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Preface xv

Mark A. Sperling

The Classification of Diabetes Mellitus:

A Conceptual Framework 1533

Diego Ize-Ludlow and Mark A. Sperling

Diabetes is the extreme manifestation of a spectrum conditions in which the balance of insulin secretion and insulin action (or insulin resistance) has been altered. Loss of euglycemia is caused by relative insulin deficiency in the presence of insulin resistance, or by absolute insulin deficiency. There are related conditions in which an alteration of insulin resistance or P-cell dysfunction exists, but because of compensation glucose homeostasis has not been lost. The elucidation of the causes of insulin resistance and P-cell failure and the attention to the different degrees of insulin deficiency and insulin resistance allow for better diagnosis, treatment, and prevention of diabetes and its related conditions.

Type 1 Diabetes Mellitus: Etiology, Presentation, and Management 1553

Michael J. Haller, Mark A. Atkinson, and Desmond Schatz

This article reviews our current understanding of the etiology, presentation, and management of type 1 diabetes. The discussion includes a review of the natural history of diabetes, the complex relationship between genetic and environmental risk for type 1 diabetes, and current methods for prediction of type 1 diabetes. The article also reviews the current management of children who have new-onset type 1 diabetes, age-appropriate management goals, and diabetes complications. Finally, the article discusses the future of diabetes screening programs and the progress toward the ultimate goal of curing type 1 diabetes.

Type 2 Diabetes Mellitus in Youth: The Complete Picture to Date 1579

Neslihan Gungor, Tamara Hannon, Ingrid Libman, Fida Bacha, and Silva Arslanian

Type 2 diabetes mellitus is a heterogeneous condition in which the clinical manifestation of hyperglycemia is a reflection of the impaired balance between insulin sensitivity and insulin secretion. Clinical experience and research in youth type 2 diabetes mellitus are in an early stage because of the relative novelty of the condition in pediatrics. This article discusses the amassed information in type 2 diabetes mellitus of youth to date with respect to the epidemiology, pathophysiology, risk factors, clinical presentation, screening, and management strategies.

Pediatric Diabetic Ketoacidosis and Hyperglycemic

Hyperosmolar State 1611

Nicole Glaser

Diabetic ketoacidosis is an important complication of diabetes in children and is the most frequent diabetes-related cause of death in childhood. The pathophysiology of this condition can be viewed as an exaggeration of the normal physiologic mechanisms responsible for maintaining an adequate fuel supply to the brain and other tissues during periods of fasting and physiologic stress. The optimal therapy has been a subject of controversy, particularly because the most frequent serious complication of diabetic ketoacidosis— cerebral edema—and the relationship of this complication to treatment are incompletely understood. In this article, the author reviews the pathophysiology of diabetic ketoacidosis and its complications and presents an evidence-based approach to the management of this condition.

Monogenic and Other Unusual Causes of

Diabetes Mellitus 1637

Meranda Nakhla and Constantin Polychronakos

This article covers some unusual or rare causes of diabetes mellitus chosen not necessarily on the basis of frequency or rarity, but rather on the basis of how well the disease and its implications in diabetes management is understood. A specific diagnosis is of help in these rare syndromes but not absolutely necessary for optimal management. The basic principles of diabetes management are well-defined, regardless of etiology. What is important is to understand the relative contribution of insulin resistance versus insulin deficiency, regardless of etiology, as the most important guide to management.

Insulin Analogues in Children and Teens with Type 1

Diabetes: Advantages and Caveats 1651

Marianna Rachmiel, Kusiel Perlman, and Denis Daneman

This article reviews the advantages to and caveats of the use of newer insulin formulations (insulin analogues) and regimens in children and teens who have type 1 diabetes, their affect on glycemic control, frequency of hypoglycemic events, daily insulin requirements, and adverse affects such as excessive weight gain, which provides a further major challenge in adolescents. We also address briefly the use of adjunctive agents in the treatment of type 1 diabetes in children and teens.

