Endocrinology, Diabetes, and Metabolism Commons^™

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …

Steroid Receptor Coactivators – Their Role In Immunity, Yosi Gilad, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid Receptor Coactivators (SRCs) are essential regulators of transcription with a wide range of impact on human physiology and pathology. In immunology, SRCs play multiple roles; they are involved in the regulation of nuclear factor-κB (NF-κB), macrophage (MΦ) activity, lymphoid cells proliferation, development and function, to name just a few. The three SRC family members, SRC-1, SRC-2 and SRC-3, can exert their immunological function either in an independent manner or act in synergy with each other. In certain biological contexts, one SRC family member can compensate for lack of activity of another member, while in other cases one SRC can …

The Prevalence And Spectrum Of Reported Incidental Adrenal Abnormalities In Abdominal Computed Tomography Of Cancer Patients: The Experience Of A Comprehensive Cancer Center, Aiham Qdaisat, Sara Bedrose, Obadah Ezzeldin, Ahmed W Moawad, Sai-Ching J Yeung, Khaled M Elsayes, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: The increasing use of computed tomography (CT) has identified many patients with incidental adrenal lesions. Further evaluation of these lesions is often dependent on the language used in the radiology report. Compared to the general population, patients with cancer have a higher risk for adrenal abnormalities, yet data on the prevalence and type of incidental adrenal lesions reported on radiologic reports in cancer patients is limited. In this study, we aimed to determine the prevalence and nature of adrenal abnormalities as an incidental finding reported on radiology reports of cancer patients evaluated for reasons other than suspected adrenal pathology. …

De Novo Glycine Synthesis Is Reduced In Adults With Morbid Obesity And Increases Following Bariatric Surgery, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Chun Fan Lee, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance.

OBJECTIVE: Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m

METHODS: [1,2-

RESULTS: Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced

CONCLUSION: Hypoglycinemia …

"It Just Kind Of Feels Like A Different World Now:" Stress And Resilience For Adolescents With Type 1 Diabetes In The Era Of Covid-19, Maeve B O'Donnell, Marisa E Hilliard, Viena T Cao, Miranda C Bradford, Krysta S Barton, Samantha Hurtado, Brenda Duran, Samantha Garcia Perez, Kiswa S Rahman, Samantha Scott, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Chuan Zhou, Abby R Rosenberg, Joyce P Yi-Frazier

Faculty, Staff and Students Publications

PURPOSE: The COVID-19 pandemic has been a major stressor for adolescents. Given the unique implications of the pandemic for youth with type 1 diabetes (T1D), who already navigate multiple stressors as a function of their chronic condition, we aimed to describe the impact of the pandemic on adolescents with T1D and describe their coping strategies and resilience resources.

RESEARCH METHOD: In a 2-site (Seattle WA, Houston TX) clinical trial of a psychosocial intervention targeting stress/resilience, adolescents 13-18 years old with T1D ≥ 1 year and elevated diabetes distress were enrolled August 2020 - June 2021. Participants completed a baseline survey …

Lipid Dysfunction And Adrenomedullin Expression In Omental Versus Subcutaneous Adipose Tissues In Diabetic Pregnancies, Yuanlin Dong, Ancizar Betancourt, Michael A Belfort, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy but the underlying mechanism remains obscure. The aims of this study are to examine if omental adipose tissue (OMAT) and subcutaneous AT (SCAT) differentially express proinflammatory and lipid metabolic adipokines, and if so, whether their regional differences have implications on lipid metabolism in GDM. Paired samples of OMAT and SCAT were excised from pregnant women in scheduled Cesarean sections with non-obese (NOBS), obese (OBS) and GDM. The results showed that the mRNA of monocyte chemoattractant protein (MCP)-1, macrophage marker CD68, and cytokines IL-6, IL-8, and TNF-α are …

Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, …

Breakthroughs In Hormonal Male Contraception, Alexander Patton, Seth Vann

Physician Assistant Capstones, 2020-current

Objective: Assess the efficacy of a nestorone plus testosterone gel at suppressing progestin levels and spermatogenesis.

Design: Systematic literature review.

Methods: Searches were done in PubMed and Dartmouth library using the terms nestorone, randomized control trial, human, and male. Limits used while searching included published in the last 10 years, randomized control trials, and English.

Results: Using the search criteria the following three studies were found that met the inclusion/exclusion criteria of this study: Ilani et al, Zitzmann et al, and Anawalt et al. All three studies were found on PubMed and reference the Ilani et al study.

