime risk of developing diabetes and diabetes-free life expectancy. The main data inputs used were as follows: age-, sex- and BMI-specific incidence rates of diabetes in urban India taken from the Centre for Cardiometabolic Risk Reduction in South Asia (2010-2018); age-, sex- and urban-specific rates of mortality from period lifetables reported by …

Assessing Disease Severity Of Diabetic Retinopathy Using Novel Graphical Interpretation Of Flicker Electroretinogram, Anjalee Choudhury, Jonas Moses, Victor Gonzalez

MEDI 9331 Scholarly Activities Clinical Years

Purpose: To assess the clinical value of reporting full-field electroretinogram (eg, flicker ERG) findings graphically to determine the severity of diabetic retinopathy (DR) within an office-based setting.

Methods: Patients with type 2 diabetes mellitus were included and classified into varying degrees of DR based on presence and severity. Flicker ERG responses were recorded and compared between groups.

Results: Between the varying disease stages, significant differences in the mean magnitude and phase values were found. There was also a significant difference between the proportions of the magnitude and phase color-coded frequencies between groups of severity and threat to …

Upper Vs. Lower Extremity: Does The Site Of Steroid Injection Have A Different Effect On Blood Glucose Levels In Patients With Diabetes?, Emilyn Anderi

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising Twu J, Patel N, Wolf JM, Conti Mica M. Impact of variation of corticosteroid dose, injection site, and multiple injections on blood glucose measurement in diabetic patients. J Hand Surg Am. 2018;43(8):738-744. https://doi.org/10.1016/j.jhsa.2018.06.005 for a patient with diabetes and osteoarthritis.

Mir-30a Targets Gene Networks That Promote Browning Of Human And Mouse Adipocytes, Pradip K Saha, Mark P Hamilton, Kimal Rajapakshe, Vasanta Putluri, Jessica B Felix, Peter Masschelin, Aaron R Cox, Mandeep Bajaj, Nagireddy Putluri, Cristian Coarfa, Sean M Hartig

Faculty, Staff and Students Publications

MicroRNA-30a (miR-30a) impacts adipocyte function, and its expression in white adipose tissue (WAT) correlates with insulin sensitivity in obesity. Bioinformatic analysis demonstrates that miR-30a expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of miR-30a function in fat cells remain unclear. Here, we expanded our understanding of how miR-30a expression contributes to antidiabetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity and metabolic functions in adipocytes. We found that WAT isolated from diabetic patients shows reduced miR-30a levels and diminished expression of the canonical PPARγ target genes ADIPOQ and FABP4 relative to lean counterparts. In human adipocytes, …

Effect Of High Glucose On Ocular Surface Epithelial Cell Barrier And Tight Junction Proteins, Saleh M. Alfuraih, Ashley Barbarino, Christopher Ross, Kiumars Shamloo, Vishal Jhanji, Miao Zhang, Ajay Sharma

Pharmacy Faculty Articles and Research

PURPOSE. Patients with diabetes mellitus are reported to have ocular surface defects, impaired ocular surface barrier function, and a higher incidence of corneal and conjunctival infections. Tight junctions are critical for ocular surface barrier function. The present study was designed to investigate the effect of high glucose exposure on human corneal and conjunctival epithelial cell barrier function and tight junction proteins.

METHODS. Human corneal and conjunctival epithelial cells were exposed to 15 mM and 30 mM glucose for 24 and 72 hours. The barrier function was measured using transepithelial electrical resistance (TEER). The cell migration was quantified using scratch assay. …

Localizing An Occult Insulinoma By Selective Calcium Arterial Stimulation Test: First Ever Experience And A New Dimension To Diagnosis In Pakistan, Muhammad Owais Rashid, Sumerah Jabeen, Zareen Kiran,, Khurram Minhas, Muhammad Azeemuddin, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Insulinomas are rare, usually benign, solitary tumours accounting for 60% of islet cell tumours. These tumours can be difficult to localize preoperatively due to their small size. We present a challenging case of a 40 year old male with frequent hypoglycaemic spells and endogenous hypoglycaemia who presented as a diagnostic dilemma. Patient had an occult insulinoma with inconclusive CT Abdomen, MRI Abdomen and Octreotide scan. The final localization of the tumour was made by selective arterial calcium stimulation testing (SCAT), done for the first time in Pakistan at Aga Khan University Hospital. This was followed by successful distal pancreatectomy as …

