Endocrinology, Diabetes, and Metabolism Commons^™

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 …

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 …

The Significant Role Of Amino Acid Metabolic Reprogramming In Cancer, Xiaohong Liu, Bo Ren, Jie Ren, Minzhi Gu, Lei You, Yupei Zhao

Faculty, Staff and Student Publications

Amino acid metabolism plays a pivotal role in tumor microenvironment, influencing various aspects of cancer progression. The metabolic reprogramming of amino acids in tumor cells is intricately linked to protein synthesis, nucleotide synthesis, modulation of signaling pathways, regulation of tumor cell metabolism, maintenance of oxidative stress homeostasis, and epigenetic modifications. Furthermore, the dysregulation of amino acid metabolism also impacts tumor microenvironment and tumor immunity. Amino acids can act as signaling molecules that modulate immune cell function and immune tolerance within the tumor microenvironment, reshaping the anti-tumor immune response and promoting immune evasion by cancer cells. Moreover, amino acid metabolism can …

Using Item Response Theory To Identify Key Symptoms Of Insomnia In A Sample Of University Students With Probable Eating Disorders, Kara A. Christensen Pacella, Brianne N. Richson, Nicole A. Short, Angeline R. Bottera, Leah A. Irish, Victoria L. Perko, Kelsie T. Forbush

Psychology Faculty Research

Purpose

Researchers have theorized that interactions between appetitive and circadian disruptions result in increased eating disorder (ED) symptoms and insomnia. However, it is unclear how specific insomnia symptoms present among people with EDs and if the latent structure of insomnia in this population is similar to that of people with insomnia disorder.

Methods

We conducted a secondary analysis of data collected on ED and insomnia symptoms using a subset of students with probable EDs at a large Midwestern American university. Item response theory (IRT) for polytomous items was performed to identify item difficulty, discrimination, and information parameters for the Insomnia …

Social Marketing And The Challenges Of Participant Recruitment, Tom Baranowski, Teresia M O'Connor, John A Jimenez-Garcia, Kavita Radhakrishnan, Elva M Arrendondo, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Recruitment of research participants often has not obtained a desired sample size, thereby becoming a major problem inhibiting investigators' ability to adequately test the specified hypotheses. Social marketing with its four Ps, originally developed by the business world to sell products and adapted for public health initiatives, is proposed as a dynamic comprehensive conceptual framework to apply marketing principles and practices to enhance participant recruitment. Applying a social marketing approach to research recruitment would require initial investigation to understand the motivations of the target audience in regard to research participation, and continued research throughout the main project to adapt the …

Voices Of Wisdom: Geriatric Interviews On Self-Management Of Type 2 Diabetes In The United States-A Systematic Review And Metasynthesis, David F Lo, Ahmed Gawash, Kunal P Shah, Jasmine Emanuel, Brandon Goodwin, Don D Shamilov, Gaurav Kumar, Nathan Jean, Christian P White

Rowan-Virtua School of Osteopathic Medicine Departmental Research

This review is aimed at unraveling the intricacies of diabetic self-management among geriatric people, drawing on current insights and understanding the complex paths geriatric people navigate. A wide search was conducted in health-oriented databases, including CINAHL, Embase, PsycINFO, MEDLINE, PubMed, Web of Science, and Cochrane Library, while gray literature was excluded. The search combined keywords and subject headings, focusing on the geriatric population, diabetes, self-management, and qualitative research. A three-tiered screening process was employed, with titles and then abstracts initially reviewed. Full-text analysis followed, with disagreements resolved among reviewers. In total, there were 248 participants included across these eight studies. …

Urban-Rural Disparities In Food Insecurity And Weight Status Among Children In The United States, Jayna M Dave, Tzuan A Chen, Alexandra N Castro, Mamie A White, Elizabeth A Onugha, Sloane Zimmerman, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Place of residence (urban versus rural) is a contextual determinant of health that has received less attention in the food insecurity literature. The purpose of this study was to assess the urban–rural disparity in the prevalence of food insecurity and weight status among US children. Using data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 with three age groups of children (2–5, 6–11, and 12–17 years old), the associations of weight status and child and household food security status by urban–rural residence were examined using Rao–Scott Chi-square tests. Statistical significance was set at p < 0.05. Children living in urban areas were significantly more likely to experience household food insecurity (29.15%) compared to their rural counterparts (19.10%), among those aged 6–11 years. The associations between children’s weight status and child and household food security status were significant for children living in urban areas overall and different age groups but not for children living in rural areas. These trends were more pronounced in older age groups. Given the link between food insecurity and higher obesity rates, particularly among urban children, this study highlights the importance of incorporating food security interventions into future obesity prevention programs.

