Translational Research Methods for Diabetes, Obesity and Cardiometabolic Drug Development

1. Front Matter

   Pages i-xii

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2. Review of Clinical Investigation Methodologies

   1. Front Matter

      Pages 1-1

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   2. Methods for Quantifying Insulin Sensitivity and Determining Insulin Time-Action Profiles

      • Andrew J. Krentz, Lutz Heinemann, Marcus Hompesch

      Pages 3-43

   3. Assessment of β-Cell Function

      • Andrew J. Krentz, Lutz Heinemann, Marcus Hompesch

      Pages 45-69

   4. Isotopic Tracers for the Measurement of Metabolic Flux Rates

      • Carine Beysen, Marc K. Hellerstein, Scott M. Turner

      Pages 71-97

   5. Imaging Techniques for the Assessment of Ectopic Fat in Liver and Skeletal Muscle

      • Gavin Hamilton, Michael S. Middleton, Elhamy R. Heba, Claude B. Sirlin

      Pages 99-119

   6. Positron-Emission Tomography and Computed Tomography Measurement of Brown Fat Thermal Activation: Key Tools for Developing Novel Pharmacotherapeutics for Obesity and Diabetes

      • Monte S. Buchsbaum, Alex DeCastro

      Pages 121-137

   7. Assessment of Body Composition

      • Mark Punyanitya, Paul R. Clark

      Pages 139-167

   8. Measurement of Energy Expenditure

      • Klaas R. Westerterp

      Pages 169-187

   9. Omics: Potential Role in Early-Phase Drug Development

      • Harald Grallert, Carola S. Marzi, Stefanie M. Hauck, Christian Gieger

      Pages 189-222

3. Emerging and Complementary Research Methods; Ethical and Regulatory Considerations

   1. Front Matter

      Pages 223-223

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   2. Early Phase Metabolic Research with Reference to Special Populations

      • Linda A. Morrow, Andrew J. Krentz

      Pages 225-242

   3. Quantitative Approaches in Translational Research: An Overview

      • Puneet Gaitonde, Shannon A. Miller, Mirjam N. Trame, Stephan Schmidt

      Pages 243-264

   4. Computational Modelling of Energy Metabolism and Body Composition Dynamics

      • Kevin D. Hall

      Pages 265-282

   5. Regulatory Considerations for Early Clinical Development of Drugs for Diabetes, Obesity, and Cardiometabolic Disorders

      • G. Alexander Fleming

      Pages 283-304

4. Back Matter

   Pages 305-312

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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.

• cardiometabolic
• efficacy
• glucose clamp
• insulin resistance
• obesity
• type 2 diabetes
• diabetes
• metabolic disease

“An important resource for researchers to orient themselves in the choice of correct study techniques, for both metabolic studies related to drug development and clinical studies. … it is also a great resource for experienced researchers in the field as a useful compendium of the major and emerging techniques already used in the study of the pathophysiology of metabolism, and as a valuable aid to researchers beginning studies in the field for choosing the most appropriate techniques for their purposes.” (Stefania Camastra, Pharmaceutical Medicine, Vol. 30, 2016)

• Profil Institute for Clinical Research, Chula Vista, USA

  Andrew J. Krentz, Lutz Heinemann, Marcus Hompesch

Andrew J Krentz, Senior Director of Scientific Services at the Profil Institute, is a clinical academic with more than three decades of experience in diabetes and cardiometabolic medicine. He holds a visiting chair at the Bedfordshire & Hertfordshire Postgraduate Medical School, University of Bedfordshire UK where he was Associate Professor before joining Profil. Prior to this he was a senior physician in internal medicine, diabetes & endocrinology at Southampton University Hospitals, UK. Lutz Heinemann, Senior Scientific Consultant at the Profil Institute, has acted as scientific advisor for Profil Institute since the company’s inception in 2004. He consults on the design of clinical trial protocols and in the publication of study results. He is also co-founder of Profil Institute for Metabolic Research in Neuss, Germany and led the company as CEO for 10 years until 2009. Prior to that, Prof. Dr. Heinemann spent 17 years performing diabetes-related clinical and experimental research at the Department of Metabolic Diseases and Nutrition, a World Health Organization Collaborating Center of Diabetes, at Heinrich-Heine University of Düsseldorf in Germany. Marcus Hompesch, President and Chief Executive Officer, Profil Institute, is an expert in the field of metabolic diseases, a licensed physician and entrepreneur. His experience in designing, performing and publishing clinical studies in metabolic diseases has been gained through over 18 years of work as clinician and clinical researcher. Dr. Hompesch established Profil Institute for Clinical Research in San Diego, CA in 2003.

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