Frequency Of Silent Carotid Artery Stenosis In Diabetics And Its Associated Factors: An Analysis In Tertiary Care Hospital, Faiza Sadaqat Ali, Nimrah Bader, Bader Faiyaz Zuberi, Sabiha Banu

Section of Diabetes, Endocrinology and Metabolism

Objective: To estimate frequency of silent carotid artery stenosis and its associated factors in diabetic patients attending a tertiary care hospital.
Methods: This cross-sectional study was conducted in tertiary care Civil Hospital, Karachi from March 2019 to September 2019,. A total of 166 patients with Diabetes Mellitus were included in this study. Brief history was taken for the duration of DM, treatment, and smoking habits. Carotid artery stenosis (CAS) wafrs measured by Doppler ultrasound of right and left common, internal, and external carotid arteries.
Results: Frequency of silent carotid artery stenosis (CAS) in diabetic patients was observed in 28.92% (48/166) …

Serum Immune Profiling Of Patients With Polycystic Ovary Syndrome, Hifsa Mobeen, Muhammad Kashif, Ahmed Nadeem, Faheem Shahzad, Romeeza Tahir, Afia Abbas, Nadeem Afzal

Makara Journal of Health Research

Background: Polycystic ovary syndrome (PCOS), the most prevalent hormonal disorder in females, is characterized by low levels of progesterone, which causes increased estrogen levels leading to production of various anti and auto-antibodies. This study aimed to estimate and compare levels of anti-nuclear antibodies (ANA), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG), and anti-islet cell antibodies (anti-ICAb) in patients with PCOS and healthy controls.

Methods: The present comparative study included 82 subjects divided into two groups with 41 individuals in each group. Group I included healthy subjects, while Group II included patients diagnosed with PCOS. Blood samples were collected to determine …

The Utility Of Ultrasound In The Preoperative Localization Of Primary Hyperparathyroidism: Insights From Pakistan, Tehseen Fatima, Bhagwan Das, Saadia Sattar, Sumerah Jabeen, Abid Abbas Khan, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Objective: We aimed to evaluate and compare the diagnostic performance of ultrasound (US) and 99m-Tc sestamibi scintigraphy for the preoperative localization of primary hyperparathyroidism (PHPT).
Methods: This retrospective study was conducted at the Aga Khan University Hospital in Karachi, Pakistan, and comprised the data of patients with PHPT who underwent parathyroidectomy from 2008 to 2017. Preoperative US and 99m-Tc sestamibi scintigraphy findings were recorded and compared to surgical and histological findings, which were taken as a reference standard.
Results: The sensitivity of US in the preoperative localization of PHPT was 88.3%, positive predictive value (PPV) was 94.6%, and accuracy …

Changing Prevalence Of Gestational Diabetes Mellitus During Pregnancy Over More Than A Decade, Aisha Sheikh, Lumaan Sheikh

Section of Diabetes, Endocrinology and Metabolism

No abstract provided.

Modulation Of Inflammatory Pathway By Inflammatory Inhibitor Jsh-23 Mitigates Diabetic Retinopathy., Rubens Petit Homme

Electronic Theses and Dissertations

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). Its pathology is consisted of the breakdown of the blood-retinal barrier (BRB), particularly the inner blood-retinal barrier (iBRB). The exact mechanism that leads to the iBRB impairment and the development of DR has not been elucidated yet. However, chronic inflammation that is hallmark of the type I DM has recently become a key focus in DR study. Hyperglycemia causes dysregulation of nuclear factor-kappa B (NF-kB); and its constant activation increases the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular adhesion molecule-1 (ICAM-1) in the …

A Novel Serpinb1 Single-Nucleotide Polymorphism Associated With Glycemic Control And Β-Cell Function In Egyptian Type 2 Diabetic Patients, Dina H. Kassem, Aya Adel, Ghada H. Sayed, Mohamed M. Kamal

Pharmacy

Aims: Serine protease inhibitor B1 (SerpinB1) is a neutrophil elastase inhibitor that has been proved to be associated with type 2 diabetes mellitus and pancreatic β-cell proliferation. In this study, we investigated 2 SERPINB1 SNPs, rs114597282 and rs15286, regarding their association with diabetes risk and various anthropometric and biochemical parameters in Egyptian type 2 diabetic patients.

