Endocrine System Diseases Commons^™

Development Of Canagliflozin Nanocrystals Sublingual Tablets In The Presence Of Sodium Caprate Permeability Enhancer: Formulation Optimization, Characterization, Sammar Fathy Elhabal, Mohamed A El-Nabarawi, Nashwa Abdelaal, Mohamed Fathi Mohamed Elrefai, Shrouk A Ghaffar, Mohamed Mansour Khalifa, Passant M Mohie, Dania S Waggas, Ahmed Mohsen Elsaid Hamdan, Samar Zuhair Alshawwa, Essa M Saied, Nahla A Elzohairy, Tayseer Elnawawy, Rania A Gad, Nehal Elfar, Hanaa Mohammed, Mohammad Ahmad Khasawneh

Faculty, Staff and Students Publications

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants …

Rehydration Rates And Outcomes In Overweight Children With Diabetic Ketoacidosis, Kathleen M Brown, Nicole S Glaser, Julie K Mcmanemy, Andrew Depiero, Lise E Nigrovic, Kimberly S Quayle, Michael J Stoner, Jeff E Schunk, Jennifer L Trainor, Leah Tzimenatos, Arleta Rewers, Sage R Myers, Maria Y Kwok, Simona Ghetti, T Charles Casper, Cody S Olsen, Nathan Kuppermann, Pediatric Emergency Care Applied Research Network Diabetic Ketoacidosis Fluid Study Group

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: The Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis (DKA) (FLUID) Trial found that rapid fluid infusion does not increase the risk of cerebral injury. Concern persists, however, whether fluid rates should be adjusted for overweight or obese patients. We used the FLUID Trial database to evaluate associations between fluid infusion rate and outcomes in these patients.

METHODS: We compared children and youth who were overweight, obese, or normal weight, in regard to protocol adherence, mental status changes, time to DKA resolution, and electrolyte abnormalities. We investigated associations between outcomes and the …

Trajectories Of Egfr And Risk Of Albuminuria In Youth With Type 2 Diabetes: Results From The Today Cohort Study, Laure El Ghormli, Hui Wen, Diane Uschner, Morey W Haymond, Kara S Hughan, Katherine Kutney, Lori Laffel, Sherida E Tollefsen, Elia N Escaname, Jane Lynch, Petter Bjornstad, Today Study Group

Faculty, Staff and Students Publications

BACKGROUND: We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories.

RESULTS: At baseline, participants' mean age …

Assessment And Prevention Of Hypoglycaemia In Primary Care Among Us Veterans: A Mixed Methods Study, Scott J Pilla, Kayla A Meza, Mary Catherine Beach, Judith A Long, Howard S Gordon, Jeffrey T Bates, Donna L Washington, Barbara G Bokhour, Anais Tuepker, Somnath Saha, Nisa M Maruthur

Faculty, Staff and Students Publications

BACKGROUND: Hypoglycaemia from diabetes treatment causes morbidity and lower quality of life, and prevention should be routinely addressed in clinical visits.

METHODS: This mixed methods study evaluated how primary care providers (PCPs) assess for and prevent hypoglycaemia by analyzing audio-recorded visits from five Veterans Affairs medical centres in the US. Two investigators independently coded visit dialogue to classify discussions of hypoglycaemia history, anticipatory guidance, and adjustments to hypoglycaemia-causing medications according to diabetes guidelines.

FINDINGS: There were 242 patients (one PCP visit per patient) and 49 PCPs. Two thirds of patients were treated with insulin and 40% with sulfonylureas. Hypoglycaemia history …

Precision Recruitment And Engagement Of Individuals At Risk For Diabetes And Hypertension In Clinical Trials (Predhict): A Randomized Trial For An E-Persuasive Mobile Application To Inform Decision Making About Clinical Trials, Azizi Seixas, Shannique Richards, Jesse Q Moore, Chigozirim Izeogu, Laronda A Hollimon, Peng Jin, Girardin Jean-Louis

Faculty, Staff and Student Publications

The primary objective of this randomized trial was to test the effectiveness of the PREDHiCT digital application, which provides educational and supportive navigation to increase willingness to participate in a future clinical trial. The second objective was to test whether PREDHiCT increased clinical trial literacy or enhanced psychological facilitators of clinical trial participation, such as altruism. To test these two objectives, we conducted a 1-month remote decentralized trial with 100 participants who either have a personal or family history of cardiometabolic health conditions, such as hypertension, diabetes, and obesity. Results indicated significant changes in altruism (mean: -2.94 vs. 0.83;

