Endocrinology, Diabetes, and Metabolism Commons^™

Anoctamin 4 Channel Currents Activate Glucose-Inhibited Neurons In The Mouse Ventromedial Hypothalamus During Hypoglycemia, Longlong Tu, Jonathan C Bean, Yang He, Hailan Liu, Meng Yu, Hesong Liu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Kristine M Conde, Mengjie Wang, Yongxiang Li, Bing Feng, Peiyu Gao, Zhao-Lin Cai, Makoto Fukuda, Mingshan Xue, Qingchun Tong, Yongjie Yang, Lan Liao, Jianming Xu, Chunmei Wang, Yanlin He, Yong Xu

Faculty, Staff and Student Publications

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood …

Global, Regional, And National Burden Of Diabetes From 1990 To 2021, With Projections Of Prevalence To 2050: A Systematic Analysis For The Global Burden Of Disease Study 2021, Kanyin Liane Ong, Lauryn K. Stafford, Susan A. Mclaughlin, Edward J. Boyko, Stein Emil Vollset, Amanda E. Smith, Bronte E. Dalton, Joe Duprey, Jessica A. Cruz, Hailey Hagins, Paulina A. Lindstedt, Amirali Aali, Yohannes Habtegiorgis Abate, Melsew Dagne Abate, Mohammadreza Abbasian, Zeinab Abbasi-Kangevari, Mohsen Abbasi-Kangevari, Samar Abd Elhafeez, Rami Abd-Rabu, Deldar Morad Abdulah, Abu Yousuf Md Abdullah, Veincent Christian Pepito

Ateneo School of Medicine and Public Health Publications

Background

Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050.

Methods

Estimates of diabetes prevalence and burden were computed in …

Diabetes Technology Meeting 2022, Jingtong Huang, Andrea M Yeung, Ashley Y Dubord, Howard Wolpert, Peter G Jacobs, Wei-An Lee, Andjela Drincic, Elias K Spanakis, Jennifer L Sherr, Priya Prahalad, Alexander Fleming, Victoria C Hsiao, Tejaswi Kompala, Rayhan A Lal, Maya Fayfman, Barry H Ginsberg, Rodolfo J Galindo, Andreas Stuhr, J Geoffrey Chase, Bijan Najafi, Umesh Masharani, Jane Jeffrie Seley, David C Klonoff

Center on Aging Staff Publications

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 3 to November 5, 2022. Meeting topics included (1) the measurement of glucose, insulin, and ketones; (2) virtual diabetes care; (3) metrics for managing diabetes and predicting outcomes; (4) integration of continuous glucose monitor data into the electronic health record; (5) regulation of diabetes technology; (6) digital health to nudge behavior; (7) estimating carbohydrates; (8) fully automated insulin delivery systems; (9) hypoglycemia; (10) novel insulins; (11) insulin delivery; (12) on-body sensors; (13) continuous glucose monitoring; (14) diabetic foot ulcers; (15) the environmental impact of diabetes technology; and (16) spinal …

Orchestration Of Mirna Patterns By Testosterone And Dietary Tomato Carotenoids During Early Prostate Carcinogenesis In Tramp Mice, Lei Wan, Jennifer M Thomas-Ahner, Dennis K Pearl, John W Erdman, Nancy E Moran, Steven K Clinton

Children’s Nutrition Research Center Staff Publications

Background: The integrative effects of prostate cancer risk factors, such as diet and endocrine status, on cancer-associated miRNA expression are poorly defined.

Objectives: This study aimed to define the influence of androgens and diet (tomato and lycopene) on prostatic miRNA expression during early carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model.

Methods: Wild type (WT) and TRAMP mice were fed control, tomato-containing, or lycopene-containing diets from 4 to 10 weeks of age. Mice underwent either sham (intact) or castration surgery at 8 wk, and half of the castrated mice received testosterone (2.5 mg/kg body weight/d) at 9 …

Data Sharing: Putting Nature’S Policy To The Test, Xiwei Chen, Stephanie L Dickinson, Anna L M Macagno, Chelsie M Parker, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Towards A Model Of Biliary Atresia – Pilot Feasibility Study In Newborn Piglets, Thora Wesenberg Helt, Lene Buelund, Lise Borgwardt, Thomas Eriksen, Lars Johansen, Robin De Nijs, Soren Holm, Douglas G Burrin, Thomas Thymann, Vibeke Brix Christensen

Children’s Nutrition Research Center Staff Publications

Biliary atresia (BA) is a rare congenital liver disease with unknown etiology, and it is the most common indication for liver transplantation in children. As BA infants suffer from intestinal malabsorption and neurodevelopmental deficits, it is necessary to identify optimal medical and nutritional strategies using appropriate neonatal animal models. We aim to determine the feasibility of using newborn piglets with surgically induced cholestasis (bile duct ligation (BDL)) to mimic clinical features of BA. Six piglets were subjected to abdominal surgery on day 4 after birth. The bile ducts were ligated, and the piglet were followed for up to 12 days. …