Materials and Methods: A total of 160 subjects (62 control and 98 type 2 diabetic patients) participated in this study. Various anthropometric and biochemical parameters were assessed. Genotyping assay for the two SNPs was done using TaqMan genotyping assays. The association of rs15286 variants …

A 2-Hour Diabetes Self-Management Education Program For Patients With Low Socioeconomic Status Improves Short-Term Glycemic Control, Michael G. Jakoby Iv, Melissa Schleder, Vickie Luff, Cynthia Yergler, Albert Botchway, Cheryl Burns

Journal of Patient-Centered Research and Reviews

Diabetes self-management education (DSME) improves glycemic control, but patients with low socioeconomic status face institutional and personal barriers to receiving DSME. A retrospective single cohort study of a 2-hour group DSME program prioritizing accessibility and completion of a tightly focused curriculum was performed to determine if glycemic control improved and whether a longer, more comprehensive, prospective evaluation of the program is indicated. All patients who participated in the program from September 2017 to December 2018 were included in the analysis. The primary study endpoint was change in hemoglobin A1c (HbA1c) from baseline. A total of 58 out of 94 patients …

Assessing College Students’ Perceived Risk For Developing Type 2 Diabetes Mellitus, Carletta Weatherspoon

Doctor of Nursing Practice (DNP) Translational and Clinical Research Projects

This study assesses the effectiveness of an evidence-based educational intervention affecting the perception of the risk for developing type 2 diabetes (T2DM) in college students and examined relationships between demographic factors and perception of risk for T2DM. Seventy-seven students from the Georgia College Association of Nursing Students (GCANS) and the Personal Health and Fitness Class participated. Of these, 43 participants completed the post-educational email survey. Instruments measured demographic characteristics, perception of risk for developing diabetes, and diabetes risk. The Risk Perception Survey for Developing Diabetes (RPS-DD) assessed students’ perception of risk at baseline and one week post intervention. There was …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Glycemic Control And Infections Among Us Hemodialysis Patients With Diabetes Mellitus, Jinnie J Rhee, Yuanchao Zheng, Sai Liu, Maria E Montez-Rath, Richard J Hamill, Julie H Ishida, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

INTRODUCTION: Patients with diabetes mellitus (DM) on hemodialysis (HD) may be particularly vulnerable to infections.

METHODS: We used merged data from the United States Renal Data System and electronic health records data from a large US dialysis provider to retrospectively examine the association between glycemic control and infections in these patients. Adult patients with DM aged ≥18 years who initiated in-center maintenance HD treatment from 2006 to 2011 and survived >90 days were included. Quarterly mean time-averaged hemoglobin A1c (HbA1c) values were categorized into

RESULTS: In a cohort of 33,753 eligible patients, those with higher HbA1c levels had higher rates …

Rapamycin Treatment Correlates Changes In Primary Cilia Expression With Cell Cycle Regulation In Epithelial Cells, Maha Jamal, Ane C.F. Nunes, Nosratola D. Vaziri, Ramani Ramchandran, Robert L. Bacallao, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are sensory organelles that regulate cell cycle and signaling pathways. In addition to its association with cancer, dysfunction of primary cilia is responsible for the pathogenesis of polycystic kidney disease (PKD) and other ciliopathies. Because the association between cilia formation or length and cell cycle or division is poorly understood, we here evaluated their correlation in this study. Using Spectral Karyotyping (SKY) technique, we showed that PKD and the cancer/tumorigenic epithelial cells PC3, DU145, and NL20-TA were associated with abnormal ploidy. We also showed that PKD and the cancer epithelia were highly proliferative. Importantly, the cancer epithelial cells …

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …

Implementing A Basal-Bolus Insulin Regimen Via A Manual Insulin Pump Device, Helen Stearns

Doctor of Nursing Practice Final Manuscripts

Abstract

Purpose:The purpose of this evidence-based practice project is to decrease glycated hemoglobin (HgbA1C) levelsby initiating use of a manual insulin pump in patients with Type II Diabetes Mellitus (T2DM) with poor glycemic control who are on multiple daily insulin injections (MDII).

Background: Uncontrolled hyperglycemia is associated with a myriad of complications and co-morbidities that are generally associated with vascular changes that include nephropathy, neuropathy, blindness, stroke, and heart disease (Winter et al., 2015). Coronary artery disease and cerebrovascular disease alone accounts for approximately 65% of the deaths in diabetic patients (Molinaro & Dauscher, 2017). Achieving and maintaining therapeutic …

Change In Sex Of Rearing In Individuals With Disorders Of Sex Development, Michelle Knoll

Research Days

No abstract provided.