Endocrinology, Diabetes, and Metabolism Commons^™

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. …

A Multi-Omics Atlas Of The Human Retina At Single-Cell Resolution, Qingnan Liang, Xuesen Cheng, Jun Wang, Leah Owen, Akbar Shakoor, John L Lillvis, Charles Zhang, Michael Farkas, Ivana K Kim, Yumei Li, Margaret Deangelis, Rui Chen

Faculty, Staff and Students Publications

Cell classes in the human retina are highly heterogeneous with their abundance varying by several orders of magnitude. Here, we generated and integrated a multi-omics single-cell atlas of the adult human retina, including more than 250,000 nuclei for single-nuclei RNA-seq and 137,000 nuclei for single-nuclei ATAC-seq. Cross-species comparison of the retina atlas among human, monkey, mice, and chicken revealed relatively conserved and non-conserved types. Interestingly, the overall cell heterogeneity in primate retina decreases compared with that of rodent and chicken retina. Through integrative analysis, we identified 35,000 distal cis-element-gene pairs, constructed transcription factor (TF)-target regulons for more than 200 …

Neighbourhood‐Level Social Deprivation And The Risk Of Recurrent Heart Failure Hospitalizations In Type 2 Diabetes, Salil V. Deo, Sadeer Al-Kindi, Yakov Elgudin, Eiran Gorodeski, Sanjay Rajagopalan

Faculty Scholarship

Background: The importance of type 2 diabetes mellitus (T2D) in heart failure hospitalizations (HFH) is acknowledged. As information on the prevalence and influence of social deprivation on HFH is limited, we studied this issue in a racially diverse cohort. Methods: Linking data from US Veterans with stable T2D (without prevalent HF) with a zip-code derived population-level social deprivation index (SDI), we grouped them according to increasing SDI as follows: SDI: group I: ≤20; II: 21-40; III: 41-60; IV: 61-80; and V (most deprived) 81-100. Over a 10-year follow-up period, we identified the total (first and recurrent) number of HFH episodes …

Development Of A Biomarker Panel For Assessing Cardiovascular Risk In Diabetic Patients With Chronic Limb-Threatening Ischemia (Clti): A Prospective Study, Elisabetta Nardella, Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Enrica Rossini, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Medicine Faculty Papers

BACKGROUND: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), …

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 …

Tenofovir Induced Hypokalaemia - A Case Report, Ankisha Gupta, Kiran P. K, Rajendra Prasad S

Digital Journal of Clinical Medicine

Tenofovir, an important medication for HIV/AIDS, carries the risk of hypokalemia in patients receiving treatment. Factors such as dietary deficits, vomiting, or diarrhea further increase this risk. Tenofovir acts as a mitochondrial toxin by inhibiting the DNA polymerase gamma enzyme, crucial for mitochondrial DNA replication. Consequently, ATP generation is depleted through the aerobic pathway, leading to dysfunction in the proximal tubule. This dysfunction manifests as renal acidosis type 2, which involves reduced bicarbonate excretion by the proximal tubule, resulting in renal bicarbonate wasting and decreased serum bicarbonate levels. Consequently, the lumen of the distal nephron becomes negatively charged, leading to …

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 …

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 …

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 …

Systematic Assessment Of The Contribution Of Structural Variants To Inherited Retinal Diseases, Shu Wen, Meng Wang, Xinye Qian, Yumei Li, Keqing Wang, Jongsu Choi, Mark E Pennesi, Paul Yang, Molly Marra, Robert K Koenekoop, Irma Lopez, Anna Matynia, Michael Gorin, Ruifang Sui, Fengxia Yao, Kerry Goetz, Fernanda Belga Ottoni Porto, Rui Chen

