It has been a challenge for us to edit this volume of Endocrinology and Metabo lism: Progress in Research and Clinical Practice. The topic of the pathogenesis of insulin-dependent, type I diabetes mellitus is particularly appropriate for this series, since advances in this area have been made, to a large extent, by applying state-of-the-art laboratory techniques to clinical samples. Over the last several years, a number of lines of evidence have been gathered, suggesting that classic type I diabetes mellitus results from the autoimmune des truction of pancreatic beta-cells in genetically susceptible individuals. This hypothesis is particularly appealing because it offers a rational approach to the prevention of diabetes by immunosuppression. We have tried to present a balanced, authoritative summary of the information currently available to support the autoimmune hypothesis for the pathogenesis of human type I diabetes, to place this information in historical perspective, to include relevant information from animal models of type I diabetes in which more invasive experimentation is ethical, and, finally, to update the reader on the current status of attempts to intervene in the progression of diabetes with immunosuppressive drugs. New York, New York Fredda Ginsberg-Fellner Robert C. McEvoy Contents Preface.. . . .. .. .. . . . . . . . . . . . . ... . . . . . . . . . . . .. . . . . . . .. . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xl . . . . . . . . . . . . . 1. The Autoimmune Hypothesis of Insulin-Dependent Diabetes: 1965 to the Present . . . . . . . . . . . . ..................... . . . . . .

Glucagon III complements "Glucagon I" and "II" published in 1983 in this series as "Vols. 66/I" and "II." These three volumes truly represent a "glucagon encyclopedia" and as such have no competitors in the scientific literature worldwide. In this volume, the most recent data on glucagon molecular biology are reviewed together with clinically relevant information on the role of glucagon in the pathophysiology of diabetes, the place of glucagon in medical imaging or in emergency medicine. Chapters are devoted to newly identified members of the glucagon family such as glucagon-like peptide-1 (GLP-1) and oxyntomodulin. Glucagon III is a comprehensive review of all information published on this important hormone since 1983 and is "the" reference book on the subject.

The prevalence of metabolic syndrome (MS) is rising in developing countries and developed countries at such high rates that it is now considered a worldwide public health problem of pandemic proportions. Yet its spread can usually be mitigated by diet and lifestyle behavior. Nutritional Intervention in Metabolic Syndrome brings together coverage of dietary patterns and dietary components to create a complete understanding of the mechanisms by which these diets and components may improve metabolic syndrome. It then presents information on how to treat MS through lifestyle change and nutritional intervention. Witten by experts, the book focuses on diet therapy, nutritional intervention, and oxidative stress in metabolic syndrome. It presents information on dietary patterns in metabolic syndrome, including Mediterranean style diets, DASH, and low calorie diets. The text then provides an understanding of the physiopathology mechanisms in metabolic syndrome and strategies to treat these conditions through nutritional intervention. Chapters cover prevalence of MS, pathophysiology, MS in systemic lupus erythematosus and rheumatoid arthritis, gene-nutrient interactions, MS in adolescents and children, lifestyle change and physical activity, and various effects of dietary components in MS. Research studies examining food groups are important, and there is a trend in the literature to verify the relationship between dietary patterns and cardiovascular risk factors. However, studies examining dietary components, such as olive oil, soy-based products, n-3 polyunsaturated fatty acids, berries, whole grains, nuts, dairy foods, tea, coffee, and alcoholic beverages are also important. The coverage of both in this book gives you an understanding of the pathophysiology underlying MS that you can use to develop strategies to prevent and treat these conditions through nutritional intervention.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

Atherosclerosis leading to coronary heart disease and to cerebrovascular disorders is the number one cause of death in industrialized societies. For the last two decades, great ad vances have been made in understanding the pathogenesis of those disorders. Recent studies have revealed that the earliest event in atherogenesis is the adhesion of circulating leukocytes to the vascular endothelial cells and their migration into the subendothelial space. These cells are known to playa central role in the formation of a fatty streak consist ing of lipid-laden foam cells. As pathological events continue, the lesion is converted to a more fibrous lesion associated with vascular smooth muscle cells. To solve the enigma of this complicated process, intensive studies in molecular biology have disclosed the genes involved in those events. Some of the genes have been verified by creation of novel animal models, which have led to novel therapeutic strategies for subjects with atherosclerosis. This volume contains papers presented at the International Symposium on Lipoprotein Metabolism and Atherogenesis held in Kyoto December 5-8, 1998, supported in part by the Japan Intractable Diseases Research Foundation. The following three topics were the focus of the three-day program: I) The molecular approach to studying risk factors and prevention 2) The creation of novel animal models 3) Lipoprotein disorder as a cause of activation of vascular endothelial cells Thirty distinguished researchers from the United States, the United Kingdom, Austria, Finland, Australia, and Japan were invited."

