Endocrinology, Diabetes, and Metabolism Commons^™

The Role Of Gip Receptor In The Cns For The Pathogenesis Of Obesity, Makoto Fukuda

Children’s Nutrition Research Center Staff Publications

Glucose-dependent insulinotropic polypeptide (GIP) (also known as gastric inhibitory polypeptide) is a hormone produced in the upper gut and secreted to the circulation in response to the ingestion of foods, especially fatty foods. Growing evidence supports the physiological and pharmacological relevance of GIP in obesity. In an obesity setting, inhibition of endogenous GIP or its receptor leads to decreased energy intake, increased energy expenditure, or both, eventually causing weight loss. Further, supraphysiological dosing of exogenous long-lasting GIP agonists alters energy balance and has a marked antiobesity effect. This remarkable yet paradoxical antiobesity effect is suggested to occur primarily via the …

Opportunities To Address Obesity Disparities Among High-Risk Latino Children And Adolescents, Erica G Soltero, Teresia M O'Connor, Deborah Thompson, Gabriel Q Shaibi

Children’s Nutrition Research Center Staff Publications

Purpose of review: This review highlights obesity-related disparities among Latino children and adolescents, discusses the social determinants of health (SDoH) that drive disparities, and presents case studies of strategies for reducing disparities and promoting health equity.

Recent findings: Recommended strategies for reducing obesity-related disparities include the use of culturally grounded programming, multi-sector collaborations, and technology. We present two exemplar studies that demonstrate that integrating cultural values and enhancing the overall cultural fit of prevention programs can increase engagement among high-risk Latino families. We also examine the use of multi-sector collaborations to build community capacity and address key SDoH that impact …

Theoretical Mediators Of Diabetes Risk And Quality Of Life Following A Diabetes Prevention Program For Latino Youth With Obesity, Erica G Soltero, Stephanie L Ayers, Marvyn A Avalos, Armando Peña, Allison N Williams, Micah L Olson, Yolanda P Konopken, Felipe G Castro, Kimberly J Arcoleo, Colleen S Keller, Donald L Patrick, Justin Jager, Gabriel Q Shaibi

Children’s Nutrition Research Center Staff Publications

Purpose: This study tested self-efficacy and social support for activity and dietary changes as mediators of changes in type 2 diabetes related outcomes following a lifestyle intervention among Latino youth.

Setting and intervention: Latino adolescents (14-16 years) with obesity (BMI% = 98.1 ± 1.4) were randomized to a 3-month intervention (n = 67) that fostered self-efficacy and social support through weekly, family-centered sessions or a comparison condition (n = 69).

Measures: Primary outcomes included insulin sensitivity and weight specific quality of life. Mediators included self-efficacy, friend, and family social support for health behaviors. Data was collected at baseline, 3-months, 6-months, …

Challenges In Feeding Children Posed By The Covid-19 Pandemic: A Systematic Review Of Changes In Dietary Intake Combined With A Dietitian's Perspective, Heather Campbell, Alexis C Wood

Children’s Nutrition Research Center Staff Publications

Purpose of review: To examine the evidence that the dietary quality of children changed between the period preceding the COVID-19 pandemic and the first year during the pandemic.

Recent findings: A systematic review of the evidence for dietary changes occurring as a result of the pandemic-related restrictions, in Part I of this article, yielded 38 original research articles. These articles had conflicting results, some describing improvements in overall quality and some describing deteriorations. As a whole the studies were characterized by a low study quality, and children were poorly represented. Taken together, these studies do not provide enough evidence to …

Tcf7l2 Genetic Variants Do Not Influence Insulin Sensitivity Or Secretion Indices In Autoantibody-Positive Individuals At Risk For Type 1 Diabetes, Maria J Redondo, Megan V Warnock, Ingrid M Libman, Laura E Bocchino, David Cuthbertson, Susan Geyer, Alberto Pugliese, Andrea K Steck, Carmella Evans-Molina, Dorothy Becker, Jay M Sosenko, Fida Bacha, Type 1 Diabetes Trialnet Study Group

Children’s Nutrition Research Center Staff Publications

Objective: We aimed to test whether type 2 diabetes (T2D)-associated TCF7L2 genetic variants affect insulin sensitivity or secretion in autoantibody-positive relatives at risk for type 1 diabetes (T1D).

Research design and methods: We studied autoantibody-positive TrialNet Pathway to Prevention study participants (N = 1,061) (mean age 16.3 years) with TCF7L2 single nucleotide polymorphism (SNP) information and baseline oral glucose tolerance test (OGTT) to calculate indices of insulin sensitivity and secretion. With Bonferroni correction for multiple comparisons, P values < 0.0086 were considered statistically significant.

