IMPORTANCE OF PERSISTENT CELLULAR AND HUMORAL IMMUNE CHANGES BEFORE DIABETES DEVELOPS - PROSPECTIVE-STUDY OF IDENTICAL-TWINS

Objectives-To determine the pattern of cellular and humoral immune cha nges associated with insulin dependent diabetes before diabetes develo ps. Design-Prospective study over 10 years of 25 non-diabetic identica l twins of patients with insulin dependent diabetes. The non-diabetic twins were followed up either till they developed diabetes or to the e nd of the study. Setting-Teaching hospital. Subjects-25 non-diabetic i dentical cotwins of patients with diabetes; 46 controls of the same se x and similar age tested over the same period. Of the 25 twins (total follow up 144 patient years), 10 developed diabetes (prediabetic twins ); the remainder were followed up for a mean of 7.7 years. Main outcom e measures-Results of glucose tolerance tests or fasting blood glucose concentrations at each sample point. Measurements of activated T lymp hocytes, expressing the HLA-DR antigen, islet cell antibodies, and ins ulin autoantibodies in samples. Results-All 10 prediabetic twins had b oth cellular and humoral changes initially and in most samples before diabetes was diagnosed (activated T lymphocytes in 39/40, islet cell a ntibodies in 45/47, and insulin autoantibodies to islet cells and insu lin were detected infrequently (in 8/54, 6/69, and 0/69 samples, respe ctively). The combination of cellular and humoral (islet cell antibodi es or insulin autoantibodies) immune changes were detected in all 10 o f the prediabetic twins but in only one of the 15 nondiabetic twins (P <0.001). The positive predictive value in this cohort of increased per centages of activated T cells and the presence of antibodies to islet cells or insulin on two consecutive occasions was 100%. Conclusion-Mos t of the twins had cellular or humoral immune changes at some stage. A combination of cellular and humoral immune changes and their tendency to persist is highly predictive of insulin dependent diabetes and dis tinguishes twins who develop diabetes from those who do not.