Considerable research over the last few decades has identified circulating autoantibodies directed against pancreatic islet cell antigens (ICAs) in patients with type one (insulin dependent) diabetes mellitus (IDDM) and also their first-degree relatives. Tests for these antibodies are of value in both young children at risk for juvenile diabetes and adults at risk for adult onset type 1 diabetes.



The Disease Process



Autoantibodies to ICA include:

1) Glutamic Acid Decarboxylase (GAD) antibodies;        

2) IA-2 ( tyrosine phosphatase-like protein) antibodies; 

3)  insulin autoantibodies.

The autoimmune destruction of the insulin-producing pancreatic beta cells, the hallmark of type 1 diabetes, occurs over an extended period of time and eventually leads to full blown or overt diabetes mellitus. During this extended pre-clinical phase of the disease, the presence of autoantibodies to ICA is a good early predictor of autoimmune disease development. With early screening and identification of this risk, lifestyle changes and therapies can be addressed to help minimize the risk of severe disease.



Glutamic Acid Decarboxylase (GAD65 ) Antibodies



GAD antibodies were first seen in several neurological disorders, including Stiff-Man Syndrome and cerebellar ataxia-4.  Later research found that GAD antibodies are seen in 70-90 percent of prediabetic and type 1 diabetic patients including adult onset diabetics with type 1 diabetes. GAD antibodies have been shown to be the most significant single marker for identifying persons at risk of developing IDDM. GAD antibodies are generally more prevalent in older children and late-onset type 1 diabetes. In these groups, GAD antibodies have been detected as many as 10 years before the onset of clinical disease.



IA-2 Antibodies



The tyrosine phosphatase-like protein called IA-2 is another target of antibody destruction associated with the development of IDDM. IA-2 antibodies are found in approximately 50-75 percent of diabetes patients at and prior to disease onset. IA-2 antibodies are more prevalent in young patients and are usually associated with rapid progression to overt disease.



Insulin Autoantibodies



Autantibodies to insulin, which are the only beta-cell specific antibodies in IDDM, indicate evidence of ongoing destruction of islet cells. Autoantibodies to insulin are predominantly found, although not exclusively, in children younger than 5 years developing diabetes.

In insulin-naïve (untreated) patients, the prevalence of insulin autoantibodies nears 100% in very young children and is almost absent in new patients diagnosed with adult onset diabetes. However, once patients begin insulin therapy, they develop insulin antibodies that are indistinguishable from the antibodies to natural insulin seen in young children with diabetes who have not yet been treated with insulin.

Resource: Kronus, Diagnostics Newlsetter from Medcompare