Conclusion: Nestorone …

Role Of Serum Amyloid A In Abdominal Aortic Aneurysm And Related Cardiovascular Diseases, Preetha Shridas, Avery C. Patrick, Lisa R. Tannock

Internal Medicine Faculty Publications

Epidemiological data positively correlate plasma serum amyloid A (SAA) levels with cardiovascular disease severity and mortality. Studies by several investigators have indicated a causal role for SAA in the development of atherosclerosis in animal models. Suppression of SAA attenuates the development of angiotensin II (AngII)-induced abdominal aortic aneurysm (AAA) formation in mice. Thus, SAA is not just a marker for cardiovascular disease (CVD) development, but it is a key player. However, to consider SAA as a therapeutic target for these diseases, the pathway leading to its involvement needs to be understood. This review provides a brief description of the pathobiological …

Abdominal Paraganglioma In A Patient With Fever Of Unknown Origin, Samantha Sokoloff, Barbara Simon

Department of Medicine Faculty Papers

Reaxys Chemistry database information SciVal Topics Funding details

Abstract

Introduction: Paragangliomas have a wide range of clinical presentations. A significant portion of these tumors are discovered as abdominal masses on imaging or palpation in patients without typical symptoms of catecholamine excess [1]. This case reports a 28-year-old female who presented with fever of unknown origin and was found to have an abdominal mass on CT imaging. This mass was biopsied prior to a complete evaluation and confirmed to be a paraganglioma. Case report: We discuss the case of a 28 year-old-female who presented to the Endocrinology office after she was …

Attenuation Of Autoimmune Phenomena In A Patient With Autoimmune Polyglandular Syndrome Type 1., Jill Jacobson, Julia Broussard, Courtney Marsh, Brandon D. Newell

Manuscripts, Articles, Book Chapters and Other Papers

Autoimmune polyglandular syndrome type 1 (APS1) is a progressive life-threatening illness with no known cure. Current treatments involve replacement of the hormone deficiencies that result from autoimmune destruction of multiple endocrine organs. We report on a girl whose disease was progressing rapidly until she began on immunosuppressive agents. A healthy 6-year-old girl with no remarkable medical history presented with new onset hypocalcemic seizures and primary hypoparathyroidism. Howell-Jolly bodies consistent with autoimmune hyposplenism were also noted. Genetic testing revealed compound heterozygosity for 2 disease-associated variants in the autoimmune regulator (AIRE) gene. She later developed elevated liver enzymes, primary adrenal insufficiency, and …

The Efficacy Of Plant-Based Dietary Program In Patients With Diabetes: A Pilot Study, Reuben Adatorwovor, Nisha Sharma, Dakota Mccoy, Sharon Wasserstrom, Matthew Robinson, Jacquelyn Nyenhuis, Sowmya Suryanarayanan

Biostatistics Faculty Publications

Dietary choices play a key role in insulin sensitivity among diabetes patients. An 8-week pilot study was conducted to evaluate whether a mostly plant-based dietary program will lead to improvement in biochemical markers in adults with diabetes. The dietary program included educational presentations, weekly cooking demonstrations and small group discussions. A sample of thirty-two adults with diabetes (types 1 and 2) were recruited and seventeen (53%) completed the study. Matched-pair tests and Fishers exact tests were used to compare the changes in means and proportion of the participants’ responses. There were changes in HbA1c, lipids, CRP (mg/L), cholesterol (mg/dL), HDL …

Macrophages Expressing Uncoupling Protein 1 Increase In Adipose Tissue In Response To Cold In Humans, Brian S. Finlin, Hasiyet Memetimin, Amy L. Confides, Beibei Zhu, Philip M. Westgate, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

Acute cold induces beige adipocyte protein marker expression in human subcutaneous white adipose tissue (SC WAT) from both the cold treated and contralateral leg, and the immune system regulates SC WAT beiging in mice. Cold treatment significantly increased the gene expression of the macrophage markers CD68 and 86 in SC WAT. Therefore, we comprehensively investigated the involvement of macrophages in SC WAT beiging in lean and obese humans by immunohistochemistry. Cold treatment significantly increased CD163/CD68 macrophages in SC WAT from the cold treated and contralateral legs of lean and obese subjects, and had similar effects on CD206/CD68 macrophages, whereas the …

Hypothalamic Steroid Receptor Coactivator-2 Regulates Adaptations To Fasting And Overnutrition, Yongjie Yang, Yanlin He, Hailan Liu, Wenjun Zhou, Chunmei Wang, Pingwen Xu, Xing Cai, Hesong Liu, Kaifan Yu, Zhou Pei, Ilirjana Hyseni, Makoto Fukuda, Qingchun Tong, Jianming Xu, Zheng Sun, Bert W O'Malley, Yong Xu

Faculty, Staff and Students Publications

The neuroendocrine system coordinates metabolic and behavioral adaptations to fasting, including reducing energy expenditure, promoting counterregulation, and suppressing satiation and anxiety to engage refeeding. Here, we show that steroid receptor coactivator-2 (SRC-2) in pro-opiomelanocortin (POMC) neurons is a key regulator of all these responses to fasting. POMC-specific deletion of SRC-2 enhances the basal excitability of POMC neurons; mutant mice fail to efficiently suppress energy expenditure during food deprivation. SRC-2 deficiency blunts electric responses of POMC neurons to glucose fluctuations, causing impaired counterregulation. When food becomes available, these mutant mice show insufficient refeeding associated with enhanced satiation and discoordination of anxiety …

