Endocrinology, Diabetes, and Metabolism Commons^™

Correspondence Attention For Facial Appearance Simulation, Xi Fang, Daeseung Kim, Xuanang Xu, Tianshu Kuang, Nathan Lampen, Jungwook Lee, Hannah H Deng, Michael A K Liebschner, James J Xia, Jaime Gateno, Pingkun Yan

Faculty, Staff and Students Publications

In orthognathic surgical planning for patients with jaw deformities, it is crucial to accurately simulate the changes in facial appearance that follow the bony movement. Compared with the traditional biomechanics-based methods like the finite-element method (FEM), which are both labor-intensive and computationally inefficient, deep learning-based methods offer an efficient and robust modeling alternative. However, current methods do not account for the physical relationship between facial soft tissue and bony structure, causing them to fall short in accuracy compared to FEM. In this work, we propose an Attentive Correspondence assisted Movement Transformation network (ACMT-Net) to predict facial changes by correlating facial …

Severity-Adjusted Evaluation Of Liver Transplantation On Health Outcomes In Urea Cycle Disorders, Roland Posset, Sven F Garbade, Florian Gleich, Svenja Scharre, Jürgen G Okun, Andrea L Gropman, Sandesh C S Nagamani, Ann-Catrin Druck, Friederike Epp, Georg F Hoffmann, Stefan Kölker, Matthias Zielonka

Faculty, Staff and Students Publications

Purpose: Liver transplantation (LTx) is performed in individuals with urea cycle disorders when medical management (MM) insufficiently prevents the occurrence of hyperammonemic events. However, there is a paucity of systematic analyses on the effects of LTx on health-related outcome parameters compared to individuals with comparable severity who are medically managed.

Methods: We investigated the effects of LTx and MM on validated health-related outcome parameters, including the metabolic disease course, linear growth, and neurocognitive outcomes. Individuals were stratified into "severe" and "attenuated" categories based on the genotype-specific and validated in vitro enzyme activity.

Results: LTx enabled metabolic stability by prevention of …

What Weight Changes Really Happened During Covid-19 Among Older Adults?, John A Batsis, Dennis T Villareal

Faculty, Staff and Students Publications

No abstract provided.

Transitioning From An In-Person Intervention To Augmented Text Messaging During Covid-19 In Mexican Americans With Prediabetes: The Starr County Diabetes Prevention Randomized Clinical Trial, Sharon A Brown, Mary A Winter, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis

Faculty, Staff and Student Publications

PURPOSE: The purpose of the study was to explore the feasibility of using commonly available technology, such as text messaging, for diabetes prevention in rural Mexican American communities during COVID-19.

METHODS: Participants were selected from a diabetes prevention study funded by the National Institutes of Health that, prior to COVID-19, involved in-person group intervention sessions. Participants were predominantly female adults born in Mexico and Spanish-speaking. A subsample (n = 140) was divided into 3 cohorts: (1) 50 who completed the initial in-person intervention prior to the COVID-19 research pause, (2) 60 who needed additional support sessions to complete the intervention …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissue, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Children’s Nutrition Research Center Staff Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

Gut Microbiota And Blood Metabolites Related To Fiber Intake And Type 2 Diabetes, Zheng Wang, Brandilyn A Peters, Bing Yu, Megan L Grove, Tao Wang, Xiaonan Xue, Bharat Thyagarajan, Martha L Daviglus, Eric Boerwinkle, Gang Hu, Yasmin Mossavar-Rahmani, Carmen R Isasi, Rob Knight, Robert D Burk, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D).

METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at …

Pilot Study To Assess The Effectiveness Of The Sustainable Culturally Adaptive Nutrition Program (Scan) To Improve Adherence To The National Diabetes Prevention Program, William B Perkison, Pierre Fwelo, Fernanda Velasco-Huerta, Natalia I Heredia, James J Yang, Sidra S Beg, Belinda M Reininger, Serena A Rodriguez, Maha Almohamad, Catherine Pulicken, Ella Garza, Grace E White, Maria E Fernandez

Faculty, Staff and Student Publications

PURPOSE: The Sustainable Culturally Adapted Nutrition Program (SCAN) is a novel adaptation to the National Diabetes Prevention Program (NDPP) that aims to improve attendance and effectiveness. This paper presents its feasibility and impact through the initial 6-month outcomes.

DESIGN: A pragmatic quasi-experimental pilot study with intervention (DPP plus SCAN) and control (DPP only) groups.

SAMPLES AND INCLUSION CRITERIA: Sustainable Culturally Adapted Nutrition Program participants were recruited from federally qualified health center (FQHC) clinic patients enrolled in a NDPP in Houston, Texas. Participants needed to be (1) ≥18 years old, (2) body mass index >25, (3) no prior diagnosis of diabetes, …

Generation Of Sst-P2a-Mcherry Reporter Human Embryonic Stem Cell Line Using The Crispr/Cas9 System (Wae001-A-2c), Tongran Zhang, Feng Zhang, Nannan Wang, Tao Xu, Lingqiang Zhu, Lihua Chen, Huisheng Liu

Faculty, Staff and Student Publications

Somatostatin (SST)-producing pancreatic delta-cells play an important role in maintaining the balance of insulin and glucagon secretion within the islets. This study aimed to generate a human embryonic stem cell (hESC) line with a SST-P2A-mCherry reporter using CRISPR/Cas9 system. The SST-P2A-mCherry reporter cell line was shown to maintain typical pluripotent characteristics and able to be induced into SST-producing pancreatic delta-cells. The generation of the cell line would provide useful platform for the characterization of stem cell-derived delta-cells, discovery of delta-cell surface markers and investigation of paracrine mechanisms, which will ultimately promote the drug discovery and cell therapy of diabetes mellitus.

Single-Cell Analysis Of Age-Related Changes In Leukocytes Of Diabetic Mouse Hindpaws, James M Nichols, Hoang Vu Pham, Eric F Lee, Rajasekaran Mahalingam, Andrew J Shepherd

Faculty, Staff and Student Publications

Complications associated with Type 1 and Type 2 diabetes, such as diabetic peripheral neuropathy and diabetic foot ulcers, are a growing health-care concern. In addition, this concern increases as diabetic patients age due to their increased susceptibility to complications. To address this growing problem, it is important to understand fluctuations in physiology which lead to pathological changes associated with the metabolic disturbances of diabetes. Our study explores dysregulation of immune cell populations in the hindpaws of healthy and diabetic mice at 12 and 21 weeks of age using single-cell RNA sequencing to provide insight into immune disruptions occurring in the …

Trends In Us Public Confidence In Science And Opportunities For Progress, Arthur Lupia, David B Allison, Kathleen Hall Jamieson, Jennifer Heimberg, Magdalena Skipper, Susan M Wolf

Children’s Nutrition Research Center Staff Publications

In recent years, many questions have been raised about whether public confidence in science is changing. To clarify recent trends in the public's confidence and factors that are associated with these feelings, an effort initiated by the National Academies' Strategic Council for Research Excellence, Integrity, and Trust (the Strategic Council) analyzed findings from multiple survey research organizations. The Strategic Council's effort, which began in 2022, found that U.S. public confidence in science, the scientific community, and leaders of scientific communities is high relative to other civic, cultural, and governmental institutions for which researchers regularly collect such data. However, confidence in …

Adipose Tissue Dysfunction And Energy Balance Paradigms In People Living With Hiv, Claudia E Ramirez Bustamante, Neeti Agarwal, Aaron R Cox, Sean M Hartig, Jordan E Lake, Ashok Balasubramanyam

