The Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) study. HLA antigens and haplotypes as risk factors for the development of IDDM in IDDM patients and their siblings

Abstract

The relationships between HLA antigens, sex, age at diagnosis, season of onset and insulin-dependent diabetes mellitus (IDDM) were studied in a consecutive admissions series of newly-diagnosed IDDM patients at Children's Hospital of Pittsburgh. In agreement with the findings of others, the strongest positive associations between IDDM and HLA antigens were seen with DR3 and DR4 (odds ratios (OR) of 3.5 and 4.4, respectively), while a very strong negative association was observed with DR2 (OR of 0.1). Male patients were significantly more likely than female patients to possess DR3 while female patients were significantly more likely to be DR4+. No consistent relationships were found between HLA antigens and either age at diagnosis or season of onset. Using a life table approach, the cumulative risk of IDDM by age 24 in HLA-identical siblings of IDDM patients was estimated to be 10.3%. This risk was significantly greater than the risks to either HLA-haploidentical siblings (2.2%) or to HLA-nonidentical siblings (1.0%), whose risks were not significantly different. B7 + HLA-identical siblings of patients appeared to be protected from the effects of HLA-identicality--their cumulative risk by age 24 was estimated to be only 2.3%.