Diseases Commons^™

Effect Of Biological Variation In Hba1c And Blood Glucose On The Diagnosis Of Prediabetes, James M. Hempe, Shengping Yang, Daniel S. Hsia

School of Medicine Faculty Publications

Introduction: People with a low or high haemoglobin glycation index (HGI) have lower or higher HbA1c than other people with the same FPG. This study compared the prevalence of prediabetes based on FPG, 2hOGTT and HbA1c in people with low, moderate or high HGI. Methods: Prediabetes was diagnosed based on ADA cutpoints in 10,488 NHANES participants without self-reported diabetes. HGI was calculated as the difference between a participant's observed HbA1c and a predicted HbA1c where predicted HbA1c = 0.024 FPG + 3.1. Participants were divided into low (HGI < −0.15%), moderate (HGI −0.15% to +0.15%) and high (HGI > +0.15%) HGI subgroups. Results: The prevalence of prediabetes was 42.4% based on …

Differential Effects Of Bariatric Surgery And Caloric Restriction On Hepatic One-Carbon And Fatty Acid Metabolism, Arnon Haran, Michael Bergel, Doron Kleiman, Liron Hefetz, Hadar Israeli, Sarah Weksler-Zangen, Bella Agranovich, Ifat Abramovich, Rachel Ben-Haroush Schyr, Eyal Gottlieb, Danny Ben-Zvi

Faculty, Staff and Student Publications

Weight loss interventions, including dietary changes, pharmacotherapy, or bariatric surgery, prevent many of the adverse consequences of obesity, and may also confer intervention-specific benefits beyond those seen with decreased weight alone. We compared the molecular effects of different interventions on liver metabolism to understand the mechanisms underlying these benefits. Male rats on a high-fat, high-sucrose diet underwent sleeve gastrectomy (SG) or intermittent fasting with caloric restriction (IF-CR), achieving equivalent weight loss. The interventions were compared to

Satisfaction With Participation In The First Steps Behavioral Intervention: Experiences Of Parents Of Young Children With Newly Diagnosed Type 1 Diabetes, Marissa N Baudino, Hailey Inverso, Christine Wang, Carrie Tully, Wendy Levy, Lauren Clary, Katherine A Gallagher, Maureen Monaghan, Randi Streisand, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: Parents of young children with new-onset type 1 diabetes (T1D) often experience significant distress and struggle with T1D management during a challenging developmental stage. The First STEPS (Study of Type 1 in Early childhood and Parenting Support) trial evaluated a stepped-care behavioral intervention comprising increasingly intensive intervention steps (peer parent coach, cognitive-behavioral counseling, consultations with diabetes educator and psychologist) based on need. The intervention improved parental depressive symptoms compared to usual care. Subsequently, we examined parent satisfaction with the intervention to guide potential implementation and refinement for future trials.

METHODS: Participants were 157 parents of young children newly diagnosed …

Reversal Of Dual Epigenetic Repression Of Non-Canonical Wnt-5a Normalises Diabetic Corneal Epithelial Wound Healing And Stem Cells, Ruchi Shah, Tanya M Spektor, Daniel J Weisenberger, Hui Ding, Rameshwar Patil, Cynthia Amador, Xue-Ying Song, Steven T Chun, Jake Inzalaco, Sue Turjman, Sean Ghiam, Jiho Jeong-Kim, Sasha Tolstoff, Sabina V Yampolsky, Onkar B Sawant, Yaron S Rabinowitz, Ezra Maguen, Pedram Hamrah, Clive N Svendsen, Mehrnoosh Saghizadeh, Julia Y Ljubimova, Andrei A Kramerov, Alexander V Ljubimov

Faculty, Staff and Student Publications

AIMS/HYPOTHESIS: Diabetes is associated with epigenetic modifications including DNA methylation and miRNA changes. Diabetic complications in the cornea can cause persistent epithelial defects and impaired wound healing due to limbal epithelial stem cell (LESC) dysfunction. In this study, we aimed to uncover epigenetic alterations in diabetic vs non-diabetic human limbal epithelial cells (LEC) enriched in LESC and identify new diabetic markers that can be targeted for therapy to normalise corneal epithelial wound healing and stem cell expression.