Faculty, Staff and Students Publications

Over the past 4 decades, the clinical care of people living with HIV (PLWH) evolved from treatment of acute opportunistic infections to the management of chronic, noncommunicable comorbidities. Concurrently, our understanding of adipose tissue function matured to acknowledge its important endocrine contributions to energy balance. PLWH experience changes in the mass and composition of adipose tissue depots before and after initiating antiretroviral therapy, including regional loss (lipoatrophy), gain (lipohypertrophy), or mixed lipodystrophy. These conditions may coexist with generalized obesity in PLWH and reflect disturbances of energy balance regulation caused by HIV persistence and antiretroviral therapy drugs. Adipocyte hypertrophy characterizes visceral …

Adipose Triglyceride Lipase Is A Therapeutic Target In Advanced Prostate Cancer That Promotes Metabolic Plasticity, Dominik Awad, Pham Hong Anh Cao, Thomas L Pulliam, Meredith Spradlin, Elavarasan Subramani, Tristen V Tellman, Caroline F Ribeiro, Riccardo Muzzioli, Brittany E Jewell, Hubert Pakula, Jeffrey J Ackroyd, Mollianne M Murray, Jenny J Han, Mei Leng, Antrix Jain, Badrajee Piyarathna, Jingjing Liu, Xingzhi Song, Jianhua Zhang, Albert R Klekers, Justin M Drake, Michael M Ittmann, Cristian Coarfa, David Piwnica-Worms, Mary C Farach-Carson, Massimo Loda, Livia S Eberlin, Daniel E Frigo

Faculty, Staff and Students Publications

UNLABELLED: Lipid metabolism plays a central role in prostate cancer. To date, the major focus has centered on de novo lipogenesis and lipid uptake in prostate cancer, but inhibitors of these processes have not benefited patients. A better understanding of how cancer cells access lipids once they are created or taken up and stored could uncover more effective strategies to perturb lipid metabolism and treat patients. Here, we identified that expression of adipose triglyceride lipase (ATGL), an enzyme that controls lipid droplet homeostasis and a previously suspected tumor suppressor, correlates with worse overall survival in men with advanced, castration-resistant prostate …

Dietary Intake And Continuous Blood Glucose Measurement In Nurses Working Either 12-Hour Day Shifts Or Night Shifts, Rachel Carlson, Teresa Rangel, Lindsey Miller, Sushana Sudhi

Providence Nursing Research Conference 2023 – Present

Background:

Night shift work is essential in the hospital yet shift work among nurses is linked to negative outcomes such as chronic fatigue and cardiometabolic illnesses. Furthermore, nurses working night shift are more likely to have aberrant glucose levels, defined as greater than 140 mg/dl. Currently, it is unclear whether nurses working night shift eat differently than those working day shift which may explain aberrant glucose levels.

Purpose:

To determine whether night shift nurses have altered glucose levels and dietary intake compared to day shift nurses.

Methods/Approach:

Nurses regularly working full time 12-hour night shifts (n=12) or full time …

The Utility Of Interventional Anesthesia, Kylie Daguio, Kiley Jackson, Samantha Boever, Andrew Chang, James Keane, Leonard B. Goldstein

SOMA Faculty Publications

no abstract

The Association Between Diet Quality And Glycemic Outcomes Among People With Type 1 Diabetes., Melanie B. Gillingham, Martin Chase Marak, Michael C. Riddell, Peter Calhoun, Robin L. Gal, Susana R. Patton, Peter G. Jacobs, Jessica R. Castle, Mark A. Clements, Francis J. Doyle, Michael R. Rickels, Corby K. Martin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The amount and type of food consumed impacts the glycemic response and insulin needs of people with type 1 diabetes mellitus (T1DM). Daily variability in consumption, reflected in diet quality, may acutely impact glycemic levels and insulin needs.

OBJECTIVE: Type 1 Diabetes Exercise Initiative (T1DEXI) data were examined to evaluate the impact of daily diet quality on near-term glycemic control and interaction with exercise.

