Endocrine System Diseases Commons^™

Thyroid Hormone Synthesis Continues Despite Biallelic Thyroglobulin Mutation With Cell Death, Xiaohan Zhang, Aaron P. Kellogg, Cintia E. Citterio, Hao Zhang, Dennis Larkin, Yoshiaki Morishita, Héctor M. Targovnik, Viviana A. Balbi, Peter Arvan

Pharmacy Faculty Articles and Research

Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe …

In Men With Obesity, T2dm Is Associated With Poor Trabecular Microarchitecture And Bone Strength And Low Bone Turnover, Francesca Vigevano, Giulia Gregori, Georgia Colleluori, Rui Chen, Vimlin Autemrongsawat, Nicola Napoli, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

INTRODUCTION: Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown.

METHODS: Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay, body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry, whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography. Data were compared among metabolically healthy obese (MHO) and metabolically …

Pheochromocytoma Presenting As Testicular Pain: An Unusual Case Report, Jinal K. Patel, Varun Reddy, Gauthier L. Stepman, Debra Angelo, Johnathan Frunzi

Endocrinology

Pheochromocytoma (PCC) is a rare catecholamine-secreting tumor that arises from chromaffin cells of the adrenal medulla which are derived from the neural crest. This report illustrates a 51-year-old Caucasian male with a history of hypertension diagnosed two years ago who presented to the hospital due to acute onset of right testicular pain of 3-day duration. Laboratory results and imaging revealed a presumptive diagnosis of PCC. The patient had undergone robot-assisted laparoscopic right adrenalectomy 14 days after being diagnosed with PCC due to perioperative management with phenoxybenzamine. The final pathology report revealed a PCC. At follow-up two weeks after discharge, the …

Physical Activity Patterns Among Adults With Arthritis And Diabetes Who Receive Self-Management Education, A. M. Hall, J. R. Churilla, D. C. Segura, M. R. Richardson, T. M. Johnson

Showcase of Osprey Advancements in Research and Scholarship (SOARS)

Project of Merit Winner

PURPOSE: To examine the physical activity (PA) patterns among adults with arthritis and diabetes who receive self-management education. METHODS: Sample (n=28,860) included adults (≥ 18 years of age), with arthritis and diabetes who participated in the 2019 Behavioral Risk Factor Surveillance System. Categories of PA were classified as highly active (HACT), moderately active (MACT), low activity (LACT), and inactive (INACT). Multinomial logistic regression analyses adjusted for age, gender, body mass index, race, smoking status, and socioeconomic status. RESULTS: When compared to a referent group of inactive adults, our findings suggest that adults with arthritis and diabetes …

Time To First Blood Glucose Determination And Administration Of Intravenous Glucose At Birth In Extremely Low Birth Weight Infants, Jihan Esmail, Ramasubbareddy Dhanireddy Md

Longitudinal Scholar's Project

Background: Extremely low birth weight (ELBW) infants are prone to hypoglycemia unless intravenous glucose is administered within an hour (golden hour) of life. These infants often require resuscitation at birth, but monitoring and intervention for hypoglycemia may be delayed.

Objectives: (1) Study the time to first blood glucose determination and IV glucose administration at birth in ELBW infants, (2) determine the incidence of hypoglycemia, <47mg/dl, and severe hypoglycemia, <40mg/dl, at admission, (3) determine risk factors for hypoglycemia, and (4) compare clinical outcomes at discharge between hypoglycemic and euglycemic infants.

Methods: 244 ELBW (≤1000g birth weight) infants born during Jan 2017- Feb 2020 at the Regional One Health NICU, Memphis, TN were included in the study. Data collected included maternal and infant clinical, demographic, and outcomes …

Hyperglycemia During The First Three Days Of Life Increases The Risk Of Retinopathy Of Prematurity In Extremely Low Birth Weight Infants, Jihan M. Esmail, Ramasubbareddy Dhanireddy Md

Longitudinal Scholar's Project

Background: The association between hyperglycemia and ROP has been inconsistent in previous studies. Extremely low birth weight (ELBW) infants are at high risk for ROP. They also experience hypoglycemia initially and hyperglycemia while receiving IV glucose infusion. The effect of initial hypoglycemia on hyperglycemia associated ROP risk is unknown.

Objective: To study the effect of initial hypoglycemia and subsequent hyperglycemia during the first three days of life on the incidence of ROP and severe ROP in ELBW (birth weight ≤1000g) infants.

