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Prediction of type 1 diabetes mellitus

Massimo Pietropaolo, MD
Section Editors
Irl B Hirsch, MD
Joseph I Wolfsdorf, MB, BCh
Deputy Editor
Jean E Mulder, MD


Type 1 diabetes mellitus is an autoimmune disease arising through a complex interaction of both genetic and immunologic factors [1]. The increase in understanding of the pathogenesis of type 1 diabetes mellitus has made it possible to consider intervention to delay the autoimmune disease process in an attempt to delay or even prevent the onset of hyperglycemia (figure 1). Although no successful strategy for the prevention of type 1 diabetes has yet been identified, subjects who are at high risk for type 1 diabetes can be identified using a combination of immune, genetic, and metabolic markers.

This topic will review the use of genetic, immunologic, and metabolic markers to predict type 1 diabetes. The definition, epidemiology, pathogenesis, and prevention of type 1 diabetes are discussed in detail elsewhere. (See "Classification of diabetes mellitus and genetic diabetic syndromes" and "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents" and "Pathogenesis of type 1 diabetes mellitus" and "Prevention of type 1 diabetes mellitus".)


Type 1 diabetes mellitus is an autoimmune disease arising through a complex interaction of both genetic and immunologic factors [1]. It is usually caused by an immune-mediated destruction of the insulin-producing beta cells in the islets of Langerhans [2]. Immune-mediated type 1 diabetes is called type 1A to distinguish it from some rarer cases in which an autoimmune etiology cannot be determined (type 1B); the latter are said to be idiopathic [3]. The term type 1 diabetes used here refers to type 1A, or autoimmune diabetes. (See "Classification of diabetes mellitus and genetic diabetic syndromes".)

Genetic – Type 1 diabetes occurs in genetically susceptible subjects. It is a polygenic disease with a small number of genes having large effects, (ie, human leukocyte antigen [HLA]) and a large number of genes having small effects. Risk of type 1 diabetes progression is conferred by specific HLA DR/DQ alleles (eg, DRB1*03-DQB1*0201 [DR3] or DRB1*04-DQB1*0302 [DR4]). In addition, HLA alleles such as DQB1*0602 are associated with dominant protection from disease in multiple populations [4]. (See 'Genetic markers' below.)

Immunologic – Similar to the majority of autoimmune diseases, type 1 diabetes usually has a relapsing remitting disease course with autoantibody and T cellular responses to islet autoantigens that precede the clinical onset of the disease process. The immunological diagnosis of autoimmune diseases relies primarily on the detection of autoantibodies directed to islet autoantigens in the serum of type 1 diabetic patients. Although their pathogenic significance remains uncertain, they have the practical advantage of serving as surrogate biomarkers for predicting the clinical onset of type 1 diabetes. (See 'Immunologic markers' below.)

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Literature review current through: Dec 2017. | This topic last updated: Jun 08, 2016.
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