Faculty, Staff and Students Publications

Despite increasing success in determining genetic diagnosis for patients with inherited retinal diseases (IRDs), mutations in about 30% of the IRD cases remain unclear or unsettled after targeted gene panel or whole exome sequencing. In this study, we aimed to investigate the contributions of structural variants (SVs) to settling the molecular diagnosis of IRD with whole-genome sequencing (WGS). A cohort of 755 IRD patients whose pathogenic mutations remain undefined were subjected to WGS. Four SV calling algorithms including include MANTA, DELLY, LUMPY and CNVnator were used to detect SVs throughout the genome. All SVs identified by any one of these …

Clinical Characteristics, Management, And 5-Year Survival Compared Between No Standard Modifiable Risk Factor (Smurfless) And ≥ 1 Smurf Acs Cases: An Analysis Of 15,051 Cases From Pakistan, Sana Sheikh, Ghazal Peerwani, Bashir Hanif, Salim S. Virani

Section of Cardiology

Background: There has been an increase in Acute Coronary Syndrome (ACS) patients without standard modifiable risk factors i.e. hypertension, diabetes, dyslipidemia, and tobacco use (SMuRFless) compared to the patients with ≥ 1 SMuRF but this has not been studied in South Asia despite them being a high-risk population. We conducted a comparative analysis of first episodes of ACS cases admitted to a tertiary cardiac center in Pakistan between SMuRFless and ≥ 1 SMuRF patients for clinical presentation, management, in-hospital, and 5-year mortality.
Methods: We undertook a retrospective study and data of 15,051 patients admitted at Tabba Heart Institute (THI) with …

Expert Search For The "A Scoping Review Of The Relation Between Toothbrushing And Diabetes Knowledge, Glycemic Control, And Oral Health Outcomes In People With Type 2 Diabetes", Kelly K. O'Brien, Ruth D. Lipman

Expert Search Strategies

This search strategy was constructed to support the research for the peer reviewed article listed above. Full article abstract:

OBJECTIVE | Given the bidirectional relationship between type 2 diabetes and periodontal disease, this study sought to compile the available data regarding the relationship between home oral hygiene, specifically toothbrushing, and glycemic control and oral health in people with type 2 diabetes

METHODS | A systematic scoping review was conducted using a combination of controlled vocabulary and keyword terms for type 2 diabetes and home oral care in PubMed and CINHAL. Publications from the past 20 years were considered for inclusion. …

Central Hypothyroidism Following Neonatal Graves' Presentation, Emily Metzinger, Kelsee Halpin

Posters

Background: Neonatal Graves’ disease is a rare disorder of neonatal autoimmune hyperthyroidism secondary to the transplacental passage of thyroid-stimulating hormone receptor antibodies. Although neonatal Graves’ disease is transient, it is associated with cardiac dysfunction, intrauterine growth restriction, prematurity, craniosynostosis, and developmental delay and can be life-threatening. Additionally, infants with neonatal Graves’ disease can rarely present with primary or central hypothyroidism later in infancy or childhood. This is suspected to be due to the disruption in the hypothalamic-pituitary-thyroid axis or development of the thyroid gland. Clinical Case: Here we describe a case of neonatal Graves’ disease that has been complicated by …

Birth Weight Moderates The Association Between Obesity And Mortality Rate, Gregory Pavela, Nengjun Yi, Luis Mestre, Pengcheng Xun, David B Allison

Children’s Nutrition Research Center Staff Publications

Purpose: The strength of the association between obesity and mortality rate (MR) varies by body mass index (BMI) and sociodemographic groups. We test the hypothesis that the association between obesity and MR varies, in part, due to the moderating effect of parental BMI and birth weight.

Methods: Data come from the 1958 National Child Development Study, an ongoing longitudinal dataset initiated in 1958 with baseline measures of birth weight from 18,059 infants born in Great Britain over 1 week. We tested whether the association between BMI and MR was moderated by parental BMI and birth weight using generalized additive proportional …

Comparison Of Female Ovarian Reserve Before Vs After Covid-19 Vaccination, Liubin Yang, Samantha Neal, Tiffany Lee, Andrew Chou, Amy K Schutt, William Gibbons

Children’s Nutrition Research Center Staff Publications

This cohort study examines the association of COVID-19 vaccination with levels of anti-Mullerian hormone and antral follicle count in women seeking fertility treatment.

