Translational research methods for diabetes, obesity and cardiometabolic drug development : a focus on early phase clinical studies /dc Andrew J. Krentz, Lutz Heinemann, Marcu Hompesch, editors

The world is beset by a pandemic of obesity and type 2 diabetes and the need for new drugs is startlingly clear; recent years have seen a huge increase in research activity to fill this gap. The development of new drugs for diabetes and obesity must be founded upon a sound appreciation of the pathophysiology of these common disorders. The dual defects of insulin resistance and impaired insulin secretion are fundamental to the pathogenesis and progression of obesity-associated type 2 diabetes. There is a need to explain how new drugs can counter insulin resistance and insulin deficiency to a broad range of professionals, from clinical scientists active in early (and later) phase drug development to specialist physicians and increasingly primary care doctors who must tailor drug regimens to the individual patient. Clinical research methods for measuring insulin action and insulin secretion have become well-established in proof-of-mechanism studies; however, selection of the best techniques is by no means straightforward. The purpose of the book is to aid the selection of the most appropriate techniques for assessing insulin action, insulin secretion and body composition in humans (with particular reference to new drugs) in phase 1 and 2 studies and aid the understanding of drug effects and non-drug treatment strategies on key biochemical-hormonal defects of obesity and type 2 diabetes. The book will assume a working knowledge of human physiology relating to glucose metabolism and will be of interest to biomedical scientists, pharmacologists, academics involved in metabolic research and clinicians practicing in these specialties. Front Matter....Pages i-xii Front Matter....Pages 1-1 Methods for Quantifying Insulin Sensitivity and Determining Insulin Time-Action Profiles....Pages 3-43 Assessment of β-Cell Function....Pages 45-69 Isotopic Tracers for the Measurement of Metabolic Flux Rates....Pages 71-97 Imaging Techniques for the Assessment of Ectopic Fat in Liver and Skeletal Muscle....Pages 99-119 Positron-Emission Tomography and Computed Tomography Measurement of Brown Fat Thermal Activation: Key Tools for Developing Novel Pharmacotherapeutics for Obesity and Diabetes....Pages 121-137 Assessment of Body Composition....Pages 139-167 Measurement of Energy Expenditure....Pages 169-187 Omics: Potential Role in Early-Phase Drug Development....Pages 189-222 Front Matter....Pages 223-223 Early Phase Metabolic Research with Reference to Special Populations....Pages 225-242 Quantitative Approaches in Translational Research: An Overview....Pages 243-264 Computational Modelling of Energy Metabolism and Body Composition Dynamics....Pages 265-282 Regulatory Considerations for Early Clinical Development of Drugs for Diabetes, Obesity, and Cardiometabolic Disorders....Pages 283-304 Back Matter....Pages 305-312 This book aims to aid the selection of the most appropriate techniques for use in early phase (1 and 2) clinical studies of new drugs for diabetes, obesity, and related cardiometabolic disease. Clinical research methods for assessing the pharmacokinetics and pharmacodynamics of new diabetes drugs, e.g. the euglycaemic clamp technique, have become well-established in proof-of-mechanism studies; however, selection of the best techniques is by no means straightforward. This book will aid the understanding of the need for new pharmacotherapies for type 1 diabetes, type 2 diabetes, and obesity and the molecular targets of drugs currently in development. Emerging technologies including the omics disciplines are considered together with practical and ethical issues of early phase clinical trials in subjects with cardiometabolic disorders. Translational Research Methods for Diabetes, Obesity and Cardiometabolic Drug Development will be of interest to biomedical scientists, pharmacologists, academics involved in metabolic research and clinicians practicing in these specialties This book reviews techniques for assessing insulin action, insulin secretion and body composition, with reference to new drugs, in phase 1 & 2 studies. Adds to understanding of drug effects and non-drug treatment strategies in obesity and type 2 diabetes.