METHODS: Using the Remote Food Photography Method, ≤8 d of dietary intake data were analyzed per participant. Diet quality was quantified with the Healthy Eating Index-2015 (HEI), where a score of 100 indicates the highest-quality …

Diabetes Study Of Children Of Diverse Ethnicity And Race: Study Design, Maria J Redondo, Kylie K Harrall, Deborah H Glueck, Mustafa Tosur, Serife Uysal, Andrew Muir, Elizabeth G Atkinson, Melanie R Shapiro, Liping Yu, William E Winter, Michael Weedon, Todd M Brusko, Richard Oram, Kendra Vehik, William Hagopian, Mark A Atkinson, Dana Dabelea, Discover Study Group

Faculty, Staff and Students Publications

AIMS: Determining diabetes type in children has become increasingly difficult due to an overlap in typical characteristics between type 1 diabetes (T1D) and type 2 diabetes (T2D). The Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) programme is a National Institutes of Health (NIH)-supported multicenter, prospective, observational study that enrols children and adolescents with non-secondary diabetes. The primary aim of the study was to develop improved models to differentiate between T1D and T2D in diverse youth.

MATERIALS AND METHODS: The proposed models will evaluate the utility of three existing T1D genetic risk scores in combination with data on …

Impact Of Supplementation With L-Citrulline/Arginine After Liver Transplantation In Individuals With Urea Cycle Disorders, Roland Posset, Sven F Garbade, Florian Gleich, Sandesh C S Nagamani, Andrea L Gropman, Friederike Epp, Nesrine Ramdhouni, Ann-Catrin Druck, Georg F Hoffmann, Stefan Kölker, Matthias Zielonka

Faculty, Staff and Students Publications

Objective: Liver transplantation (LTx) is an intervention when medical management is not sufficiently preventing individuals with urea cycle disorders (UCDs) from the occurrence of hyperammonemic events. Supplementation with L-citrulline/arginine is regularly performed prior to LTx to support ureagenesis and is often continued after the intervention. However, systematic studies assessing the impact of long-term L-citrulline/arginine supplementation in individuals who have undergone LTx is lacking to date.

Methods: Using longitudinal data collected systematically, a comparative analysis was carried out by studying the effects of long-term L-citrulline/arginine supplementation vs. no supplementation on health-related outcome parameters (i.e., anthropometric, neurological, and cognitive outcomes) in individuals …

Endocrine-Sensitive Disease Rate In Postmenopausal Patients With Estrogen Receptor-Rich/Erbb2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, Or Their Combination: A Phase 3 Randomized Clinical Trial, Cynthia X Ma, Vera J Suman, Souzan Sanati, Kiran Vij, Meenakshi Anurag, A Marilyn Leitch, Gary W Unzeitig, Jeremy Hoog, Aranzazu Fernandez-Martinez, Cheng Fan, Richard A Gibbs, Mark A Watson, Travis J Dockter, Olwen Hahn, Joseph M Guenther, Abigail Caudle, Erika Crouch, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Mothaffar F Rimawi, Anna Weiss, Eric P Winer, Kelly K Hunt, Charles M Perou, Matthew J Ellis, Ann H Partridge, Lisa A Carey

Faculty, Staff and Students Publications

IMPORTANCE: Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)-positive/ERBB2 (formerly HER2)-negative breast cancer. However, the combination has not been tested in early-stage disease.

OBJECTIVE: To determine whether neoadjuvant fulvestrant or A+F increases the rate of pathologic complete response or ypT1-2N0/N1mic/Ki67 2.7% or less residual disease (referred to as endocrine-sensitive disease) over anastrozole alone.

