Endocrinology, Diabetes, and Metabolism Commons^™

A Cluster Randomized Trial Of Xylitol Chewing Gum For Prevention Of Preterm Birth: The Ppax Trial, Gregory C Valentine, Kathleen M Antony, Haleh Sangi-Haghpeykar, Alexis C Wood, Rose Chirwa, Saukani Petro, Mary Dumba, Deborah Nanthuru, Cynthia Shope, Jesse Mlotha-Namarika, Jeffrey Wilkinson, Joshua Aagaard, Ellen J Aagaard, Maxim D Seferovic, Judy Levison, Peter Kazembe, Kjersti M Aagaard

Children’s Nutrition Research Center Staff Publications

Background: Maternal periodontal disease is associated with preterm and low-birthweight deliveries, but randomized trials of likely efficacious treatments (e.g., dental scaling and root planing) during pregnancy have not reduced these adverse outcomes. As an alternative, we hypothesized that periconception initiation of xylitol chewing gum would reduce the occurrence of preterm or low-birthweight deliveries among a historical high-prevalence population in Malawi.

Methods: We conducted an open-label, parallel-enrollment, matched-pair, cluster-randomized, controlled clinical trial across eight health centers (sites) in and around Lilongwe, Malawi. Sites were paired by anticipated delivery volume and randomized to prenatal and oral health education alone (active control) or …

Heterozygous Hereditary Vitamin D-Dependent Rickets Type 2a (Vddr2a) In A Patient Presenting With Pseudoarthrosis, Risa Goldberg, Gunjan Umarji, Serge Jabbour

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

This case report is centered on an atypical presentation of Hereditary Vitamin D-dependent Rickets 2A (VDDR2A), a rare disorder caused by defects in the gene encoding the vitamin D receptor (VDR). While this disorder is primarily autosomal recessive in inheritance, this case demonstrates that a single heterozygous variant in the VDR gene could be linked to both phenotypic and laboratory manifestations of this condition. To understand the pathogenesis of this condition, one must know the typical roles of vitamin D, calcium, and parathyroid hormone (PTH) in maintaining homeostasis in the body. This case report focuses on the underlying pathogenesis of …

Vestibular Neurons Link Motion Sickness, Behavioural Thermoregulation And Metabolic Balance In Mice, Longlong Tu, Xing Fang, Yongjie Yang, Meng Yu, Hailan Liu, Hesong Liu, Na Yin, Jonathan C Bean, Kristine M Conde, Mengjie Wang, Yongxiang Li, Olivia Z Ginnard, Qingzhuo Liu, Yuhan Shi, Junying Han, Yi Zhu, Makoto Fukuda, Qingchun Tong, Benjamin Arenkiel, Mingshan Xue, Yang He, Chunmei Wang, Yong Xu

Children’s Nutrition Research Center Staff Publications

Motion sickness is associated with thermoregulation and metabolic control, but the underlying neural circuitry remains largely unknown. Here we show that neurons in the medial vestibular nuclei parvocellular part (MVePC) mediate the hypothermic responses induced by motion. Reactivation of motion-sensitive MVePC neurons recapitulates motion sickness in mice. We show that motion-activated neurons in the MVePC are glutamatergic (MVePCGlu), and that optogenetic stimulation of MVePCGlu neurons mimics motion-induced hypothermia by signalling to the lateral parabrachial nucleus (LPBN). Acute inhibition of MVePC-LPBN circuitry abrogates motion-induced hypothermia. Finally, we show that chronic inhibition of MVePCGlu neurons prevents diet-induced obesity and improves glucose homeostasis …

