Translational Research Methods in Diabetes, Obesity, and Nonalcoholic Fatty Liver Disease

1. Front Matter

   Pages i-xi

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2. Review of Clinical Investigative Methods

   1. Front Matter

      Pages 1-1

      PDF

   2. Quantification of Insulin Action in Human Subjects

      • Andrew J. Krentz, Christian Weyer, Marcus Hompesch

      Pages 3-35

   3. Assessment of Islet Alpha- and Beta-Cell Function

      • Sten Madsbad, Jens J. Holst

      Pages 37-74

   4. Pharmacokinetic and Pharmacodynamic Assessment of Novel and Biosimilar Insulins

      • Andrew J. Krentz, Christian Weyer, Marcus Hompesch

      Pages 75-100

   5. Measurement of Energy Expenditure

      • Klaas R. Westerterp

      Pages 101-119

   6. Quantifying Appetite and Satiety

      • Catherine Gibbons, John E. Blundell

      Pages 121-140

   7. Non-invasive Quantitative Magnetic Resonance Imaging and Spectroscopic Biomarkers in Nonalcoholic Fatty Liver Disease and Other Cardiometabolic Diseases Associated with Ectopic Fat Deposition

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

      Pages 141-160

   8. Structural and Functional Imaging of Muscle, Heart, Endocrine Pancreas and Kidneys in Cardiometabolic Drug Development

      • Olof Eriksson, Paul Hockings, Edvin Johansson, Lars Johansson, Joel Kullberg

      Pages 161-189

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

      • Monte S. Buchsbaum, Alex DeCastro

      Pages 191-210

   10. Isotopic Tracers for the Measurement of Metabolic Flux Rates

       • Carine Beysen, Thomas E. Angel, Marc K. Hellerstein, Scott M. Turner

       Pages 211-243

   11. Role of Tissue Biopsy in Drug Development for Nonalcoholic Fatty Liver Disease and Other Metabolic Disorders

       • Andrew J. Krentz, Pierre Bedossa

       Pages 245-274

   12. Utility of Invasive and Non-invasive Cardiovascular Research Methodologies in Drug Development for Diabetes, Obesity and NAFLD/NASH

       • Gerardo Rodriguez-Araujo, Andrew J. Krentz

       Pages 275-308

   13. Omics: Potential Role in Early Phase Drug Development

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

       Pages 309-347

3. Preclinical Drug Development and Transitioning to Clinical Studies

   1. Front Matter

      Pages 349-349

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   2. Peptide Drug Design for Diabetes and Related Metabolic Diseases

      • Niels C. Kaarsholm

      Pages 351-368

   3. Animal Models of Type 2 Diabetes, Obesity and Nonalcoholic Steatohepatitis – Clinical Translatability and Applicability in Preclinical Drug Development

      • Henrik H. Hansen, Gitte Hansen, Thomas Secher, Michael Feigh, Sanne S. Veidal, Keld Fosgerau et al.

      Pages 369-403

   4. Drug Development for Diabetes Mellitus: Beyond Hemoglobin A1c

      • Fernando Bril, Marta Iruarrizaga-Lejarreta, Cristina Alonso

      Pages 405-421

   5. Emerging Circulating Biomarkers for The Diagnosis and Assessment of Treatment Responses in Patients with Hepatic Fat Accumulation, Nash and Liver Fibrosis

      • Marta Iruarrizaga-Lejarreta, Fernando Bril, Mazen Noureddin, Pablo Ortiz, Shelly C. Lu, José M. Mato et al.

      Pages 423-448

   6. Quantitative Approaches in Translational Cardiometabolic Research: An Overview

      • Farzaneh Maleki, Puneet Gaitonde, Shannon Miller, Mirjam N. Trame, Paul M. Coen, Parag Garhyan et al.

      Pages 449-466

This book aims to aid the selection of the most appropriate methods for use in early phase (1 and 2) clinical studies of new drugs for diabetes, obesity, non-alcoholic fatty liver disease (NAFLD) and related cardiometabolic disorders.

Clinical research methods to assess the pharmacokinetics and pharmacodynamics of new diabetes drugs, e.g. the euglycemic clamp technique, have become well-established in proof-of-mechanism studies.  However, selection of the most appropriate techniques is by no means straightforward. Moreover, the application of such methods must conform to the regulatory requirements for new drugs.

This book discusses the need for new pharmacotherapies for diabetes, obesity and NAFLD and the molecular targets of drugs currently in development.  Emerging technologies including functional imaging, circulating biomarkers and omics are considered together with practical and ethical issues pertaining to early phase clinical trials in subjects with cardiometabolic disorders.

Translational Research Methods in Diabetes, Obesity, and Non-Alcoholic Fatty Liver Disease is of interest to biomedical scientists, pharmacologists, academics involved in metabolic research and clinicians practicing in these specialties.

• obesity
• diabetes
• non-alcoholic fatty liver disease
• glucose-lowering drugs
• glucose clamp
• insulin resistance
• cardiometabolic disease
• metabolic disease

• ProSciento, Chula Vista, USA

  Andrew J. Krentz, Christian Weyer, Marcus Hompesch

Andrew J Krentz, Senior Research Fellow at ProSciento, is a clinical academic with more than three decades of experience in diabetes and cardiometabolic medicine. He is currently a visiting professor at the University of Reading, UK. Prior to this he was a senior physician and senior lecturer at University Hospital Southampton, UK. He has held research positions at the University of California San Diego and the New Mexico School of Medicine, USA. He is editor-in-chief of ‘Cardiovascular Endocrinology & Metabolism’ and has published more than 100 articles in peer-reviewed medical journals.


Christian Weyer is a pharmaceutical executive with over 20 years of experience in the drug development focused on diabetes, obesity, and NAFLD/NASH.  As head of R&D at Amylin Pharmaceuticals and Intercept Pharmaceutics, he has contributed to the development, regulatory approval and/or life cycle management of several first-in-class medicines in the areas of type 1 and type 2 diabetes, lipodystrophy, and progressive non-viral liver diseases, as well as to the mid and late-stage development of novel drug candidates for obesity and NASH. Dr Weyer previously served as President and Chief Development Officer at ProSciento and as visiting fellow with the National Institutes of Health, NIDDK, and has authored over 100 peer-reviewed publications in the field of endocrinology and metabolism. 
 
Marcus Hompesch, Chief Executive Officer and Chairman of the Board, ProSciento is a recognized 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 20 years of work as clinician and clinical researcher. To date Dr Hompesch has authored more than 90 publications, has been editor and author of a textbook on translational research methods and is editor-in-chief of the journal ‘Endocrinology, Diabetes & Metabolism’. He established ProSciento, Inc., CA in 2003

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