Distinct Transcriptomic Profiles In Children Prior To The Appearance Of Type 1 Diabetes-Linked Islet Autoantibodies And Following Enterovirus Infection, Jake Lin, Elaheh Moradi, Karoliina Salenius, Suvi Lehtipuro, Tomi Häkkinen, Jutta E Laiho, Sami Oikarinen, Sofia Randelin, Hemang M Parikh, Jeffrey P Krischer, Jorma Toppari, Åke Lernmark, Joseph F Petrosino, Nadim J Ajami, Jin-Xiong She, William A Hagopian, Marian J Rewers, Richard E Lloyd, Kirsi J Rautajoki, Heikki Hyöty, Matti Nykter, Teddy Study Group

Faculty, Staff and Students Publications

Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first. In particular, gene dosage-driven expression of GSTM1 is associated with GADA autoantibody positivity. Moreover, compared with controls, we …

Evidence-Based Intervention For Decreasing Chronic Kidney Progression In Patients With Type Ii Diabetes Mellitus, Lynn M. Johnson

Student Scholarly Projects

Practice Problem: The overall management of Type II Diabetes Mellitus (DM II) and the complications that accompany along with comorbidities are debilitating and financially exhausting. The American Diabetes Association dietary recommends a consistent low-carbohydrate diet to maintain optimal blood glucose levels to prevent complications and progression of other comorbidities. Uncontrolled diabetes mellitus leads to the development of chronic kidney disease (CKD) which can lead to the progression to End Stage Renal Disease.

PICOT: In patients in the outpatient setting aged 18 years and older(P), how does the ADA dietary guidelines for patients with type II DM(I) compared with patients self-reported …

Dietary Analysis For Hashimoto’S Thyroiditis: An Integrative Review, Evan Thompson, Alison Hultquist

Master of Science in Nursing Final Projects

Abstract

Hashimoto’s Thyroiditis (HT) is the leading cause of primary hypothyroidism in the United States. In HT, there is an infiltration by lymphocytes which leads to the production of autoantibodies against the thyroid gland. Throughout this integrative review, the aim was to evaluate the effectiveness of micronutrient supplementation and dietary management as adjunct treatments in HT. The purpose was to assist primary care providers in the development of a more holistic plan of care. Literature published within the past seven years was gathered and reviewed from PubMed, CINAHL, and Cochrane Library. Findings indicate that many patients with HT may benefit …

Gonadotropin-Secreting And Thyrotropin-Secreting Pituitary Adenomas: A Single-Center Experience, Manjiri Karlekar, Chakra Diwaker, Vijaya Sarathi, Anurag Lila, Anima Sharma, Saba Samad Memon, Virendra Patil, Tushar Bandgar

Faculty, Staff and Student Publications

OBJECTIVE: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India.

MATERIALS AND METHODS: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical(inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas.

RESULTS: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, …

Mechanisms And Treatment Options For Hyperthyroid-Induced Osteoporosis: A Narrative Review, Robert M. Branstetter 4th, Rahib K. Islam, Collin A. Toups, Amanda N. Parra, Zachary Lee, Shahab Ahmadzadeh, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Normal thyroid hormone levels are crucial for the homeostasis of many metabolic cycles and processes throughout the human body. Thyroid dysfunction, such as thyrotoxicosis, can result from many different etiologies, including Graves' disease (GD), toxic multinodular goiter (MNG), and toxic adenoma. These hyperthyroid disease states can cause devastating complications and disease, including the disruption of the bone remodeling cycle and skeletal development, which can result in osteoporosis. Osteoporosis is characterized by a decrease in bone mineral density and a propensity for fragility fractures. In addition to patients with overt hyperthyroidism, studies have provided evidence of other high-risk patient demographics, such …

Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lisa E. Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E. Schunk, Michael J. Stoner, Arleta Rewers, Julie K. Mcmanemy, Kimberly S. Quayle, Jennifer L. Trainor, Leah Tzimenatos, Jonathan E. Bennett, Maria Y. Kwok, Sage R. Myers, Kathleen M. Brown, T. Charles Casper, Cody S. Olsen, Nicole S. Glaser

Department of Emergency Medicine Faculty Papers

Background.

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of childhood diabetes. However, the influence of demographic factors on presentation are not well-defined.

Methods.

We included children from 12 centers who were <18 years with DKA (glucose > 300 mg/dL, serum pH < 7.25, or serum bicarbonate <15 mEq/L) enrolled in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Trial. Data were also collected for children who presented to the centers during the enrollment period but were not enrolled due to disease or treatment-related reasons. We compared demographic, clinical, and biochemical findings among children with newly and previously diagnosed diabetes and children in different age groups.