Messes: Software For Transforming Messy Research Datasets Into Clean Submissions To Metabolomics Workbench For Public Sharing, P. Travis Thompson, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

In recent years, the FAIR guiding principles and the broader concept of open science has grown in importance in academic research, especially as funding entities have aggressively promoted public sharing of research products. Key to public research sharing is deposition of datasets into online data repositories, but it can be a chore to transform messy unstructured data into the forms required by these repositories. To help generate Metabolomics Workbench depositions, we have developed the MESSES (Metadata from Experimental SpreadSheets Extraction System) software package, implemented in the Python 3 programming language and supported on Linux, Windows, and Mac operating systems. MESSES …

Association Of Timing Of Moderate-To-Vigorous Physical Activity With Changes In Glycemic Control Over 4 Years In Adults With Type 2 Diabetes From The Look Ahead Trial, Jingyi Qian, Qian Xiao, Michael P Walkup, Mace Coday, Melissa L Erickson, Jessica Unick, John M Jakicic, Kun Hu, Frank A J L Scheer, Roeland J W Middelbeek, Look Ahead Research Group

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to determine the association of the time-of-day of bout-related moderate-to-vigorous physical activity (bMVPA) with changes in glycemic control across 4 years in adults with overweight/obesity and type 2 diabetes.

RESEARCH DESIGN AND METHODS: Among 2,416 participants (57% women; mean age, 59 years) with 7-day waist-worn accelerometry recording at year 1 or 4, we assigned bMVPA timing groups based on the participants' temporal distribution of bMVPA at year 1 and recategorized them at year 4. The time-varying exposure of bMVPA (≥10-min bout) timing was defined as ≥50% of bMVPA occurring during the same time period (morning, midday, afternoon, …

Arsenic Metabolism, Diabetes Prevalence, And Insulin Resistance Among Mexican Americans: A Mendelian Randomization Approach, Margaret C Weiss, Yu-Hsuan Shih, Molly Scannell Bryan, Brian P Jackson, David Aguilar, Eric L Brown, Goo Jun, Craig L Hanis, Maria Argos, Robert M Sargis

Faculty, Staff and Student Publications

BACKGROUND: Differences in arsenic metabolism capacity may influence risk for type 2 diabetes, but the mechanistic drivers are unclear. We evaluated the associations between arsenic metabolism with overall diabetes prevalence and with static and dynamic measures of insulin resistance among Mexican Americans living in Starr County, Texas.

METHODS: We utilized data from cross-sectional studies conducted in Starr County, Texas, from 2010-2014. A Mendelian randomization approach was utilized to evaluate the associations between arsenic metabolism and type 2 diabetes prevalence using the intronic variant in the arsenic methylating gene, rs9527, as the instrumental variable for arsenic metabolism. to further assess mechanisms …

Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response To Metformin And Glipizide In Sugar-Mgh, Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, Miriam S Udler, Aaron Leong, Josep M Mercader, Jose C Florez

Faculty, Staff and Student Publications

AIMS/HYPOTHESIS: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.

METHODS: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping …

Creativity In Energy Balance, Obesity And Feeding Behavior Research, Some Thoughts, Stephen J French, David B Allison

Children’s Nutrition Research Center Staff Publications

This review provides an overview of examples of especially creative work related to the fields of ingestive behavior, energetics (defined as the study of the acquisition, storage, and use of metabolizable energy by biological organisms and the causes and consequences of such acquisition, storage, and use), and nutrition, focusing on both individual works and discoveries, as well as bodies of works and in some cases the working styles of particular scientists. The paper then discusses some principles extracted from our observations as well as from the literature on creativity pointing out some factors that seem to make for more creative …

Ndufs4 Regulates Cristae Remodeling In Diabetic Kidney Disease, Koki Mise, Jianyin Long, Daniel L Galvan, Zengchun Ye, Guizhen Fan, Irina I Serysheva, Travis I Moore, Jun Wada, Paul T Schumacker, Benny H Chang, Farhad R Danesh

Faculty, Staff and Student Publications

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generated diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model to investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that these conditional mice exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify …

Hyperinsulinemic Hypoglycemia And Growth Hormone Deficiency Secondary To 20p11 Deletion., Erica Wee, John Herriges, Kavitha Dileepan, Sarah Tsai, Joseph Alaimo, Emily Paprocki

Manuscripts, Articles, Book Chapters and Other Papers

Hypoglycemia is concerning for neurological complications in infants and children. Determining the cause of hypoglycemia is essential in providing appropriate treatment. Hyperinsulinism and growth hormone deficiency are known causes of hypoglycemia but are not commonly found together. We report a 4-month-old boy who presented with severe hypoglycemia and was found to have both hyperinsulinism and growth hormone deficiency. Treatment with both recombinant human growth hormone and diazoxide led to blood glucose normalization. Subsequently, he was found to have a genetic diagnosis of 20p11.22p11.21 deletion. 20p11 deletions have been associated with hypopituitarism, most commonly seen in growth hormone deficiency causing hypoglycemia. …

Global, Regional, And National Burden Of Diabetes From 1990 To 2021, With Projections Of Prevalence To 2050: A Systematic Analysis For The Global Burden Of Disease Study 2021, Kavita Batra, Numerous Authors, See List Below

School of Medicine Faculty Research

Background:

Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050.