METHODS: Human LEC were isolated, or organ-cultured corneas were obtained, from autopsy eyes from non-diabetic (59.87±20.89 years) and diabetic (71.93±9.29 years) donors. The …

Anoctamin 4 Channel Currents Activate Glucose-Inhibited Neurons In The Mouse Ventromedial Hypothalamus During Hypoglycemia, Longlong Tu, Jonathan C Bean, Yang He, Hailan Liu, Meng Yu, Hesong Liu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Kristine M Conde, Mengjie Wang, Yongxiang Li, Bing Feng, Peiyu Gao, Zhao-Lin Cai, Makoto Fukuda, Mingshan Xue, Qingchun Tong, Yongjie Yang, Lan Liao, Jianming Xu, Chunmei Wang, Yanlin He, Yong Xu

Faculty, Staff and Student Publications

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood …

Opportunistic Detection Of Type 2 Diabetes Using Deep Learning From Frontal Chest Radiographs, Ayis Pyrros, Stephen M. Borstelmann, Ramana Mantravadi, Zachary Zaiman, Kaesha Thomas, Brandon Price, Eugene Greenstein, Nasir Siddiqui, Melinda Willis, Ihar Shulhan, John Hines-Shah, Jeanne M. Horowitz, Paul Nikolaidis, Matthew P. Lungren, Jorge Mario Rodríguez-Fernández, Judy Wawira Gichoya, Sanmi Koyejo, Adam E. Flanders, Nishith Khandwala, Amit Gupta, John W. Garrett, Joseph Paul Cohen, Brian T. Layden, Perry J. Pickhardt, William Galanter

Department of Radiology Faculty Papers

Deep learning (DL) models can harness electronic health records (EHRs) to predict diseases and extract radiologic findings for diagnosis. With ambulatory chest radiographs (CXRs) frequently ordered, we investigated detecting type 2 diabetes (T2D) by combining radiographic and EHR data using a DL model. Our model, developed from 271,065 CXRs and 160,244 patients, was tested on a prospective dataset of 9,943 CXRs. Here we show the model effectively detected T2D with a ROC AUC of 0.84 and a 16% prevalence. The algorithm flagged 1,381 cases (14%) as suspicious for T2D. External validation at a distinct institution yielded a ROC AUC of …

Vitamin B2 Enables Regulation Of Fasting Glucose Availability, Peter M Masschelin, Pradip Saha, Scott A Ochsner, Aaron R Cox, Kang Ho Kim, Jessica B Felix, Robert Sharp, Xin Li, Lin Tan, Jun Hyoung Park, Liping Wang, Vasanta Putluri, Philip L Lorenzi, Alli M Nuotio-Antar, Zheng Sun, Benny Abraham Kaipparettu, Nagireddy Putluri, David D Moore, Scott A Summers, Neil J Mckenna, Sean M Hartig

Faculty, Staff and Students Publications

Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrophy. In our study, depleting FAD pools in mice with a vitamin B2-deficient diet (B2D) caused phenotypes associated with organic acidemias and other IEMs, including reduced body weight, hypoglycemia, and fatty liver disease. Integrated discovery approaches revealed B2D tempered fasting activation of target genes for the nuclear receptor PPARα, including those required for gluconeogenesis. We also found …

Long-Term Continuous Glucose Monitor Use In Very Young Children With Type 1 Diabetes: One-Year Results From The Sence Study, Michelle A Van Name, Lauren G Kanapka, Linda A Dimeglio, Kellee M Miller, Anastasia Albanese-O'Neill, Persis Commissariat, Sarah D Corathers, Kara R Harrington, Marisa E Hilliard, Barbara J Anderson, Jennifer C Kelley, Lori M Laffel, Sarah A Macleish, Brandon M Nathan, William V Tamborlane, R Paul Wadwa, Steven M Willi, Kristen M Williams, Kupper A Wintergerst, Stephanie Woerner, Jenise C Wong, Daniel J Desalvo

Faculty, Staff and Students Publications

OBJECTIVES: Achieving optimal glycemic outcomes in young children with type 1 diabetes (T1D) is challenging. This study examined the durability of continuous glucose monitoring (CGM) coupled with a family behavioral intervention (FBI) to improve glycemia.

STUDY DESIGN: This one-year study included an initial 26-week randomized controlled trial of CGM with FBI (CGM+FBI) and CGM alone (Standard-CGM) compared with blood glucose monitoring (BGM), followed by a 26-week extension phase wherein the BGM Group received the CGM+FBI (BGM-Crossover) and both original CGM groups continued this technology.

