1. The Metabolic Research Area (MRA) supports research into obesity, insulin resistance, diabetes and disorders of energy balance. We aim to increase the understanding of metabolic disorders in order to improve the care and clinical management of patients. Disturbances in energy balance and/or body composition are a feature of metabolic disorders such as lipodystrophy, resistance to thyroid hormone, Huntington’s disease and obesity. Observations made in these disorders require reference measurements from healthy volunteers for comparison. In an innovative approach, our WTCRF has developed a project to assemble a substantial bank of reference metabolic data from a broad cross-section of the healthy population. Published papers using reference data from this study:  Savage, D.B., Murgatroyd, P.R. et al (2005) Energy expenditure and adaptive responses to an acute hypercaloric fat load in humans with lipodystrophy, The Journal of Endocrinology & Metabolism.  Savage, D.B., Semple, R. K. et al (2009) Complement abnormalities in acquired lipodystrophy revisited, The Journal of Endocrinology & Metabolism. Interpretation and use of the data Body composition, in particular fat free mass (FFM), is the major determinant of energy expenditure. For more information, or if you would like to consider becoming a volunteer for this study, please contact: Pip Raymond-Barker, Clinical Research Assistant Tel: 01223 506077 or email: crf-volunteer@medschl.cam.ac.uk Additional Measurements Hunger & Satiety: Visual analogue scales record perception at various time points Activity: Actiheart & Actiband measures minor activity and heart rate. Fasting blood & urine: blood count, lipids, insulin, glucose, thyroid hormones, catecholamines, nitrogen excretion. BODPOD measures body weight and body volume and estimates body fat and fat free mass from the known densities of fat and the fat free body. It has a greater upper weight limit than DXA and can be used during pregnancy. Patients with thyroid underactivity have a reduced resting energy expenditure. Macronutrient utilisation can be quantified during calorimetry. This graph illustrates the repletion of the body’s carbohydrate stores over 36h in a carbohydrate depleted participant on an energy balanced diet. Whilst in the room calorimeter, energy expenditure is analysed for each half hour. Total (24h) energy expenditure and macronutrient oxidation rates in lipodystrophic (LD) and control subjects on either an energy balanced or high fat diet. Note the excess fat oxidised and energy expended by LD subjects following consumption of a high fat diet. Control Lipodystrophy Reference Measurements for Studies of Metabolism P. Raymond-Barker, E. Marriott, P. R. Murgatroyd & V.K.K..Chaterjee  Body composition using dual energy X-ray absorptiometry (DXA). Study Design Up to 200 normal, healthy volunteers will be enrolled into different protocols providing the following measurements:  Resting energy expenditure using ventilated canopy calorimetry. Ventilated canopy calorimetry enables reliable and rapid estimation of resting energy expenditure (REE) and can be performed in 20 minutes. Room calorimetry provides measurements over a longer period (36h). As well as REE, this also quantifies sleeping metabolic rate (SMR), total (24h) energy expenditure and macronutrient oxidation.  Total (24h) energy expenditure. Measurements are made under conditions of either energy balance or altered diet e.g. high fat. C-EBC-HFLD-EBLD-HF 0 2 4 6 8 10 12 14 CHO Fat ns P<0.005 ns P< 0.0005 Protein Energy MJ d Control n=7 Lipodystrophy n=7 EB HF EB HF EB = energy balance HF = 30% excess energy as fat DXA is a fast and accurate method to quantify fat, lean and body mass and bone mineral density, involving very low dose radiation exposure.  Body composition using the BODPOD.