Endocrinology, Diabetes, and Metabolism Commons^™

International Expert Consensus On The Current Status And Future Prospects Of Artificial Intelligence In Metabolic And Bariatric Surgery, Mohammad Kermansaravi, Sonja Chiappetta, Shahab Shahabi Shahmiri, Julian Varas, Chetan Parmar, Yung Lee, Jerry T. Dang, Asim Shabbir, Daniel Hashimoto, Amir Hossein Davarpanah Jazi, Ozanan R. Meireles, Edo Aarts, Hazem Almomani, Aayad Alqahtani, Ali Aminian, Estuardo Behrens, Dieter Birk, Felipe J. Cantu, Ricardo V. Cohen, Maurizio De Luca, Nicola Di Lorenzo, Bruno Dillemans, Mohamad Hayssam Elfawal, Daniel Moritz Felsenreich, Michel Gagner, Hector Gabriel Galvan, Carlos Galvani, Khaled Gawdat, Omar M. Ghanem, Et Al

School of Medicine Faculty Publications

Artificial intelligence (AI) is transforming the landscape of medicine, including surgical science and practice. The evolution of AI from rule-based systems to advanced machine learning and deep learning algorithms has opened new avenues for its application in metabolic and bariatric surgery (MBS). AI has the potential to enhance various aspects of MBS, including education and training, decision-making, procedure planning, cost and time efficiency, optimization of surgical techniques, outcome and complication prediction, patient education, and access to care. However, concerns persist regarding the reliability of AI-generated decisions and associated ethical considerations. This study aims to establish a consensus on the role …

Exploring Profiles Of Fathers Integrating Food And Physical Activity Parenting Practices, John A Jimenez-Garcia, Louise C Mâsse, Robert L Newton, Salma M Musaad, Alicia Beltran, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

Objective: This study aims to identify fathers' profiles integrating food parenting practices (FPP) and physical activity parenting practices (PAPP).

Design: We analysed cross-sectional data. The fathers completed the reduced FPP and PAPP item banks and socio-demographic and family dynamics (co-parenting and household responsibility) questionnaires. We identified fathers' profiles via latent profile analysis. We explored the influence of social determinants, child characteristics and family dynamics on fathers' profiles using multinomial logistic regression.

Setting: Online survey in the USA.

Participants: Fathers of 5-11-year-old children.

Results: We analysed data from 606 fathers (age = 38 ± 8·0; Hispanic = 37·5 %). Most fathers …

Genetic Associations With C-Peptide Levels Before Type 1 Diabetes Diagnosis In At-Risk Relatives, Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric A Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo

Children’s Nutrition Research Center Staff Publications

Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms are associated with C-peptide preservation before type 1 diabetes diagnosis.

Methods: We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known single nucleotide polymorphisms and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis.

Results: Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before …

Parent Feedback On The Reducing Emotional Distress For Childhood Hypoglycemia In Parents (Redchip) Intervention: A Qualitative Analysis., Nicole A. Kahhan, Maryjane S. Campbell, Mark A. Clements, Kimberly A. Driscoll, Amy I. Milkes, Holly K. O'Donnell, Susana R. Patton

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Severe hypoglycemia is more common among young children with type 1 diabetes mellitus (T1DM) than older youth, and parents report significant hypoglycemia fear (HF). Parents experiencing HF describe constant and extreme worry about the occurrence of hypoglycemia and may engage in potentially risky behaviors to avoid hypoglycemia. Our team developed and tested a behavioral intervention, Reducing Emotional Distress for Childhood Hypoglycemia in Parents (REDCHiP), to decrease HF in parents of young children with T1DM. Here, we qualitatively analyzed parent feedback to refine and optimize future intervention iterations.

METHODS: The randomized pilot study included parents (n = 73) of …

Successful Limb Salvage In A Severe Diabetic Foot Infection: A Case Study Of Aggressive Surgical Intervention And Grafting Technique, Stephanie N. Campbell, Amanda Killeen, Michael Sobolevsky

Research Symposium

Background: Severe necrotizing diabetic foot infections are known to have high morbidity, high amputation risk, and high complication rates. Efforts at preserving the limb require significant surgical efforts and lengthy wound care. This process is more complicated in patients with significant housing instability.