Quality-Of-Care Measures For Cardio-Oncology: An Ic-Os And Acc Cardio-Oncology Leadership Council Perspective, Vijay U Rao, Anita Deswal, Daniel Lenihan, Susan Dent, Teresa Lopez-Fernandez, Alexander R Lyon, Ana Barac, Nicolas Palaskas, Ming Hui Chen, Hector R Villarraga, Diego Sadler, Courtney M Campbell, Kerry Skurka, Matt J Wagner, Matthias Totzeck, Kathryn J Ruddy, Paul Heidenreich, Randal Thomas, Daniel Addison, Sarju Ganatra, Richard Cheng, David Reeves, Arjun K Ghosh, Joerg Herrmann

Children’s Nutrition Research Center Staff Publications

This document serves as a perspective on quality assessments in the discipline of cardio-oncology. We aim to define the current landscape, identify needs for quality and outcome improvements, and propose a roadmap for establishing viable metrics to improve patient care. Specifically, this document: 1) addresses the current lack of measurable high-quality metrics in cardio-oncology and their implications; 2) highlights needs and topic-specific barriers; 3) illustrates the process and application of a measurable quality metric; and 4) provides a framework to demonstrate measurable value for the growing population of patients with cancer and cardiovascular diseases.

Demographic Clinical Trial Diversity Assessment Methods: Use Of Real-World Data, Hua Chen, Nnadozie Emechebe, Sudeep Karve, Leon Raskin, Jailene Leal, Ning Cheng, Wendy Sebby, Kim Ribeiro, Samuel Crawford

Children’s Nutrition Research Center Staff Publications

Diversity in clinical trials is defined by the inclusion of clinical trial participants from various demographic groups that are representative of the broader population impacted by a disease state. Diversity in clinical trials is critical in identifying potential differences in safety and efficacy of treatments across races, ethnicities, ages, sexes, or other variables. In the United States, clinical trial diversity is often benchmarked against US Census data, which may limit the representativeness of patient demographics in clinical trials. Disease-specific, demographic estimates from real-world data (RWD) can facilitate benchmarking of clinical trials, support trial enrollment and the development of trial diversity …

Circulating Short-Chain And Branched Short-Chain Fatty Acids And The Risk Of Incident Type 2 Diabetes: Findings From The 4c Study, Shuangyuan Wang, Hong Lin, Xiaojing Jia, Yiting Lin, Chunyan Hu, Mian Li, Yu Xu, Min Xu, Jie Zheng, Xinjie Zhao, Yanli Li, Lulu Chen, Tianshu Zeng, Ruying Hu, Zhen Ye, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Guijun Qin, Qin Wan, Gang Chen, Meng Dai, Di Zhang, Bihan Qiu, Xiaoyan Zhu, Ruixin Liu, Xiao Wang, Xulei Tang, Zhengnan Gao, Feixia Shen, Xuejiang Gu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Guixia Wang, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Yiming Mu, Guowang Xu, Shenghan Lai, Donghui Li, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu

Faculty, Staff and Student Publications

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) …

Telehealth Is Effective In The Evaluation Of Individuals With Undiagnosed Rare Disorders: An Undiagnosed Diseases Network Study, Queenie K-G Tan, Allyn Mcconkie-Rosell, Rachel Mahoney, Rebecca C Spillmann, Kelly Schoch, Sirisak Chanprasert, Maria T Acosta, Camilo Toro, Jill A Rosenfeld, James P Orengo, Daryl A Scott, Jorge L Granadillo, Kathleen Sisco, Daniel J Wegner, Mustafa Tekin, Stephanie Bivona, Léshon Peart, Lance Rodan, Devon Bonner, Matthew T Wheeler, Jonathan A Bernstein, Maura Ruzhnikov, Undiagnosed Diseases Network, David R Adams, Fuki M Hisama, Vandana Shashi

Faculty, Staff and Students Publications

Patients with undiagnosed and/or rare disorders frequently manifest dysmorphic and neurological features. There is a lack of information on the effectiveness of telehealth in the evaluation of these disorders. We thus compared an unassisted virtual physical examination (PE) with an in-person PE in undiagnosed individuals and also assessed participant telehealth satisfaction. Twenty-six individuals enrolled in the Undiagnosed Diseases Network study underwent an in-home synchronous virtual PE, and a subsequent in-person PE, by the same clinician. The participants completed surveys on telehealth usability and provider empathy. On PE, general appearance and craniofacial features showed near perfect agreement (κ = 0.81-1.00) between …