Insulin Pump Treatment of Childhood Type 1 Diabetes 1677

Stuart A. Weinzimer, Kristin A. Sikes, Amy T. Steffen, and William V. Tamborlane

Current goals for the treatment of children and adolescents with type 1 diabetes mellitus include achieving near-normal blood sugar levels, minimizing the risk of hypoglycemia, optimizing quality of life, and preventing or delaying long-term microvascular complications. Continuous subcutaneous insulin infusion (CSII) provides a treatment option that can assist in the attainment of all of these goals in all ages of children. Usage of CSII has been demonstrated to reduce glycosylated hemoglobin levels and frequency of severe hypo-glycemia, without sacrifices in safety, quality of life, or weight gain, particularly in conjunction with the use of new insulin analogs and improvements in pump technology. Clinical studies of safety and efficacy of CSII in children are reviewed.

Oral Agents in Managing Diabetes Mellitus in Children and Adolescents 1689

Elka Jacobson-Dickman and Lynne Levitsky

Type 2 diabetes mellitus is a chronic disease with potentially devastating long-term complications. Despite the tremendous body of research and experience in the adult population, relatively little is established regarding this condition and its optimal management in children and adolescents. The pediatric community awaits results of ongoing trials as well as further study of optimal intervention in children, as they continue to extrapolate management practices from their adult counterparts.

Hypoglycemia: A Complication of Diabetes Therapy in Children 1705

Christopher Ryan, Nursen Gurtunca, and Dorothy Becker

The experience of hypoglycemia is probably the most feared and hated consequence of life with type 1 diabetes among pediatric patients and their parents. Although transient detrimental effects are clearly disturbing and may have severe results, there is surprisingly little evidence of long-term CNS damage, even after multiple hypoglycemic episodes, except in rare instances. Despite the latter evidence, we advocate that every treatment regimen be designed to prevent hypoglycemia without inducing unacceptable hyperglycemia and increasing the risk of micro- and macrovascu-lar complications.

Complications of Diabetes Mellitus in Childhood 1735

Sarah J. Glastras, Fauzia Mohsin, and Kim C. Donaghue

Complications of diabetes include retinopathy, nephropathy, neuropathy, macrovascular disease, and associated autoimmune diseases. Clinical manifestations of complications uncommonly present in childhood and adolescence. Screening during the early years can identify subclinical disease and it offers an opportunity for early intervention. The Diabetes and Complications Control Trial has provided evidence for the long-term benefits of good glycemic control in preventing and delaying the onset of microvascular complications. Complications begin to manifest during adolescence, during which time all efforts should be made to educate and support young persons in achieving optimal diabetes control.

The Psychologic Context of Pediatric Diabetes 1755

Tim Wysocki, Lisa M. Buckloh, Amanda Sobel Lochrie, and Holly Antal

During the past few decades, there has been an explosion of behavioral science research on family management of pediatric diabetes. This article distills the major conclusions from that literature, emphasizing how primary care providers can apply these findings in clinical practice.

A Look to the Future: Prediction, Prevention, and Cure Including Islet Transplantation and

Stem Cell Therapy 1779

Anna Casu, Massimo Trucco, and Massimo Pietropaolo

Type 1 diabetes mellitus (T1DM) is characterized by the almost complete absence of insulin secretion, which is secondary to an autoimmune destruction or dysfunction of the insulin-producing cells of the pancreatic islets of Langerhans. Because T1DM is an autoimmune disease with a long preclinical course, the predictive testing of individuals before the clinical onset of the disease has provided a real opportunity for the identification of risk markers and the design of therapeutic intervention. With such a high degree of predictability using a combination of immunologic markers, strategies to prevent T1DM may become possible. A number of novel therapeutic strategies are under investigation in newly diagnosed T1DM patients and might ultimately be applied to prevent T1DM.

Cumulative Index 2005 1805

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