This is our third edition of Diabetes Mellitus: A Fundamental and Clinical Text, and again we have assembled a volume that encompasses the major advances in the basic molecular, cellular, and genetic components of diabetes, the epidemiology and pathophysiology of this disease, as well as a discussion of standard and new therapeutic modalities. Given the success of the first two editions, we have decided to maintain a similar format, with new chapters and some new authors reflecting the numerous exciting advances in the field. As before, the book is divided into ten parts; each section is subdivided into individual chapters contributed by experts in that particular field.
The first section covers the basic pathophysiology of insulin secretion. Of particular note, we have consolidated some of the chapters on the physiology of insulin secretion and recruited two well-established groups (Geoffrey Sharp and Louis Philipson) to join in these contributions. There is still a great deal of emphasis on the potential negative roles of gluco- and lipotoxicity on β-cell function and pathology and on the exciting aspect of glucagon-like peptide 1 (GLP-1) as a therapeutic agent to enhance both insulin secretion as well as to increase islet cell mass in diabetic patients.
Our knowledge of the molecular basis of the signaling pathways mediating the various physiologic effects of insulin is steadily advancing. New substrates and signaling molecules have been identified, and missing pieces of the puzzle are being filled in with these new discoveries. One area that is still being debated is the specificity of insulin action that is noted both in a cell-specific and a biologic action–specific manner. Each chapter has been updated to reflect the advances in these fields of research. Of note is the exciting new chapter describing the knockout mouse models, an area that has exploded since the previous edition of this book and has given us new and exciting insights into insulin action and glucose homeostasis in the whole animal.
The section on type 1 diabetes mellitus once again describes autoimmune and genetic bases for this condition and all the major advances made over the past few years. The section that follows describes the importance of hyperglycemia in causing diabetic complications and discusses the standard modalities for therapy of type 1 diabetes, as well as novel and innovative approaches. Of particular interest are the advances in islet cell transplantation and stem cell biology for potential islet cell development, two areas of critical concern to biologists, physicians, and patients with type 1 diabetes.
The cause of type 2 diabetes (Part VI) remains elusive. It is generally believed to be a polygenic disorder affecting insulin secretion and insulin action. Insulin resistance is often present even before the development of overt diabetes, with the abnormalities in insulin secretion occurring later. Although progress has been made in identifying mutations in candidate genes, these usually involve only a small minority of patients with type 2 diabetes. Positional cloning strategies are also being used to this end. Perhaps the most impressive genetic results are those seen in patients with maturity-onset diabetes of the young (MODY), in which more than five genes have been identified.
In contrast to the limited advances in diabetes gene discovery, remarkable progress has been made with regard to the pathophysiology of type 2 diabetes. Again, lipotoxicity, in addition to glucotoxicity, can affect both insulin secretion and insulin action. In addition, progress is being made in elucidating the role of adipose tissue in the pathogenesis of obesity-associated insulin resistance, including many of the adipocyte-secreted factors that may allow the adipose tissue to “talk” to other insulin-sensitive organs such as liver and muscle.
Although the U.K. Prospective Diabetes Study convincingly demonstrated that complications of diabetes can be prevented using sulfonylureas, metformin, or insulin, the results of the prevention trials are equally exciting. The latest one from the United States is called the Diabetes Prevention Program (DPP), and it clearly demonstrated that lifestyle changes (diet and exercise) in predisposed individuals with impaired glucose tolerance can prevent the development of diabetes; these results confirmed earlier trials from China and Finland. The DPP further demonstrated that younger adults with the potential to develop type 2 diabetes benefit from metformin treatment. Therapy of type 2 diabetes is also advancing with the concept of earlier use of combination oral agents and earlier introduction of insulin when appropriate. In addition, there is a chapter that addresses new and developing therapies that enhance insulin action, a chapter that allows the reader to gain insights into the research on potential new drugs.
Since the last edition, many new avenues of research have developed, and established areas have taken new directions. We have asked the original authors to rewrite or update their chapters to reflect these advances. In addition, new authors have been recruited who reflect the new areas of research. Each chapter is written as a focused review accompanied by extensive and updated reference lists, an active choice made by us to enable our readers to derive maximum information within a limited period while providing a resource for further in-depth researching of the area of interest. We sincerely hope that we achieve this goal. We are again indebted to all of the contributing authors and co-authors for their scholarly approach and their willingness to participate in this endeavor. Without their contributions, this book could not be successfully completed. Finally, the staff at Lippincott Williams & Wilkins deserve special mention for their patience during the months of assembling more than one hundred chapters.
Disclaimer: This work was not performed as official NIH duties for D. L. or BMS for S. I. T.