LATE PROGRESSION TO DIABETES AND EVIDENCE FOR CHRONIC BETA-CELL AUTOIMMUNITY IN IDENTICAL-TWINS OF PATIENTS WITH TYPE-I DIABETES

Previous studies suggest that after 6 years of discordance, identical twin pairs rarely become concordant for type I diabetes. With up to 39 years of follow-up from the onset of diabetes in the index twin, we d etermined how many discordant twins have evidence of beta-cell autoimm unity and how many develop overt diabetes. We longitudinally followed 23 pairs of identical twins (or triplets) that were selected from a to tal group of 30 pairs because they were discordant for type I diabetes when first ascertained. Seven developed diabetes after 3, 3, 7, 8, 9, 31, and 36 years of discordance. By survival analysis, the concordanc e after 10 years from the onset of diabetes in the index twin was esti mated as 23% (95% confidence interval, 5-40%), increasing to 38% (95% confidence interval, 8-69%) after 31 years, Among 16 twins remaining n ondiabetic at last follow-up (8-39 years of discordance), 12 were asse ssed with serial intravenous glucose tolerance tests and a total of 40 7 measurements by radioassay of antibodies against three defined autoa ntigens (glutamic acid decarboxylase, insulin, and the recently cloned molecule ICA512). Two-thirds (8 of 12) had evidence of beta-cell auto immunity (persistently positive autoantibody levels) and/or first-phas e insulin release less than the Ist percentile of control subjects, In summary, identical twins may develop diabetes after a prolonged perio d of discordance and approximately two-thirds of long-term discordant twins have evidence of persistent beta-cell autoimmunity and/or beta-c ell damage, The concordance for beta-cell autoimmunity, therefore, is much higher than for overt diabetes, This suggests that additional env ironmental or non-Mendelian genetic factors or time are required for t he development of type I diabetes.