GAD Autoantibodies Define Specific Phenotype of Adult-Onset Diabetes

A high titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes. Dr. Raffaella Buzzetti lead investigator stated that, “our results indicate that both autoimmunity and insulin resistance may contribute to the pathogenesis of diabetes in adults with a variable degree of synergism, as reflected by titers of GAD antibodies."

Dr. Buzzetti of La Sapienza University, Rome and colleagues note that slowly progressive autoimmune diabetes in adults is often indistinguishable from classic type 2 diabetes.

Patients with autoimmune diabetes, they add, are usually diagnosed via the presence of antibodies to GAD (GADAs), with or without associated cytoplasmic islet cell antibodies and protein tyrosine phosphatase IA-2 antibodies (IA-2As).

To investigate further, the team examined data from 4,250 type 2 diabetic patients and found that 4.5% had GADAs or IA-2As or both.

The patients with autoimmune diabetes showed a clinical phenotype significantly different from that of type 2 diabetes, including higher fasting glucose and A1C and lower BMI and uric acid.

In addition, compared with those with low GADA titers, patients with high GADA titers had more prominent traits of insulin deficiency, a profile of more severe autoimmunity, and a lower prevalence of metabolic syndrome.

In light of these findings, the researchers conclude that there are patients with a "high GADA titer in which the autoimmune process is presumably strong enough to induce diabetes with no major contribution by other concomitant factors and a second group with low GADA titers, reflecting a less intense autoimmune process, with associated features of insulin resistance."

Diabetes Care April, 2007;30:932-938.

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