Results: None, one, and two T2D-linked TCF7L2 alleles were present in 48.1%, 43.9%, and 8.0% of the participants, respectively. Insulin sensitivity …

Diabetes Detection And Prevention In Dermatology, Alexandra Ngo, Luise Froessl, John Wesley Mcwhorter, William Brett Perkison, Rajani Katta

Faculty, Staff and Student Publications

We are currently in the midst of an international epidemic of diabetes mellitus (DM) and prediabetes. The prevalence of DM in the United States is estimated at 9.4% of the population across all ages, while an estimated 1 in 3 Americans (33.9%) has prediabetes. According to the WHO, about 60 million people suffer from diabetes in the European Region. Dermatologists may play an important role in tackling this epidemic via efforts to improve early detection of both diabetes and prediabetes. Dermatologists often treat patients with, or at risk of, diabetes. This includes patients who present with cutaneous manifestations such as …

Hiv-1 Viral Protein R Couples Metabolic Inflexibility With White Adipose Tissue Thermogenesis, Neeti Agarwal, Dinakar Iyer, Pradip Saha, Aaron R Cox, Yan Xia, Netanya S Utay, Anoma Somasundaram, Ulrich Schubert, Jordan E Lake, Sean M Hartig, Ashok Balasubramanyam

Faculty, Staff and Students Publications

Persons living with HIV (PLWH) manifest chronic disorders of brown and white adipose tissues that lead to diabetes and metabolic syndrome. The mechanisms that link viral factors to defective adipose tissue function and abnormal energy balance in PLWH remain incompletely understood. Here, we explored how the HIV accessory protein viral protein R (Vpr) contributes to adaptive thermogenesis in two mouse models and human adipose tissues. Uncoupling protein 1 (UCP1) gene expression was strongly increased in subcutaneous white adipose tissue (WAT) biopsy specimens from PLWH and in subcutaneous WAT of the Vpr mice, with nearly equivalent mRNA copy number. Histology and …

Oral Minimal Model For Gestational Diabetes, Sarah Peters

Symposium of Student Scholars

Gestational diabetes is one of the most common issues that a pregnant woman encounters that could result in harm to both the woman and child. Due to this issue, the woman’s glucose and insulin levels should be carefully monitored throughout her pregnancy to assess the need for prescribed diabetic medication to help regulate those levels. In this research, the objectives is to develop a MATLAB computer program of the Oral Minimal Model, which is a model that can be used to estimate a person’s insulin sensitivity from an oral glucose tolerance test (OGTT) where plasma glucose and insulin levels are …

Glycosaminoglycans As Biomarkers For Mucopolysaccharidoses And Other Disorders, Paige Amendum, Shaukat Khan, Seiji Yamaguchi, Hironori Kobayashi, Yasuhiko Ago, Yasuyuki Suzuki, Betul Celik, Estera Rintz, Jobayer Hossain, Wendi Xiao, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Glycosaminoglycans (GAGs) are present in proteoglycans, which play critical physiological roles in various tissues. They are known to be elevated in mucopolysaccharidoses (MPS), a group of rare inherited metabolic diseases in which the lysosomal enzyme required to break down one or more GAG is deficient. In a previous study, we found elevation of GAGs in a subset of patients without MPS. In the current study, we aim to investigate serum GAG levels in patients with conditions beyond MPS. In our investigated samples, the largest group of patients had a clinical diagnosis of viral or non-viral encephalopathy. Clinical diagnoses and conditions …

There Is Insufficient Evidence To Recommend Bremelanotide For Hypoactive Sexual Desire Disorder, Scott Yaekle Md, Halima Ali Md, Carol Baker Md

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent discussion for a patient with Hypoactive Sexual Desire Disorder.

Correcting For Sparsity And Interdependence In Glycomics By Accounting For Glycan Biosynthesis, Bokan Bao, Benjamin P Kellman, Austin W T Chiang, Yujie Zhang, James T Sorrentino, Austin K York, Mahmoud A Mohammad, Morey W Haymond, Lars Bode, Nathan E Lewis

Children’s Nutrition Research Center Staff Publications

Glycans are fundamental cellular building blocks, involved in many organismal functions. Advances in glycomics are elucidating the essential roles of glycans. Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps. Furthermore, the overlap of measured glycans can be low across samples. We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power. …

Subacute Thyroiditis Secondary To Moderna Covid-19 Vaccine: A Case Report Of A Rare Manifestation, Mayank Patel, Marika Shahid, Ahmad Khawaja, Chibuzor Ejike, Kavitha Vemuri

Advances in Clinical Medical Research and Healthcare Delivery

The SARS-CoV-2 led to a global pandemic, infecting millions of lives within only a short period of time. The symptoms of the disease vary with a subset of the population developing debilitating sequelae. Through the emergency use authorization (EUA), multiple vaccines have been released against the novel virus in record time. Long term and rare sequelae from the vaccine are poorly understood. DeQuervain’s subacute thyroiditis is a self-limiting and painful inflammation of the thyroid gland usually associated with viral infections. We report a rare case of subacute thyroiditis in a healthy 46-year-old woman presenting with a painful swelling in the …

Daily Energy Expenditure Through The Human Life Course, Herman Pontzer, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marjije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Teresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia Loechl, Amy H Luke, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at …

Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Na Li, Mingyang Huang, Mason Bartels, Sophie Dogné, Shangang Zhao, Xi Chen, Clair Crewe, Leon Straub, Lavanya Vishvanath, Zhuzhen Zhang, Mengle Shao, Yongjie Yang, Christy M Gliniak, Ruth Gordillo, Gordon I Smith, William L Holland, Rana K Gupta, Bingning Dong, Nathalie Caron, Yong Xu, Yucel Akgul, Samuel Klein, Philipp E Scherer

Faculty, Staff and Students Publications

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma …

Perceptions And Practices Of Indigenous Populations About Diabetes In Guatemala, Liesl Cohn De Leon

International Programs

Diabetes is becoming a common disease among indigenous populations in Guatemala. They perceive diabetes not only as a medical disease, but also a condition linked to emotions. They say they have total confidence in the official health system, but in practice they rely on the ancestral Mayan knowledge of the healers and spiritual guides to complement biomedical treatments.

Simple Energy Balance Or Microbiome For Childhood Obesity Prevention?, Tom Baranowski, Kathleen J Motil

Children’s Nutrition Research Center Staff Publications

Obesity prevention interventions generally have either not worked or had effects inadequate to mitigate the problem. They have been predicated on the simple energy balance model, which has been severely questioned by biological scientists. Numerous other etiological mechanisms have been proposed, including the intestinal microbiome, which has been related to childhood obesity in numerous ways. Public health research is needed in regard to diet and the microbiome, which hopefully will lead to effective child obesity prevention.

Dose Adjustment Of Antidiabetic Medications In Chronic Kidney Disease, Matthew Salvatore Snyder, Joshua Fogel, Svetlana Pyatigorskaya, Sofia Rubinstein

Publications and Research

Purpose: The purpose of this study is to identify whether Internal Medicine house-staff (IMHS) have awareness and knowledge about the correct dosage of antidiabetic medications for patients with chronic kidney disease (CKD), as dosing errors result in adverse patient outcomes for those with diabetes mellitus (DM) and CKD.

Methods: There were 353 IMHS surveyed to evaluate incorrect level of awareness of medication dose adjustment in patients with CKD (ILA) and incorrect level of knowledge of glomerular filtration rate level for medication adjustment (ILK-GFR) for Glipizide, Pioglitazone, and Sitagliptin.

Results: Lack of awareness and knowledge was high, with the highest for …

Monogenic Diabetes In Youth With Presumed Type 2 Diabetes: Results From The Progress In Diabetes Genetics In Youth (Prodigy) Collaboration, Jennifer N Todd, Jeffrey W Kleinberger, Haichen Zhang, Shylaja Srinivasan, Sherida E Tollefsen, Lynne L Levitsky, Lorraine E Levitt Katz, Jeanie B Tryggestad, Fida Bacha, Giuseppina Imperatore, Jean M Lawrence, Catherine Pihoker, Jasmin Divers, Jason Flannick, Dana Dabelea, Jose C Florez, Toni I Pollin

Children’s Nutrition Research Center Staff Publications

Objective: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes.

Research design and methods: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic …

Family-Based Obesity Prevention Interventions Among Hispanic Children And Families: A Scoping Review, Erica G Soltero, Armando Peña, Veronica Gonzalez, Edith Hernandez, Guisela Mackey, Chishinga Callender, Jayna M Dave, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

This scoping review examined intervention and sample characteristics of family-based obesity prevention interventions among Hispanic youth. This review also examined the degree to which existing interventions were culturally-adapted, acknowledged social determinants of health (SDoH), and collaborated with community stakeholders. A comprehensive search across Medline Ovid, Embase, Scopus, PsycInfo, and Pubmed was used to identify 13 studies primarily based in the U.S. (92.3%). Data was extracted by two independent reviewers. Most used a randomized control trial design (69.2%), a behavior change theory (84.6%), and reported moderate to high (≥70%) retention (69.2%). Studies targeted improvements in physical activity (69.2%) and fruit and …

A Machine Learning Case-Control Classifier For Schizophrenia Based On Dna Methylation In Blood, Chathura J Gunasekara, Eilis Hannon, Harry Mackay, Cristian Coarfa, Andrew Mcquillin, David St Clair, Jonathan Mill, Robert A Waterland

Children’s Nutrition Research Center Staff Publications

Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case–control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); …