A total of 317 unrelated Danish patients with insulin-dependent diabetes mellitus
(IDDM) have been HLA-DR typed and the antigen and phenotype frequencies compared with
those in 1177 unrelated Danish controls. The strong positive associations with DR3
and 4 and the strong negative one with DR2 were confirmed, and the remaining antigens
showed a hierarchy from weakly positive to strongly negative associations: DRw9, w8,
1, 5, w6, 7. The study population included various special groups of patients selected
in order to study heterogeneity: very early (less than 5 years) and very late (greater
than 40 years) onset IDDM, pregnancy-induced IDDM, IDDM nephropathy, and long-term
(greater than 40 years) survivors without complications. When comparing these groups,
the following minor differences were seen: the DR3,4 phenotype is significantly (p
= .02) more frequent in IDDM with onset before age 20 (35%) than in other cases (24%),
and in familial IDDM (48%) than in other cases (28%); the frequency of the DR4 antigen
was significantly (p = .008) more frequent in long-term survivors (86%) than in other
patients (69%), while it was significantly (p = .02) less frequent in IDDM nephropathy
(63%) than in long-term survivors. However, apart from the age-at-onset heterogeneity,
which was suspected a priori, these differences may be due to chance, and the main
conclusion of this study is that the HLA-DR associations in IDDM are indeed extraordinarily
homogeneous irrespective of the clinical characteristics at onset and course of the
disease.