Endocrinology, Diabetes, and Metabolism Commons^™

Child Weight Status: The Role Of Feeding Styles And Highly Motivated Eating In Children, Maria A Papaioannou, Thomas G Power, Teresia M O'Connor, Jennifer O Fisher, Nilda E Micheli, Sheryl O Hughes

Children’s Nutrition Research Center Staff Publications

Although parental feeding plays an important role in child eating and weight status, high food motivation among children may also be a factor shaping how feeding impacts child weight. This study explored whether individual differences in preschool children’s food motivation interacted with mothers’ feeding styles in predicting subsequent child weight status. Participants included 129 Hispanic Head Start mother/child dyads. Data were collected at ages 4–5 years (Time 1) and 7–9 (Time 3). Staff measured heights/weights and observed children in an eating in the absence of hunger task. Mothers reported on feeding styles/practices and children’s eating behaviors. A principal components analysis …

Population Pharmacokinetics And Exposure–Response Analysis For The Phase 3 Cosmic-311 Trial Of Cabozantinib For Radioiodine-Refractory Differentiated Thyroid Cancer, Neang S. Ly, Jing Li, Raffaella Faggioni, Lorin K. Roskos, Marcia S Brose

Kimmel Cancer Center Faculty Papers

Background and Objective

In the USA, cabozantinib was approved for the treatment of patients aged ≥ 12 years with radioiodine-refractory differentiated thyroid cancer (DTC) who progressed on prior vascular endothelial growth factor (VEGFR)-targeted therapy based on the Phase 3 COSMIC-311 trial, which evaluated cabozantinib 60 mg/day versus placebo. Approved dosing is 60 mg/day for adults and for pediatric patients aged ≥ 12 years with body surface area (BSA) ≥ 1.2 m2, and 40 mg/day for pediatric patients aged ≥ 12 years with BSA < 1.2 m2. This report describes a population pharmacokinetic (PopPK) and exposure–response analysis of COSMIC-311.

Methods

A PopPK model was developed using concentration-time data from COSMIC-311 and 6 other cabozantinib studies. The …

Taking A Load Off: User Perceptions Of Smart Offloading Walkers For Diabetic Foot Ulcers Using The Technology Acceptance Model, M G Finco, Gozde Cay, Myeounggon Lee, Jason Garcia, Elia Salazar, Tze-Woei Tan, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

People with diabetic foot ulcers (DFUs) are commonly prescribed offloading walkers, but inadequate adherence to prescribed use can be a barrier to ulcer healing. This study examined user perspectives of offloading walkers to provide insight on ways to help promote adherence. Participants were randomized to wear: (1) irremovable, (2) removable, or (3) smart removable walkers (smart boot) that provided feedback on adherence and daily walking. Participants completed a 15-item questionnaire based on the Technology Acceptance Model (TAM). Spearman correlations assessed associations between TAM ratings with participant characteristics. Chi-squared tests compared TAM ratings between ethnicities, as well as 12-month retrospective fall …

Mglu5 Inhibition In The Basolateral Amygdala Prevents Estrous Cycle-Dependent Changes In Cue-Induced Cocaine Seeking, Claire M. Corbett, Emily N. D. Miller, Jessica A. Loweth

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany Breon Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Markey Cancer Center Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 μmole PCB126 per kg of body weight via oral gavage on postnatal …

Validation Of The Entrainment Signal Regularity Index And Associations With Children’S Changes In Bmi, Jennette P Moreno, Kevin M Hannay, Amy R Goetz, Olivia Walch, Philip Cheng

Children’s Nutrition Research Center Staff Publications

Objective: This study examined the validity of a novel metric of circadian health, the Entrainment Signal Regularity Index (ESRI), and its relationship to changes in BMI during the school year and summer.

Methods: In a longitudinal observational data set, this study examined the relationship between ESRI score and children's (n = 119, 5- to 8-year-olds) sleep and physical activity levels during the school year and summer, differences in ESRI score during the school year and summer, and the association of ESRI score during the school year and summer with changes in BMI across those time periods.