Comparison Between Antigen And Aalelic Hla Mismatches, And The Risk Of Acute Rejection In Kidney Transplant Recipients, Ryan Gately, Anne Taverniti, Narelle Watson, Armando Teixeira-Pinto, Esther Ooi, Rowena Lalji, Ross Francis, Lucy Sullivan, William Mulley, Kate Wyburn, Scott Campbell, Carmel Hawley, Germaine Wong, Wai H. Lim

Research outputs 2022 to 2026

Deceased donor kidney allocation relies on HLA compatibility at the antigen level, as optimal matching reduces the risk of acute rejection. Whether HLA allele-level mismatches improve, the prediction of acute rejection after transplantation remains unclear. Using data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) from 2017 to 2020, HLA antigenic and allelic mismatches between recipients and deceased donors were calculated with imputation of two-field allelic equivalents undertaken where required. The discordance between antigen and allele mismatches was calculated, and oblique random survival forest models were used to predict acute rejection. Predictive performance of antigen (HLA-A, -B, …

Prevalence Of Autoimmune Diabetes Among Aboriginal Australians: The Fremantle Diabetes Study Phase Ii, Timothy M.E. Davis, Christine S. Bundell, Stephen Chubb, Daniel Mcaullay, Wendy A. Davis

Research outputs 2022 to 2026

The prevalence of autoimmune diabetes was assessed in 113 indigenous and 1555 non-indigenous participants in the Fremantle Diabetes Study Phase II. Both type 1 diabetes (3.5% vs. 8.2%) and latent autoimmune diabetes of adults diagnosed based on glutamic acid decarboxylase antibody (GADA) positivity (1.0% vs. 5.7%) were lower in Aboriginal participants (P = 0.101 and 0.039 respectively). Six Aboriginals with GADA-negative type 2 diabetes were positive for tyrosine phosphatase-related islet antigen 2 antibodies but did not exhibit relative insulin deficiency.

Resting Energy Expenditure And Metabolic Features In Children With Septo-Optic Dysplasia, David J. Cullingford, Jacqueline A. Curran, Mary B. Abraham, Aris Siafarikas, A. Marie Blackmore, Jenny Downs, Catherine S.Y. Choong

Research outputs 2022 to 2026

Context: Septo-optic dysplasia (SOD) is a major cause of congenital hypopituitarism and is known to be associated with overweight and obesity in up to 44% of children. Given the role of the hypothalamus in hormonal regulation, we sought to assess the association of resting energy expenditure (REE), appetite and physical activity with SOD. Objective: To characterize REE and other metabolic features in patients with SOD and evaluate relationships with elevated body mass index (BMI). Methods: Children with SOD above 5 years of age attending Perth Children's Hospital participated. A CosMED Q-NRG indirect calorimeter was used to calculate mean measure REE …

Most Elderly Patients With Subclinical Hypothyroidism Do Not Need To Be Treated, Risheng Xu, Nicola Abate, Nalini Ram, Kristina Little

Faculty, Staff and Students Publications

Whether subclinical hypothyroidism should be treated in elderly patients (≥ 65 years) is controversial. The authors argue for a personalized, wait-and-see approach rather than universal treatment, pointing out that randomized clinical trials have not shown that levothyroxine treatment makes any difference in terms of hard clinical end points, quality of life, or hypothyroid symptom relief in elderly patients with this condition.

