Endocrinology, Diabetes, and Metabolism Commons^™

[Lele] Incorporating Physiological Constraints In Estimates Of Post-Prandial Insulin Secretion Rate, Justin K. Garrish, Christine L. Chan, Douglas Nychka, Cecilia Diniz Behn

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Rare Case Of Visual Hallucinations In A 60-Year-Old Female With A Recurring Pituitary Macroadenoma, Angelica Alday, Farah Qureshi, Kayvan Mirhadi

Advances in Clinical Medical Research and Healthcare Delivery

Pituitary adenomas are the third most frequently occurring primary intracranial tumor and are benign neoplasms that can have profound clinical implications. While most of these masses cause hormone hypersecretion, they may also be clinically silent until they elicit symptoms of mass effect, including severe headaches and visual field defects such as bitemporal hemianopia. This report highlights an atypical presentation of a pituitary adenoma that could be valuable for internists to consider when forming a differential diagnosis for patients with hallucinations. We discuss a case of a 60-year-old woman with a recent history of multiple emergency department visits for ongoing urinary …

Prevalent Vertebral Fracture Is Associated With Incident Cardiovascular Disease Events In Older Individuals Referred For Bone Densitometry, John T. Schousboe, Barret A. Monchka, J. Michael Davidson, Douglas Kimelman, Syed Zulqarnain Gilani, Zaid Ilyas, Siobhan Reid, Joshua R. Lewis, William D. Leslie

Research outputs 2022 to 2026

Background: It is unknown if prevalent vertebral fracture (PVFx) captured on bone density vertebral fracture assessment (VFA) images predicts incident CVD events. Methods: 11,760 individuals (mean [SD] age 75.7 [6.8] years, 94 % female) had VFA contemporaneously with bone densitometry in Manitoba, Canada, between February 2010 and December 2017, of whom 1919 (16.3 %) had ≥1 PVFx. This cohort was followed over a mean (SD) 3.8 (2.3) years for Major Adverse Cardiovascular Events (MACE, composite of hospitalization for myocardial infarction, non-hemorrhagic stroke, or all-cause mortality) and other CVD events (hospitalization for coronary artery disease, congestive heart failure, peripheral vascular disease, …

Mortality Among Transgender Persons: A Taiwan Matched-Population And Sibling-Comparison Cohort Study, Chih-Wei Hsu, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Po-Yen Chen, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Background: Transgender persons have been reported to experience excess mortality, but evidence is dominated by Western cohorts and seldom addresses familial confounding.

Methods: We conducted a nationwide, retrospective cohort study using two prespecified comparison designs: matched population controls (1:4, matched on legal sex and birth date) and within-family cisgender sibling comparisons. Transgender persons were identified by ≥2 psychiatrist-recorded gender identity disorder diagnoses during 2001-2021; cohort entry required age ≥6 years. Participants were followed until death or December 31, 2022. We compared all-cause, external-cause (suicide and accidents), and internal-cause mortality using Cox regression adjusted for sociodemographics and medical comorbidity.

Findings: Among …

Concerns Regarding The Standard Deviation Of Individual Responses For Assessing Treatment Response Heterogeneity, Aaron R Caldwell, David B Allison, Andrew W Brown, Gary L Gadbury, Thirupathi Reddy Mokalla, R Drew Sayer, Andrew D Vigotsky

Children’s Nutrition Research Center Staff Publications

The estimation of treatment response heterogeneity (TRH) is increasingly important as medicine moves toward personalized approaches. While various statistical methods have been proposed to quantify TRH in parallel-group trials, the standard deviation of individual responses (SDIR) has gained prominence within physiological research. This method is intended to quantify individual response variation by comparing standard deviations of change scores between intervention and control groups. We acknowledge that SDIR represents an improvement over many other flawed approaches that often involve responder counting. However, SDIR has critical limitations: 1) it cannot overcome the fundamental problem of causal inference because the correlation between potential …

Glycerol-3-Phosphate Activates Chrebp, Fgf21 Transcription And Lipogenesis In Citrin Deficiency, Vinod Tiwari, Byungchang Jin, Olivia Sun, Edwin D J Lopez Gonzalez, Min-Hsuan Chen, Xiwei Wu, Hardik Shah, Andrew Zhang, Mark A Herman, Cassandra N Spracklen, Russell P Goodman, Charles Brenner

