MULTIPLE ANTIBODY STATUS IN TYPE-1 DIABETIC-PATIENTS AND SUBJECTS AT VARIOUS RISK WITH ISLET-CELL ANTIBODIES

The frequency of 37/40 kD antibodies and their association with other pancreatic humoral markers were studied in 109 recently diagnosed Type 1 diabetic patients and 116 subjects with islet-cell antibodies (ICA) at various risk for this disease (64 relatives of Type 1 diabetic pat ients, 23 schoolchildren with no family history of diabetes, and 29 pa tients with Graves' disease). At the time of diagnosis, 37/40 kD antib odies were detected in 45 % of Type la and 77 % of Type Ih diabetic pa tients (p=0.03). Antibodies to glutamic acid decarboxyiase (GAD) and/o r 37/40 kD were present with the same frequency as ICA (86 %). The fre quency of 37/40 kD antibodies was not significantly different between the 3 groups at risk, in contrast with GAD antibodies which were found at a lower frequency in schoolchildren (p < 0.02). Frequencies of oth er pancreatic markers (ICA cross-reactive with mouse pancreas and insu lin autoantibodies) and the combination of ICA with at least two other markers were significantly higher in relatives than in the other grou ps at risk (p < 0.02). Out of 216 ICA-positive non-diabetic subjects, 10 developed diabetes. All 10 displayed 37/40kD and/or GAD antibodies during the prediabetic phase. In 8 of these 10 patients, ICA was combi ned with at least two other markers, whereas this association was dete cted in only 17 of the remaining 106 subjects who did not progress to diabetes (p < 10(-4)). Thus, 37/40 kD antibodies were found in about h alf of Type 1 diabetic patients, and with a higher frequency in Type 1 b than 1a. In ICA-positive non-diabetic subjects, our data confirm tha t a combination of multiple antibodies, including GAD antibodies and 3 7/40 kD antibodies, can enhance the predictive value for diabetes. Com parison of ICA-positive relatives of diabetic patients, schoolchildren and patients with Graves' disease revealed distinct frequencies and c ombinations of markers of diabetes. This might reflect different patte rns of progression among these 3 groups.