Type 1 diabetes mellitus (T1D) is an autoimmune disease that results from the cell-mediated destruction of islet beta cells. Approximately 12,000 to 15,000 children and adults annually develop T1D. The most recent Standards of Medical Care in Diabetes, supports testing for islet cell autoantibodies to facilitate the early diagnosis of T1D. Early diagnosis can reduce the rate of diabetic ketoacidosis and its associated morbidity and mortality.
The onset of T1D is preceded by the synthesis of autoantibodies to insulin and islet cell antigens. Detection of one or more islet cell autoantibodies is a strong predictor for progression to type I diabetes. The five-year cumulative risk for developing diabetes has been estimated to be 17% if seropositive for 1 antibody, 39% if seropositive for 2 antibodies, and 70% if seropositive for 3 antibodies. These autoantibodies can often be detected by age 3.
Some adults have slowly progressive T1D that has been classified as latent autoimmune diabetes of adulthood (Type 1.5 diabetes). They may be initially diagnosed as having type 2 diabetes (T2D) because of their adult onset of disease and their initial insulin independence. Testing for islet cell autoantibodies is helpful in distinguishing T1D from T2D in these patients.
Glutamic acid decarboxylase (GAD) is an enzyme involved in the synthesis of the neurotransmitter, gamma-aminobutyric acid (GABA). Glutamic acid decarboxylase (GAD) is present in highest concentration in brain and pancreatic beta cells. Antibodies specific for the 65 kDa isoform of glutamic acid decarboxylase (GAD65) comprise the majority of pancreatic islet cell autoantibodies. GAD65 antibody is the most frequently detected pancreatic islet antibody and is helpful in assessing a person's predisposition to T1D and distinguishing T1D from T2D.
GAD65 autoantibody also serves as a marker of predisposition to other autoimmune diseases that occur with T1D such as Graves' disease, Hashimoto's thyroiditis, hypothyroidism, pernicious anemia, premature ovarian failure, Addison's disease and vitiligo.
GAD65 antibodies are not specific for T1D and may be present in patients with a variety of autoimmune neurologic disorders including stiff-man syndrome, neuromyelitis optica, myasthenia gravis, Lambert-Eaton syndrome and dysautonomia. Patients with stiff-person syndrome typically have high concentrations of GAD65 autoantibodies of 20 nmol/L or higher.
GAD65 antibodies are detectable in the plasma of about 8% of healthy people over the age of 50 years, but usually at low levels.
Reference range is 0-0.02 nmol/L.
For more information, see the article entitled “Islet Cell Antibodies.
References
American Diabetes A. (2) classification and diagnosis of diabetes. Diabetes Care 2015;38 Suppl:S8–S16.
Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: A scientific statement of the Endocrine Society, and the American Diabetes Association. Diabetes Care 2015;38:1964–74
Nambam B, Aggarwal S, Jain A. Latent autoimmune diabetes in adults: A distinct but heterogeneous clinical entity. World J Diabetes. 2010 Sep 15;1(4):111-5).
Schlosser M, Mueller PW, Torn C, et al. Participating L. Diabetes antibody standardization program: Evaluation of assays for insulin autoantibodies. Diabetologia 2010;53:2611–20.
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