Faculty, Staff and Students Publications

Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms …

Dysregulated Mitochondrial Energy Metabolism Drives The Progression Of Mucosal Field Effects To Invasive Bladder Cancer, Sangkyou Lee, Sung Yun Jung, Pawel Kuś, Jolanta Bondaruk, June Goo Lee, Roman Jaksik, Nagireddy Putluri, Khanh N Dinh, David Cogdell, Huiqin Chen, Yishan Wang, Jiansong Chen, Neema Navai, Colin Dinney, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Charles C Guo, Peng Wei, Marek Kimmel, Bogdan Czerniak

Faculty, Staff and Students Publications

Multiplatform mutational and gene expression profiling complemented with proteomic and metabolomic spatial mapping were used on the whole-organ scale to identify the molecular profile of bladder cancer evolution from field effects. Analysis of the mutational landscape identified three types of mutations, referred to as α, β, and γ. Time modeling of the mutations revealed that carcinogenesis may span 30 years and can be divided into dormant and progressive phases. The α mutations developed in the dormant phase. The progressive phase lasted 5 years and was signified by expanding β mutations, but it was driven to invasive cancer by γ mutations. …

Myeloid-Specific Camkk2 Deficiency Protects Against Diet-Induced Obesity And Insulin Resistance By Rewiring Metabolic Gene Expression And Enhancing Energy Expenditure, Andrea R Ortiz, Kevin Nay, Brittany A Stork, Adam M Dean, Sean M Hartig, Cristian Coarfa, Surafel Tegegne, Christopher Rm Asquith, Daniel E Frigo, Brian York, Anthony R Means, Mark A Febbraio, John W Scott

Faculty, Staff and Students Publications

Objective: Obesity is associated with chronic, low-grade inflammation in metabolic tissues such as liver, adipose tissue and skeletal muscle implicating insulin resistance and type 2 diabetes as inflammatory diseases. This inflammatory response involves the accumulation of pro-inflammatory macrophages in these metabolically relevant organs. The Ca2+-calmodulin-dependent protein kinase kinase-2 (CAMKK2) is a key regulator of cellular and systemic energy metabolism, and a coordinator of macrophage-mediated inflammatory responses. However, its role in obesity-associated metabolic dysfunction is not fully defined. The aim of this study was to determine the contribution of CAMKK2 to the regulation of inflammation and systemic metabolism during diet-induced obesity. …

Risk Score Roulette: A Cautionary Tale Of Polygenic Risk Score Reliability, Diane Xue, Elizabeth E Blue, Alexis C Wood, Jerome I Rotter, Alison E Fohner

Children’s Nutrition Research Center Staff Publications

Genetic risk prediction for Alzheimer's disease (AD) has high potential impact, yet few studies have assessed the reliability of various polygenic risk score (PRS) methods at the individual level. Here, we evaluated the reliability of AD PRS estimates among 6338 participants from the Multi-Ethnic Study of Atherosclerosis. We compared four PRS models that have been previously associated with dementia risk. Despite similar population-level performance metrics, inter-model reliability of individual-level risk assessment was low, even among individuals classified in the top and bottom deciles. These findings raise serious concerns about the downstream application of PRS for guiding interventions for AD.

Scrotal Temperature Change During Running In Naked Humans, Yasuho Takii, Makoto Fukuda, Kazuyuki Kanosue, Tamae Yoda

Children’s Nutrition Research Center Staff Publications

Male reproductive organs are functionally affected by high body temperature. This study aimed to clarify the thermoregulation mechanisms of the human scrotum during running, and experiments were conducted to investigate temperature changes in the whole body and the scrotum. Eleven male long-distance runners performed treadmill running at 60%[Formula: see text] for 60 min in an indoor environment at 27 °C and 40% relative humidity. Immediately after the start of the run, the skin temperatures in areas other than the scrotum decreased or showed a tendency to decrease. In contrast, the scrotal temperature increased immediately after the start of the run. …

Factor Structure Of Food And Physical Activity Parenting Practices Among Us Fathers By Ethnicity And Survey Language: A Cross Sectional Study, Salma M A Musaad, Louise C Mâsse, Alicia Beltran, Oriana Perez, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

Background: Parenting practices contribute to children’s eating and physical activity behaviors, and thereby their risk of obesity and associated medical conditions. Fathers may engage in different parenting practices than mothers. The objective of this study was therefore to establish psychometrically sound tools in English and Spanish for measuring Physical Activity Parenting Practices (PAPP) and Food Parenting Practices (FPP) for Hispanic and non-Hispanic fathers of diverse races for use in future studies, such as evaluations of family-based obesity interventions targeted at fathers.

