Front Cover; Controversies In Diabetic Neuropathy; Copyright; Contents; Contributors; Preface; Section I: Clinical Context; Chapter One: A Brief Introduction to the History and Controversies of Clinical Trials in Diabetic Neuropathy; References; Chapter Two: Neuropathy in the DCCT/EDIC-What Was Done Then and What We Would Do Better Now; 1. Introduction; 2. Neuropathy Outcomes Assessments; 2.1. DCCT and EDIC Design; 2.1.1. Assessment of DSPN in DCCT; 2.1.2. Assessment of DSPN in EDIC; 2.1.3. Additional DSPN Measures in EDIC; 2.1.4. Assessment of CAN in DCCT; 2.1.5. Assessment of CAN in EDIC

3. Complementary Assessments in EDIC3.1. Evaluation of Urologic Complications; 3.2. Gastroparesis; 3.3. Other Evaluations in EDIC; 4. DCCT/EDIC Findings; 4.1. DSPN and CAN Outcomes in the DCCT and EDIC Study; 5. Discussion; 5.1. DCCT/EDIC and Contemporary Neuropathy Trials Design; References; Chapter Three: The Perfect Clinical Trial; 1. Introduction; 2. Study Aims: Prevent DSP, Prevent Progression, or Reverse DSP?; 3. Selection of Study Participants; 4. Trial Duration; 5. Study End Points; 6. Core Labs and Training; 7. Intervention; 8. Study Conduct

9. Streamlined Ethics and Contracts Process10. Summary; References; Section II: New Models of Diabetic Neuropathy; Chapter Four: An Introduction to the History and Controversies of Animal Models of Diabetic Neuropathy; 1. Why Use Animal Models?; 2. What Species?; 3. What Diabetogenic Insult?; 4. STZ Toxicity; 5. Novel Models; References; Chapter Five: Can Diabetic Neuropathy Be Modeled In Vitro?; 1. Introduction; 2. Diabetic Neuropathy; 3. The Somatosensory Nervous System; 4. Can We Model Diabetic Neuropathy In Vitro?; 4.1. Choice of Cells; 4.1.1. Immortalized Cell Lines

4.1.2. Primary Tissue Culture4.1.3. Induced Pluripotent Stem Cells; 4.2. Choice of Stimuli; 4.3. Choice of Output Measure; 4.3.1. Life or Death?; 4.3.2. Altered Bioenergetics and Oxidative Stress; 4.3.3. Neuronal Hyperexcitability; 4.3.4. Axonal Degeneration and Regeneration; 4.4. Looking Forward to a Better In Vitro Model of Diabetic Neuropathy; 5. Conclusions; Acknowledgments; References; Chapter Six: Alternatives to the Streptozotocin-Diabetic Rodent; 1. Introduction; 2. Rodent Models of Obesity; 2.1. High-Fat Fed Sprague-Dawley Rats and C57Bl6/J Mice; 2.2. Zucker Rats

3. Rodent Models of Type 2 Diabetes3.1. Zucker Diabetic Fatty Rats; 3.2. Spontaneously Diabetic Torii Rat; 3.3. Zucker Diabetic Sprague-Dawley Rat; 3.4. Goto-Kakizaki Rat; 3.5. BioBreeding Zucker Diabetic Rat; 3.6. Otsuka Long-Evans Tokushima Fatty Rat; 3.7. Ob/ob and db/db Mice; 3.8. Tsumura Suzuki Obese Diabetes Mouse; 3.9. Combined High-Fat Fed, Low-Dose Streptozotocin Models of Type 2 Diabetes; 3.10. Streptozotocin-Nicotinamide Rat; 4. Rodent Models of Type 1 Diabetes; 4.1. Spontaneously Hypertensive Rat; 4.2. BioBreeding/Worcester Rat; 4.3. Ins2Akita Mouse; 4.4. Nonobese Diabetic Mouse