https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)60591-7.pdf

Type 1 Diabetes

Summary Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.

Type 1 diabetes

The pivotal problem of comorbidity research lies in the psychometric foundation it rests on, that is, latent variable theory, in which a mental disorder is viewed as a latent variable that causes a constellation of symptoms. From this perspective, comorbidity is a (bi)directional relationship between multiple latent variables. We argue that such a latent variable perspective encounters serious problems in the study of comorbidity, and offer a radically different conceptualization in terms of a network approach, where comorbidity is hypothesized to arise from direct relations between symptoms of multiple disorders. We propose a method to visualize comorbidity networks and, based on an empirical network for major depression and generalized anxiety, we argue that this approach generates realistic hypotheses about pathways to comorbidity, overlapping symptoms, and diagnostic boundaries, that are not naturally accommodated by latent variable models: Some pathways to comorbidity through the symptom space are more likely than others; those pathways generally have the same direction (i.e., from symptoms of one disorder to symptoms of the other); overlapping symptoms play an important role in comorbidity; and boundaries between diagnostic categories are necessarily fuzzy.

/pdf/comorbidity-a-network-perspective-3hmyj5htzt.pdf

Comorbidity: a network perspective.

Type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, is a chronic disease characterized by insulin deficiency due to pancreatic β-cell loss and leads to hyperglycaemia. Although the age of symptomatic onset is usually during childhood or adolescence, symptoms can sometimes develop much later. Although the aetiology of T1DM is not completely understood, the pathogenesis of the disease is thought to involve T cell-mediated destruction of β-cells. Islet-targeting autoantibodies that target insulin, 65 kDa glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter 8 - all of which are proteins associated with secretory granules in β-cells - are biomarkers of T1DM-associated autoimmunity that are found months to years before symptom onset, and can be used to identify and study individuals who are at risk of developing T1DM. The type of autoantibody that appears first depends on the environmental trigger and on genetic factors. The pathogenesis of T1DM can be divided into three stages depending on the absence or presence of hyperglycaemia and hyperglycaemia-associated symptoms (such as polyuria and thirst). A cure is not available, and patients depend on lifelong insulin injections; novel approaches to insulin treatment, such as insulin pumps, continuous glucose monitoring and hybrid closed-loop systems, are in development. Although intensive glycaemic control has reduced the incidence of microvascular and macrovascular complications, the majority of patients with T1DM are still developing these complications. Major research efforts are needed to achieve early diagnosis, prevent β-cell loss and develop better treatment options to improve the quality of life and prognosis of those affected.

Type 1 Diabetes Mellitus

Type 1 diabetes.

Type 1 diabetes is preventable in animal models and predictable in humans. The increase in our knowledge of basic immunology has allowed the initiation of large-scale clinical efforts to prevent diabetes.

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Immunoendocrinology: Scientific and Clinical Aspects

The Immunopathogenesis of Type I Diabetes Mellitus Immunogenetics and Immunopathogenesis of the NOD Mouse Immunotherapy of the BB Rat Immunotherapy of the NOD Mouse Cyclosporine for Type I Diabetes: Lessons from First Clinical Trials and New Perspectives Immune Interventional Studies in Type I Diabetes: Summary of the London (Canada) and Canadian-European Experience Azathioprine Immunotherapy for Insulin-Dependent Diabetes: US Trials Azathioprine Immunotherapy: Australian Trials Immunomodulatory Drugs in Type I Diabetes Immunotherapy of Uveitis Immunotherapy of Graves' Eye Disease Immunopathogenesis and Therapy of Gonadal Disorders and Infertility Pathogenesis and Immunotherapy of Cogan's Syn-drome Immunotherapeutic Approaches for Multiple Sclerosis Myasthenia Gravis Toward More Selective Therapies to Block Autoimmunity Index

Immunotherapy of Diabetes and Selected Autoimmune Diseases

In the field of immunology, type 1 diabetes has become one of the major areas of investigation with studies that span from characterization of key molecules to trials for the prevention of the disease. Type 1 Diabetes : Molecular, Cellular and Clinical Immunology communicates both the background and the most recent understanding of this disorder, which will almost certainly be central to elucidating the etiology of autoimmunity, and in particular of organ specific autoimmunity. The book covers immunogenetics, immunopathogenesis, epidemiology, disease prediction and clinical application of current knowledge. Both scientists seeking to understand and prevent type 1 diabetes/autoimmunity as well as physicians caring for families with type 1 diabetes will be interested in this book.

George S. Eisenbarth

Papers

Type 1 Diabetes

Type 1 diabetes.

Immunoendocrinology: Scientific and Clinical Aspects

Immunotherapy of Diabetes and Selected Autoimmune Diseases

Immunology of type 1 diabetes