This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anorexia Nervosa (AN) is a common eating disorder characterized by an extreme loss of weight. Anorexia nervosa is a common condition and is estimated to affect more than 1% of all children, adolesents and young adults. Ten percent of patients with anorexia nervosa will pursue a chronic, unremitting course, and 10% will eventually die from the disease. The mortality rate in people with anorexia nervosa is more than 12 times as high as the mortality rate in the general population. Death is often caused by cardiac arrhythmias, precipitated by diminshed heart muscle mass and electrolyte abnormalities. Ther is an increased risk of metabolic disease and death associated with AN, the prevalence of which is increasing in this country. The metabolic and inflammatory aspects of AN are not known. The purpose if this study is to fill this gap and provide a better understanding of the pathogenesis of this condition. We will determine the effects of severe weight loss and weight regain in patients with anorexia nervosa on: 1. Lipoprotein metabolism: VLDL-triglyceride (TG) and VLDL-apolipoprotein B (apoB) synthetic rates. 2. Liver protein synthetic function: retinol binding protein synthetic rate and albumin synthetic rate. 3. Markers of inflammation: Plasma C-reactive protein (CRP) concentrations, plasma cytokine concentrations, plasma fibrinogen concentration, fibrinogen fractional synthetic rates (FSR) and monocyte cytokine production. 4. Body composition and regional fat distribution: fat mass and fat-free mass, intra-abdominal and abdominal subcutaneous fat masses, and intra-hepatic lipid content. 5. Basal substrate metabolism: glucose production (glucose rate of appearance in plasma [Ra]), glucose disposal (glucose rate of disappearance in plasma [Rd]) and lipolysis [FFA Ra and glycerol Ra]. We will evaluate these specific aims by infusing stable isotope labeled tracers to measure VLDL-TG, apoB FSR, albumin FSR, fibrinogen FSR, inflammatory markers and cytokine response to peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (Samonella typhimurium). Total body fat and fat-free mass will be determined by dual energy x-ray absorptiometry (DXA). Abdominal (subcutaneous and intra abdominal) adipose tissue mass will be quantified by magnetic resonance imaging (MRI) and intra-hepatic lipid content will be measured with magnetic resonance spectroscopy (MRS). Stable isotope labeled tracers will be used to measure basal substrate lipoprotein kinetics

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000036-46
Application #
7377220
Study Section
Special Emphasis Panel (ZRR1-CR-4 (02))
Project Start
2006-04-01
Project End
2007-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
46
Fiscal Year
2006
Total Cost
$5,414
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Kelsey, Megan M; Braffett, Barbara H; Geffner, Mitchell E et al. (2018) Menstrual Dysfunction in Girls From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study. J Clin Endocrinol Metab 103:2309-2318
Kleinberger, Jeffrey W; Copeland, Kenneth C; Gandica, Rachelle G et al. (2018) Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genet Med 20:583-590
Berkowitz, Robert I; Marcus, Marsha D; Anderson, Barbara J et al. (2018) Adherence to a lifestyle program for youth with type 2 diabetes and its association with treatment outcome in the TODAY clinical trial. Pediatr Diabetes 19:191-198
Arslanian, Silva; El Ghormli, Laure; Kim, Joon Young et al. (2018) The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in ?-Cell Function in TODAY. Diabetes Care :
Kriska, Andrea; El Ghormli, Laure; Copeland, Kenneth C et al. (2018) Impact of lifestyle behavior change on glycemic control in youth with type 2 diabetes. Pediatr Diabetes 19:36-44
Venditti, E M; Tan, K; Chang, N et al. (2018) Barriers and strategies for oral medication adherence among children and adolescents with Type 2 diabetes. Diabetes Res Clin Pract 139:24-31
Gidding, Samuel S; Bacha, Fida; Bjornstad, Petter et al. (2018) Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study. J Pediatr 192:86-92.e5
Scherzer, Rebecca; Heymsfield, Steven B; Rimland, David et al. (2017) Association of serum albumin and aspartate transaminase with 5-year all-cause mortality in HIV/hepatitis C virus coinfection and HIV monoinfection. AIDS 31:71-79
Kadkhodayan, Ana; Lin, C Huie; Coggan, Andrew R et al. (2017) Sex affects myocardial blood flow and fatty acid substrate metabolism in humans with nonischemic heart failure. J Nucl Cardiol 24:1226-1235
Yoon, Hyejin; Belmonte, Krystal C; Kasten, Tom et al. (2017) Intra- and Inter-individual Variability of microRNA Levels in Human Cerebrospinal Fluid: Critical Implications for Biomarker Discovery. Sci Rep 7:12720

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