RESULTS: Time in range (70-180 mg/dL) did not improve with …

Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response To Metformin And Glipizide In Sugar-Mgh, Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, Miriam S Udler, Aaron Leong, Josep M Mercader, Jose C Florez

Faculty, Staff and Student Publications

AIMS/HYPOTHESIS: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.

METHODS: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping …

Association Of Timing Of Moderate-To-Vigorous Physical Activity With Changes In Glycemic Control Over 4 Years In Adults With Type 2 Diabetes From The Look Ahead Trial, Jingyi Qian, Qian Xiao, Michael P Walkup, Mace Coday, Melissa L Erickson, Jessica Unick, John M Jakicic, Kun Hu, Frank A J L Scheer, Roeland J W Middelbeek, Look Ahead Research Group

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to determine the association of the time-of-day of bout-related moderate-to-vigorous physical activity (bMVPA) with changes in glycemic control across 4 years in adults with overweight/obesity and type 2 diabetes.

RESEARCH DESIGN AND METHODS: Among 2,416 participants (57% women; mean age, 59 years) with 7-day waist-worn accelerometry recording at year 1 or 4, we assigned bMVPA timing groups based on the participants' temporal distribution of bMVPA at year 1 and recategorized them at year 4. The time-varying exposure of bMVPA (≥10-min bout) timing was defined as ≥50% of bMVPA occurring during the same time period (morning, midday, afternoon, …

Diabetes Technology Meeting 2022, Jingtong Huang, Andrea M Yeung, Ashley Y Dubord, Howard Wolpert, Peter G Jacobs, Wei-An Lee, Andjela Drincic, Elias K Spanakis, Jennifer L Sherr, Priya Prahalad, Alexander Fleming, Victoria C Hsiao, Tejaswi Kompala, Rayhan A Lal, Maya Fayfman, Barry H Ginsberg, Rodolfo J Galindo, Andreas Stuhr, J Geoffrey Chase, Bijan Najafi, Umesh Masharani, Jane Jeffrie Seley, David C Klonoff

Center on Aging Staff Publications

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 3 to November 5, 2022. Meeting topics included (1) the measurement of glucose, insulin, and ketones; (2) virtual diabetes care; (3) metrics for managing diabetes and predicting outcomes; (4) integration of continuous glucose monitor data into the electronic health record; (5) regulation of diabetes technology; (6) digital health to nudge behavior; (7) estimating carbohydrates; (8) fully automated insulin delivery systems; (9) hypoglycemia; (10) novel insulins; (11) insulin delivery; (12) on-body sensors; (13) continuous glucose monitoring; (14) diabetic foot ulcers; (15) the environmental impact of diabetes technology; and (16) spinal …

Accuracy Of Artificial Intelligence In Estimating Best-Corrected Visual Acuity From Fundus Photographs In Eyes With Diabetic Macular Edema, William Paul, Philippe Burlina, Rohita Mocharla, Neil Joshi, Zhuolin Li, Sophie Gu, Onnisa Nanegrungsunk, Kira Lin, Susan B Bressler, Cindy X Cai, Jun Kong, T Y Alvin Liu, Hadi Moini, Weiming Du, Fouad Amer, Karen Chu, Robert Vitti, Farshid Sepehrband, Neil M Bressler

Faculty, Staff and Students Publications

IMPORTANCE: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely.

OBJECTIVE: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information.

DESIGN, SETTING, AND PARTICIPANTS: Deidentified color fundus …

Ndufs4 Regulates Cristae Remodeling In Diabetic Kidney Disease, Koki Mise, Jianyin Long, Daniel L Galvan, Zengchun Ye, Guizhen Fan, Irina I Serysheva, Travis I Moore, Jun Wada, Paul T Schumacker, Benny H Chang, Farhad R Danesh

Faculty, Staff and Student Publications

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generated diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model to investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that these conditional mice exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify …

Secretogranin Iii Selectively Promotes Vascular Leakage In The Deep Vascular Plexus Of Diabetic Retinopathy, Liyang Ji, Prabuddha Waduge, Yan Wu, Chengchi Huang, Avinash Kaur, Paola Oliveira, Hong Tian, Jinsong Zhang, J Timothy Stout, Christina Y Weng, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Diabetic retinopathy (DR), a leading cause of vision loss in working-age adults, induces mosaic patterns of vasculopathy that may be associated with spatial heterogeneity of intraretinal endothelial cells. We recently reported that secretogranin III (Scg3), a neuron-derived angiogenic and vascular leakage factor, selectively binds retinal vessels of diabetic but not healthy mice. Here, we investigated endothelial heterogeneity of three retinal vascular plexuses in DR pathogenesis and the therapeutic implications. Our unique in vivo ligand binding assay detected a 22.7-fold increase in Scg3 binding to retinal vessels of diabetic mice relative to healthy mice. Functional immunohistochemistry revealed that Scg3 predominantly binds …

Sodium-Glucose Cotransporter 2 Inhibitors To Decrease The Uric Acid Concentration-A Novel Mechanism Of Action, Anna Kochanowska, Przemysław Rusztyn, Karolina Szczerkowska, Stanisław Surma, Aleksandra Gąsecka, Miłosz J Jaguszewski, Łukasz Szarpak, Krzysztof J Filipiak

Faculty, Staff and Students Publications

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are glucose-lowering agents whose positive impact on cardiovascular risk has been described extensively. Not only do they influence lipid profile, blood pressure, atherosclerosis risk, hemoglobin level, and insulin resistance, but they also reduce cardiovascular events, all-cause mortality, and hospitalization rates. Some of these effects may be due to their impact on serum uric acid (SUA) concentration. Findings from nine meta-analyses showed that, indeed, SGLT2is significantly reduce SUA. The data on the drug- and dose-dependency of this effect were inconclusive. Several factors alternating the beneficial effects of SGLT2is on SUA, such as glycated hemoglobin concentration (HbA1c), …

Targeting Energy Intake And Circadian Biology To Engage Mechanisms Of Aging In Older Adults With Obesity: Calorie Restriction And Time-Restricted Eating, Satchidananda Panda, Geraldine Maier, Dennis T Villareal

Faculty, Staff and Students Publications

With the rise in obesity across age groups, it has been a hindrance to engaging in physical activity and mobility in older adults. Daily calorie restriction (CR) up to 25% has been the cornerstone of obesity management even though the safety in older adults remains incompletely understood. Although some adults can follow CR with clinically significant weight loss and improved health metrics, CR faces 2 obstacles-many fail to adopt CR and even among those who can adopt it short term, long-term compliance can be difficult. Furthermore, there is a continuing debate about the net benefits of CR-induced weight loss in …

Transmembrane Stem Factor Nanodiscs Enhanced Revascularization In A Hind Limb Ischemia Model In Diabetic, Hyperlipidemic Rabbits, Eri Takematsu, Miles Massidda, Gretchen Howe, Julia Goldman, Patricia Felli, Lei Mei, Gregory Callahan, Andrew Sligar, Richard Smalling, Aaron Baker

Faculty, Staff and Student Publications

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. …

Whole Genome Analysis For 163 Grnas In Cas9-Edited Mice Reveals Minimal Off-Target Activity, Kevin A Peterson, Sam Khalouei, Nour Hanafi, Joshua A Wood, Denise G Lanza, Lauri G Lintott, Brandon J Willis, John R Seavitt, Robert E Braun, Mary E Dickinson, Jacqueline K White, K C Kent Lloyd, Jason D Heaney, Stephen A Murray, Arun Ramani, Lauryl M J Nutter

Faculty, Staff and Students Publications

Genome editing with CRISPR-associated (Cas) proteins holds exceptional promise for "correcting" variants causing genetic disease. To realize this promise, off-target genomic changes cannot occur during the editing process. Here, we use whole genome sequencing to compare the genomes of 50 Cas9-edited founder mice to 28 untreated control mice to assess the occurrence of S. pyogenes Cas9-induced off-target mutagenesis. Computational analysis of whole-genome sequencing data detects 26 unique sequence variants at 23 predicted off-target sites for 18/163 guides used. While computationally detected variants are identified in 30% (15/50) of Cas9 gene-edited founder animals, only 38% (10/26) of the variants in 8/15 …

Early Postpartum Hba1c After Hyperglycemia First Detected In Pregnancy-Imperfect But Not Without Value, Ankia Coetzee, David R Hall, Mari Van De Vyver, Magda Conradie

