Type 1 diabetes mellitus (DM) is insulin-dependent diabetes (IDDM). It is now becoming increasingly recognized that this disease is an “organ specific” form of autoimmune disease that results in destruction of the pancreatic islet cells and their products. These antibodies are used to differentiate type 1 DM from type 2 non-insulin-dependent DM. Nearly 90% of young diabetics have one or more of these autoantibodies at the time of their diagnosis. Type 2 diabetics have low or negative titers.
These antibodies often appear years before the onset of symptoms. The panel is useful to screen relatives of IDDM patients who are at risk for developing the disease. Sixty percent to 80% of first-degree relatives with both ICA and IAA will develop IDDM within 10 years. GAD Ab provides confirmatory evidence. The presence of these antibodies identifies which gestational diabetic will eventually require insulin permanently. Once recognized, preventive diabetic treatment is instituted. This may include counseling plus antibody and glucose monitoring.
Because insulin antibodies appear in nearly all patients with diabetes treated with exogenous (human, bovine, or porcine) insulin, testing for the presence of these antibodies must precede insulin administration. Insulin antibodies develop from impurities in animal insulin or from antigenic stimulation of the insulin molecule. With the increased use of human insulin, the frequency of anti-insulin antibodies has significantly decreased.
The most common type of anti-insulin antibody is immunoglobulin (Ig) G, but IgA, IgM, IgD, and IgE also have been reported. Most of these insulin antibodies do not cause clinical problems, but they may complicate most insulin assays. Anti-insulin antibodies act as insulin-transporting proteins and bind the free insulin. This can reduce the amount of insulin available for glucose metabolism. They may also contribute to insulin resistance (daily insulin requirements exceeding 200 units/day for 2 days). IgM, especially, may cause insulin resistance. Insulin allergy (most common with animal insulin) may result from IgE antibodies to insulin.
These insulin antibodies are diagnostic of factitious hypoglycemia from surreptitious administration of insulin. In these cases, C-peptide studies may also determine whether hypoglycemia is caused by insulin abuse, because C-peptide is not produced when exogenous insulin is administered.
When anti-insulin antibodies are measured by radiobinding assay, radioactive scans within 7 days before the test may interfere with the test result.
Causes of High Diabetes Mellitus Autoantibody
Insulin Resistance: The anti-insulin antibodies bind insulin and thereby diminish the amount of free insulin available for glucose metabolism.
Allergies to Insulin: Although allergies occur most frequently with the use of animal-generated insulin, they can still occur with human insulin. A rash or lymphadenopathy may be the result of such an allergy.
Factitious Hypoglycemia: Because most patients develop anti-insulin antibodies to exogenous insulin, the identification of these antibodies supports the secretive self-administration of insulin in a patient who denies the use of insulin.