Tumor necrosis factor microsatellite polymorphism influences the development of insulin dependency in adult-onset diabetes patients with the DRB1*1502-DQB1*0601 allele and anti-glutamic acid decarboxylase antibodies

Recently, several studies have demonstrated that tumor necrosis factor micr osatellite polymorphism (TNF alpha) contributes to the susceptibility of ty pe 1 diabetes. This study investigates the influence of TNF alpha on the pr edisposition to insulin dependency in adult-onset diabetic patients with ty pe 1 diabetes-protective human leukocyte antigen haplotypes. The TNF alpha of three groups of DRB1*1;1502-DQB1*0601-positive diabetic patients who had initially been nonketotic and noninsulin dependent for more than 1 yr was analyzed. Group A included 11 antibodies to glutamic acid decarboxylase (GA Dab)-positive patients who developed insulin dependency within 4 yr of diab etes onset. Group B included 11 GADab-positive patients who remained nonins ulin dependent for more than 12 yr. Group C included 12 GADab-negative type 2 diabetes, and a control group included 18 nondiabetic subjects. In the g roup C and control subjects, DRB1*1502-DQB1*0601 was strongly associated wi th the TNF alpha 13 allele. DRB1*1502-DQB1*0601 was strongly associated wit h the TNFal2 allele among the group A patients, but not among the group B p atients. Interestingly, sera from all patients with non-TNF alpha 12 and no n-TNF alpha 13 in group B reacted with GAD65 protein by Western blot. These results suggest that TNFa is associated with a predisposition to progressi on to insulin dependency in GADab/DRB1*1502-DQB1*0601-positive diabetic pat ients initially diagnosed with type 2 diabetes and that determination of th ese patients' TNF alpha genotype may allow for better prediction of their c linical course.