Endocrinology, Diabetes, and Metabolism Commons^™

Diabetes Technology Meeting 2023, Tiffany Tian, Rachel E Aaron, Ashley Y Dunova, Johan H Jendle, David Kerr, Eda Cengiz, Andjela Drincic, John C Pickup, Kong Y Chen, Naomi Schwartz, Douglas B Muchmore, Halis K Akturk, Carol J Levy, Signe Schmidt, Riccardo Bellazzi, Alan H B Wu, Elias K Spanakis, Bijan Najafi, James Geoffrey Chase, Jane Jeffrie Seley, David C Klonoff

Center on Aging Staff Publications

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.

Optimal Humanized Scg3-Neutralizing Antibodies For Anti-Angiogenic Therapy Of Diabetic Retinopathy, Chengchi Huang, Prabuddha Waduge, Avinash Kaur, Hong Tian, Christina Y Weng, John Timothy Stout, Iok-Hou Pang, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Secretogranin III (Scg3) is a diabetic retinopathy (DR)-restricted angiogenic factor identified in preclinical studies as a target for DR therapy. Previously, our group generated and characterized ML49.3, an anti-Scg3 monoclonal antibody (mAb) which we then converted into an EBP2 humanized antibody Fab fragment (hFab) with potential for clinical application. We also generated anti-Scg3 mT4 mAb and related EBP3 hFab. In this study, to identify the preferred hFab for DR therapy, we compared all four antibodies for binding, neutralizing and therapeutic activities in vitro and in vivo. Octet binding kinetics analyses revealed that ML49.3 mAb, EBP2 hFab, mT4 mAb and EBP3 …

Transcriptional Coactivation Of Nrf2 Signaling In Cardiac Fibroblasts Promotes Resistance To Oxidative Stress, Lisa K Mcclendon, Rainer B Lanz, Anil Panigrahi, Kristan Gomez, Michael J Bolt, Min Liu, Fabio Stossi, Michael A Mancini, Clifford C Dacso, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

We recently discovered that steroid receptor coactivators (SRCs) SRCs-1, 2 and 3, are abundantly expressed in cardiac fibroblasts (CFs) and their activation with the SRC small molecule stimulator MCB-613 improves cardiac function and dramatically lowers pro-fibrotic signaling in CFs post-myocardial infarction. These findings suggest that CF-derived SRC activation could be beneficial in the mitigation of chronic heart failure after ischemic insult. However, the cardioprotective mechanisms by which CFs contribute to cardiac pathological remodeling are unclear. Here we present studies designed to identify the molecular and cellular circuitry that governs the anti-fibrotic effects of an MCB-613 derivative, MCB-613-10-1, in CFs. We …

Characteristics Of Patients With Spontaneous Coronary Artery Dissection Presenting With Sudden Cardiac Arrest In The United States And The Potential Role Of Implantable Cardioverter Defibrillator Therapy, Chayakrit Krittanawong, Yusuf Kamran Qadeer, Song Peng Ang, Zhen Wang, Mahboob Alam, Samin Sharma, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a disease entity that often occurs in young, healthy women and can cause life-threatening ventricular arrhythmias and sudden cardiac arrest. However, the characteristics and outcomes of SCAD with cardiac arrest are not well characterized.

METHODS: This study investigated the baseline characteristics of SCAD patients with cardiac arrest using the National Inpatient Sample (NIS) database between 2016 and 2020. In addition, we also sought to determine the potential impact that implantable cardioverter defibrillator (ICD) therapy had on morbidity and mortality in SCAD patients presenting with cardiac arrest.

RESULTS: Our findings showed that the SCAD …

Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana

Faculty, Staff and Students Publications

The interplay between asthma and glucose metabolism disorders, such as hyperglycemia, has gained increasing attention due to the potential exacerbation of asthma symptoms and severity. This review explores the complex relationship between hyperglycemia and asthma, emphasizing the pathophysiological links, the impact of glucose metabolism disorders on asthma, and the effects of asthma medications on glucose levels. Hyperglycemia, often induced by asthma treatments like corticosteroids, has been associated with an increased risk of asthma exacerbations. This review delves into the pathophysiology underlying this association, highlighting the role of insulin resistance, metabolic syndrome, and obesity in both the development and management of …

Experiences Of Parent Coaches In An Intervention For Parents Of Young Children Newly Diagnosed With Type 1 Diabetes, Carrie Tully, Manuela Sinisterra, Wendy Levy, Christine H Wang, John Barber, Hailey Inverso, Marisa E Hilliard, Maureen Monaghan, Randi Streisand

Faculty, Staff and Students Publications

Objectives: This paper explores parent coaching experiences supporting parents of young children newly diagnosed with type 1 diabetes in a clinical trial.

