190 pages

Date published 
May 2007

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Diabetes and Its Complications Table of Contents

Diabetes and Its Complications: Strategies to Advance Therapy and Optimize R&D

By Allan B. Haberman, PhD

Chapter 1
1.1. Risk Factors for Type 2 Diabetes
Preventing Development of Diabetes in Prediabetic Individuals

1.2. Growth in Prevalence of Diabetes
Worldwide Increase in Obesity
1.3. Economic Burden of Diabetes
1.4. Market Size for Current Diabetes Drugs
1.5. Unmet Medical Needs in Diabetes
Type 2 Diabetes
Type 1 Diabetes

Chapter 2
Type 1 Diabetes as an Autoimmune Disease
2.1. Genetic and Environmental Determination of Type 1 Diabetes
Genetic Determinants
Environmental Determinants
2.2. Pathogenesis of Type 1 Diabetes
Trials of Agents to Prevent or Ameliorate Type 1 Diabetes in Patients with Prediabetes or New-Onset Diabetes
Anti-CD3 Agents
New Approaches to Treatment of Established Type 1 Diabetes

Chapter 3
Type 2 Diabetes as a Metabolic Disease
3.1. Obesity as a Cause of Insulin Resistance and Beta-Cell Dysfunction
Adipokines, Obesity, and Insulin Resistance
Free Fatty Acids as a Critical Factor in Both Insulin Resistance and Beta-Cell Dysfunction
Obesity, Inflammation, and Insulin Resistance
Salicylates as Therapeutic Drugs
Chemical Chaperones as Therapeutic Agents: PBA and TUDCA
3.2. Genetic Factors in Development of Beta-Cell Dysfunction
Activating Mutations in the KCNJ11 Gene
TCF7L2: A Major Risk Factor for Late-Onset Type 2 Diabetes
Type 2 Diabetes Is Caused by a Combination of Genetic Risk Factors

Chapter 4
Current Diagnosis and Treatment of Diabetes
4.1. Diagnosis of Diabetes
4.2. Treatment of Diabetes
Diet and Exercise
Concurrent Treatment of Other Aspects of the Metabolic Syndrome
4.3. Insulin Products
Insulin Formulations with Different Durations of Action
Long-Acting Insulin Glargine
Inhaled Insulin
4.4. Established Oral Antidiabetics
Biguanides: Metformin
Alpha-glucosidase Inhibitors
4.5. Type 2 Diabetes Management Using the Established Oral Antidiabetics and Insulin
ADA/EASD Consensus Statement
ADA/EASD Panel’s Recommendations versus Traditional Treatments
De-emphasis of Newer Drugs in the Panel’s Recommendations
Disagreement with the Panel’s Findings

Chapter 5
Novel and emerging antidiabetic drugs
5.1. Approved and Pipeline Drugs Belonging to Drug Classes Introduced into the Market since 2005
Amylin Analogs: Pramlintide
Incretin Mimetics
Dipeptidyl Peptidase-IV Inhibitors
Outlook for the Newly Introduced Antidiabetic Drugs
5.2. Novel Classes of Antidiabetics in Corporate Pipelines
PPARa/PPARg Dual Agonists (Glitazars)
PPARg Partial Agonists
FK614 and PA-082
PPARg ,b ,a
Cannabinoid-1 Receptor Antagonists
RIO-Diabetes Study
11 Beta-hydroxysteroid Dehydrogenase Type 1
Sodium Glucose Cotransporter-2 Inhibitors
Glucokinase Activators

Chapter 6
Early-Stage Drugs and Novel Therapeutic Strategies for Type 2 Diabetes
6.1. Does the Lack of Scientific Knowledge of Type 2 Diabetes Hamper Development of Effective Treatments?
6.2. The Inadequacy of Animal Models in Type 2 Diabetes
6.3. Strategies for Making Drug Discovery and Development More Effective
Dealing with Multiple Molecular "Causes" of Disease by Hitting More than 1 Target
Whole-Pathway Approaches
Biology-Driven Drug Discovery
Biomarkers and Translational Medicine
Animal Models and Complex Diseases
6.4. The Diabetes Survey and Issues Related to Strategies to Improve the Effectiveness of Drug Discovery and Development
6.5. Selected Research-Stage Agents and Novel Therapeutic Strategies for Type 2 Diabetes
Small-Molecule GLP-1 Receptor Agonists
Ago-Allosteric Modulators
Protein Tyrosine Phosphatase 1B Inhibitors
Preclinical Development of Small-Molecule PTP1B Inhibitors
Development of Antisense Drugs: ISIS 113715
AMP-Activated Protein Kinase Activators
CytRx Corporation’s RNAi-Based Drug Discovery Programs in Type 2 Diabetes and Obesity
Receptor-Interacting Protein 140
Sirtuin Modulators
Ghrelin Antagonists (Growth Hormone Secretagog Receptor Antagonists)
GPR119 Agonists
6.6. Conclusions: Development of Novel Antidiabetics and the CHI Diabetes Survey

Chapter 7
Diabetic Complications
7.1. Microvascular Complications
Diabetic Retinopathy
Diabetic Neuropathy
Diabetic Nephropathy
7.2. Prevention of Diabetic Complications
7.3. Pathogenesis of Diabetic Complications
Four Pathogenic Pathways in Diabetic Complications
A Unifying Model for Induction of Microvascular Diabetic Complications
Induction of Macrovascular Complications in Insulin-Resistant and Diabetic Individuals
7.4. Novel Drugs and Therapeutic Strategies for Diabetic Complications
Drugs for Diabetic Complications in Clinical Trials
Ranibizumab and Pegaptanib
7.5. Novel Therapeutic Strategies for Diabetic Complications
Therapeutic Strategies Based on Brownlee’s Unified Diabetic Complications Model
Development of Transketolase Activators
Development of PARP Inhibitors
Development of Catalytic Antioxidants
A Novel Therapeutic Strategy for Diabetic Retinopathy Based on Targeting Extracellular Carbonic Anhydrase and Kallikrein

Chapter 8
8.1. A Disease of Progress
8.2. Where to Go from Here
8.3. Addressing Unmet Needs
8.4. Aiming for Multiple Targets



Company Index with Web addresses