Case Presentation: A 53-year-old male with uncontrolled diabetes (A1c 7.9%), housing insecurity, food insecurity presented with severe necrotizing diabetic foot infection with ascending cellulitis, infectious hemorrhagic bullae, multi-compartment abscesses of the foot and anterior leg. It is known that patients with diabetes are at increased risk of both amputation and surgical interventions than patients without diabetes. This …

An Endocrine Enigma: The Implications Of Pembrolizumab Therapy, Miguel A. Lopez, Mario Trujillo Acosta, Jose Romero Villarreal Calderon, Laura Garcia

Research Symposium

Disorders of the endocrine system are a potential complication of cancer treatment despite newer immunotherapy agents holding promise to improve patient outcomes. Breast cancer in particular requires pharmacologic intervention based on the receptor positivity. For example, a triple negative workup often requires neoadjuvant therapy with the newer immunotherapy agent pembrolizumab. Clinicians should be aware of the potential adverse effects of this drug, most notably adrenal insufficiency. This case follows a 52 year old hispanic female patient with a history of triple negative left sided breast cancer on immunotherapy with pembrolizumab, who presented to the emergency department after a syncopal episode …

Subcutaneous Insulin Aspart Every 4 Hours In The Treatment Of Covid-19 Patients With Mild-To-Moderate Diabetic Ketoacidosis: A Case Series, Dararat Chiewchalermsri, Chayanin Wanittansirichok, Chutintorn Sriphrapradang

Journal of Community Hospital Internal Medicine Perspectives

This case series evaluates the efficacy and safety of subcutaneous (SC) insulin Aspart administered every four hours for managing mild-to-moderate diabetic ketoacidosis (DKA) in COVID-19 patients, addressing a current evidence gap. We conducted a retrospective review of confirmed COVID-19 patients over 15 years old who developed mild to moderate DKA between July 2020 and October 2021. Insulin Aspart was administered at 0.4 units/kg SC every 4 hours, reduced to 0.2 units/kg when blood glucose (BG) decreased to/dL, and SC basal insulin was initiated at 0.15-0.2 units/kg at DKA diagnosis. A total of seven patients, with a mean age of 67.4±13.2 …

Navigating Thyroid Crises: A Nationwide Analysis Of The Weekend Effect And Mortality Trends In Myxedema Coma (2016-2020), Mariam Hashmi, Zubair Hassan Bodla, Fatima Niaz, Umer Farooq, Zahra Niaz, Christopher L. Bray, Peters Okonoboh

Journal of Community Hospital Internal Medicine Perspectives

Our objective was to utilize the National Inpatient Sample (NIS) database for analyzing the outcomes of myxedema coma based on the day of admission and explore five-year mortality trends. This retrospective cohort study examined in-patient mortality and secondary outcomes of patients with myxedema coma from 2016 to 2020 using the NIS database. Patients were selected using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes and divided into weekday and weekend admission groups. From 174,776,205 discharges, 5,095 patients were included. Mean age of admitted patients was higher on weekdays (67.1 year) than weekends (66.5), with females constituting 69.4% and …

Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background/Objectives: Pathway annotations of non-macromolecular (relatively small) biomolecules facilitate biological and biomedical interpretation of metabolomics datasets. However, low pathway annotation levels of detected biomolecules hinder this type of interpretation. Thus, predicting the pathway involvement of detected but unannotated biomolecules has a high potential to improve metabolomics data analysis and omics integration. Past publications have only made use of the Kyoto Encyclopedia of Genes and Genomes-derived datasets to develop machine learning models to predict pathway involvement. However, to our knowledge, the Reactome knowledgebase has not been utilized to develop these types of predictive models.

Methods: We created a dataset ready for …

Insulin Clearance At Randomisation And In Response To Treatment In Youth With Type 2 Diabetes: A Secondary Analysis Of The Today Randomised Clinical Trial, Kristen J Nadeau, Silva A Arslanian, Fida Bacha, Sonia Caprio, Lily C Chao, Ryan Farrell, Kara S Hughan, Maria Rayas, Melinda Tung, Kaitlyn Cross, Laure El Ghormli

Children’s Nutrition Research Center Staff Publications

Aims/hypothesis: Insulin resistance and compensatory hyperinsulinaemia are core features leading to beta cell failure in youth-onset type 2 diabetes. Insulin clearance (IC) is also a key regulator of insulin concentrations, but few data exist on IC in youth-onset type 2 diabetes. In a secondary analysis of our Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomised clinical trial, we investigated potential sex-, race-, ethnicity- and treatment-related differences in IC in youth-onset type 2 diabetes and aimed to identify metabolic phenotypes associated with IC at baseline and in response to metformin, metformin plus a lifestyle intervention, and metformin …

Leveraging Artificial Intelligence And Machine Learning To Accelerate Discovery Of Disease-Modifying Therapies In Type 1 Diabetes., Melanie R. Shapiro, Erin M. Tallon, Matthew E. Brown, Amanda L. Posgai, Mark A. Clements, Todd M. Brusko