Methods: In a trial for 157 parents, those in the intervention arm (n = 116) were paired with a parent coach (n = 37; Mage = 37.9 years, SD = 3.9; 94.6% mothers, 81.1% White non-Hispanic). Parent coaches provided diabetes-specific social support. Parent coaches completed monthly surveys and satisfaction/feasibility surveys, with a subset (n = 7) undergoing qualitative interviews at the end of this study.

Results: There were 2262 contacts between participants and their parent coaches, averaging …

Safety Of Treating Acute Pulmonary Embolism At Home: An Individual Patient Data Meta-Analysis, Dieuwke Luijten, Delphine Douillet, Kim Luijken, Cecile Tromeur, Andrea Penaloza, Olivier Hugli, Drahomir Aujesky, Stefano Barco, Joseph R Bledsoe, Kyle E Chang, Francis Couturaud, Paul L Den Exter, Carme Font, Menno V Huisman, David Jimenez, Christopher Kabrhel, Jeffrey A Kline, Stavros Konstantinides, Thijs Van Mens, Remedios Otero, W Frank Peacock, Olivier Sanchez, William B Stubblefield, Luca Valerio, David R Vinson, Philip Wells, Maarten Van Smeden, Pierre-Marie Roy, Frederikus A Klok

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis.

METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events …

Recruiting Transgender Men In The Southeastern United States For Genital Microbiome Research: Lessons Learned, Olivia Van Gerwen, Z. Alex Sherman, Emma Sophia Kay, Jay Wall, Joy Lewis, Isaac Eastlund, Keonte J. Graves, Saralyn Richter, Angela Pontius, Kristal J. Aaron, Krishmita Siwakoti, Ben Rogers, Evelyn Toh, Jacob H. Elnaggar, Christopher M. Taylor, Nicholas J. Van Wagoner, Christina A. Muzny

School of Medicine Faculty Publications

Background Transgender men (TGM) are underrepresented in genital microbiome research. Our prospective study in Birmingham, AL investigated genital microbiota changes over time in TGM initiating testosterone, including the development of incident bacterial vaginosis (iBV). Here, we present lessons learned from recruitment challenges encountered during the conduct of this study. Methods Inclusion criteria were assigned female sex at birth, TGM or non-binary identity, age ≥18 years, interested in injectable testosterone but willing to wait 7 days after enrollment before starting, and engaged with a testosterone-prescribing provider. Exclusion criteria were recent antibiotic use, HIV/STI infection, current vaginal infection, pregnancy, or past 6 …

Single Cell Dual-Omic Atlas Of The Human Developing Retina, Zhen Zuo, Xuesen Cheng, Salma Ferdous, Jianming Shao, Jin Li, Yourong Bao, Jean Li, Jiaxiong Lu, Antonio Jacobo Lopez, Juliette Wohlschlegel, Aric Prieve, Mervyn G Thomas, Thomas A Reh, Yumei Li, Ala Moshiri, Rui Chen

Faculty, Staff and Students Publications

The development of the retina is under tight temporal and spatial control. To gain insights into the molecular basis of this process, we generate a single-nuclei dual-omic atlas of the human developing retina with approximately 220,000 nuclei from 14 human embryos and fetuses aged between 8 and 23-weeks post-conception with matched macular and peripheral tissues. This atlas captures all major cell classes in the retina, along with a large proportion of progenitors and cell-type-specific precursors. Cell trajectory analysis reveals a transition from continuous progression in early progenitors to a hierarchical development during the later stages of cell type specification. Both …

A Machine Learning Model For Risk Stratification Of Postdiagnosis Diabetic Ketoacidosis Hospitalization In Pediatric Type 1 Diabetes: Retrospective Study, Devika Subramanian, Rona Sonabend, Ila Singh

Faculty, Staff and Students Publications

BACKGROUND: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in pediatric type 1 diabetes (T1D), occurring in approximately 20% of patients, with an economic cost of $5.1 billion/year in the United States. Despite multiple risk factors for postdiagnosis DKA, there is still a need for explainable, clinic-ready models that accurately predict DKA hospitalization in established patients with pediatric T1D.

OBJECTIVE: We aimed to develop an interpretable machine learning model to predict the risk of postdiagnosis DKA hospitalization in children with T1D using routinely collected time-series of electronic health record (EHR) data.