Results.

Of the 1,679 DKA episodes in 1,553 children, 799 (47.5%) episodes occurred in children with newly diagnosed diabetes and 396 (23.6%) were severe (pH < 7.1). Newly diagnosed children <6 years of age were not more likely to have severe DKA in terms of pH, but had more severe hypocarbia and higher blood urea nitrogen levels, factors previously associated with the risk of cerebral injury. Lower socioeconomic status (SES) (based on family income and maternal education level) were associated with more severe DKA in new onset children, and recurrent DKA in the previously diagnosed children.

Conclusions.

Greater efforts are needed to identify the children with diabetes early and to prevent recurrent DKA, particularly among children in low-SES groups. Young children with DKA may need more intensive monitoring due to higher …

Improving Effective Care In Obese Patients In A Primary Care Clinic, Amy Miller

Journal of Interprofessional Practice and Collaboration

Background: Obesity is a preventable epidemic and costs the United States $200 billion annually. The leading causes of death are linked to obesity.

Local Problem: In a chart review, 53% of patients at a northeast Louisiana primary care clinic were obese. However, none were offered comprehensive lifestyle intervention. The aim was to increase the percentage of patients with BMI < 30 kg/m2 to 60% over 8 weeks.

Methods: A rapid-cycle quality improvement initiative was implemented using four Plan-Do-Study-Act cycles over 8 weeks. Each cycle produced tests of change related to screening, patient and team engagement, and assessing effective care. Run charts and aggregate tables were used to analyze …

Cgm Use With Interprofessional Therapy Management Improves Hba1c Levels In T2dm Patients, Stephen R. Hill, Courtney Robertson, Teri B. O'Neal, Sonia Garner

Journal of Interprofessional Practice and Collaboration

Background

Type 2 Diabetes Mellitus (T2DM) is a chronic disease state with increased complications over time from uncontrolled glucose. Significant data has shown benefits of continuous glucose monitoring (CGM) in reducing glycated hemoglobin (HbA1c) levels of Type 1 Diabetes Mellitus (T1DM) patients, but a lack of robust evidence is seen in T2DM. This study assessed the impact of short-term CGM placement on HbA1c levels in T2DM.

Objectives

The primary outcome was the change in baseline HbA1c levels in patients with T2DM up to six months after CGM placement. Secondary outcomes assessed intensification of diabetes medications made by an interprofessional team …

Enhancing Diabetes Care In Lmics: Insights From A Multinational Consensus, Jose Carlos Miranda, S Abbas Raza, Babatope Kolawole, Jahanzeb Kamal Khan, Atiba Alvi, Fariha Sadiq Ali, Ejim Emmanuel Chukwudi, Nanik Ram, Amira Oluwatoyin

Section of Diabetes, Endocrinology and Metabolism

The International Cardio-Metabolic Forum held a plenary session to establish a multinational consensus on the challenges faced in diabetes management within lower-middle-income countries (LMICs) and their potential solutions. Stakeholders, including patients, family/caretakers, healthcare professionals, and healthcare policymakers & organizations, participated in discussions. The audience of 280 doctors from 15 different countries (Pakistan, Qatar, Sri Lanka, Kenya, Myanmar, Georgia, Nigeria, Philippines, Uzbekistan, Iraq, Tanzania, Cambodia, Kazakhstan, South Sudan and Libya) was divided into 4 groups led by Group Leaders to represent each stakeholder group. Questionnaires addressing key challenges and solutions specific to each group were used to facilitate consensus development. Participants …

Diabetes-Associated Hyperglycemia Causes Rapid-Onset Ocular Surface Damage, Judy Weng, Christopher Ross, Jacob Baker, Saleh Alfuraih, Kiumars Shamloo, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The metabolic alterations due to chronic hyperglycemia are well-known to cause diabetes-associated complications. Short-term hyperglycemia has also been shown to cause many acute changes, including hemodynamic alterations and osmotic, oxidative, and inflammatory stress. The present study was designed to investigate whether diabetes-associated hyperglycemia can cause rapid-onset detrimental effects on the tear film, goblet cells, and glycocalyx and can lead to activation of an inflammatory cascade or cellular stress response in the cornea.