Methods: We conducted a preliminary assessment of the psychometric properties of a reduced version of the PAPP and FPP …

Biallelic Loss-Of-Function Variants In C19orf44 Lead To Retinal Degeneration, Hafiz Muhammad Jafar Hussain, Wang Meng, Yumei Li, Sabika Firasat, Mark E Pennesi, Michael B Gorin, Bin Guan, Rebecca Lynn Clark, Emma Fale-Olsen, Ranya Al Rawi, Aime Agather, Laryssa A Huryn, Paul Yang, Anna Matynia, Rui Chen

Faculty, Staff and Students Publications

Background: Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs.

Methods: All patients underwent comprehensive ophthalmological evaluation, including retinal imaging (fundus autofluorescence and macular optical coherence tomography) and electroretinogram testing. Whole exome sequencing and whole genome sequencing were performed on patients with clinically unsolved IRD, and data were analysed using an in-house pipeline to identify causal variants. Subsequently, Sanger sequencing was performed to …

Dietary Patterns For Weight And Glycemic Management In Persons With Type 1 Diabetes: A Meta-Analysis Of Clinical Trials, Daria Igudesman, Laura M Nally, Alyssa A Grimshaw, Craig G Gunderson, Elizabeth G Considine, Laura M Jacobsen, Mustafa Tosur, Peter A Gottlieb, Irl B Hirsch, Lori M Laffel, Jennifer L Sherr, Chantal Mathieu, Richard E Pratley

Children’s Nutrition Research Center Staff Publications

Background: Medical nutrition therapy is fundamental for managing glycemia and weight in type 1 diabetes, yet dietary guidance specific to this population and relevant subgroups is lacking.

Purpose: We synthesized the interventional literature investigating diet patterns for glycemic and weight management in youth and adults with type 1 diabetes, with attention to interindividual variation that suggests the need for precision approaches. The protocol was prospectively registered (CRD42024519941).

Data sources: AMED, CINAHL, Cochrane Library, Ovid MEDLINE, Ovid Embase, Google Scholar, and Web of Science Core Collection were searched from January 2011 to June 2024.

Study selection: Clinical trials ≥4 weeks with …

Two Commonly Reported Incidental Variants In Otc Are Associated With Late-Onset Disease, Steven H Lang, Russell S Lo, Gareth A Cromie, Aimée M Dudley, Nicholas Ah Mew, Kara Simpson, Vernon Reid Sutton, Sandra Darilek, Saima Ali, Matthew T Snyder, Brendan Lee, Ronit Marom, Sandesh C S Nagamani, Lindsay C Burrage

Faculty, Staff and Students Publications

Asymptomatic individuals with pathogenic variants in OTC, the gene encoding ornithine transcarbamylase are increasingly being identified through cascade testing, carrier screening, or as secondary findings from genome-wide sequencing tests. However, guidance for counseling and management of such individuals is currently lacking. We selected two common OTC variants for phenotypic and functional characterization: NM_000531.6:c.118C>T p.(Arg40Cys) and NM_000531.6:c.1061T>G p.(Phe354Cys). The former is the most frequently reported pathogenic/likely pathogenic missense variant present in gnomAD, and the latter has been frequently encountered in our clinical practice. We performed a retrospective chart review at our center, queried the database of the Urea Cycle …

The Cardioprotective Effects Of Adiponectin In Diabetes., Tara Kazemi, Yuanjie Mao, Tina Zhang

Ambulatory and Primary Care Articles

PURPOSE OF REVIEW: Adiponectin, a hormone secreted by adipocytes, plays a crucial role in maintaining metabolic balance and supporting cardiovascular health. Although it is known for its protective effects, such as improving insulin sensitivity, reducing inflammation, and maintaining endothelial function, there are paradoxical associations between high adiponectin levels and increased cardiovascular mortality-referred to as the "adiponectin paradox"-which complicates its clinical interpretation. This review explores the cardioprotective effects of adiponectin in both type 1 and type 2 diabetes, focusing on its potential to regulate glucose metabolism and prevent cardiovascular complications.

RECENT FINDINGS: By reviewing key studies, the article evaluates adiponectin's diverse …

Understanding The Nutrition Ecology And Related Distal And Proximal Research Gaps Impacting School-Aged Children's And Adolescents' Functioning-A Report From The "Biomarkers Of Nutrition For Development: Knowledge Indicating Dietary Sufficiency (Bond-Kids)" Project Working Group 2., Maureen M Black, Meg M Bruening, Amy Carroll-Scott, Jayna M Dave, Kristie L Ebi, Lora L Iannotti, Susan L Johnson, Lorrene D Ritchie, Elizabeth Y Jimenez, Alison L Steiber, Daniel J Raiten