METHODS: We conducted a retrospective case-control …

Severe Polyarticular Gout Flare Inducing Diabetic Ketoacidosis: A Case Report, John Rovig, Jose Lazarte Loayza, Sana Gurz, Jessica Chung, Winn Chatham

School of Medicine Faculty Research

Diabetic ketoacidosis (DKA) is a serious condition that is triggered by multiple stressors, including processes linked to inflammation. Gout is an inflammatory process that has not been directly linked to DKA, but it affects similar pathways, affecting glycemic control. This case illustrates the link between DKA and gout flares with emphasis on the nuanced management of gout in the setting of DKA.

Pembrolizumab Induced Hyponatremia. A Case Report, Mouna Reghis, Taanvi Gowdar, Arjun Sekar

Advances in Clinical Medical Research and Healthcare Delivery

Hyponatremia is the most common electrolyte abnormality inpatient. Medications are a common cause of this. Cancer treatment has evolved with immune check point inhibitors replacing conventional chemotherapy agents. Pembrolizumab, which is a program cell death receptor-1 ligand has been shown to cause endocrinopathies. We describe a case of hyponatremia due to pembrolizumab

Population-Level Trends In Self-Reported Healthcare Utilization Among Older Adults In Mexico With And Without Cognitive Impairment, José Eduardo Cabrero Castro, Rebeca Wong, Rafael Samper Ternent, Brian Downer

Faculty, Staff and Student Publications

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico.

METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and …

Lipid Droplet-Associated Hydrolase Mobilizes Stores Of Liver X Receptor Sterol Ligands And Protects Against Atherosclerosis, Young-Hwa Goo, Janeesh Plakkal Ayyappan, Francis D Cheeran, Sushant Bangru, Pradip K Saha, Paula Baar, Sabine Schulz, Todd A Lydic, Bernhard Spengler, Andreas H Wagner, Auinash Kalsotra, Vijay K Yechoor, Antoni Paul

Faculty, Staff and Students Publications

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression …

379. Sglt Inhibitors: The Biology Of Sglt Inhibition With Dr. Katherine Tuttle, Katherine Tuttle

Articles, Abstracts, and Reports

No abstract provided.

Horizons-Easd Elearning, Katherine Tuttle

Articles, Abstracts, and Reports

No abstract provided.

Enriching The Pcos Lifestyle, Callie Coleman

Electronic Theses and Dissertations

Polycystic Ovary Syndrome (PCOS) is an endocrine disorder affecting approximately 4 – 20% of women worldwide. It is associated with insulin resistance, fertility problems, and an increased susceptibility to chronic conditions through multiple inflammatory pathways. Women with PCOS are also at increased risk for disordered eating. The Mediterranean diet is associated with decreased inflammation and risk of chronic conditions, and intuitive eating principles are associated with decreased disordered eating patterns. The purpose of this study was to determine if a six-week nutrition education workshop incorporating information and skills related to both the Mediterranean lifestyle and intuitive eating principles can improve …

Individually Randomized Trial Mislabeled As A Cluster-Randomized Trial Comment On: “Effectiveness Of Wearable Technology To Optimize Youth Soccer Players’ Off-Training Behaviour And Training Responses: A Cluster-Randomized Trial”, Jean Michel R S Leite, Jasmine Jamshidi-Naeini, Colby J Vorland, Lilian Golzarri-Arroyo, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Management Of Diabetic Ketoacidosis In Children: Does Early Insulin Glargine Help Improve Outcomes?, Rebecca Ohman-Hanson, G Todd Alonso, Laura Pyle, Ryan Mcdonough, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition.

OBJECTIVE: This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia.

METHODS: Patients agedChildren's Mercy Kansas City between October 2012 and October 2016 were reviewed. They were categorized as Early (>4 h …

Effect Of Semaglutide On Regression And Progression Of Glycemia In People With Overweight Or Obesity But Without Diabetes In The Select Trial, Steven E Kahn, John E Deanfield, Ole Kleist Jeppesen, Scott S Emerson, Trine Welløv Boesgaard, Helen M Colhoun, Robert F Kushner, Ildiko Lingvay, Bartolome Burguera, Grzegorz Gajos, Deborah Bade Horn, Irene M Hramiak, Ania M Jastreboff, Alexander Kokkinos, Michael Maeng, Ana Laura S A Matos, Francisco J Tinahones, A Michael Lincoff, Donna H Ryan, Select Trial Investigators

Faculty, Staff and Student Publications

OBJECTIVE: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes.

RESEARCH DESIGN AND METHODS: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c

RESULTS: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference …