The presence of HLA-DR 3 was analysed in 745 patients with Type 1 (insulin-dependent) diabetes with age at diagnosis between 1-19 years. HLA-DR 3 and/or 4 was found in 678/745 (91%) of the patients. Presence of DR2 with neither DR 3 nor 4 was demonstrated in 15 patients. Patients with HLA-DR 3 without DR 4 presented with Type 1 diabetes more evenly over the year; they also presented without incidence peaks at 7 years or 10-11 years, as seen especially in DR 3/4 patients. The DR 3 patients more often had mild disease with less ketonuria at diagnosis, less often ketoacidotic symptoms and more often a subsequent partial remission. The apparently more severe disease among diabetic girls may, at least to some extent, be explained by their higher prevalence of HLA-DR 4. The differences found were similar in North America and Europe. The results suggest that Type 1 diabetes is a genetically heterogeneous disease and that HLA-typing may be a useful marker of this heterogeneity.
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