Results: The ESRI score …

Tfeb-Mediated Lysosomal Exocytosis Alleviates High-Fat Diet-Induced Lipotoxicity In The Kidney, Jun Nakamura, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Satoshi Minami, Atsushi Takahashi, Jun Matsuda, Shinsuke Sakai, Hiroaki Yonishi, Shihomi Maeda, Sho Matsui, Isao Matsui, Takayuki Hamano, Masatomo Takahashi, Maiko Goto, Yoshihiro Izumi, Takeshi Bamba, Miwa Sasai, Masahiro Yamamoto, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Shuhei Nakamura, Tamotsu Yoshimori, Andrea Ballabio, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown. Here, we found that palmitic acid strongly promoted dephosphorylation and nuclear translocation of transcription factor EB (TFEB) by inhibiting the mechanistic target of rapamycin kinase complex 1 pathway in a Rag GTPase-dependent manner, though these effects gradually diminished after extended treatment. We then investigated the role of TFEB in the pathogenesis of obesity-related kidney …

Promoting Health Equity: Identifying Parent And Child Reactions To A Culturally-Grounded Obesity Prevention Program Specifically Designed For Black Girls Using Community-Engaged Research, Haley Allen, Chishinga Callender, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

The Butterfly Girls (BFG) Study is a culturally and developmentally appropriate online obesity prevention program for 8-10-year-old Black girls designed with key stakeholders in the Black community. This multi-methods investigation, conducted with parent-child dyads who participated in an outcome evaluation of the intervention, aimed to understand parent and child reactions to the program. We were particularly interested in understanding perceptions regarding its cultural and developmental appropriateness, relevance and acceptability. Program participation and survey data (demographics, parent and child write-in comments on process evaluation surveys) were analyzed. Participation data demonstrated high adherence in treatment and comparison groups. Descriptive statistics were calculated …

Tracking The Evolution Of Esophageal Squamous Cell Carcinoma Under Dynamic Immune Selection By Multi-Omics Sequencing, Sijia Cui, Nicholas Mcgranahan, Jing Gao, Peng Chen, Wei Jiang, Lingrong Yang, Li Ma, Junfang Liao, Tian Xie, Congying Xie, Tariq Enver, Shixiu Wu

Children’s Nutrition Research Center Staff Publications

Intratumoral heterogeneity (ITH) has been linked to decreased efficacy of clinical treatments. However, although genomic ITH has been characterized in genetic, transcriptomic and epigenetic alterations are hallmarks of esophageal squamous cell carcinoma (ESCC), the extent to which these are heterogeneous in ESCC has not been explored in a unified framework. Further, the extent to which tumor-infiltrated T lymphocytes are directed against cancer cells, but how the immune infiltration acts as a selective force to shape the clonal evolution of ESCC is unclear. In this study, we perform multi-omic sequencing on 186 samples from 36 primary ESCC patients. Through multi-omics analyses, …

Dual-Specificity Phosphatases 22-Deficient T Cells Contribute To The Pathogenesis Of Ankylosing Spondylitis, Ming-Han Chen, Huai-Chia Chuang, Yi-Chen Yeh, Chung-Tei Chou, Tse-Hua Tan

Children’s Nutrition Research Center Staff Publications

Background: Dual-specificity phosphatases (DUSPs) can dephosphorylate both tyrosine and serine/threonine residues of their substrates and regulate T cell-mediated immunity and autoimmunity. The aim of this study was to investigate the potential roles of DUSPs in ankylosing spondylitis (AS).

Methods: Sixty AS patients and 45 healthy controls were enrolled in this study. Associations of gene expression of 23 DUSPs in peripheral T cells with inflammatory cytokine gene expression and disease activity of AS were analyzed. Finally, we investigated whether the characteristics of AS are developed in DUSP-knockout mice.

Results: The mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 in peripheral …

Diabetes Of Unclear Type In An Adolescent Boy With Multiple Islet-Cell Autoantibody Positivity Successfully Managed With Glucagon-Like Peptide-1 Receptor Agonist Alone: A Case Report, Olivia Z B Ginnard, Maria J Redondo, Sarah K Lyons

Children’s Nutrition Research Center Staff Publications

Diabetes classification has traditionally considered type 1 and type 2 diabetes as 2 separate entities with different pathogenic mechanisms. However, clinicians and researchers see increasingly more exceptions to this conventional paradigm, leading to a concept of mixed phenotypes in diabetes classification. Herein we report the case of an adolescent with unclear diabetes type due to the presence of obesity, robust endogenous insulin production, multiple islet autoantibody positivity and severe hyperglycemia at diabetes diagnosis that has been successfully treated with liraglutide therapy alone. Our case report highlights the difficulty of diabetes classification and subsequent need for personalized medicine with regard to …

How Much Did It Cost To Develop And Implement An Ehealth Intervention For A Minority Children Population That Overlapped With The Covid-19 Pandemic?, Alexandra Monashefsky, Dar Alon, Tom Baranowski, Tiago V Barreira, Kelly A Chiu, Amy Fleischman, Melanie C Green, Shirley Huang, Ronald C Samuels, Caio Victor Sousa, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: eHealth interventions using active video games (AVGs) offer an alternative method to help children exercise, especially during a pandemic where options are limited. There is limited data on costs associated with developing and implementing such interventions.

Objectives: We quantified the costs of delivering an eHealth RCT intervention among minority children during COVID-19.

Methods: We categorized the total trial cost into five subcategories: intervention material development, advertising and recruitment, intervention delivery, personnel salaries, and COVID-19-related equipment costs.

Results: The total RCT cost was $1,927,807 (Direct: $1,227,903; Indirect: $699,904) with three visits required for each participant. The average cost per participant …

How Much Did It Cost To Develop And Implement An Ehealth Intervention For A Minority Children Population That Overlapped With The Covid-19 Pandemic?, Alexandra Monashefsky, Dar Alon, Tom Baranowski, Tiago V Barreira, Kelly A Chiu, Amy Fleischman, Melanie C Green, Shirley Huang, Ronald C Samuels, Caio Victor Sousa, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: eHealth interventions using active video games (AVGs) offer an alternative method to help children exercise, especially during a pandemic where options are limited. There is limited data on costs associated with developing and implementing such interventions.

Objectives: We quantified the costs of delivering an eHealth RCT intervention among minority children during COVID-19.

Methods: We categorized the total trial cost into five subcategories: intervention material development, advertising and recruitment, intervention delivery, personnel salaries, and COVID-19-related equipment costs.

Results: The total RCT cost was $1,927,807 (Direct: $1,227,903; Indirect: $699,904) with three visits required for each participant. The average cost per participant …

Bilirubin Nanoparticle Treatment In Obese Mice Inhibits Hepatic Ceramide Production And Remodels Liver Fat Content, Zachary A. Kipp, Genesee J. Martinez, Evelyn A. Bates, Agil B. Maharramov, Robert M. Flight, Hunter N. B. Moseley, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Studies have indicated that increasing plasma bilirubin levels might be useful for preventing and treating hepatic lipid accumulation that occurs with metabolic diseases such as obesity and diabetes. We have previously demonstrated that mice with hyperbilirubinemia had significantly less lipid accumulation in a diet-induced non-alcoholic fatty liver disease (NAFLD) model. However, bilirubin’s effects on individual lipid species are currently unknown. Therefore, we used liquid chromatography-mass spectroscopy (LC-MS) to determine the hepatic lipid composition of obese mice with NAFLD treated with bilirubin nanoparticles or vehicle control. We placed the mice on a high-fat diet (HFD) for 24 weeks and then treated …

Age And Racial Disparities In The Utilization Of Anticancer, Antihypertension, And Anti-Diabetes Therapies, And In Mortality In A Large Population-Based Cohort Of Older Women With Breast Cancer, Xianglin L Du, Lulu Song

Faculty, Staff and Student Publications

OBJECTIVE: This study examined the receipt of therapies for cancer, hypertension, and diabetes in association with age and racial disparities in mortality among women with breast cancer.

METHODS: This study identified 92,829 women diagnosed with breast cancer at age ≥ 65 years in 2007-2015 with follow-up to 2016 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database.

RESULTS: There were substantial age and racial disparities in the prevalence of hypertension and diabetes, which was higher in women ≥ 75 (86.3% and 32.0%) than younger women 65-74 (72.8% and 29.3%), and the highest in Black women (91.1% and 49.1%), followed …

Relationships Between Urinary Metals And Diabetes Traits Among Mexican Americans In Starr County, Texas, Usa, Margaret C Weiss, Yu-Hsuan Shih, Molly Scannell Bryan, Brian P Jackson, David Aguilar, Craig L Hanis, Maria Argos, Robert M Sargis

Faculty, Staff and Student Publications

Hispanics/Latinos have higher rates of type 2 diabetes (T2D), and the origins of these disparities are poorly understood. Environmental endocrine-disrupting chemicals (EDCs), including some metals and metalloids, are implicated as diabetes risk factors. Data indicate that Hispanics/Latinos may be disproportionately exposed to EDCs, yet they remain understudied with respect to environmental exposures and diabetes. The objective of this study is to determine how metal exposures contribute to T2D progression by evaluating the associations between 8 urinary metals and measures of glycemic status in 414 normoglycemic or prediabetic adults living in Starr County, Texas, a Hispanic/Latino community with high rates of …

Emotional Distress, Self-Management, And Glycemic Control Among Participants Enrolled In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study, Jeffrey S Gonzalez, Heidi Krause-Steinrauf, Ionut Bebu, Gladys Crespo-Ramos, Claire J Hoogendoorn, Aanand D Naik, Andrea Waltje, Elizabeth Walker, Dominic Ehrmann, Janet Brown-Friday, Andrea Cherrington

Faculty, Staff and Student Publications

OBJECTIVE: We examined emotional distress in relation to metformin adherence, overall diabetes self-management, and glycemic control among adults with early type 2 diabetes (T2DM) enrolled in the GRADE study.

METHODS: Linear regression models examined cross-sectional associations of baseline depression symptoms and diabetes distress with adherence to metformin, self-management, and HbA1c, adjusting for covariates. Cognitive-affective (e.g., sadness) and somatic (e.g., sleep/appetite disturbance) depression symptoms and diabetes distress subscales were also examined.

RESULTS: This substudy of 1,739 GRADE participants (56 % Non-Hispanic White, 18 % Non-Hispanic Black, 17 % Hispanic, 68 % male, mean[SD] age = 57.96[10.22] years, diabetes duration = 4.21[2.81] …

Acculturation, Dietary Behaviors, And Macronutrient Intake Among Mexican Americans With Prediabetes: 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

PURPOSE: The purpose of the study was to examine the influences of sex and acculturation on dietary behaviors, macronutrient intake, and dietary quality in participants enrolled in a diabetes prevention initiative in Starr County, Texas.

METHODS: Baseline data from the Starr County diabetes prevention study (N = 300) were analyzed-acculturation (country of origin, years in Starr County, language and food preferences), depressive symptoms (Patient Health Questionnaire-9), healthy eating self-efficacy (Weight Efficacy Lifestyle Questionnaire-Short Form), diet quality (USDA Healthy Eating Index), fat avoidance (Fat Avoidance Scale, Spanish version), and macronutrients. Descriptive statistics and univariate analysis of covariance were used to examine …

Energy Intake At The Intersection Of The Clock And Ageing, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Calorie restriction and timed dietary intake are two approaches known to increase lifespan or delay age-associated diseases. New studies reveal the importance of the ‘how much’ and ‘when’ of dietary intake in ageing modulation and collectively demonstrate how protection of the internal clock by diet can delay the ageing process.

Glucocorticoid Therapy As First-Line Treatment In Primary Hypophysitis: A Systematic Review And Individual Patient Data Meta-Analysis, Brijesh Krishnappa, Ravikumar Shah, Saba Samad Memon, Chakra Diwaker, Anurag R Lila, Virendra A Patil, Nalini S Shah, Tushar R Bandgar

Faculty, Staff and Student Publications

OBJECTIVES: High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.

DESIGN: We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (12 weeks) of glucocorticoid treatment according to disease severity.

RESULTS: A total of 153 PAH patients from 83 publications were included. The median age at presentation was 41 (32.5-48) years with a female preponderance (70.3%). Visual field recovery was significantly better with i.v. …