Three groups of patients with insulin-dependent diabetes mellitus, ascertained by different procedures, were investigated for HLA-A, B, C and D antigens (n = 164), and a subset (n = 93) for HLA-DR. Both HLA-D/DR3 and D/DR4 were strongly positively associated and D/DR2 was negatively associated with insulin-dependent diabetes. HLA-DR+ was found to be a better marker for insulin-dependent diabetes than Dw4. The HLA-B associations (B8, B15 and B18) were clearly secondary to the increases of HLA-D/DR3 and D/DR 4. The HLA associations did not differ between familial and isolated cases indicating that these two groups may well have a common genetic background. Based on analysis of HLA-haplotype sharing in affected sibling pairs, a simple dominant model of inheritance could be ruled out, and a simple recessive model was found unlikely. The relative risks for the HLA-Dw3,4 and HLA-DR3,4 phenotype were 21.2 and 44.4 respectively and exceeded those of both the HLA-Dw3 and HLA-DR3 (5.6 and 4.3) as well as the HLA-Dw4 and DR4 (10.1 and 10.5) phenotypes. This argues against an intermediate genetic model but further studies are needed to clarify whether there is more than one susceptibility gene for insulin-dependent diabetes mellitus within the HLA-system.

The incidence, sex, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus (j.i.d.m.) were studied retrospectively on one third of the Danish population 1970-1974. The j.i.d.m. incidence remained fairly constant during the study period, the average being 13.2 per 100000 per year. The total number of boys exceeded the number of girls by 27%. A marked peak of incidence was found at 12-14 years, earlier for females than for males. A seasonal variation in onset (diagnosis) of j.i.d.m. was observed with the lowest number of new cases in May-July. The j.i.d.m. incidence seemed to show socioeconomic differences, being highest in those parts of the survey area with lower status.

The relationship between the HLA system and insulin-dependent diabetes mellitus (IDDM) is reviewed. Data compiled by the HLA and Disease Registry reveal that HLA-B8 and/or Dw3 are associated with IDDM in all populations studied so far, but further population studies in non-Caucasian populations should be performed. In Caucasians, HLA-Dw2 renders protection against IDDM while HLA-Dw3 and Dw4 are associated with susceptibility to IDDM. The exact mode of inheritance of susceptibility to IDDM remains to be established. Involvement of at least two genes is likely. Heterogeneity of IDDM is highly possible and should be a matter of major interest in diabetes research.

autopsy study of the islets of Langerhans in acute-onset juvenile diabetes mellitus. Acta path. microbiol. scand. Sect. A, 85: 699-706, 1977.The existence of lymphocytic inflammation of the islets of Langerhans-insulitis-in the early stages of juvenile diabetes mellitus (j.d.m.) has been a matter of discussion. In order to evaluate the possible occurrence of insulitis in early j.d.m. the present autopsy study was performed. From the years 1943 to 1974 blocks of pancreatic tissue were collected from 11 juvenile diabetics aged less than 30 years and dying within 2 months after the onset of diabetic symptoms. Pancreatic tissue blocks from 22 age-and-sex-matched sudden, unexpected deaths served as control material. 5-micron thick sections from the 33 blocks were stained with hematoxylin-eosin, aldehyde-fuchsin and silver. l-micron sections were stained with toluidine blue. Islets were found in all the control cases, and Aand B-cell granulations were distinct. Insulitis was absent.Islets were also present in all the diabetic cases. No difference in islet number between the controls and the diabetics was apparent, The diabetic islets were morphologically heterogeneous. No difference beween controls and diabetics could be demonstrated in respect of A-cell number and granulation. However, B-cell granulation was demonstrable in only 1 case, and in that case in extremely reduced proportion. Insulitis was present to varying degrees in 6 of the diabetics.In this material, like others, insulitis seems most frequent in the diabetics aged less than 10 years. No conclusion can be drawn from this study about whether an infectious agent, an autoimmune process, or a combination of these, causes the insulitis. However, the findings presented suggest the existence of a lymphocytic insulitis as a feature of early j.d.m.