Calcitriol Unleashed: A Rare Culprit In Hypercalcemia Associated With Rare Primary Pancreatic Lymphoma - A Case Report, Dania Kaur, Abhinav Vyas, Sowmya Sagireddy, Rabia Qazi, Sarah Elsayed, Jyoti Verma, Prutha Pathak, Rachna Valvani

Journal of Community Hospital Internal Medicine Perspectives

Hypercalcemia of Malignancy is a complicated condition often linked to parathyroid hormone, parathyroid hormone-related peptide, or bone metastasis. This report presents a unique case of calcitriol-mediated hypercalcemia in an 89-year-old female with primary pancreatic lymphoma, highlighting the rarity and complexity of this presentation. Initially, the patient's condition was thought to be related to sarcoidosis, but the recurrence of hypercalcemia led to the discovery of pancreatic B-cell lymphoma as the underlying cause. It also emphasizes the need to explore new treatment options. Interestingly, it demonstrates the successful use of cinacalcet in treating calcitriol-induced hypercalcemia in malignancies, which could be a potential …

Immunotherapy Induced Adrenal Insufficiency: An Underdiagnosed Cause Of Persistent Hypotension In Cancer, Nina H. Cheng, Hannah Lee, Divya Balchander, Remy Mimms, Mahesh Krishnamurthy

Journal of Community Hospital Internal Medicine Perspectives

Endocrinopathies following immunotherapy have infrequently been documented in the literature. Adrenal insufficiency is a rare consequence of pembrolizumab immunotherapy, with incidence reported to be between 0.98 and 1.3%. We present the case of a 34-year-old female with triple negative breast cancer on chemotherapy who presented with generalized weakness with tachycardia, tachypnea and hypotension unresponsive to fluids. Despite initial improvement with intravenous hydrocortisone and midodrine, the patient continued to be symptomatically hypotensive following discharge and required re-admission. AM cortisol level was found to be < 0.5 ug/dl and ACTH was

Trans-Ancestral Genetic Risk Factors For Treatment-Related Type 2 Diabetes Mellitus In Survivors Of Childhood Cancer, Cindy Im, Achal Neupane, Jessica L Baedke, Brian Lenny, Angela Delaney, Stephanie B Dixon, Eric J Chow, Sogol Mostoufi-Moab, Tianzhong Yang, Melissa A Richard, M Monica Gramatges, Philip J Lupo, Noha Sharafeldin, Smita Bhatia, Gregory T Armstrong, Melissa M Hudson, Kirsten K Ness, Leslie L Robison, Yutaka Yasui, Carmen L Wilson, Yadav Sapkota

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Type 2 diabetes mellitus (T2D) is a prevalent long-term complication of treatment in survivors of childhood cancer, with marked racial/ethnic differences in burden. In this study, we investigated trans-ancestral genetic risks for treatment-related T2D.

Patients and methods: Leveraging whole-genome sequencing data from the St Jude Lifetime Cohort (N = 3,676, 304 clinically ascertained cases), we conducted ancestry-specific genome-wide association studies among survivors of African and European genetic ancestry (AFR and EUR, respectively) followed by trans-ancestry meta-analysis. Trans-/within-ancestry replication including data from the Childhood Cancer Survivor Study (N = 5,965) was required for prioritization. Three external general population T2D polygenic …

Dose-Dependent Effects Of Dnmt3a In An Inducible Murine Model Of Krasg12d-Driven Leukemia, Jason H Rogers, Allison Rosen, Jaime M Reyes, Shamika Ketkar, Shannon E Conneely, Rohit Gupta, Luibin Yang, Matthew B Miller, Geraldo Medrano, Rogelio Aguilar, Nneka Uchenda, Margaret A Goodell, Rachel E Rau

Children’s Nutrition Research Center Staff Publications

DNMT3A mutations are frequently found in clonal hematopoiesis and a variety of hematologic malignancies including acute myeloid leukemia (AML). An assortment of mouse models have been engineered to explore the tumorigenic potential and malignant lineage bias due to loss of function of DNMT3A in consort with commonly co-mutated genes in myeloid malignancies such as Flt3, Nras, Kras, and c-Kit. We employed several tamoxifen-inducible Cre-ER^T2 murine model systems to study the effects of constitutively active Kras^G12D-driven myeloid leukemia (Kras) development together with heterozygous (3aHet) or homozygous Dnmt3a deletion (3aKO). Due to the rapid generation of …

Nfatc1 Is Required For Vitamin D- And Phosphate-Mediated Regulation Of Osteocyte Lacuno-Canalicular Remodeling, Supriya Jagga, Ashleigh Hughes, Niusha Manoochehri Arash, Melissa Sorsby, Daniel J Brooks, Paola Divieti Pajevic, Eva S Liu

Staff and Researcher Publications

Osteocytes are embedded in lacunae and connected by canaliculi (lacuno-canalicular network, LCN). Bones from mice with X-linked hypophosphatemia (Hyp), which have impaired production of 1,25 dihydroxyvitamin D (1,25D) and hypophosphatemia, have abnormal LCN structure that is improved by treatment with 1,25D or an anti-FGF23 targeting antibody, supporting roles for 1,25D and phosphate in regulating LCN remodeling. Bones from mice lacking the vitamin D receptor (VDR) in osteocytes (Vdrf/f;Dmp1Cre+) and mice lacking the sodium phosphate transporter 2a (Npt2aKO), which have low serum phosphate with high serum 1,25D, have impaired LCN organization, demonstrating that osteocyte-specific actions of 1,25D and hypophosphatemia regulate LCN …

Outcomes Of The Emdataresource Cryo-Em Ligand Modeling Challenge, Catherine L Lawson, Andriy Kryshtafovych, Grigore D Pintilie, Stephen K Burley, Jiří Černý, Vincent B Chen, Paul Emsley, Alberto Gobbi, Andrzej Joachimiak, Sigrid Noreng, Michael G Prisant, Randy J Read, Jane S Richardson, Alexis L Rohou, Bohdan Schneider, Benjamin D Sellers, Chenghua Shao, Elizabeth Sourial, Chris I Williams, Christopher J Williams, Ying Yang, Venkat Abbaraju, Pavel V Afonine, Matthew L Baker, Paul S Bond, Tom L Blundell, Tom Burnley, Arthur Campbell, Renzhi Cao, Jianlin Cheng, Grzegorz Chojnowski, K D Cowtan, Frank Dimaio, Reza Esmaeeli, Nabin Giri, Helmut Grubmüller, Soon Wen Hoh, Jie Hou, Corey F Hryc, Carola Hunte, Maxim Igaev, Agnel P Joseph, Wei-Chun Kao, Daisuke Kihara, Dilip Kumar, Lijun Lang, Sean Lin, Sai R Maddhuri Venkata Subramaniya, Sumit Mittal, Arup Mondal, Nigel W Moriarty, Andrew Muenks, Garib N Murshudov, Robert A Nicholls, Mateusz Olek, Colin M Palmer, Alberto Perez, Emmi Pohjolainen, Karunakar R Pothula, Christopher N Rowley, Daipayan Sarkar, Luisa U Schäfer, Christopher J Schlicksup, Gunnar F Schröder, Mrinal Shekhar, Dong Si, Abhishek Singharoy, Oleg V Sobolev, Genki Terashi, Andrea C Vaiana, Sundeep C Vedithi, Jacob Verburgt, Xiao Wang, Rangana Warshamanage, Martyn D Winn, Simone Weyand, Keitaro Yamashita, Minglei Zhao, Michael F Schmid, Helen M Berman, Wah Chiu

Children’s Nutrition Research Center Staff Publications

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein-nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: Escherichia coli beta-galactosidase with inhibitor, SARS-CoV-2 virus RNA-dependent RNA polymerase with covalently bound nucleotide analog and SARS-CoV-2 virus ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. The quality of submitted ligand models and surrounding atoms were analyzed by visual inspection and quantification of local map quality, model-to-map …

Association Of Candidate Single-Nucleotide Polymorphism Genotypes With Plasma And Skin Carotenoid Concentrations In Adults Provided A Lycopene-Rich Juice, Anna C Norman, Daniel G Palmer, Nancy E Moran, James N Roemmich, Shanon L Casperson

Children’s Nutrition Research Center Staff Publications

Background: Carotenoids are fat-soluble phytochemicals with biological roles, including ultraviolet protective functions in skin. Spectroscopic skin carotenoid measurements can also serve as a noninvasive biomarker for carotenoid consumption. Single-nucleotide polymorphisms (SNPs) in metabolic genes are associated with human plasma carotenoid concentrations; however, their relationships with skin carotenoid concentrations are unknown.

Objectives: The objective of this study was to determine the relationship between 13 candidate SNPs with skin and plasma carotenoid concentrations before and after a carotenoid-rich tomato juice intervention.