Neonatal Outcomes And Congenital Anomalies In Pregnancies Affected By Hypothyroidism, Zareen Kiran,, Aisha Sheikh, Khadija N Humayun, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Background: Maternal hypothyroidism has been reported to have concerns over neonatal outcomes, not only in the context of neurocognitive development but also in the short term as birth weight and neonatal jaundice.
Patients and methods: We conducted a cross-sectional retrospective study on 638 cases who delivered live births in the Aga Khan University Hospital after ethical approval. Data were collected on hypothyroid pregnant females who were diagnosed before conception or during their antenatal visits during the year 2008-2016. Neonatal outcomes were noted for birth weight, maturity, and neonatal jaundice, neonatal hypothyroidism, neonatal respiratory distress syndrome, sepsis, hypocalcaemia, congenital anomalies, need …

Data-Driven Statin Initiation Evaluation And Optimization For Prediabetes Population, Muhenned A. Abdulsahib

Graduate Theses and Dissertations

This dissertation develops quantitative models to support medical decision making of statininitiation considering the uncertainty in disease progression for prediabetes patients. A mathematical model is built to help medical decision-makers take action of statin initiation under uncertainty in future prediabetes progressions. The association between cholesterol drug use, such as statin, and elevating glucose level attracted considerable amounts of attention in the literature. Statin effects on glucose vary with respect to different levels of glucose. The first chapter of this dissertation introduces the problem and an overview of the tools that will be used to solve it. In the second chapter …

A Staged Approach To Address Youth Unresponsive To Initial Obesity Intervention: A Randomized Clinical Trial, Katherine R Arlinghaus, Daniel P O'Connor, Tracey A Ledoux, Sheryl O Hughes, Craig A Johnston

Children’s Nutrition Research Center Staff Publications

Background/objective: Maintenance interventions inherently require BMI improvement to maintain. This overlooks individuals initially unresponsive to obesity interventions. Staged pediatric clinical treatment guidelines were adapted to the school setting to develop an escalated treatment option for individuals initially unresponsive. This staged randomized controlled trial examined differences between escalated treatment (Take CHARGE!) and a maintenance program (PE Planners). Take CHARGE was hypothesized to have greater improvements in BMI as a percentage of the 95th BMI Percentile (%BMIp95) than PE Planners.

Subjects/methods: From 2018 to 2020, 171 middle and high schoolers (BMI Percentile ≥ 85) were recruited from a Houston school district to …

5-Ht Recruits Distinct Neurocircuits To Inhibit Hunger-Driven And Non-Hunger-Driven Feeding, Yanlin He, Xing Cai, Hailan Liu, Krisitine M Conde, Pingwen Xu, Yongxiang Li, Chunmei Wang, Meng Yu, Yang He, Hesong Liu, Chen Liang, Tingting Yang, Yongjie Yang, Kaifan Yu, Julia Wang, Rong Zheng, Feng Liu, Zheng Sun, Lora Heisler, Qi Wu, Qingchun Tong, Canjun Zhu, Gang Shu, Yong Xu

Children’s Nutrition Research Center Staff Publications

Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HTDRN) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HTDRN to hypothalamic arcuate nucleus (5-HTDRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT2C and 5-HT1B receptors, whereas activation of 5-HTDRN to ventral tegmental area (5-HTDRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HTDRN …

Dash Diet Adherence And Cognitive Function: Multi-Ethnic Study Of Atherosclerosis, George D Daniel, Haiying Chen, Alain G Bertoni, Stephen R Rapp, Annette L Fitzpatrick, José A Luchsinger, Alexis C Wood, Timothy M Hughes, Gregory L Burke, Kathleen M Hayden

Children’s Nutrition Research Center Staff Publications

Background and aims: The Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet has been associated with better cognitive function in studies of predominantly White participants; few studies have examined this association in diverse cohorts. Our objective was to examine the association between the DASH diet and cognitive function in the diverse Multi-Ethnic Study of Atherosclerosis (MESA) cohort.

Methods: Among 4169 MESA participants, we evaluated prospectively, the association between DASH diet adherence and cognitive function. Participants completed a food frequency questionnaire at baseline (2000-2002) and cognitive function was assessed using the Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding …

Intermittent Bolus Feeding Does Not Enhance Protein Synthesis, Myonuclear Accretion, Or Lean Growth More Than Continuous Feeding In A Premature Piglet Model, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Barbara Stoll, Candace C Style, Mariatu A Verla, Oluyinka O Olutoye, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Children’s Nutrition Research Center Staff Publications

Optimizing enteral nutrition for premature infants may help mitigate extrauterine growth restriction and adverse chronic health outcomes. Previously, we showed in neonatal pigs born at term that lean growth is enhanced by intermittent bolus compared with continuous feeding. The objective was to determine if prematurity impacts how body composition, muscle protein synthesis, and myonuclear accretion respond to feeding modality. Following preterm delivery, pigs were fed equivalent amounts of formula delivered either as intermittent boluses (INT; n = 30) or continuously (CONT; n = 14) for 21 days. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and muscle growth was …