Manuscripts, Articles, Book Chapters and Other Papers

Progress in developing therapies for the maintenance of endogenous insulin secretion in, or the prevention of, type 1 diabetes has been hindered by limited animal models, the length and cost of clinical trials, difficulties in identifying individuals who will progress faster to a clinical diagnosis of type 1 diabetes, and heterogeneous clinical responses in intervention trials. Classic placebo-controlled intervention trials often include monotherapies, broad participant populations and extended follow-up periods focused on clinical endpoints. While this approach remains the 'gold standard' of clinical research, efforts are underway to implement new approaches harnessing the power of artificial intelligence and machine learning …

Rising Mortality Rates Linked To Type-2 Diabetes And Obesity In The United States: An Observational Analysis From 1999 To 2022, Mushood Ahmed, Abdullah Nofal, Aimen Shafiq, Hira Javaid, Areeba Ahsan, Zain Ali Nadeem, Raheel Ahmed, Mahboob Alam, Mamas A Mamas, Marat Fudim, Gregg C Fonarow

Faculty, Staff and Students Publications

Background: The prevalence of type 2 diabetes (T2D) and obesity are increasing in the United States. However, population-level data for mortality trends due to T2D and obesity are limited. This study aims to assess these death trends among adults in the United States categorized by sex, race, and geographical location.

Methods: We queried the CDC-WONDER database for multiple cause of death data of adults aged ≥25 years. The crude mortality rates (CMR), age-adjusted mortality rates (AAMRs), annual percent change (APC), and the average APC (AAPC) along with a 95% confidence interval (CI) were analyzed.

Results: From 1999 to 2022, a …

Pskh1 Kinase Activity Is Differentially Modulated Via Allosteric Binding Of Ca2+ Sensor Proteins, Christopher R Horne, Toby A Dite, Samuel N Young, Lucy J Mather, Laura F Dagley, Jared L Johnson, Tomer M Yaron-Barir, Emily M Huntsman, Leonard A Daly, Dominic P Byrne, Antonia L Cadell, Boaz H Ng, Jumana Yousef, Dylan H Multari, Lianju Shen, Luke M Mcaloon, Gerard Manning, Mark A Febbraio, Anthony R Means, Lewis C Cantley, Maria C Tanzer, David R Croucher, Claire E Eyers, Patrick A Eyers, John W Scott, James M Murphy

Children’s Nutrition Research Center Staff Publications

Protein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung, and kidney cancers. However, little is known about PSKH1 regulatory mechanisms, leading to its classification as a “dark” kinase. Here, we used biochemistry and mass spectrometry to define PSKH1’s consensus substrate motif, protein interactors, and how interactors, including Ca2+ sensor proteins, promote or suppress activity. Intriguingly, despite the absence of a canonical Calmodulin binding motif, Ca2+-Calmodulin activated PSKH1 while, in contrast, the ER-resident Ca2+ sensor of the Cab45, Reticulocalbin, Erc55, Calumenin (CREC) family, Reticulocalbin-3, suppressed PSKH1 catalytic activity. In …

Regulating Chemoresistance And Cancer Stemness: The Cdh17-Yap Pathway In Distinct Cellular States Of Lung Cancer Ctc Clusters, Zujun Que, Dan Qi, Yun Yang, Wang Yao, Jiajun Liu, Yan Li, Yuanyuan Yu, Luyao Wang, Fangfei Li, Ge Zhang, Erxi Wu, Jianhui Tian

Children’s Nutrition Research Center Staff Publications

Background: Drug resistance in metastatic lung cancer significantly contributes to patient mortality. This study explores the role of circulating tumor cells (CTCs), the precursors to metastasis, in driving this resistance. We aim to delineate the unique biological traits of CTC clusters in lung cancer and elucidate the mechanisms underlying their resistance to chemotherapy.

Methods: We used an ultralow adsorption plate to establish a CTC suspension culture system. Comparisons between adherent and suspension cultures of CTC-TJH-01 cells were made via Cell Counting Kit-8 (CCK-8), western blot, immunofluorescence, and flow cytometry assays to evaluate cell proliferation, drug resistance, and cancer stemness. The …

Erythritol, Erythronate, And Cardiovascular Outcomes In Older Adults In The Aric Study, Layla A Abushamat, Bing Yu, Ron C Hoogeveen, Caroline Sun, Chao Cheng, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jane Eb Reusch, Elizabeth Selvin, Chiadi E Ndumele, Vijay Nambi, Christie M Ballantyne

Faculty, Staff and Student Publications

BACKGROUND: Circulating erythritol, an endogenously produced metabolite and an artificial sweetener, is associated with cardiovascular outcomes.

