Clinical Information

The onset of autoimmune diabetes mellitus (type 1 diabetes mellitus) is preceded (and accompanied) by the appearance of autoantibodies to a variety of pancreatic islet cell antigens in serum, including insulin. The level of these autoantibodies is generally low and may even fall during follow-up. In genetically predisposed, but disease-free, individuals (first degree relatives of patients with type 1 diabetes or individuals with permissive human leukocyte antigen [HLA] alleles), detection of multiple islet cell autoantibodies is a strong predictor for subsequent development of type I diabetes.

Once type 1 diabetes has fully manifested, insulin autoantibody levels usually fall to low or undetectable levels. However, after insulin therapy is initiated, autoantibody production may recur as a memory response. Insulin autoantibody production is more common when therapeutic insulin of animal origin is used (rarely used in contemporary practice). Larger therapeutic doses may be required because of antibody-induced insulin resistance.

Insulin antibodies may be found in nondiabetic individuals complaining of hypoglycemic attacks. In this setting their presence can be an indicator of "factitious hypoglycemia" due to the surreptitious injection of insulin, rather than to a clinical problem (eg, insulinoma). However, insulin autoantibodies in nondiabetic subjects can occasionally develop without exposure to exogenous insulin and may rarely become a cause of episodic hypoglycemia. Anti-idiotypic autoantibodies against insulin autoantibodies have been demonstrated in some cases. Interaction of these antibodies with insulin autoantibodies could displace bound insulin from the insulin autoantibodies, resulting in hypoglycemia.

In addition to IgG and IgM insulin autoantibodies, IgE antibodies (identified by the fluorescence enzyme immunoassay) may occur. IgE insulin autoantibodies result in immediate hypersensitivity reactions, such as urticaria, but do not lead to insulin resistance or hypoglycemia as can be seen with the IgG antibodies. This test only determines the presence of IgG and IgM antibodies, not IgE antibodies.

In conjunction with family history, HLA-typing and measurement of other islet cell autoantibodies (glutamic acid decarboxylase [GAD65] antibody and islet cell antigen 2 antibody [IA-2]), insulin autoantibody testing helps predict the future development of type I diabetes in asymptomatic children, adolescents, and young adults. Inclusion of a recently described fourth autoantibody (zinc transporter 8: ZnT8) further enhances the prediction of type 1 diabetes occurrence and its distinction from type 2 diabetes.