Type 1 diabetes: A predictable disease

Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by loss of insulin producing beta cells and reliance on exogenous insulin for survival. T1D is one of the most common chronic diseases in childhood and the incidence is increasing, especially in children less than 5 years of age. In individuals with a genetic predisposition, an unidentified trigger initiates an abnormal immune response and the development of islet autoantibodies directed against proteins in insulin producing beta cells. There are currently four biochemical islet autoantibodies measured in the serum directed against insulin, glutamic decarboxylase, islet antigen 2, and zinc transporter 8. Development of islet autoantibodies occurs before clinical diagnosis of T1D, making T1D a predictable disease in an individual with 2 or more autoantibodies. Screening for islet autoantibodies is still predominantly done through research studies, but efforts are underway to screen the general population. The benefits of screening for islet autoantibodies include decreasing the incidence of diabetic ketoacidosis that can be life threatening, initiating insulin therapy sooner in the disease process, and evaluating safe and specific therapies in large randomized clinical intervention trials to delay or prevent progression to diabetes onset.

Keywords: Autoantibodies; Autoimmunity; Diabetes prevention; Screening; Type 1 diabetes.

Figure 1

Stages in the development of type 1 diabetes adapted from the initial model proposed by George Eisenbarth. In genetically at risk individuals an unknown trigger, presumably environmental, initiates an autoimmune response that results in loss of beta cell mass. Before metabolic disturbances occur, islet autoantibodies (insulin, glutamic decarboxylase, islet antigen 2, zinc transporter 8) are measureable in serum. As beta cell mass decreases, potentially in a relapsing-remitting manner, there is loss of endogenous insulin release and ensuing hyperglycemia. Within this model, there are opportunities for type 1 diabetes (T1D) prevention in genotypically high risk individuals (primary prevention) and in autoantibody positive individuals (secondary prevention). Interventions to preserve remaining beta cell mass at diagnosis are also possible (tertiary prevention).

Figure 2

Insulin autoantibodies are often the first antibody to develop in young children. In contrast, adults most often are GAD65 and IA-2 autoantibody positive at diagnosis. The ZnT8 antibody is the most recently identified autoantibody with commercial testing now available. T1D: Type 1 diabetes; GAD65: Glutamic decarboxylase; IA-2: Islet antigen 2; ZnT8: Zinc transporter 8.

Figure 3

The measurement of serum islet autoantibodies has made type 1 diabetes a predictable disease. Early identification of islet autoantibody positive individuals leads to improved clinical outcomes by decreasing the risk for diabetic ketoacidosis and potentially preserving beta cell mass through clinical prevention trials. T1D: Type 1 diabetes; INIT-II: Intranasal Insulin Trial.