DESIGN, SETTING, AND PARTICIPANTS: A phase 3 randomized clinical trial assessing differences in clinical and correlative outcomes between each of the fulvestrant-containing arms and the anastrozole arm. Postmenopausal women with clinical stage II to III, ER-rich (Allred score 6-8 or …

A Case Of Diffuse Thyroid Lipomatosis With Amyloid Deposits Presenting With Thyrotoxicosis, Adrian M Gonzalez-Gil, Marco A Ruiz-Santillan, Bahar K Force, Ruchi Gaba

Faculty, Staff and Students Publications

Diffuse thyroid lipomatosis (DTL) is a rare entity of unknown etiology that can be associated with amyloidosis and rarely, thyrotoxicosis. Here, we present a case of DTL with amyloid deposits and concurrent thyrotoxicosis. A 64-year-old South-Asian woman with a several-year history of an enlarging goiter, unintentional weight loss, and work-up 10 months prior suggestive of thyroiditis presented with a viral syndrome in setting of several weeks of progressive fatigue. Her examination was notable for resting sinus tachycardia and massive painless goiter. Initial work-up revealed nephrotic range proteinuria with hypoalbuminemia, which progressed to end-stage-renal disease, elevated inflammatory markers, and elevated free …

Increased Plasma Branched Short-Chain Fatty Acids And Improved Glucose Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Arianne Aslamy, Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Patricia A Sheridan, Kari E Wong, Gautam Ramesh, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Faculty, Staff and Students Publications

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of …

Ketamine For Pain In Sickle Cell Disease Reduces Opioid Usage, Christina O Onyebuchi, Corrie E Chumpitazi, Jennifer L Placencia, Andrea N Jackson, Jennifer L Jones, Laura Torres, Venée N Tubman

Faculty, Staff and Students Publications

CONTEXT: Pain attributable to sickle cell disease (SCD) is often unpredictable, recurrent, and requires complex treatments. Subanesthetic ketamine infusion has been studied in other diseases and disorders, but there is still limited data on its efficacy in pain management for SCD.

OBJECTIVES: The primary objective is to determine if subanesthetic ketamine infusion reduces pain scores and opioid requirements in hospitalized pediatric patients with SCD.

RESULTS: Forty-six admissions among 22 patients between February 2018 and December 2019 were analyzed. We observed decrease in pain scores within 24 hours of ketamine initiation in 34 of 46 admissions (mean pain score per patient …

Chronic Glp1 Therapy Reduces Postprandial Il6 In Obese Humans With Prediabetes, Vala Hamidi, Hongyu Wang, Vi Pham, Karla Bermudez Saint Andre, Heinrich Taegtmeyer, Absalon D Gutierrez

Faculty, Staff and Student Publications

Single-dose glucagon-like peptide 1 (GLP1) therapy increases postprandial plasma IL6 levels in prediabetic, obese humans. GLP1-IL6 interactions underly multiple antidiabetic effects, but these may differ after acute versus chronic therapy. This study examines postprandial effects of GLP1 after chronic therapy. Seven humans (six Black) with prediabetes and obesity completed 6 weeks of exenatide extended release therapy. Then subjects returned for pre- and post-meal measurements of plasma IL6, GLP1, glucagon, and related inflammatory markers. Weight, which was measured before and after therapy, did not change. Plasma IL6 decreased from baseline to postmeal state ( = 0.016), with decreases in free fatty …