Methods: In this randomized, controlled trial, participants (n = 80) were provided with lycopene-rich vegetable juice providing low (13.1 mg), medium …

Personal Light Exposure Patterns And Incidence Of Type 2 Diabetes: Analysis Of 13 Million Hours Of Light Sensor Data And 670,000 Person-Years Of Prospective Observation, Daniel P Windred, Angus C Burns, Martin K Rutter, Chris Ho Ching Yeung, Jacqueline M Lane, Qian Xiao, Richa Saxena, Sean W Cain, Andrew J K Phillips

Faculty, Staff and Student Publications

BACKGROUND: Light at night disrupts circadian rhythms, and circadian disruption is a risk factor for type 2 diabetes. Whether personal light exposure predicts diabetes risk has not been demonstrated in a large prospective cohort. We therefore assessed whether personal light exposure patterns predicted risk of incident type 2 diabetes in UK Biobank participants, using ∼13 million hours of light sensor data.

METHODS: Participants (N = 84,790, age (M ± SD) = 62.3 ± 7.9 years, 58% female) wore light sensors for one week, recording day and night light exposure. Circadian amplitude and phase were modeled from weekly light data. Incident …

Transdermal Oestradiol And Exercise In Androgen Deprivation Therapy (Estracise): Protocol, Ilkka Jussila, Juha P. Ahtiainen, Eija K. Laakkonen, Aino Siltari, Antti Kaipia, Tiina Jokela, Minta Kärkkäinen, Rob Newton, Truls Raastad, Heini Huhtala, Teemu J. Murtola, Heikki Seikkula

Research outputs 2022 to 2026

Objective: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. Study Design and Methods: The primary endpoint of this open-label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT-induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality …

Identification Of Immune-Associated Biomarkers Of Diabetes Nephropathy Tubulointerstitial Injury Based On Machine Learning: A Bioinformatics Multi-Chip Integrated Analysis, Lin Wang, Jiaming Su, Zhongjie Liu, Shaowei Ding, Yaotan Li, Baoluo Hou, Yuxin Hu, Zhaoxi Dong, Jingyi Tang, Hongfang Liu, Weijing Liu

Faculty, Staff and Student Publications

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN.

METHODS: The …

Changes In Lean Body Mass With Glucagon-Like Peptide-1-Based Therapies And Mitigation Strategies, Ian J. Neeland

Faculty Scholarship

Weight loss induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucagon-like peptide-1 receptor (GLP-1R)/glucose-dependent insulinotropic polypeptide receptor agonists is coming closer to the magnitudes achieved with surgery. However, with greater weight loss there is concern about potential side effects on muscle quantity (mass), health and function. There is heterogeneity in the reported effects of GLP-1-based therapies on lean mass changes in clinical trials: in some studies, reductions in lean mass range between 40% and 60% as a proportion of total weight lost, while other studies show lean mass reductions of approximately 15% or less of total weight lost. There …

The Glucosylamine Oxidation Pathway Of Vitamin C Recycling, James M. Hempe, Daniel S. Hsia, Arthur Hagar, Larry Byers

School of Medicine Faculty Publications

The proposed glucosylamine oxidation pathway (GOP) is a two-step, intraerythrocyte, thermodynamically favorable nonenzymatic reaction that first binds glucose to the N-terminal valine of beta globin (βVal1) to form a closed-chain glucosylamine that can spontaneously reduce oxidized vitamin C to its antioxidant form. This review summarizes analytical, biochemical and clinical research supporting the existence of the GOP and the surprising hypothesis that βVal1 glucosylamine is a reducing agent that works cooperatively with reduced glutathione to dynamically regulate vitamin C recycling during naturally occurring periods of transiently or chronically elevated blood glucose and oxidant production. Rationale for the existence of the GOP …

Mediterranean Diet Information On Tiktok And Implications For Digital Health Promotion Research: Social Media Content Analysis, Margaret Raber, Haley Allen, Sophia Huang, Maria Vazquez, Echo Warner, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: The Mediterranean diet has been linked to reduced risk for several cardiometabolic diseases. The lack of a clear definition of the Mediterranean diet in the scientific literature and the documented proliferation of nutrition misinformation on the internet suggest the potential for confusion among consumers seeking web-based Mediterranean diet information.

Objective: We conducted a social media content analysis of information about the Mediterranean diet on the influential social media platform, TikTok, to examine public discourse about the diet and identify potential areas of misinformation. We then analyzed these findings in the context of health promotion to identify potential challenges and …