Methods: Mouse models of type 1 and type 2 diabetes were used. Tear film volume, goblet cell number, and corneal glycocalyx area were measured on …

Clonal Hematopoiesis Of Indeterminate Potential (Chip) And Incident Type 2 Diabetes Risk, Deirdre K Tobias, Alisa K Manning, Jennifer Wessel, Sridharan Raghavan, Kenneth E Westerman, Alexander G Bick, Daniel Dicorpo, Eric A Whitsel, Jason Collins, Adolfo Correa, L Adrienne Cupples, Josée Dupuis, Mark O Goodarzi, Xiuqing Guo, Barbara Howard, Leslie A Lange, Simin Liu, Laura M Raffield, Alex P Reiner, Stephen S Rich, Kent D Taylor, Lesley Tinker, James G Wilson, Peitao Wu, April P Carson, Ramachandran S Vasan, Myriam Fornage, Bruce M Psaty, Charles Kooperberg, Jerome I Rotter, James Meigs, Joann E Manson

Faculty, Staff and Student Publications

OBJECTIVE: Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in atherosclerotic coronary heart disease (CHD) and all-cause mortality, but its association with incident type 2 diabetes (T2D) is unknown. We hypothesized that CHIP is associated with elevated risk of T2D.

RESEARCH DESIGN AND METHODS: CHIP was derived from whole-genome sequencing of blood DNA in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) prospective cohorts. We performed analysis for 17,637 participants from six cohorts, without prior T2D, cardiovascular disease, …

Obesity Dominates Early Effects On Cardiac Structure And Arterial Stiffness In People With Type 2 Diabetes, Layla A Abushamat, Daniel Enge, Takashi Fujiwara, Michal Schäfer, Ethan W Clark, Erin K Englund, Rebecca L Scalzo, Aspen Johnston, Deirdre Rafferty, Irene E Schauer, Mary O Whipple, Kendall Hunter, Amy G Huebschmann, Kristen J Nadeau, Kelly Jarvis, Alex J Barker, Judith G Regensteiner, Jane E B Reusch

Faculty, Staff and Students Publications

OBJECTIVE: Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D.

METHODS: Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was …

Comprehensive Evaluation And New Recommendations In The Use Of Gafchromic Ebt3 Film, Kevin Liu, Patrik Gonçalves Jorge, Ramesh Tailor, Raphaël Moeckli, Emil Schüler

Faculty, Staff and Student Publications

BACKGROUND: Gafchromic film's unique properties of tissue-equivalence, dose-rate independence, and high spatial resolution make it an attractive choice for many dosimetric applications. However, complicated calibration processes and film handling limits its routine use.

PURPOSE: We evaluated the performance of Gafchromic EBT3 film after irradiation under a variety of measurement conditions to identify aspects of film handling and analysis for simplified but robust film dosimetry.

METHODS: The short- (from 5 min to 100 h) and long-term (months) film response was evaluated for clinically relevant doses of up to 50 Gy for accuracy in dose determination and relative dose distributions. The dependence …

Gastrointestinal Infections Modulate The Risk For Insulin Autoantibodies As The First-Appearing Autoantibody In The Teddy Study, Maria Lönnrot, Kristian F Lynch, Marian Rewers, Åke Lernmark, Kendra Vehik, Beena Akolkar, William Hagopian, Jeffrey Krischer, Rickhard A Mcindoe, Jorma Toppari, Anette-G Ziegler, Joseph F Petrosino, Richard Lloyd, Heikki Hyöty, Teddy Study Group

Faculty, Staff and Students Publications

OBJECTIVE: To investigate gastrointestinal infection episodes (GIEs) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.

RESEARCH DESIGN AND METHODS: GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool virome was characterized in a nested case-control study.

RESULTS: GIE reports (odds ratio [OR] 2.17 [95% CI 1.39-3.39]) as well as Norwalk viruses found in stool (OR 5.69 [1.36-23.7]) at(OR 0.48 [0.35-0.68]). GIE reports at any other age were associated with an increase in …

Ascertainment Of Minimal Clinically Important Differences In The Diabetes Distress Scale-17: A Secondary Analysis Of A Randomized Clinical Trial, Jack Banks, Amber B Amspoker, Elizabeth M Vaughan, Lechauncy Woodard, Aanand D Naik

Faculty, Staff and Student Publications

IMPORTANCE: The Diabetes Distress Scale-17 (DDS-17) is a common measure of diabetes distress. Despite its popularity, there are no agreed-on minimal clinically important difference (MCID) values for the DDS-17.

OBJECTIVE: to establish a distribution-based metric for MCID in the DDS-17 and its 4 subscale scores (interpersonal distress, physician distress, regimen distress, and emotional distress).

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized clinical trial used baseline and postintervention data from a hybrid (implementation-effectiveness) trial evaluating Empowering Patients in Chronic Care (EPICC) vs an enhanced form of usual care (EUC). Participants included adults with uncontrolled type 2 diabetes (glycated …