Children’s Nutrition Research Center Staff Publications

Nutrition is critical to the health, development, and well-being of children and adolescents, operating through nutrients and the social and physical influences of dietary behaviors. Child and adolescent growth and development depend on complex biological systems interacting with the nutrition ecology. In this review, we focus on bidirectional interactions with the multilevel nutrition ecology, including distal systems (climate, geopolitical, and food systems) and proximal systems (community food options; health, social, and food services; and school policies and programs), all mediated by the family. Thus, the impact of nutrition on children's and adolescents' functional outcomes is dependent on understanding the multilevel …

Dual Targeting Of Orphan Nuclear Receptors Nr4a1 And Nr4a2 For Nonhormonal Endometriosis Therapy, Wai Ning Tiffany Tsui, Yuri Park, Srijana Upadhyay, Da Mi Kim, Lei Zhang, Gus Wright, Amanuel Hailemariam, Arafat Rahman Oany, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Previous studies show that orphan nuclear receptor 4A1 (NR4A1) regulates endometriotic cell growth, survival, estrogen receptor β (ERβ), mechanistic target of rapamycin signaling and fibrosis. NR4A2 is also expressed in epithelial and stromal derived endometriotic cells, and in this study the effects of 1,1-bis(3'-indolyl)-(3,5-disubstitutedphenyl)methane (DIM-3,5) dual NR4A1/nuclear receptor 4A2 (NR4A2) ligands and knockdown of NR4A1 and NR4A2 were investigated. The dual NR4A1/2 DIM-3,5 analogs inhibited previously identified proendometriotic pathways and gene products, and they also inhibited TWIST1 and multiple markers associated with epithelial-to-mesenchymal transition (EMT). The results show that both NR4A1 and NR4A2 regulate the same pathways, including endometriotic cell …

Diabetes-Related Foot Complications And Socioeconomic Influences Among Hispanic Males In South Texas: A Scoping Review, Mariana J. Rodriguez, Demian Rodriguez, Amanda L. Killeen

School of Podiatric Medicine - Student Research

Introduction: Diabetes mellitus is the 7^th leading cause of death in the United States and is 6^th in the state of Texas. Counties from South Texas are primarily affected with higher rates of diabetes than both the state and national average. Diabetes mellitus is a complex and progressive disease which can affect multiple systems of the body, leading to serious complications if untreated, especially in the lower extremities. Uncontrolled diabetes is often associated with diabetic foot ulcers (DFU), foot infections, and lower extremity amputations (LEA). South Texas is a region predominantly populated by Hispanic Americans who are disproportionally …

Associations Among Human Milk Polyunsaturated Fatty Acids And Infant Sleep Patterns: A Cross-Sectional Study, Ana M Palacios, Dominick J Lemas, Bridget E Young, Erik Parker, Stephanie Dickinson, Nandi Marshall, Kelly L Sullivan, Haley Wilt, Michelle I Cardel, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Infant sleep is critical for cognitive, emotional, and long-term health outcomes. Although diet-sleep relationships are established, limited research has explored how polyunsaturated fatty acids (PUFAs) in human milk (HM) relate to infant sleep.

Objectives: This study aims to examine associations between PUFAs in HM and sleep patterns in 2-mo-old infants exclusively fed with HM.

Methods: This cross-sectional secondary analysis used data from a lactation cookie trial involving 131 parents of healthy, term infants. Participants provided a fasting HM sample and completed sociodemographic and Brief Infant Sleep Questionnaire surveys. Multivariate linear models were adjusted for infant sex assigned at birth, …

Repeated Withdrawal Of A Glpr Agonist Induces Hyperleptinemia And Deteriorates Metabolic Health In Obese Aging Um-Het3 Mice, Nisi Jiang, Jiyuan Yin, Noah Lawrence, Jieyi Meng, Laurence T Maeyens, Ziying Xu, Xin Li, Mbolle Ekane, Ariana Chaudhary, Pengju Cao, Guannan Li, Carolina Solis-Herrera, Yi Zhu, Shangang Zhao

Children’s Nutrition Research Center Staff Publications

GLP-1-based therapy is highly effective in combating aging-associated metabolic diseases. However, the metabolic effects of frequent withdrawal from this therapy in aged, obese mice have not been previously studied. In this study, aged obese UM-HET3 mice were assigned to three groups: Group 1 received no liraglutide treatment (Lira OFF); Group 2 underwent 3 cycles of treatment followed by withdrawal (Lira ON/OFF); and Group 3 remained on continuous treatment (Lira ON). As expected, mice in Group 3 showed reduced body weight and food intake, along with improved metabolic health. In contrast, mice in Group 2 developed hyperleptinemia and visceral fat expansion, …