Faculty, Staff and Student Publications

BACKGROUND: South African women of childbearing age are disproportionally affected by obesity and at significant risk of Type 2 Diabetes Mellitus (T2DM). Unless pregnant, they do not readily undergo screening for T2DM. With a local focus on improved antenatal care, hyperglycemia is often first detected in pregnancy (HFDP). This may erroneously be attributed to Gestational Diabetes Mellitus (GDM) in all without considering T2DM. Glucose evaluation following pregnancy is essential for early detection and management of women with T2DM in whom persistent hyperglycemia is to be expected. Conventional testing with an oral glucose tolerance test (OGTT) is cumbersome, prompting investigation for …

Comparison Of Medical Management Versus Parathyroidectomy In Patients With Mild Primary Hyperparathyroidism: A Meta-Analysis., Katherine A. Cironi, Peter P. Issa, Aaron L. Albuck, Christina Mccarthy, Leely Rezvani, Mohammad Hussein, Xinyi Luo, Mohamed Shama, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

Background: Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2–1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT. Study Design: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines …

A Nurse-Led Telehealth Program For Diabetes Foot Care: Feasibility And Usability Study, Hsiao-Hui Ju, Rashmi Momin, Stanley Cron, Jed Jularbal, Jeffery Alford, Constance Johnson

Faculty, Staff and Student Publications

BACKGROUND: Diabetes mellitus can lead to severe and debilitating foot complications, such as infections, ulcerations, and amputations. Despite substantial progress in diabetes care, foot disease remains a major challenge in managing this chronic condition that causes serious health complications worldwide.

OBJECTIVE: The primary aim of this study was to examine the feasibility and usability of a telehealth program focused on preventive diabetes foot care. A secondary aim was to descriptively measure self-reported changes in diabetes knowledge, self-care, and foot care behaviors before and after participating in the program.

METHODS: The study used a single-arm, pre-post design in 2 large family …

Acute Suppurative Thyroiditis Secondary To Gemella With Extensive Complications, Amber Champion

Department of Internal Medicine Faculty Research

A young woman developed thyroid storm secondary to acute suppurative thyroiditis, with Gemella morbillorum bacteremia. Her case was complicated by neck abscess, Lemierre syndrome (septic thrombophlebitis of the internal jugular vein), mediastinitis, and pleural effusion. She was treated for thyroid storm including steroids and antibiotics. The infectious complications required several surgical procedures and interventions and a prolonged hospital stay, but she ultimately made a full recovery. Complications from suppurative thyroiditis can be rapid and widespread; swift recognition and treatment by a multidisciplinary team can help to prevent complications.

Steroid Receptor Coactivator 3 Is A Key Modulator Of Regulatory T Cell-Mediated Tumor Evasion, Sang Jun Han, Prashi Jain, Yosef Gilad, Yan Xia, Nuri Sung, Mi Jin Park, Adam M Dean, Rainer B Lanz, Jianming Xu, Clifford C Dacso, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivator 3 (SRC-3) is most strongly expressed in regulatory T cells (Tregs) and B cells, suggesting that it plays an important role in the regulation of Treg function. Using an aggressive E0771 mouse breast cell line syngeneic immune-intact murine model, we observed that breast tumors were "permanently eradicated" in a genetically engineered tamoxifen-inducible Treg-cell-specific SRC-3 knockout (KO) female mouse that does not possess a systemic autoimmune pathological phenotype. A similar eradication of tumor was noted in a syngeneic model of prostate cancer. A subsequent injection of additional E0771 cancer cells into these mice showed continued resistance to tumor …

Genetic Studies Of Paired Metabolomes Reveal Enzymatic And Transport Processes At The Interface Of Plasma And Urine, Pascal Schlosser, Nora Scherer, Franziska Grundner-Culemann, Sara Monteiro-Martins, Stefan Haug, Inga Steinbrenner, Burulça Uluvar, Matthias Wuttke, Yurong Cheng, Arif B Ekici, Gergely Gyimesi, Edward D Karoly, Fruzsina Kotsis, Johanna Mielke, Maria F Gomez, Bing Yu, Morgan E Grams, Josef Coresh, Eric Boerwinkle, Michael Köttgen, Florian Kronenberg, Heike Meiselbach, Robert P Mohney, Shreeram Akilesh, Gckd Investigators, Miriam Schmidts, Matthias A Hediger, Ulla T Schultheiss, Kai-Uwe Eckardt, Peter J Oefner, Peggy Sekula, Yong Li, Anna Köttgen