Genetic Drivers Of Heterogeneity In Type 2 Diabetes Pathophysiology, Ken Suzuki, Konstantinos Hatzikotoulas, Lorraine Southam, Henry J Taylor, Xianyong Yin, Kim M Lorenz, Ravi Mandla, Alicia Huerta-Chagoya, Giorgio E M Melloni, Stavroula Kanoni, Nigel W Rayner, Ozvan Bocher, Ana Luiza Arruda, Kyuto Sonehara, Shinichi Namba, Simon S K Lee, Michael H Preuss, Lauren E Petty, Philip Schroeder, Brett Vanderwerff, Mart Kals, Fiona Bragg, Kuang Lin, Xiuqing Guo, Weihua Zhang, Jie Yao, Young Jin Kim, Mariaelisa Graff, Fumihiko Takeuchi, Jana Nano, Amel Lamri, Masahiro Nakatochi, Sanghoon Moon, Robert A Scott, James P Cook, Jung-Jin Lee, Ian Pan, Daniel Taliun, Esteban J Parra, Jin-Fang Chai, Lawrence F Bielak, Yasuharu Tabara, Yang Hai, Gudmar Thorleifsson, Niels Grarup, Tamar Sofer, Matthias Wuttke, Chloé Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Soo-Heon Kwak, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Suraj S Nongmaithem, Raymond Noordam, Victor J Y Lim, Claudia H T Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M Raffield, Bram Peter Prins, Aude Nicolas, Lisa R Yanek, Guanjie Chen, Jennifer A Brody, Edmond Kabagambe, Ping An, Anny H Xiang, Hyeok Sun Choi, Brian E Cade, Jingyi Tan, K Alaine Broadaway, Alice Williamson, Zoha Kamali, Jinrui Cui, Manonanthini Thangam, Linda S Adair, Adebowale Adeyemo, Carlos A Aguilar-Salinas, Tarunveer S Ahluwalia, Sonia S Anand, Alain Bertoni, Jette Bork-Jensen, Ivan Brandslund, Thomas A Buchanan, Charles F Burant, Adam S Butterworth, Mickaël Canouil, Juliana C N Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, John Danesh, Swapan K Das, H Janaka De Silva, George Dedoussis, Latchezar Dimitrov, Ayo P Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S Emery, Daniel S Evans, Michele K Evans, Krista Fischer, James S Floyd, Ian Ford, Oscar H Franco, Timothy M Frayling, Barry I Freedman, Pauline Genter, Hertzel C Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Penny Gordon-Larsen, Myron Gross, Lindsay A Guare, Sophie Hackinger, Liisa Hakaste, Sohee Han, Andrew T Hattersley, Christian Herder, Momoko Horikoshi, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B Jonas, Torben Jørgensen, Frederick K Kamanu, Fouad R Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M Keaton, Abel N Kho, Chiea-Chuen Khor, Muhammad G Kibriya, Duk-Hwan Kim, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A Lange, Kyung Min Lee, Myung-Shik Lee, Nanette R Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E Locke, Tin Louie, Jian'an Luan, Andrea O Luk, Xi Luo, Jun Lv, Julie A Lynch, Valeriya Lyssenko, Shiro Maeda, Vasiliki Mamakou, Sohail Rafik Mansuri, Koichi Matsuda, Thomas Meitinger, Olle Melander, Andres Metspalu, Huan Mo, Andrew D Morris, Filipe A Moura, Jerry L Nadler, Michael A Nalls, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R Patel, Snehal Patil, Pei Pei, Mark A Pereira, Annette Peters, Fraser J Pirie, Hannah G Polikowsky, Bianca Porneala, Gauri Prasad, Laura J Rasmussen-Torvik, Alexander P Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Kevin Sandow, Alagu Sankareswaran, Naveed Sattar, Sebastian Schönherr, Mohammad Shahriar, Botong Shen, Jinxiu Shi, Dong Mun Shin, Nobuhiro Shojima, Jennifer A Smith, Wing Yee So, Alena Stančáková, Valgerdur Steinthorsdottir, Adrienne M Stilp, Konstantin Strauch, Kent D Taylor, Barbara Thorand, Unnur Thorsteinsdottir, Brian Tomlinson, Tam C Tran, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S Udler, Adan Valladares-Salgado, Rob M Van Dam, Jan B Van Klinken, Rohit Varma, Niels Wacher-Rodarte, Eleanor Wheeler, Ananda R Wickremasinghe, Ko Willems Van Dijk, Daniel R Witte, Chittaranjan S Yajnik, Ken Yamamoto, Kenichi Yamamoto, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Matthew Zawistowski, Liang Zhang, Wei Zheng, Leslie J Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A Province, Myriam Fornage, Craig L Hanis, Erik Ingelsson, Alan B Zonderman, Bruce M Psaty, Ya-Xing Wang, Charles N Rotimi, Diane M Becker, Fumihiko Matsuda, Yongmei Liu, Mitsuhiro Yokota, Sharon L R Kardia, Patricia A Peyser, James S Pankow, James C Engert, Amélie Bonnefond, Philippe Froguel, James G Wilson, Wayne H H Sheu, Jer-Yuarn Wu, M Geoffrey Hayes, Ronald C W Ma, Tien-Yin Wong, Dennis O Mook-Kanamori, Tiinamaija Tuomi, Giriraj R Chandak, Francis S Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M Sale, Habibul Ahsan, Ayesha A Motala, Xiao-Ou Shu, Kyong-Soo Park, J Wouter Jukema, Miguel Cruz, Yii-Der Ida Chen, Stephen S Rich, Roberta Mckean-Cowdin, Harald Grallert, Ching-Yu Cheng, Mohsen Ghanbari, E-Shyong Tai, Josee Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Donald W Bowden, Colin N A Palmer, Jaspal S Kooner, Charles Kooperberg, Simin Liu, Kari E North, Danish Saleheen, Torben Hansen, Oluf Pedersen, Nicholas J Wareham, Juyoung Lee, Bong-Jo Kim, Iona Y Millwood, Robin G Walters, Kari Stefansson, Emma Ahlqvist, Mark O Goodarzi, Karen L Mohlke, Claudia Langenberg, Christopher A Haiman, Ruth J F Loos, Jose C Florez, Daniel J Rader, Marylyn D Ritchie, Sebastian Zöllner, Reedik Mägi, Nicholas A Marston, Christian T Ruff, David A Van Heel, Sarah Finer, Joshua C Denny, Toshimasa Yamauchi, Takashi Kadowaki, John C Chambers, Maggie C Y Ng, Xueling Sim, Jennifer E Below, Philip S Tsao, Kyong-Mi Chang, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Cassandra N Spracklen, Josep M Mercader, Michael Boehnke, Jerome I Rotter, Marijana Vujkovic, Benjamin F Voight, Andrew P Morris, Eleftheria Zeggini

Faculty, Staff and Student Publications

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

Association Of Lifestyle Intervention With Risk For Cardiovascular Events Differs By Level Of Glycated Hemoglobin, Michael P Bancks, Scott J Pilla, Ashok Balasubramanyam, Hsin-Chieh Yeh, Karen C Johnson, Joseph Rigdon, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

Purpose: We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c).

Methods: Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on …

International Consensus Statement On The Radiological Evaluation Of Dysraphic Malformations Of The Spine And Spinal Cord, Ankit Balani, Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Özgür Öztekin, Valeria Capra, Martin Catala, Andrew J Copp, Neetu Kumar, Navroop Johal, M Zubair Tahir, Dominic Thompson, Dachling Pang, David M Mirsky, Mai-Lan Ho, Thierry A G M Huisman, Andrea Rossi, Kshitij Mankad

Children’s Nutrition Research Center Staff Publications

Dysraphic malformations of the spine and spinal cord (DMSSC) represent a spectrum of common congenital anomalies typically (though not exclusively) affecting the lower spinal segments. These may be responsible for varying degrees of neurologic, orthopedic, and urologic morbidity. With advances in neuroimaging, it is now possible to better diagnose and evaluate these disorders both prenatally and postnatally. Neuroimaging, performed at the right time and with technique optimization, is integral in guiding clinical management. However, the terminology used to describe these lesions has become increasingly confusing, and there is a lack of consensus regarding the essential radiologic features and their clinical …

Risk Factors For Non-Healing Wounds—A Single-Centre Study, Daniel Wolny, Ladislav Štěpánek, Dagmar Horáková, Janet Thomas, Jana Zapletalová, Mihir Sanjay Patel

Faculty, Staff and Student Publications

Background: Chronic wounds present a significant clinical, social, and economic challenge. This study aimed to objectify the risk factors of healing outcomes and the duration of chronic wounds from various etiologies. Methods: Patients treated for non-healing wounds at the surgical outpatient clinic of the Olomouc Military Hospital were involved. Data from patients treated between 8/2021 and 9/2023 were selected. Patients were mostly treated as outpatients, with microbiological follow-up indicated in cases of advanced signs of inflammation. Results: There were 149 patients who met our selection criteria (the mean age was 64.4 years). Predominant causes of wounds involved diabetes (30.9%), post-trauma …

Arterial Stiffness And Obesity As Predictors Of Diabetes: Longitudinal Cohort Study, Cancan Cui, Zhiyuan Wu, Jia Zheng, Jiaqi Chu, Jiajing Zhu, Yitian Qi, Zhenming Zhang, Zhijia Wang, Mengchao Zhang, Zhanhao Mo, Liangkai Cheng, Lei Ding, Xiaoping Kang, Lin Liu, Te Zhang

Research outputs 2022 to 2026

BACKGROUND: Previous studies have confirmed the separate effect of arterial stiffness and obesity on type 2 diabetes; however, the joint effect of arterial stiffness and obesity on diabetes onset remains unclear. OBJECTIVE: This study aimed to propose the concept of arterial stiffness obesity phenotype and explore the risk stratification capacity for diabetes. METHODS: This longitudinal cohort study used baseline data of 12,298 participants from Beijing Xiaotangshan Examination Center between 2008 and 2013 and then annually followed them until incident diabetes or 2019. BMI (waist circumference) and brachial-ankle pulse wave velocity were measured to define arterial stiffness abdominal obesity phenotype. The …

Streamlined Adeno-Associated Virus Production Using Suspension Hek293t Cells, Aditi A Kulkarni, Austin G Seal, Corinne Sonnet, Kazuhiro Oka

Faculty, Staff and Students Publications

Recombinant adeno-associated viruses (rAAVs) are valuable viral vectors for in vivo gene transfer, also having significant ex vivo therapeutic potential. Continued efforts have focused on various gene therapy applications, capsid engineering, and scalable manufacturing processes. Adherent cells are commonly used for virus production in most basic science laboratories because of their efficiency and cost. Although suspension cells are easier to handle and scale up compared to adherent cells, their use in virus production is hampered by poor transfection efficiency. In this protocol, we developed a simple scalable AAV production protocol using serum-free-media-adapted HEK293T suspension cells and VirusGEN transfection reagent. The …

Fluvoxamine Inhibits Th1 And Th17 Polarization And Function By Repressing Glycolysis To Attenuate Autoimmune Progression In Type 1 Diabetes, Yuan Zou, Jing Zhang, Fei Sun, Qianqian Xu, Longmin Chen, Xi Luo, Ting Wang, Qing Zhou, Shu Zhang, Fei Xiong, Wen Kong, Ping Yang, Qilin Yu, Shiwei Liu, Cong-Yi Wang

Faculty, Staff and Student Publications

BACKGROUND: Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed.

METHOD: Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune …

Neighborhood Environment And Poor Maternal Glycemic Control-Associated Complications Of Gestational Diabetes Mellitus, Leela V. Thomas, Claudine T. Jurkovitz, Zugui Zhang, Mitchell R. Fawcett, M. James Lenhard

Department of Medicine Faculty Papers

INTRODUCTION: Risk of complications due to gestational diabetes mellitus is increasing in the U.S., particularly among individuals from racial minorities. Research has focused largely on clinical interventions to prevent complications, rarely on individuals' residential environments. This retrospective cohort study aims to examine the association between individuals' neighborhoods and complications of gestational diabetes mellitus.

METHODS: Demographic and clinical data were extracted from electronic health records and linked to American Community Survey data from the U.S. Census Bureau for 2,047 individuals who had 2,164 deliveries in 2014-2018. Data were analyzed in 2021-2022 using Wilcoxon rank sum test and chi-square test for bivariate …