Methods: Clinical and demographic data were collected from 227 ELBW infants born during the years 2017-2019 at the Regional …

The Association Between Type-2 Diabetes Pathophysiology & Exercise Adherence, Sydney Raymond

Senior Honors Projects

According to the American Diabetes Association, 1 in 3 Americans will be diagnosed with diabetes. While some of these individuals will be prescribed medications as part of their treatment, most will also be advised to begin an exercise program to assist with blood glucose control. Additionally, while regular exercise is associated with lower HbA1C and decreased insulin/medication dependence, it is estimated that only about half of those diagnosed with diabetes will adhere to their exercise plans. Social, psychological, and physiological factors all play roles in affecting ones ability to adhere to an exercise regiment, and individuals with Type 2 Diabetes …

Rev-Erb In Gabaergic Neurons Controls Diurnal Hepatic Insulin Sensitivity, Guolian Ding, Xin Li, Xinguo Hou, Wenjun Zhou, Yingyun Gong, Fuqiang Liu, Yanlin He, Jia Song, Jing Wang, Paul Basil, Wenbo Li, Sichong Qian, Pradip Saha, Jinbang Wang, Chen Cui, Tingting Yang, Kexin Zou, Younghun Han, Christopher I Amos, Yong Xu, Li Chen, Zheng Sun

Faculty, Staff and Students Publications

Systemic insulin sensitivity shows diurnal rhythm with a peak at wakening1,2. The molecular mechanism underlying such a temporal pattern is unclear. Here we demonstrate that nuclear receptors Rev-erbα/β in the GABAergic neurons in the suprachiasmatic nucleus (SCNGABA) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviors under the regular light-dark cycles. Rev-erb regulates the rhythmic expression of genes involved in neurotransmission in the SCN and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at wakening causes glucose intolerance, while restoration …

Loss Of Bone Morphogenetic Protein-Binding Endothelial Regulator Causes Insulin Resistance, Hua Mao, Luge Li, Qiying Fan, Aude Angelini, Pradip K Saha, Huaizhu Wu, Christie M Ballantyne, Sean M Hartig, Liang Xie, Xinchun Pi

Faculty, Staff and Students Publications

Accumulating evidence suggests that chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors impact metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here, we demonstrate that BMPER is a driver of insulin sensitivity. Both global and endothelial cell-specific inducible knockout of BMPER cause hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues in mice. BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that …

Compliance With A Nurse-Driven Hypoglycemia Protocol: Time From Hypoglycemia Event To Euglycemia, Robin A. Chappell

Student Scholarly Projects

Practice Problem: Hypoglycemia is a known complication of diabetes mellitus and is considered one of the top three adverse drug events by the U.S. Department of Health and Human Services (2019) because it is common, clinically significant, measurable, and preventable.

PICOT: The PICOT question that guided this project was: In non-critical hospitalized adult patients on medical-surgical units with documented HGEs, how does active surveillance for strict adherence to a nurse-driven hypoglycemia protocol, compared to no surveillance, affect the time from hypoglycemia to euglycemia?

Evidence: Treatment of hypoglycemia is commonly inconsistent and prolonged; however, active surveillance and monitoring of a …

“It’S Pretty Hard To Make Friends Over A Zoom Meeting Room”: Understanding The Recreational Experiences Of Youth With Type 1 Diabetes During Covid-19, Ryan Malpaya, Rowan Williams

Undergraduate Research Symposium

Youth with diabetes frequently have limited access to traditional camps because of the need for accessible medical staff (Hill, E., 2019). COVID-19 has made it even more difficult for youth with type 1 diabetes to participate in any youth development programs due to the pandemic restrictions. During the pandemic, it is unknown if youth with T1D are able to engage in any recreational activities that may teach them resilience and independence in managing their medical condition. The purpose of this study was to see how youth with T1D cope in an altered recreation environment as a result of COVID-19

Using …

Single-Cell Rna-Seq Analysis Reveals Compartment-Specific Heterogeneity And Plasticity Of Microglia, Junying Zheng, Wenjuan Ru, Jay R Adolacion, Michael S Spurgat, Xin Liu, Subo Yuan, Rommel X Liang, Jianli Dong, Andrew S Potter, S Steven Potter, Ken Chen, Rui Chen, Navin Varadarajan, Shao-Jun Tang

Faculty, Staff and Students Publications

Microglia are ubiquitous central nervous system (CNS)-resident macrophages that maintain homeostasis of neural tissues and protect them from pathogen attacks. Yet, their differentiation in different compartments remains elusive. We performed single-cell RNA-seq to compare microglial subtypes in the cortex and the spinal cord. A multi-way comparative analysis was carried out on samples from C57/BL and HIV gp120 transgenic mice at two, four, and eight months of age. The results revealed overlapping but distinct microglial populations in the cortex and the spinal cord. The differential heterogeneity of microglia in these CNS regions was further suggested by their disparity of plasticity in …

Bidirectional Link Between Diabetes Mellitus And Coronavirus Disease 2019 Leading To Cardiovascular Disease: A Narrative Review., Vijay Viswanathan, Anudeep Puvvula, Ankush D Jamthikar, Luca Saba, Amer M Johri, Vasilios Kotsis, Narendra N Khanna, Surinder K Dhanjil, Misha Majhail, Durga Prasanna Misra, Vikas Agarwal, George D Kitas, Aditya M Sharma, Raghu Kolluri, Subbaram Naidu, Jasjit S Suri