Die Beitrage dieses Buches beschaftigen sich mit Autoimmunitat, Immuntherapie des Typ-I Diabetes, Virusgenese, Insulintherapie und -allergie. Schwerpunkte liegen auf den dynamischen Aspekten der Insulinsubstitution unter Berucksichtigung einer angepassten Diat und der Therapie mit oralen Antibiotika, Insulinen und Pro-Insulinen. Gleichzeitig wird anhand der Makro-Angiopathie und der Neuropathie auf die Auswirkungen der dynamischen Insulinsubstitution bei Sekundarkomplikationen hingewiesen. Die Moglichkeit der computerunterstutzten Therapiefuhrung und glukosesensorgesteuerten Biofeedback-Kontrolle werden vorgestellt. Ein umfangreiches Kapitel vermittelt den aktuellen Stand der experimentellen Forschung und der klinischen Anwendung der Pankreas- und Inselzelltransplantation.

Diabetes mellitus represents one of the most frequent and serious clinical syn dromes in contemporary medicine. Since the end of the nineteenth century, the endocrine pancreas has been implicated in the pathogenesis of this disease. Several pathologists of the twentieth century detected various lesions and mor phologic alterations in the pancreatic islets of diabetic patients, but the patho physiologic basis of their findings remained long obscure. The systematic mi croscopic work of WILLY GEPTS clarified the views and related the variety in histopathology to differences in origin, duration and clinical expression of the disease. Over the past two decades, the concept of a multifactorial origin of diabetes has become widely accepted. Various agents and mechanisms have been identified which can lead to a quantitative or qualitative deficit in pancre atic B-cells. The purpose of this book is to bring an update on the many path ways which may induce an absolute or relative insufficiency in insulin release and hence a diabetic state. Rather than bringing a complete account on all re search relevant to the understanding of the pathology of the diabetic pancreas, the authors of the various chapters of this volume have focussed on selected processes which can impair B-cell function, survival or regeneration.

an adequate oxygen supply is vital for the undisturbed development of the fetus and its functions. This book gives a synopsis of the ruling influence that oxygen has in multiple regulation sytems in the mother and especially in the fetus. The authors consider oxygen as a manipulated variable or as a corrective element during normal pregnancy, during delivery and during acute and chronic oxygen deficiency. Furthermore, they deal with the consequences that oxygen deficiency has on the fetus.

Inherited disorders of purine and pyrimidine metabolism in man lead to severe diseases. At the 2nd M}nchner Adventssymposium the state of the art as to the genetic basis, clinical aspects, and the biochemical basis has been given by leading experts in the fields concerning the following diseases: Hypoxanthine phosphoribosyltransferase deficiency (HGPRT-deficieny), adenine phosphoribosyltransferase deficiency (APRT-deficiency), hyperuricemia and gout, adenosine deaminase deficiency (ADA-deficiency, purine nucleoside phosphorylase deficiency (PNP-deficiency). All contributions of the symposium are published within this volume thus giving and overview of this most interesting field.

Biological membranes are often effected by diseases. Molecular events leading to or arising from pathological changes in the course of different diseases are as yet not clearly understood. This competent study by leading experts covers changes of the cellular environment, membranes and the metabolic functions during tissue growth and differentiation as well as aspects of abnormal organelle function in lysosomal storage diseases, peroxisomal and mitochondrial disorders, enzyme defects and regulatory defects of receptors due to oncogenes.

Responding to the dramatic scientific and technological developments in the agro-food sector and to the enormous public concern about novel food production and novel food ingredients this volume focusses on defining, classifying and reassessing the quality of food towards human nutritional needs aimed at health. It is designed for all those actively involved in the food sector and for interested lay persons and responsible consumers interested in getting information about the driving forces of the present and future food market, the food industry, and the food policy and the consumer association.