Methods:

Estimates of diabetes prevalence and burden were computed in …

Transmembrane Stem Factor Nanodiscs Enhanced Revascularization In A Hind Limb Ischemia Model In Diabetic, Hyperlipidemic Rabbits, Eri Takematsu, Miles Massidda, Gretchen Howe, Julia Goldman, Patricia Felli, Lei Mei, Gregory Callahan, Andrew Sligar, Richard Smalling, Aaron Baker

Faculty, Staff and Student Publications

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. …

Neighbourhood‐Level Social Deprivation And The Risk Of Recurrent Heart Failure Hospitalizations In Type 2 Diabetes, Salil V. Deo, Sadeer Al-Kindi, Yakov Elgudin, Eiran Gorodeski, Sanjay Rajagopalan

Faculty Scholarship

Background: The importance of type 2 diabetes mellitus (T2D) in heart failure hospitalizations (HFH) is acknowledged. As information on the prevalence and influence of social deprivation on HFH is limited, we studied this issue in a racially diverse cohort. Methods: Linking data from US Veterans with stable T2D (without prevalent HF) with a zip-code derived population-level social deprivation index (SDI), we grouped them according to increasing SDI as follows: SDI: group I: ≤20; II: 21-40; III: 41-60; IV: 61-80; and V (most deprived) 81-100. Over a 10-year follow-up period, we identified the total (first and recurrent) number of HFH episodes …

Development Of A Biomarker Panel For Assessing Cardiovascular Risk In Diabetic Patients With Chronic Limb-Threatening Ischemia (Clti): A Prospective Study, Elisabetta Nardella, Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Enrica Rossini, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Medicine Faculty Papers

BACKGROUND: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), …

Tenofovir Induced Hypokalaemia - A Case Report, Ankisha Gupta, Kiran P. K, Rajendra Prasad S

Digital Journal of Clinical Medicine

Tenofovir, an important medication for HIV/AIDS, carries the risk of hypokalemia in patients receiving treatment. Factors such as dietary deficits, vomiting, or diarrhea further increase this risk. Tenofovir acts as a mitochondrial toxin by inhibiting the DNA polymerase gamma enzyme, crucial for mitochondrial DNA replication. Consequently, ATP generation is depleted through the aerobic pathway, leading to dysfunction in the proximal tubule. This dysfunction manifests as renal acidosis type 2, which involves reduced bicarbonate excretion by the proximal tubule, resulting in renal bicarbonate wasting and decreased serum bicarbonate levels. Consequently, the lumen of the distal nephron becomes negatively charged, leading to …

Early Postpartum Hba1c After Hyperglycemia First Detected In Pregnancy-Imperfect But Not Without Value, Ankia Coetzee, David R Hall, Mari Van De Vyver, Magda Conradie

Faculty, Staff and Student Publications

BACKGROUND: South African women of childbearing age are disproportionally affected by obesity and at significant risk of Type 2 Diabetes Mellitus (T2DM). Unless pregnant, they do not readily undergo screening for T2DM. With a local focus on improved antenatal care, hyperglycemia is often first detected in pregnancy (HFDP). This may erroneously be attributed to Gestational Diabetes Mellitus (GDM) in all without considering T2DM. Glucose evaluation following pregnancy is essential for early detection and management of women with T2DM in whom persistent hyperglycemia is to be expected. Conventional testing with an oral glucose tolerance test (OGTT) is cumbersome, prompting investigation for …

A Nurse-Led Telehealth Program For Diabetes Foot Care: Feasibility And Usability Study, Hsiao-Hui Ju, Rashmi Momin, Stanley Cron, Jed Jularbal, Jeffery Alford, Constance Johnson

Faculty, Staff and Student Publications

BACKGROUND: Diabetes mellitus can lead to severe and debilitating foot complications, such as infections, ulcerations, and amputations. Despite substantial progress in diabetes care, foot disease remains a major challenge in managing this chronic condition that causes serious health complications worldwide.

OBJECTIVE: The primary aim of this study was to examine the feasibility and usability of a telehealth program focused on preventive diabetes foot care. A secondary aim was to descriptively measure self-reported changes in diabetes knowledge, self-care, and foot care behaviors before and after participating in the program.

METHODS: The study used a single-arm, pre-post design in 2 large family …