Gastroesophageal Reflux And Gastrointestinal Symptoms After Metabolic And Bariatric Surgery In Adolescents: An 8-Year Follow-Up Analysis, John B Rode, Suhail A Zeineddin, Jane C Khoury, Todd M Jenkins, Stephanie R Sisley, Anita P Courcoulas, Justin R Ryder, Marc P Michalsky, Thomas H Inge

Children’s Nutrition Research Center Staff Publications

Importance: Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed metabolic and bariatric surgery (MBS) procedures in adolescents and adults. Despite their safety and effectiveness, there is concern over postoperative gastrointestinal symptoms (GIS), especially gastroesophageal reflux symptoms (GERS), in those undergoing VSG.

Objective: To evaluate the long-term prevalence of GIS in adolescents who underwent RYGB or VSG.

Design, setting, and participants: This is a prospective, multicenter, observational cohort study at five academic referral centers in the United States. Patients were enrolled from February 28, 2007, through December 30, 2011. The analysis included 228 adolescents: 161 …

Penghambat Kanal Kalsium Sebagai Kontrol Glukosa Darah Pada Insulinoma: Sebuah Laporan Kasus, Nadhira Nizam, Ryan Tresna Putra, Anshari Saifuddin Hasibuan

Jurnal Penyakit Dalam Indonesia

Insulinoma is a rare neuroendocrine tumor of the pancreas arising from β-cells, leading to excessive insulin secretion and resultant hypoglycaemia. Surgical resection is the first-line treatment for insulinoma, but when surgery is not feasible, medical therapy is an important option. Calcium channel blockers (CCBs) such as verapamil can inhibit insulin release from β-cells and have been proposed as an adjunct therapy to help control blood glucose levels in insulinoma. We report a 43-year-old man who presented to the emergency department with decreased consciousness due to hypoglycaemia. His capillary blood glucose at home was 35 mg/dL, about 8 hours after his …

Histone Acetylation Modulators In Breast Cancer, Xueying Yuan, Jeffrey M Rosen

Faculty, Staff and Students Publications

Breast cancer is the most prevalent cancer in women worldwide. Aberrant epigenetic reprogramming such as dysregulation of histone acetylation has been associated with the development of breast cancer. Histone acetylation modulators have been targeted as potential treatments for breast cancer. This review comprehensively discusses the roles of these modulators and the effects of their inhibitors on breast cancer. In addition, epigenetic reprogramming not only affects breast cancer cells but also the immunosuppressive myeloid cells, which can facilitate breast cancer progression. Therefore, the review also highlights the roles of these immunosuppressive myeloid cells and summarizes how histone acetylation modulators affect their …

Effects Of Prebiotic Phytocompound Administration In Gestational Diabetic Dams And Its Influence On Offspring Cognitive Outcomes, Gayathri Jagadeesan, Tushar K Das, Jennifer M Mendoza, Ghalya Alrousan, Maria P Blasco-Conesa, Parimelazhagan Thangaraj, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders in both the mother and offspring as they age. Restoring gut balance could improve cognitive outcomes for both. Despite advancements in GD treatment, side effects have increased, and long-term neurocognitive impacts on offspring born to GD mothers remain underexplored. This study uses a GD mouse model, inducing pancreatic dysfunction in 3-month-old pregnant C57BL/6J mice with Streptozotocin. The efficacy and mechanism of the prebiotic phytocompound green leaf extract (

Testosterone Replacement Therapy In The Middle-Aged Male, Gina N. Demilt

Lynchburg Journal of Medical Science

The purpose of this review was to investigate the use of testosterone supplementation in the middle-aged male with a focus on the pathophysiology of testosterone throughout the lifespan, current supplementation options and their adverse effects, and the overall benefit of supplementing to enhance quality of life. A comprehensive search of electronic databases was conducted identifying studies that assessed clinical outcomes, pathophysiology, supplementation options, adverse effects and benefits of treatments. The findings suggested that testosterone levels naturally decline with age with most men developing symptoms of hypogonadism around age 60. Testosterone supplementation outside of current guidelines is not recommended, however men …