The Effects Of Gender And Country Of Origin On Acculturation, Psychological Factors, Lifestyle Factors, And Diabetes-Related Physiological Outcomes Among Mexican Americans: The Starr County Diabetes Prevention Initiative, Sharon A Brown, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, Mary A Winter, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis

Faculty, Staff and Student Publications

OBJECTIVES: Examine acculturation and psychological, lifestyle, and physiological factors based on gender and country of origin (U.S. vs. Mexico).

METHODS: Baseline data from the Starr County diabetes prevention study (

RESULTS: Participants were: predominantly female (73%); 51 years of age, on average; born in Mexico (71%); and Spanish-speaking. Individuals spent 11 of their waking hours (range = 0-18 h) in sedentary activities. Compared to females, more males spoke English and reported fewer hours in sedentary activities. Compared to participants born in Mexico, those born in the U.S. were more likely to: speak English; report depressive symptoms; and exhibit elevated BMI …

Diabetes-Related Quality Of Life Assessment In Children Following Total Pancreatectomy With Islet Autotransplantation., Jacob M. Redel, Lindsey Hornung, Deborah Elder, Jaimie D. Nathan, Sarah Corathers, Kristin L. Rich, Maisam Abu-El-Haija

Manuscripts, Articles, Book Chapters and Other Papers

Total pancreatectomy with islet autotransplantation (TPIAT) can improve pain and reduce functional impairment associated with acute recurrent or chronic pancreatitis. However, long-term glucose monitoring and insulin therapy are often required, which can adversely affect the quality of life. We sought to evaluate diabetes-related quality of life (DR-QOL) in youth who underwent TPIAT and compare it to the youth with new-onset type 1 diabetes (T1D). The Pediatric Quality of Life Inventory™ 3.2 Diabetes Module (PedsQL™ DM) was used to assess DR-QOL in 46 youth (< 20 years old) who underwent TPIAT. The PedsQL™ DM scores were analyzed for statistically significant changes and minimally important clinical differences (MCID) over time post-TPIAT. Scores at 12 months (n = 52) and 24 months (n = 58) after diagnosis of T1D. The diabetes …

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 …

An International Delphi Consensus Statement On Metabolic Dysfunction-Associated Fatty Liver Disease And Risk Of Chronic Kidney Disease, Dan-Qin Sun, Giovanni Targher, Christopher D Byrne, David C Wheeler, Vincent Wai-Sun Wong, Jian-Gao Fan, Herbert Tilg, Wei-Jie Yuan, Christoph Wanner, Xin Gao, Michelle T Long, Mehmet Kanbay, Mindie H Nguyen, Sankar D Navaneethan, Yusuf Yilmaz, Yuli Huang, Rino A Gani, Pierluigi Marzuillo, Jérôme Boursier, Huijie Zhang, Chan-Young Jung, Jin Chai, Luca Valenti, George Papatheodoridis, Giovanni Musso, Yu-Jun Wong, Mohamed El-Kassas, Nahum Méndez-Sánchez, Silvia Sookoian, Michael Pavlides, Ajay Duseja, Adriaan G Holleboom, Junping Shi, Wah-Kheong Chan, Yasser Fouad, Junwei Yang, Sombat Treeprasertsuk, Helena Cortez-Pinto, Masahide Hamaguchi, Manuel Romero-Gomez, Mamun Al Mahtab, Ponsiano Ocama, Atsushi Nakajima, Chunsun Dai, Mohammed Eslam, Lai Wei, Jacob George, Ming-Hua Zheng

Faculty, Staff and Students Publications

BACKGROUND: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no …