2023 Department of Pediatrics Academic Annual Report

nationwide consortium. The study is part of a project designed to identify the predictors of T2D in youth. This knowledge would allow us to better treat children, especially minority children, who have pre-diabetes. Drs. Schmitt and Ashraf are collaborating with Dr. Bisakha Sen at the UAB School of Public Health to better understand the trajectory of incidence of pediatric patients with T2D during the COVID-19 pandemic. They are reviewing the electronic health records and the Medicaid health claims data to quantify the rise in T2D and delineate any ethnic or socio-economic disparities. Dr. Schmitt is working on evaluating the effectiveness of continuous glucose monitors in youth with pre-diabetes. The goal of this study is to determine if having access to real-time biofeedback of activity and food choice on glucose excursions in youth with pre-diabetes reduces the progression of disease compared to standard of care alone. She has secured internal funding through the UAB Diabetes Research Center Pilot Project funding for this study (Pilot and Feasibility Award by the UAB DRC on the “Use of Continuous Glucose Monitors to Improve Outcomes in Youth with Pre-Diabetes”). Dr. Ashraf is collaborating with the Division of Pediatric Infectious Diseases (Claudette Poole, M.D., Swetha Pinninti, M.D., Suresh Boppana, M.D.) to determine the association of SARS-CoV-2 infection and comparative relative incidence of new-onset T1D and T2D in children in the state of Alabama. This study also aims to determine the association between virologic and antiviral antibody characteristics of SARS-CoV-2 infection in children with newly diagnosed T1D and those presenting with diabetic ketoacidosis (DKA) and/or hyperglycemic hyperosmolar syndrome (HHS). Moreover, the study plans to determine the association between virologic and antiviral antibody characteristics of SARS-CoV-2 infection in children with newly diagnosed T2D and those presenting with DKA and/or HHS. Mary Lauren Scott, M.D., is collaborating with the Pediatric Diabetes Consortium to examine multicenter data on COVID and T1D and T2D rates from October 2018–September 2021. She is also working with a medical student, Adam Hoseley, MS2, on a manuscript discussing our population of “double diabetes” patients found during this same time frame. Gail Mick, M.D., and Kenneth McCormick, M.D., completed an investigator-initiated placebo-controlled, double-blind trial in 97 children with new onset T1D demonstrating that oral gamma aminobutyric acid (GABA) plus glutamate decarboxylase (GAD) attenuated serum glucagon without altering beta cell function (Nat. Comm. 2022, DOI: 10.1038/s41467-022-35544-3). In collaboration with Hubert Tse, Ph.D., in the Department of Microbiology and the UAB Comprehensive Diabetes Center, a follow-up paper describes beneficial cytokine immune modulation by GABA and GABA/GAD in isolated peripheral blood mononuclear cells from trial participants that was human leukocyte antigens (HLA) haplotype related (Biomedicines 2023, DOI: 10.3390/biomedicines11071948). Together, these works demonstrate encouraging metabolic and immunoprotective actions of GABA and combination GABA/GAD in T1D that warrant future study. ENDOCRINOLOGY, LIPIDS AND METABOLISM RESEARCH Dr. Foster is participating as a site PI for a multisite polycystic ovary syndrome (PCOS) retrospective database. The University of Colorado has developed a PCOS database that is multisite supported by an NIH R21 grant with an aim of describing the presentation and treatment of adolescent patients with PCOS. Dr. Foster, has partnered with two undergraduate students to conduct a retrospective chart review of the current clinical practice for diagnosis and treatment of PCOS in our clinic. She also is assessing the incidence of eating disorder, anxiety and depression in the Children’s of Alabama Pediatric Endocrine Clinic. The primary aim is to identify mental health disease in a particularly vulnerable population of adolescent females who have PCOS. She is partnering with two medical students to complete this study. Dr. Ashraf is investigating the role of gut microbiome in the pathogenesis of T2D in children. The primary objective is to determine whether there are differences in gut microbiota in children with obesity, prediabetes and T2D contributing to the development of T2D and response to treatment. The primary aim of this project is to quantify and evaluate the difference in the composition of gut microbiota between children with obesity, prediabetes and T2D. She will also evaluate temporal changes in the gut microbiome abundance and diversity. The study also intends to test whether baseline gut microbiota before treatment initiation for T2D predicts successful response to treatment. Moreover, this project also compares the differences in lipoprotein profile and inflammatory marker concentrations before and after implementation of treatment. Dr. Ashraf is collaborating with two renowned experts in the microbiome, Dr. Vivek Lal in the Division of Neonatology and Dr. Joseph Pierre at the University of Wisconsin. Non-alcoholic fatty liver disease (NAFLD or MAFLD-metabolic dysfunction-associated fatty liver disease), once rarely observed in children and adolescents, is now the most common form of liver disease in this age group. If untreated, NAFLD can progress rapidly from simple fat infiltration to advanced stages of the disease, including steatohepatitis, fibrosis and cirrhosis, ultimately requiring liver transplantation. Dr. Ashraf collaborated with Amy Goss, Ph.D., to investigate the use of a carbohydrate-restricted diet as a treatment targeting normalization of hepatic lipid content in adolescents with non-alcoholic fatty liver disease. The preliminary data in 23 adolescents with NAFLD suggest that a weight-maintaining, low glycemic (LG), moderately carbohydrate (CHO)-restricted diet (~100 g CHO/day) significantly improved both hepatic steatosis and hepatic insulin sensitivity. Since the completion of the pilot study, they secured a 1R01DK128457-01 (PI: Amy Goss, Ph.D., Ashraf Co-I). The study included a six-month family-based intervention with two phases, a 12-week controlled isocaloric feeding phase and a 12-week free living phase, to examine the effects of a weight maintaining, moderately CHO-restricted vs. fat-restricted diet in adolescents with NAFLD on depletion of hepatic lipid content, improvement in hepatic insulin sensitivity and changes to the plasma metabolome. Leen Matalka, M.D., investigated correlation between clinical findings with rates of differentiated thyroid cancer (DTC) in a cohort of children presenting with thyroid nodules since the adoption of the 2015 American Thyroid Association (ATA) Guidelines Task Force on Pediatric Thyroid Cancer. Based on the analysis of our pediatric cohort, adoption of the 2015 ATA guidelines could lead to an increased accuracy in detecting DTC while reducing the number of patients requiring interventions, such as FNA biopsy and/or surgeries. Further, based on the cohort, it would be reasonable for thyroid nodules 1 cm or less to be monitored clinically with physical exam and ultrasonography, with further therapeutic or diagnostic intervention considered based on concerning features or parental shared decision-making.

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