Role of Bile Acids and Receptor TGR5 in Regulating Glucose and Energy Homeostasis in Gastric Bypass Patients
Fellow: Deepinder Goyal, MD
Mentor: Joseph Pisegna, MD, Professor of Medicine at UCLA and Chief of the Division of Gastroenterology and Hepatology in the VA Greater Los Angeles Healthcare System
It has been observed that advanced hepatic disease is associated with coagulation factor deficiencies and accelerated fibrinolysis — in fact, the rapid re-liquidification of incubated, clotted Approximately 80-90 percent of patients undergoing Roux-en-Y gastric bypass (RYGB) surgery show improvement in type 2 diabetes mellitus. The majority of these patients achieve remission of diabetes even before they achieve significant weight loss. This suggests a significant alteration in the basic physiology of energy balance and glucose metabolism post-RYGB.
One of the most important physiologic changes in RYGB patients is significant elevation in post-prandial levels of glucagon such as the peptide GLP-1. GLP-1 is a major insulin-releasing factor secreted by L cells in distal jejunum and ileum. However, the underlying mechanisms driving the altered secretion of GLP-1 in RYGB patients are still not well understood.
Interestingly though, patients who have undergone RYGB have been found to have significantly elevated levels of both primary and secondary bile acids due to increased entero-hepatic circulation from the altered gastrointestinal anatomy. One of the many receptors of bile acids is a newly discovered cAMP mediated cell surface G-protein coupled receptor TGR5. TGR5 has been found in liver, brown fat tissue, muscle, and endocrine cells of the gut epithelium. In-vitro activation of this receptor by bile acids and TGR5 ligands has been shown to increase secretion of GLP-1 in human and murine entero-endocrine cell lines. Furthermore, in adipose tissue, this receptor has been shown to activate de-iodinase enzyme converting inactive thyroid hormone T4 to its active form T3, thereby increasing basal metabolic rate and energy expenditure. Dr. Goyal’s study examines the effect of gastric bypass surgery on TGR5 receptor expression in the terminal ileum and correlates the levels of bile acids, TGR5 mRNA and protein with GLP-1 levels and insulin sensitivity. Dr. Goyal is also investigating the effect of gastric bypass surgery on thyroid hormone status and seeking to correlate changes in bile acids levels with serum T3/T4 ratio.
Time-Driven, Activity-Based Costing: Measuring the Costs of Implementing Quality Measures in Inflammatory Bowel Disease
Fellow: Andrew Ho, MD
Mentors: Daniel Hommes, MD, PhD, GI Quality and Center for Inflammatory Bowel Diseases; Christina Ha, MD, Center for Inflammatory Bowel Diseases
Poster Presentation: Ho AD et al. Time-driven activity based costing: Measuring the Costs of Implementing Quality Measures in Inflammatory Bowel Disease. Poster #Tu1231. Digestive Disease Week (DDW), Washington, DC (May 2015). Poster of distinction.
Emergency Room Resource Utilization Among Inflammatory Bowel Disease Patients
Fellow: Michelle Vu, MD
Mentor: Christina Ha, MD, Center for Inflammatory Bowel Diseases
Inflammatory bowel disease (IBD) is a complex, chronic condition characterized by gastrointestinal inflammation resulting in abdominal pain, diarrhea, and gastrointestinal bleeding. The disease can be complicated and follows an unpredictable course. IBD exacerbations are common, with severe cases requiring powerful immunomodulatory and biologic agents, surgical intervention, multiple physician visits and inpatient admissions. Additional data also indicates an increase in IBD-related emergency department (ED) visits in recent years. While direct medical costs of caring for IBD patients and trends in ED visits by IBD patients have previously been evaluated, none of the studies analyzed resource utilization in the emergency room setting, where IBD patients with acute complaints receive initial diagnostic and therapeutic intervention.
Given the relatively early onset of disease and normal life expectancy, IBD-associated costs per patient can surpass those of other chronic diseases. As such, it is important to identify areas where costeffective strategies that might improve quality of care have not yet been implemented. IBD patients in the ED are subject to diverse provider practices stemming from varied awareness of IBD practice guidelines. Unnecessary testing, disjointed care and lack of transparency in adherence to established guidelines in the busy ED arena are some of the potential contributors to the high cost of IBD care.
Dr. Vu’s study aims to identify patient characteristics and risk factors for ED visits among the IBD patient population, assess resource utilization in the ED setting among IBD patients, and identify potential measures to improve the quality of ED care and subsequent outpatient follow-up.
Abstract: Vu M, Phan J, Ha C. Emergency Department Healthcare Utilization among IBD Patients at an Academic Tertiary Care IBD Referral Center. Gastroenterology, April 2016 Volume 150, Issue 4, Supplement 1 Pages S799-S800
UCLA Celiac Collective: Development of Longitudinal E-Cohort of Celiac Patients
Fellow: Guy Weiss, MD
Mentor: Lin Chang, MD, Co-Director, G. Oppenheimer Center for Neurobiology of Stress and Resilience
The growing use and availability of the Internet provides innovative research opportunities for outcomes research. Dr. Weiss aims to develop a longitudinal Internet-based cohort (e-cohort) of patients with self-reported gluten-associated disorders, mainly celiac disease (CD) and non-celiac gluten sensitivity. His group is recruiting members of different celiac organizations and support groups. This e-cohort is termed the “UCLA Celiac Collective.” Participants are requested to complete a baseline survey and follow-up surveys at six-month intervals.
Since most studies of CD rely on a retrospective review of medical records or administrative data and prospective studies carry a heavy financial burden, exploring a pre-existing online community is of great academic value. Retrospective studies often lack key clinical data that can only be obtained directly from the patient (such as a detailed diet, use of over the-counter medications, and exercise). Other important patient-reported outcomes such as diet adherence, depression, anxiety, sleep disturbances, sexual dysfunction, and fatigue are often partial or lacking. The database will enable Dr. Weiss and colleagues to target specific patient populations (e.g., women, elderly, minorities, etc.) and explore disease-specific topics (screening, diet, etc.). External researchers will have the ability to submit research proposals to gain access to the unidentifiable database, and even add new survey modules. The project will span a period of several years, potentially resulting in multiple abstracts and publications in the field of CD. In addition to reduced-cost research, the UCLA Celiac Collective can be used for educational and interventional purposes.
Dr. Weiss’s study aims to create an innovative e-cohort of CD patients that will enable researchers within and outside of UCLA to examine disease-specific parameters through a comprehensive database. His group will explore the association between psychological distress (i.e., depression, anxiety and stress), motivation and competence in relation to adherence to a gluten-free diet. The value of this quality-improvement study lies in its potential to identify and improve the factors that negatively affect adherence. Consequently, CD care will improve by reducing disease activity, improving quality of life, and reducing the number of office visits, thus resulting in an overall healthcare cost reduction.