OBJECTIVES: The authors assessed associations of erythritol and its downstream metabolite, erythronate, with cardiovascular risk factors and events in older adults in the ARIC (Atherosclerosis Risk In Communities) study (visit 5, 2011-2013).

METHODS: We included 4,006 participants without prevalent cardiovascular disease and with metabolomic profiling. Erythritol and erythronate were measured by mass spectrometry. We analyzed associations of log-transformed erythritol and erythronate with cardiovascular risk factors and events using Cox proportional hazard models.

RESULTS: Participants in the highest tertiles of erythritol or erythronate were older, …

Biguanides Antithetically Regulate Tumor Properties By The Dose-Dependent Mitochondrial Reprogramming-Driven C-Src Pathway, Jun Hyoung Park, Kwang Hwa Jung, Dongya Jia, Sukjin Yang, Kuldeep S Attri, Songyeon Ahn, Divya Murthy, Tagari Samanta, Debasmita Dutta, Meron Ghidey, Somik Chatterjee, Seung Yeop Han, Diego A Pedroza, Abha Tiwari, Joyce V Lee, Caitlin Davis, Shuting Li, Vasanta Putluri, Chad J Creighton, Nagireddy Putluri, Lacey E Dobrolecki, Michael T Lewis, Jeffrey M Rosen, José N Onuchic, Andrei Goga, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

The biguanide metformin attenuates mitochondrial oxidation and is proposed as an anti-cancer therapy. However, recent clinical studies suggest increased proliferation and fatty acid β-oxidation (FAO) in a subgroup of patients with breast cancer (BC) after metformin therapy. Considering that FAO can activate Src kinase in aggressive triple-negative BC (TNBC), we postulate that low-dose biguanide-driven AMPK-ACC-FAO signaling may activate the Src pathway in TNBC. The low bioavailability of metformin in TNBC xenografts mimics metformin's in vitro low-dose effect. Pharmacological or genetic inhibition of FAO significantly enhances the anti-tumor properties of biguanides. Lower doses of biguanides induce and higher doses suppress Src …

The Unfolding Story Of Protein Misfolding Causing Alzheimer Disease In Recipients Of Human Pituitary Growth Hormone, Evan G. Graber, Sayed M. Hadi Hosseini, Darrell M. Wilson, Alan D. Rogol

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Human growth hormone (hGH) has been in clinical use for children with GH deficiency (GHD) since the late 1950s. The original formulations were considered very safe with few adverse events reported. That changed remarkably in 1985 when the first patients with GHD, who had been treated with cadaveric hGH, were diagnosed with Creutzfeldt-Jakob disease (CJD). Fortunately, that same year a robust supply of recombinant hGH was released to the market whose adverse event profile did not include CJD. Patients who had received National Hormone and Pituitary Program hGH have been continuously followed since 1985. It is clear that prions are …

Glycemic Variability And Migraine: New Insights From Glucose Monitoring, Christina A. Nelson, Kyle Reavely, Matthew Jennings, Brandon Burger, Jackson Nielsen, Amanda Page, Alexander Kim, David Sant, Kyle Bills

Annual Research Symposium

No abstract provided.

Divergence In Cellular Markers Observed In Single-Cell Transcriptomics Datasets Between Cultured Primary Trabecular Meshwork Cells And Tissues, Alice Tian, Sangbae Kim, Hasna Baidouri, Jin Li, Xuesen Cheng, Janice Vranka, Yumei Li, Rui Chen, Vijaykrishna Raghunathan

Faculty, Staff and Students Publications

The trabecular meshwork within the outflow apparatus is critical in maintaining intraocular pressure homeostasis. In vitro studies employing primary cell cultures of the human trabecular meshwork (hTM) have conventionally served as surrogates for investigating the pathobiology of TM dysfunction. Despite its abundant use, translation of outcomes from in vitro studies to ex vivo and/or in vivo studies remains a challenge. Given the cell heterogeneity, performing single-cell RNA sequencing comparing primary hTM cell cultures to hTM tissue may provide important insights on cellular identity and translatability, as such an approach has not been reported before. In this study, we assembled a …

A Systematic Review Of Persisting Tissue Health Challenges Amid Insulin Delivery System Advancements: Continuous Subcutaneous Insulin Infusion (Csii) And Lipohypertrophy In Diabetic Patients, Marlena Muszynska, Emily Awdish

Annual Research Symposium

No abstract provided.