Haploinsufficiency Of Itsn1 Is Associated With A Substantial Increased Risk Of Parkinson’S Disease, Thomas P Spargo, Chloe F Sands, Isabella R Juan, Jonathan Mitchell, Vida Ravanmehr, Jessica C Butts, Ruth B De-Paula, Youngdoo Kim, Fengyuan Hu, Quanli Wang, Dimitrios Vitsios, Manik Garg, Lawrence Middleton, Michal Tyrlik, Mirko Messa, Guillermo Del Angel, Daniel G Calame, Hiba Saade, Laurie Robak, Ben Hollis, Vishnu A Cuddapah, Huda Y Zoghbi, Joshua M Shulman, Slavé Petrovski, Ismael Al-Ramahi, Ioanna Tachmazidou, Ryan S Dhindsa

Faculty, Staff and Students Publications

Despite its significant heritability, the genetic basis of Parkinson's disease (PD) remains incompletely understood. Here, in analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls in the UK Biobank, we discover that protein-truncating variants in ITSN1 confer a substantially increased risk of PD (p = 6.1 × 10

Neighborhood Disadvantage And Inequities In Access To Preemptive And Living Kidney Transplantation, Brandon M Fairless, Oluwatunmise A Fawole, Duc T Nguyen, Ankona Banerjee, Kenneth J Nobleza, Abiodun O Oluyomi, Omar Rosales, Jayna M Dave, Elizabeth A Onugha

Children’s Nutrition Research Center Staff Publications

Key Points:

1. Pediatric patients residing in low-resource neighborhoods experienced lower rates of preemptive and living donor kidney transplantation.

2. Household-level factors (single-parent, non-English primary language, and receiving government assistance) may also affect the type of transplant received.

3. Area Deprivation Index scores offer an objective way to quantify neighborhood-level disadvantage and can enhance pretransplant screening.

Background: Living donor kidney transplant (LDKT) generally results in better outcomes than deceased donor kidney transplant (DDKT). Preemptive kidney transplant (KT) allows patients to bypass undergoing maintenance dialysis and is associated with improved patient and graft survival. Studies in the US pediatric population have shown racial-ethnic disparities …

Adipose Progenitor Cell-Derived Extracellular Vesicles Suppress Macrophage M1 Program To Alleviate Midlife Obesity, Qing Zhou, Jia Gao, Guorao Wu, Chenwei Wang, Yan Yang, Teng Huang, Yi Wang, Tiantian Yue, Zhichao Gao, Hao Xie, Fei Xiong, Ke Xiang, Tuying Yong, Wanguang Zhang, Tongtong Zhang, Wen Kong, Cai Chen, Shu Zhang, Qilin Yu, Xuemei Fan, Shiwei Liu, Yanjun Liu, Cong-Yi Wang

Children’s Nutrition Research Center Staff Publications

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs …

A Deep Sparse Capsule Network For Non-Invasive Blood Glucose Level Estimation Using A Ppg Sensor, Narmatha Chellamani, Saleh Ali Albelwi, Manimurugan Shanmuganathan, Palanisamy Amirthalingam, Emad Muteb Alharbi, Hibah Qasem Salman Alatawi, Kousalya Prabahar, Jawhara Bader Aljabri, Anand Paul

School of Public Health Faculty Publications

Diabetes, a chronic medical condition, affects millions of people worldwide and requires consistent monitoring of blood glucose levels (BGLs). Traditional invasive methods for BGL monitoring can be challenging and painful for patients. This study introduces a non-invasive, deep learning (DL)-based approach to estimate BGL using photoplethysmography (PPG) signals. Specifically, a Deep Sparse Capsule Network (DSCNet) model is proposed to provide accurate and robust BGL monitoring. The proposed model’s workflow includes data collection, preprocessing, feature extraction, and predictions. A hardware module was designed using a PPG sensor and Raspberry Pi to collect patient data. In preprocessing, a Savitzky–Golay filter and moving …