Ambulatory and Primary Care Articles

Coronavirus disease 2019 (COVID-19) is a global pandemic where several comorbidities have been shown to have a significant effect on mortality. Patients with diabetes mellitus (DM) have a higher mortality rate than non-DM patients if they get COVID-19. Recent studies have indicated that patients with a history of diabetes can increase the risk of severe acute respiratory syndrome coronavirus 2 infection. Additionally, patients without any history of diabetes can acquire new-onset DM when infected with COVID-19. Thus, there is a need to explore the bidirectional link between these two conditions, confirming the vicious loop between "DM/COVID-19". This narrative review presents …

Patterns Of Abnormal Glucose Metabolism In Acromegaly And Impact Of Treatment Modalities On Glucose Metabolism, Sajjad A. Khan, Nanik Ram, Qamar Masood

Section of Diabetes, Endocrinology and Metabolism

Background: Chronic exposure to high levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) leads to metabolic complications, most importantly dysglycemia in the form of diabetes mellitus and pre-diabetes. Dysglycemia if diagnosed early in the course of the disease can decrease complications. Treatment modalities in the form of surgery and medical therapy have varied impacts on glucose metabolism.
Objective: To determine the frequency of diabetes mellitus, impaired glucose tolerance, and impaired fasting glucose in Pakistani patients with acromegaly and to establish the impact of the intervention (surgery/medical) on glucose metabolism.
Methods: This study was a retrospective review of …

Testosterone Therapy And Bone Quality In Men With Diabetes And Hypogonadism: Study Design And Protocol, Vittoria Russo, Georgia Colleluori, Rui Chen, Sanjay Mediwala, Clifford Qualls, Michael Liebschner, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes mellitus (T2D) is often accompanied by male hypogonadism and both conditions are associated with increased risk for fractures. Testosterone (T) has been shown to improve the bone health of hypogonadal men but has not been tested in patients who also have T2D in addition to low T. To date, there is no treatment that is specifically recommended for bone disease among patients with T2D. This study will evaluate the effect of T therapy on the bone health of male veterans with low T who also have T2D.

METHODS: This is a randomized double-blind placebo-controlled trial of …

Addressing Artificial Intelligence Bias In Retinal Diagnostics, Philippe Burlina, Neil Joshi, William Paul, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

PURPOSE: This study evaluated generative methods to potentially mitigate artificial intelligence (AI) bias when diagnosing diabetic retinopathy (DR) resulting from training data imbalance or domain generalization, which occurs when deep learning systems (DLSs) face concepts at test/inference time they were not initially trained on.

METHODS: The public domain Kaggle EyePACS dataset (88,692 fundi and 44,346 individuals, originally diverse for ethnicity) was modified by adding clinician-annotated labels and constructing an artificial scenario of data imbalance and domain generalization by disallowing training (but not testing) exemplars for images of retinas with DR warranting referral (DR-referable) from darker-skin individuals, who presumably have greater …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn, Grade Research Group

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Calcaneal Ultrasound And Its Relation To Dietary And Lifestyle Factors, Anthropometry, And Vitamin D Deficiency In Young Medical Students, Lena Jafri, Hafsa Majid, Sibtain Ahmed, Ghazala Naureen, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Background: Bone quality and peak bone mass are greatly affected by lifestyle factors. The objective of the study was to investigate the relationships between anthropometry, dietary and caloric intake, body composition measurements, physical activity, and vitamin D status with quantitative ultrasound-based bone parameters among medical students.
Methods: Both male and female medical college students were included in this study. A detailed questionnaire was administered, collecting clinical, dietary, physical activity information, physical examination details, including body mass index (BMI). Body composition (total body fat, total body water, muscle mass, mean visceral fat mass, basal metabolic rate, bone mass using a bioelectrical …

Highlights From Studies Presented At The American Heart Association Scientific Session 2020: Navigating New Roads In Prevention, Aliza Hussain, Mahmoud Al Rifai, Dhruv Mahtta, Jing Liu, Vardhmaan Jain, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF THE REVIEW: This review highlights late-breaking science presented at the American Heart Association Scientific Session 2020 that demonstrated advancements in preventative cardiology and introduced novel treatment approaches for the management of chronic kidney disease, type 2 diabetes, and/or heart failure.

RECENT FINDINGS: The studies reviewed include clinical trials that assessed the use of omecamtiv in the treatment of heart failure with reduced heart failure (GALACTIC-HF); effects of sotagliflozin in patients with diabetes and recent heart failure exacerbation; cardiovascular outcomes with the use of omega-3 carboxylic acids in patients with high vascular risk and atherogenic dyslipidemia (STRENGTH) and omega-3 …