In the last decade, it has become increasingly evident that the clini- cal and morphologic changes underlying many of the complications of diabetes, including cataract formation, retinopathy, nephropathy, neuropathy, and macrovascular disease, are preceded by a variety of disturbances of biochemical and physiologic origin. Dr. Cohen has recently written a superb monograph, entitled Diabetes and Protein Glycosylation: Measurement and Biologic Relevance, in which she thoroughly explores how enhanced nonenzymatic glycosylation in uncontrolled diabetes underscores the pressing need for main- tenance of long-term euglycemia. In the present volume, The Polyol Paradigm and Complications of Diabetes, she reviews, in a most succinct and thorough manner, how another biochemical mechan- ism, involving the polyol pathway, is involved in the pathogenesis of such diabetes complications as retinopathy, neuropathy, nephropa- thy, and cataract formation. Dr. Cohen gives us a clearly written and comprehensive mono- graph, reviewing the chemistry of the polyol pathway and of the aldose reductase inhibitors, and the pathophysiologic significance of increased polyol pathway activity in a variety of tissues affected by Vlll Foreword diabetes mellitus. She insightfully describes the relationship of increased polyol pathway activity to altered metabolism of inositol- containing phospholipids and to changes in various tissue concentra- tions of myo-inositol. Finally, she provides us with a careful review of the existing experimental and clinical studies with a variety of different aldose reductase inhibitors that have been and are being performed in the hope of preventing or reversing long-term compli- cations of diabetes.

In the middle of the 17th century, the great French philosopher Rene Descartes wrote (L'Homme, J. Le Gras, Paris, 1669) that a suitable stimulation of the brain results in two types of "movements": exterior movements, designed to seek desirable ends and to avoid undesirable or harmful ones and interior movements or "passions" which through the release of "animal spirits" regulate the heart, the liver, and other organs. When it appears appropriate to meet a threat with force, the passion of rage causes the release of strong spirits, whereas when avoidance appears to be the better choice, the passion of fear causes the brain to release weak spirits. We do not know what influence, if any, Descartes had on the thinking of Walter B. Cannon (Bodily Changes in Pain, Hunger, Fear and Rage, Appleton and Co. , New York, 1920), of Hans Selye (The Story of the Adaptation Syndrome, Acta, Inc. , Montreal, 1952), ofG. W. Harris or of R. Guillemin (Hypothalamic-Hypophysial Interrelationships. A Sym posium. c. c. Thomas, Springfield, 1956), but it is interesting to reflect upon the durable value of great ideas which constantly resurface even if modified by other ideas and by new techniques, as if propelled by a preordained intellectual imperative.

One of the hallmarks of aging is the decreased capacity to adapt to changes in the environment. In a constant, controlled environment, it is often difficult to distin guish the functioning of the young organism from that of the old. However, when stresses are applied-temperature stresses, dietary stresses, infection, emotional stresses-the differences are more apparent. Frequently, the response ofthe old is delayed and may never reach the same mag'nitude as the young. These responses, in most cases, are mediated by the neuroendocrine system, which communicates via hormones, neurotransmitters, and related substances. Thus, it is important to understand the age-related changes that take place in the secretion and act ion of these substances and how these changes relate to the well-being of the whole organism. Indeed, the "neuroendocrine theory of aging" proposes that almost all of the characteristics of aging can be accounted for by dysfunction of the neuroendocrine system. A book on endocrine function and aging is particularly relevant at this time. With the advent of the techniques of molecular biology, there has bee an explo sion of knowledge concerning hormone secretion and action. Hormones, pro hormones, hormone receptors, and "second messenger" mediators rapidly are being cloned and sequenced. Such knowledge gives us important insights into the molecular workings of these substances as well as into the genetic hasis of endo crine dysfunction. These new tools are now being applied to the problem of age related changes in endocrine function."

Mitochondrial diseases are often hard to diagnose. From the time they were first researched without animal models, patients of mitochondrial diseases were of equal interest to both clinical and basic scientists. With the new research done, this book includes updates on the normal structure, function, and molecular biology of the mitochondrial respiratory chain, information on traditional diagnostical methodologies, and an overview of the diagnostic promise of new technologies. The hypermetabolism of Luft disease, although only seen twice, is also studied. There are critical reviews of symptoms and signs associated with syndromes, as well as updates on the genetic defects of either the mitochondrial or the nuclear genome responsible for many disorders.

Dyslipidemia affects almost half of American adults and is the most prevalent manageable risk factor for atherosclerosis. Lipid disorders often co-occur with other prevalent conditions such as diabetes and kidney disease; they are also often a concern with certain medication regimens (such as anti-retroviral and certain anti-psychotic agents). Proper treatment of dyslipidemia can reduce the risk of peripheral arterial disease, revascularization procedures, nonfatal myocardial infarction, stroke, and cardiac death. However, only 20% of adults meet the national guidelines for cholesterol control. As part of the Oxford American Cardiology Library, this practical handbook is designed to serve as a concise yet authoritative resource on diagnosing and treating dyslipidemia. The book is tailored to the needs of busy health care professionals treating patients in various clinical settings, and focuses on presenting essential information to clinicians who are at the forefront of the diagnosis and management of dyslipidemia. Featuring evidence-based, concise yet comprehensive discussion of key clinical concepts in addition to numerous figures, tables and illustrations, this pocket-sized handbook will serve as an invaluable guide to healthcare professionals. Features: * Authored by a renowned international group of experts on dyslipidemia. * Chapters include vignettes to enhance clinical relevance.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

The aim of this volume is to underline that promoting physical activity is crucial to preventing illness and maintaining our health, thus leading to a reduction in healthcare costs. Over the last decade studies have shown that physical exercise plays an important role in maintaining an individual's psycho-physical balance. Physical activity therefore helps in tackling today's major health challenges, including diabetes, high blood pressure, and cardiorespiratory diseases.

