Immunotherapy in Type 1 Diabetes

Abstract

Over the past decade considerable advances have been made in our knowledge of the pathogenesis of Type 1 diabetes, so that we may now hope that in the not too distant future the disease may be preventable or curable. It is almost certain that Type 1 diabetes is the consequence of an autoimmune process leading to the destruction of islet B-cells. Several immunological findings closely related to the time of clinical diagnosis were reported in the 1970s, but the striking observation in recent years has been that these abnormalities may be present in unaffected first degree relatives of Type 1 diabetic probands and in identical twins discordant for diabetes.’,’ Amongst the most frequent abnormalities described are islet cell antibodies (ICA),3 insulin autoantibodies (lAA),4 and circulating activated T lymphocyte^,^ all present at the time of diagnosis in the majority of patients. These immune markers may also be detected in genetically susceptible but otherwise euglycaemic subjects. The presence of ICA is not normally associated with an impairment of glucose tolerance, and indeed such antibodies may persist for years before the appearance of hyperglycaemia. Recent evidence suggests that siblings with ICA may show a gradual loss of the first phase insulin secretion following an intravenous glucose challenge and eventually develop diabetes,‘ although caution should be taken in the evaluation of this metabolic test.7 When they become complement fixing (CF-ICA), these antibodies are a better marker for Type 1 diabetes to develop. Although CF-ICA may merely reflect high ICA titres, their occurrence in association with a decreased first phase insulin secretion is now recognized in susceptible subjects as strong evidence that an autoimmune process directed against islet B-cells is taking place.8 The presence of IAA in the months or years prior to overt diabetes is a relatively new finding. Data from the International Workshop on IAA have shown however that the presence of these antibodies may vary according to the technique used, the prevalence ranging between virtually nil and 50 VO.’