Faculty, Staff and Students Publications

The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the …

Creating A Data Dictionary For Pediatric Autonomic Disorders, Jeffrey R Boris, Hasan Abdallah, Shelley Ahrens, Gisela Chelimsky, Thomas C Chelimsky, Philip R Fischer, John E Fortunato, Raewyn Gavin, Janice L Gilden, Renato Gonik, Blair P Grubb, Kelsey M Klaas, Erin Marriott, Lauren E Marsillio, Marvin S Medow, Lucy Norcliffe-Kaufmann, Mohammed T Numan, Erin Olufs, Laura A Pace, Paul T Pianosi, Pippa Simpson, Julian M Stewart, Sally Tarbell, Natalie R Van Waning, Debra E Weese-Mayer

Faculty, Staff and Student Publications

PURPOSE: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders.

METHODS: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which …

Analysis Of Trustworthiness And Readability Of English And Spanish Hypo- And Hyperthyroid-Related Online Patient Education Information, Chitra Parikh, Adam M. Ostrovsky

Student Papers, Posters & Projects

This study aims to determine the readability and trustworthiness of English and Spanish hypo- and hyperthyroid-related online information. Google searches were conducted for four search terms: hypothyroidism, Hashimoto's Disease, hyperthyroidism, and Graves’ Disease. For each search term, the first 10 websites were analyzed with a total of 40 websites analyzed. Readability formulas were used to determine English and Spanish readability. Trustworthiness was determined using HONcode status, JAMA Benchmark Criteria, and NLM Trustworthy Score. Overall readability largely exceeded recommended grade levels. Only 1 website (2.5%) presented information below the eighth-grade reading level based on overall Readability Consensus score, while 31 websites …

Positive Changes In Safety Perception Among Blacks With Hiv And Comorbidities: Assessment Of Social Determinants Of Health During Covid‑19, Marc Fleming, Deidra Lee, Chukwuezugo Oranu, Jon C. Schommer, Jennifer M. Cocohoba, Jennifer Cooper, Crystal K. Hodge, Saharnaz Nedjat, Kathleen Borgmann

Pharmacy Faculty Articles and Research

Purpose

This study aimed to examine the impact of the COVID-19 lockdown on social determinants of health (SDOH) among Blacks with HIV and a comorbid diagnosis of hypertension or type 2 diabetes mellitus (T2DM).

Methods

This was a longitudinal survey study. The inclusion criteria were adults ≥ 18 years and the presence of hypertension and/or diabetes, along with a positive HIV diagnosis. This study enrolled patients in the HIV clinics and chain specialty pharmacies in the Dallas-Fort Worth (DFW) area. A survey of ten questions examining SDOH was conducted before, during, and after the lockdown. A proportional odds mixed effects …

Parent Perspectives Of School/Daycare Experiences In Young Children Newly Diagnosed With Diabetes, Alexa Stern, Brenda Duran, Randi Streisand, Christine H Wang, Carrie Tully, Lauren Clary, Katherine Gallagher, Fran Cogen, Lefkothea Karaviti, Maureen Monaghan, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: A central part of family adjustment to a new diagnosis of type 1 diabetes (T1D) is integrating T1D management into the child's school/daycare. This may be particularly challenging for young children who rely on adults for their diabetes management. This study aimed to describe parent experiences with school/daycare during the first 1.5 years following a young child's T1D diagnosis.

METHODS: As part of a randomized controlled trial of a behavioral intervention, 157 parents of young children with new-onset (<2 >months) T1D reported on their child's school/daycare experience at baseline and at 9- and 15-month post-randomization. We used a mixed-methods …

Association Of Type 2 Diabetes Subgroups With Cognitive Status Without Modification From Lifestyle Intervention, Michael P Bancks, James Lovato, Ashok Balasubramanyam, Mace Coday, Karen C Johnson, Medha Munshi, Candida Rebello, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown.

OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD.

METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Ramesh Singh, Huan Meng, Tao Shen, Lance Edward V Lumahan, Steven Nguyen, Hong Shen, Subhamoy Dasgupta, Li Qin, Dileep Karri, Bokai Zhu, Feng Yang, Cristian Coarfa, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal …