Endocrinology, Diabetes, and Metabolism Commons^™

Milder Loss Of Insulin-Containing Islets In Individuals With Type 1 Diabetes And Type 2 Diabetes-Associated Tcf7l2 Genetic Variants, Maria J Redondo, Sarah J Richardson, Daniel Perry, Charles G Minard, Alice L J Carr, Todd Brusko, Irina Kusmartseva, Alberto Pugliese, Mark A Atkinson

Faculty, Staff and Students Publications

AIMS/HYPOTHESIS: TCF7L2 variants are the strongest genetic risk factor for type 2 diabetes. In individuals with type 1 diabetes, these variants are associated with a higher C-peptide AUC, a lower glucose AUC during an OGTT, single autoantibody positivity near diagnosis, particularly in individuals older than 12 years of age, and a lower frequency of type 1 diabetes-associated HLA genotypes. Based on initial observations from clinical cohorts, we tested the hypothesis that type 2 diabetes-predisposing TCF7L2 genetic variants are associated with a higher percentage of residual insulin-containing cells (ICI%) in pancreases of donors with type 1 diabetes, by examining genomic data …

Nanocurcumin Combined With Insulin Alleviates Diabetic Kidney Disease Through P38/P53 Signaling Axis, Raghu Ganugula, Nikhil K Nuthalapati, Subhash Dwivedi, Dianxiong Zou, Meenakshi Arora, Richard Friend, David Sheikh-Hamad, Rita Basu, M N V Ravi Kumar

Faculty, Staff and Students Publications

Treatments for diabetic kidney disease (DKD) mainly focus on managing hyperglycemia and hypertension, but emerging evidence suggests that inflammation also plays a role in the pathogenesis of DKD. This 10-week study evaluated the efficacy of daily oral nanoparticulate-curcumin (nCUR) together with long-acting insulin (INS) to treat DKD in a rodent model. Diabetic rats were dosed with unformulated CUR alone, nCUR alone or together with INS, or INS alone. The progression of diabetes was reflected by increases in plasma fructosamine, blood urea nitrogen, creatinine, bilirubin, ALP, and decrease in albumin and globulins. These aberrancies were remedied by nCUR+INS or INS but …

Initial Insights Into The Genetic Variation Associated With Metformin Treatment Failure In Youth With Type 2 Diabetes, Shylaja Srinivasan, Ling Chen, Miriam Udler, Jennifer Todd, Megan M Kelsey, Morey W Haymond, Silva Arslanian, Philip Zeitler, Rose Gubitosi-Klug, Kristen J Nadeau, Katherine Kutney, Neil H White, Josephine H Li, James A Perry, Varinderpal Kaur, Laura Brenner, Josep M Mercader, Adem Dawed, Ewan R Pearson, Sook-Wah Yee, Kathleen M Giacomini, Toni Pollin, Jose C Florez

Faculty, Staff and Students Publications

Metformin is the first-line treatment for type 2 diabetes (T2D) in youth but with limited sustained glycemic response. To identify common variants associated with metformin response, we used a genome-wide approach in 506 youth from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study and examined the relationship between T2D partitioned polygenic scores (pPS), glycemic traits, and metformin response in these youth. Several variants met a suggestive threshold (P < 1 × 10−6), though none including published adult variants reached genome-wide significance. We pursued replication of top nine variants in three cohorts, and rs76195229 in ATRNL1 was associated with worse metformin response in the Metformin Genetics Consortium (n = 7,812), though statistically not being significant after Bonferroni correction (P …

Factors Associated With Foot Self-Care In Patients With Diabetes-Related High-Risk Feet: A Cross-Sectional Design, Anas Ababneh, Sameh Moosa, Qusai Aljarrah, Yazan Alsoufi, Ma’En Z. Abu Qamar, Mohamad Saleh, Samiha Jarrah, Nidal A. Younes

Research outputs 2022 to 2026

Foot self-care has been commonly studied among people with diabetes. Previous research on foot self-care among those with diabetes-related high-risk feet is almost unavailable or very limited. The current study aims to fill this gap and provide a contemporary unprecedented analysis of this area of specialization. To assess the levels of, and factors associated with foot self-care among people with diabetes-related high-risk feet. A multi-center cross-sectional study from Jordan assessed the foot self-care of 107 participants with diabetes-related high-risk feet. Multiple socio-demographic, physiological, and psychosocial factors were collected, and the Arabic version of the diabetes foot self-care behavior scale was …

Enrollment Of Underrepresented Racial And Ethnic Groups In The Rare And Atypical Diabetes Network (Radiant), Mustafa Tosur, Laura Gandolfo, Ashok Balasubramanyam, Rochelle N Naylor, Toni I Pollin, Neda Rasouli, Sara J Cromer, John B Buse, Maria J Redondo, Radiant Study Group

Faculty, Staff and Students Publications

INTRODUCTION: Diabetes mellitus in underrepresented racial and ethnic groups (URG) is rapidly increasing in incidence and has worse outcomes than diabetes in non-Hispanic White individuals. Rare and Atypical Diabetes Network (RADIANT) established recruitment targets based on the racial and ethnic distribution of the USA to enroll a diverse study population. We examined participation of URG across RADIANT study stages and described strategies to enhance recruitment and retention of URG.

MATERIALS AND METHODS: RADIANT is a multicenter NIH-funded study of people with uncharacterized forms of atypical diabetes. RADIANT participants consent online and progress through three sequential study stages, as eligible.

RESULTS: …

Clinical Characterization Of Data-Driven Diabetes Clusters Of Pediatric Type 2 Diabetes, Mahsan Abbasi, Mustafa Tosur, Marcela Astudillo, Ahmad Refaey, Ashutosh Sabharwal, Maria J Redondo

Faculty, Staff and Students Publications

BACKGROUND: Pediatric Type 2 diabetes (T2D) is highly heterogeneous. Previous reports on adult-onset diabetes demonstrated the existence of diabetes clusters. Therefore, we set out to identify unique diabetes subgroups with distinct characteristics among youth with T2D using commonly available demographic, clinical, and biochemical data.

METHODS: We performed data-driven cluster analysis (K-prototypes clustering) to characterize diabetes subtypes in pediatrics using a dataset with 722 children and adolescents with autoantibody-negative T2D. The six variables included in our analysis were sex, race/ethnicity, age, BMI

RESULTS: We identified five distinct clusters of pediatric T2D, with different features, treatment regimens and risk of diabetes complications: …

Transcriptomic Analyses Of Ovarian Clear-Cell Carcinoma With Concurrent Endometriosis, Kaitlyn E Collins, Xiyin Wang, Yuliya Klymenko, Noah B Davis, Maria C Martinez, Chi Zhang, Kaman So, Aaron Buechlein, Douglas B Rusch, Chad J Creighton, Shannon M Hawkins

Faculty, Staff and Students Publications

INTRODUCTION: Endometriosis, a benign inflammatory disease whereby endometrial-like tissue grows outside the uterus, is a risk factor for endometriosis-associated ovarian cancers. In particular, ovarian endometriomas, cystic lesions of deeply invasive endometriosis, are considered the precursor lesion for ovarian clear-cell carcinoma (OCCC).

METHODS: To explore this transcriptomic landscape, OCCC from women with pathology-proven concurrent endometriosis (n = 4) were compared to benign endometriomas (n = 4) by bulk RNA and small-RNA sequencing.

RESULTS: Analysis of protein-coding genes identified 2449 upregulated and 3131 downregulated protein-coding genes (DESeq2, P< 0.05, log2 fold-change > |1|) in OCCC with concurrent endometriosis compared to endometriomas. Gene set enrichment …

Protocol For The Promoting Resilience In Stress Management (Prism) Intervention: A Multi-Site Randomized Controlled Trial For Adolescents With Type 1 Diabetes, Maeve B O'Donnell, Samantha R Scott, Britney M Ellisor, Viena T Cao, Chuan Zhou, Miranda C Bradford, Catherine Pihoker, Daniel J Desalvo, Faisal S Malik, Marisa E Hilliard, Abby R Rosenberg, Joyce P Yi-Frazier

Faculty, Staff and Students Publications

BACKGROUND: Adolescents with type 1 diabetes (T1D) are at high risk for elevated diabetes distress, which greatly impacts diabetes management, glycemic outcomes and overall quality of life. Developing protective skills and "resilience resources" to navigate adversity and manage diabetes distress has high potential to help adolescents with T1D achieve optimal behavioral, psychological, and health outcomes. The "Promoting Resilience in Stress Management" (PRISM) program is a manualized, brief, skills-based intervention delivered over 6 months via two 45-60 min one-on-one sessions and a family meeting with a PRISM coach, and supplemented by booster calls and a digital app. This trial (PRISM versus …

Malignant Insulinoma Arising From Nonfunctioning Pancreatic Neuroendocrine Tumor, Ritodhi Chatterjee, Basim Ali, Son H Nguyen, Rui Chen, Yvonne H Sada

Faculty, Staff and Students Publications

Pancreatic neuroendocrine tumors are rare neoplasms characterized into nonfunctioning (NF-PNET) and functioning (F-PNET) subtypes. F-PNETs typically involve overt symptoms related to excessive hormone secretion but may rarely present first as NF-PNETs with delayed transformation. We present a patient with known NF-PNET with liver metastases who developed hypoglycemia 2 years after initial diagnosis due to malignant insulinoma. Hypoglycemia was refractory to continuous dextrose but improved temporarily after diazoxide and hepatic artery embolization. Malignant insulinomas are usually metastatic at presentation and portend poor prognosis. Hypoglycemia may be medically managed with steroids, somatostatin analogues, and diazoxide, along with therapies to reduce tumor burden.

Development Of A Clinical Prediction Model For Diabetes In Chronic Pancreatitis: The Predict3c Study, Christie Jeon, Phil A Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D Bellin, William E Fisher, Evan L Fogel, Christopher E Forsmark, Walter G Park, Stephen K Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C Whitcomb, Dana K Andersen, Darwin L Conwell, Dhiraj Yadav, Mark O Goodarzi

Faculty, Staff and Student Publications

Objective: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

Research design and methods: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was …

Patient-Specific Analysis Of Aortic Hemodynamics And Wall Shear Stresses In Patients Undergoing Pediatric Bariatric Surgery Using 2d Phase-Contrast Mri, Oluwaferanmi S. Akande, Joao Soares, Nathan Hargan, Dr. Uyen Truong, Haeung Kang, David Lanning

Undergraduate Research Posters

Patient-Specific Analysis of Aortic Hemodynamics and Wall Shear Stresses in Patients Undergoing Pediatric Bariatric Surgery using 2D Phase-Contrast MRI

Feranmi Akande¹ Nathan Hargan² Haesung Kang³ David Lanning³ Uyen Truong⁴ João S. Soares¹

¹ Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University

² Department of Mechanical & Nuclear Engineering, College of Engineering, Virginia Commonwealth University

³ Department of Cardiology, Children’s Hospital of Richmond, Virginia Commonwealth University

Introduction: Severe obesity among today’s youth is a rising epidemic within the United States. Emerging research has linked childhood obesity with shortened life expectancy and early …

A Conserved Oxalyl-Coenzyme A Decarboxylase In Oxalate Catabolism, Ninghui Cheng, Vincent Paris, Xiaolan Rao, Xiaoqiang Wang, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

The ability to biosynthesize oxalic acid can provide beneficial functions to plants; however, uncontrolled or prolonged exposure to this strong organic acid results in multiple physiological problems. Such problems include a disruption of membrane integrity, mitochondrial function, metal chelation, and free radical formation. Recent work suggests that a CoA-dependent pathway of oxalate catabolism plays a critical role in regulating tissue oxalate concentrations in plants. Although this CoA-dependent pathway of oxalate catabolism is important, large gaps in our knowledge of the enzymes catalyzing each step remain. Evidence that an oxalyl-CoA decarboxylase (OXC) catalyzes the second step in this pathway, accelerating the …

Influence Of Waist Circumference Measurement Site On Visceral Fat And Metabolic Risk In Youth, Sojung Lee, Yejin Kim, Minsub Han

Faculty, Staff and Student Publications

Although the rate of childhood obesity seems to have plateaued in recent years, the prevalence of obesity among children and adolescents remains high. Childhood obesity is a major public health concern as overweight and obese youth suffer from many co-morbid conditions once considered exclusive to adults. It is now well demonstrated that abdominal obesity as measured by waist circumference (WC) is an independent risk factor for cardiovascular disease and metabolic dysfunction in youth. Despite the strong associations between WC and cardiometabolic risk factors, there is no consensus regarding the optimal WC measurement sites to assess abdominal obesity and obesity-related health …

Measurement Of Force And Intramuscular Pressure Changes Related To Thrust Spinal Manipulation In An In Vivo Animal Model, William R Reed, Carla R Lima, Michael A K Liebschner, Christopher P Hurt, Peng Li, Maruti R Gudavalli

Faculty, Staff and Students Publications

Simple Summary

Spinal manipulation is recommended by clinical guidelines to treat low back pain. However, our understanding of how spinal manipulation alleviates pain and knowledge of the role that viscoelastic tissue properties play in the dampening of applied spinal manipulation forces in vivo is limited. Superficial and deep intramuscular pressures and applied forces were measured using miniature pressure catheters and a force transducer during low back spinal manipulation using a clinically available spinal manipulation device (Activator V) or a feedback motor in a deeply anesthetized animal model. Viscoelastic properties of muscle and other soft tissues greatly diminished applied spinal manipulative …

Lifestyle Tools For Men’S Health And Disease Prevention: Well-Being Through Nutrition, Physical Activity, Stress Management, And Connection, Leigh A. Frame

Clinical Research and Leadership Faculty Publications

Mental health is an often-overlooked aspect of overall health and wellness (well-being). Mental illness is increasingly common with 1 in 5 American adults experiencing it annually, and 1 in 20 suffering from a serious mental illness each year [1]. Treatment rates for mental illness are lower in men (37.4%) compared to women (51.2%) [1]. Globally, treatment rates are similar with an estimated cost to the global economy of $1 trillion annually, yet less than 2% of government health expenditure is for mental health worldwide [2]. Despite this, only nine studies have been published specifically targeting men’s mental health through lifestyle …

Pleiomorphism Plurihormonal Pit-1-Positive Macroadenoma With Central Hyperthyroidism: A Rare Case Report And Literature Review, Guiliang Peng, Chuanhong Guo, Yangfan Lv, Dandan Li, Ling Zhou, Rufei Shen, Yong Chen, Xin Zheng, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

BACKGROUND: Thyrotropin-secreting pituitary neuroendocrine tumors (PitNETs) are rare pituitary adenomas that are occasionally accompanied by hypersecretion of other anterior pituitary hormones, such as growth hormone (GH) and prolactin (PRL). The clinical, biochemical, and pathological characteristics may represent diverse circumstances.

CASE PRESENTATION: In this report, a 33-year-old female diagnosed with a TSH PitNET co-secreting GH presented no obvious clinical symptoms. The main characteristics were elevated thyroid-stimulating hormone (TSH), free tri-iodothyronine (FT3), and free thyroxine (FT4) levels accompanied by slightly elevated GH and insulin-like growth factor-1 (IGF-1) levels. Magnetic resonance imaging (MRI) detected a pituitary macroadenoma (18 × 16 × 16 mm) …

Does Receiving A Sars-Cov-2 Antibody Test Result Change Covid-19 Protective Behaviors? Testing Risk Compensation In Undergraduate Students With A Randomized Controlled Trial, Christina Ludema, Molly S Rosenberg, Jonathan T Macy, Sina Kianersi, Maya Luetke, Chen Chen, Lilian Golzarri-Arroyo, Erin Ables, Kevin Maki, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Risk compensation, or matching behavior to a perceived level of acceptable risk, can blunt the effectiveness of public health interventions. One area of possible risk compensation during the SARS-CoV-2 pandemic is antibody testing. While antibody tests are imperfect measures of immunity, results may influence risk perception and individual preventive actions. We conducted a randomized control trial to assess whether receiving antibody test results changed SARS-CoV-2 protective behaviors.

Purpose: Assess whether objective information about antibody status, particularly for those who are antibody negative and likely still susceptible to SARS-CoV-2 infection, increases protective behaviors. Secondarily, assess whether a positive antibody test …

Progressive Acceleration Of Insulin Exposure Over 7 Days Of Infusion Set Wear, Jasmin R. Kastner, Timothy S. Bailey, Poul Strange, Leon Shi, Keith A. Oberg, Paul J. Strasma, Jeffrey I. Joseph, Douglas B. Muchmore

Department of Anesthesiology Faculty Papers

Insulin exposure varies over 3 days of insulin infusion set (IIS) wear making day-to-day insulin dosing challenging for people with diabetes (PWD). Here we report insulin pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C ≤8.5%, C-peptide tmax (P < 0.001), Cmax (P < 0.05), and mean residence time (P < 0.0001). Area under the insulin concentration curve (AUC0–300) declined by ∼24% from days 0 to 7 (P < 0.05). These results confirm/extend previous observations showing progressive acceleration of insulin exposure over IIS wear time. This may have implications for PWD and designers of closed-loop algorithms, although larger studies are necessary to confirm this. The study was registered in clinicaltrials.gov (NCT04398030).

Improving Glycemic Control During The Covid-19 Pandemic: A Quality Improvement Project, Megan Henderson

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

Diabetes is a costly, chronic health condition. The COVID-19 pandemic has significantly impacted the delivery of health care and exacerbated chronic health conditions, such as diabetes. Diabetes is one of the most significant comorbid conditions associated with poor COVID-19 outcomes (Cariou et al., 2020). Control of blood glucose levels during the COVID-19 pandemic has proved challenging to maintain. The purpose of this quality improvement project is to identify gaps in diabetic self-care and then implement a diabetic toolkit to improve self-efficacy of diabetes self-management. According to the American Diabetes Association (2022), self-management of diabetes, education, and support from providers is …

3d Imaging Analysis On An Organoid-Based Platform Guides Personalized Treatment In Pancreatic Ductal Adenocarcinoma, Ya'an Kang, Jenying Deng, Jianhua Ling, Xinqun Li, Yi-Ju Chiang, Eugene J Koay, Huamin Wang, Jared K Burks, Paul J Chiao, Mark W Hurd, Manoop S Bhutani, Jeffrey H Lee, Brian R Weston, Anirban Maitra, Naruhiko Ikoma, Ching-Wei D Tzeng, Jeffrey E Lee, Ronald A Depinho, Robert A Wolff, Shubham Pant, Florencia Mcallister, Matthew Hg Katz, Jason B Fleming, Michael P Kim

Faculty, Staff and Student Publications

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care …