This timely book provides an overview of topics related to obesity. These include associated health risks, childhood obesity, genetics, evaluation, treatment, behavioral strategies, and successes and failures in preventing obesity. The volume covers evaluation guidelines, different approaches to treatment, including diet, exercise, behavior, drugs, and surgery to deal with the current world-wide obesity epidemic.

This book is an organized approach to understanding bone growth and disease. It integrates anatomic and radiologic knowledge of enchondral and membranous bone growth and emphasizes the similarities of the physis and acrophysis in development. The artwork, jointly produced by artist and author, illustrates the concepts described. The identification of abnormality is aided by the explanations of the causes in terms of pattern recognition.

Research into the paraoxonase (PON) multigene family has really only blossomed in the last 10 years. Before this time only PON1 was known and research was restricted to toxicologists investigating the metabolism of organophosphate insecticides and nerve gases and a few mad scientists searching for natural substrates.

Since this time two new members PON2 and PON3 have been discovered, all 3 PONs have been shown to act as antioxidants and the PON family has taken centre stage as major players in the development of a wide variety of diseases such as cardiovascular disease, diabetes mellitus, rheumatism, Alzheimer and many more while remaining important in determining organophosphate toxicity.

In September 2006 the 2nd International Conference on Paraoxonases took place in Hajduszoboszlo, Hungary, bringing together the world's foremost experts in the field. The current book is a distillation of the plenary lectures which took place at the meeting, resulting in a comprehensive up to date, state of the art review of current paraoxonase research."

Metabolic Syndrome (MS) is a highly prevalent condition in developed countries and is a cluster of several risk factors for type 2 diabetes and cardiovascular disease that includes increased body mass index/waist circumference, visceral obesity, insulin resistance, hyperclycaemia, dyslipidaemia and hypertension, which are all major causes of morbidity and death. This volume provides a critical review and discussion of the knowledge gathered on MS and analyzes the interplay between oxidative stress, chronic inflammation and angiogenesis features. There is a special focus on recent discoveries and progress toward possible therapeutic strategies, such as the role of glucose transporters within MS; the effects of polyphenols as anti-oxidant, anti-inflammatory and anti-angiogenic compounds. The role of NFkB, nitric oxide synthases, hypoxia-inducible factors, and many other molecules that play a part in the development of oxidative stress and inflammation as well as angiogenesis is also covered. This book fills the gap between basic science and medical care, and provides the reader with the skills to apply rigorous basic science to clinical settings of metabolic syndrome-associated disorders.

A definitive review in the field of magnesium research, this book brings together the proceedings of the 11th International Magnesium Symposium in Osaka, Japan from October 22-26, 2006. Written by authorities in the area, the book provides a thorough overview of progress in the area of magnesium research. The author is one of the world's foremost magnesium researchers and reviewers, and the book provides essential reading for researchers in magnesium.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

As I read this unique volume on diabetes and pregnancy edited by Lois Jovanovic, I was struck by two themes that run throughout these collected chapters. First, this volume provides an excellent assessment of past problems, present management, and future challenges presented by dia betes in pregnancy. Orury's unique, longitudinal experience with diabetes iIi pregnancy provides the reader with an important overview, as does Coetzee's discussion of gestational diabetes. Current problems-deter mining the etiology and prevention of congenital malformations in infants of diabetic mothers (10M), assessment of antepartum fetal condition, management of pregnant patients with diabetic retinopathy, recognition of thyroid dysfunction in the pregnant diabetic woman, and understanding the multitude of metabolic sequelae observed in the 10M-are thoroughly reviewed. Finally, important considerations for future treatment and ther apy such as the adaptation of the fetal pancreas to the disordered intra uterine environment often seen in maternal diabetes, the use of fetal pan creatic tissue for transplantation, the application of exercise in the management of the pregnant woman with diabetes, and the long-term con sequences for the 10M provide an exciting glimpse into the future. The second important theme that emerges is the critical role the problem of diabetes in pregnancy has played in our understanding of maternal and fetal physiology. Clinical observations supported by basic research have emphasized the role of fetal fuels in teratogenesis.