Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset Type I (insulin-dependent) diabetes mellitus

Aims/hypothesis. To determine whether the clinical heterogeneity observed i n the development of Type I (insulin-dependent) diabetes mellitus correlate s with immunohistochemical differences observed at diagnosis. Methods. Patients (n = 17) with recent-onset diabetes clinically considered to be insulin dependent (Type I), underwent pancreatic biopsy for immunohi stological analysis. These patients were divided into two groups based on t he presence or absence of islet immunological abnormalities (insulitis or h yperexpression of MHC class I antigens or both). The patients were also HLA typed and tested for islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD-Ab). All patients were followed monthly for 2 years and their fasting plasma glucose, haemoglobin A(1C) and daily insulin doses we re recorded. The clinical course of patients with islet immunological abnor malities was compared with that of patients without those abnormalities. Results. Patients with and without islet immunological abnormalities did no t differ with regard to HLA type or islet cell antibodies. Antibodies to gl utamic acid decarboxylase correlated with the presence of insulitis and MHC class I hyperexpression. These local immunological abnormalities were also associated with higher haemoglobin A(1C) values (p < 0.05) and a trend tow ards greater insulin requirements. Further, patients with the islet abnorma lities had higher fasting plasma glucose concentrations 2 years after the b iopsy than at the time of the biopsy (p < 0.05). Conclusion/interpretation. The heterogeneous clinical course observed follo wing diagnosis in patients with Type I diabetes correlates with islet immun ological abnormalities. Insulitis and hyperexpression of MHC class I correl ate with deteriorating glycaemic control.