Abstract 539 Poster Session II, Sunday, 5/2 (poster 200)

Studies have shown that first degree relatives with high risk HLA-DQ heterodimers and presence of autoimmunity to β-cell antigens are at increased risk of developing diabetes. However, the time of progression to diabetes from the first known evidence of autoimmunity, an important factor in the design of intervention studies, seems to vary and may depend on the presence of several risk factors. We evaluated genetic (presence of HLA-DQ heterodimers) and autoimmune (ICA, GAD65 aa and/or IA-2 aa) determinants prior to diagnosis of diabetes in 68 converters to IDDM from a cohort of 5512 first degree relatives who have been followed for 17 years and who presented signs of β-cell autoimmunity. The 68 converters were classified into three groups: group I (rapid progressors) who developed IDDM in <5 years after evidence of β-cell autoimmunity (n=31), group II (slow progressors) who developed IDDM in ≥5 years after evidence of autoimmunity (n=20), and group III (LADA) who started insulin treatment 1 to 8 years after diagnosis of diabetes (n=17). The mean age at start of insulin treatment was 20.1 ± 12.9 in group I, 28.5 ± 15.2 in group II and 42.8 ± 13.4 in group III. Characteristics of the groups were as follows: (Table) These results suggest that the presence of IA-2aa alone or combined with the two other autoantibodies are more common in those who progress rapidly to clinical IDDM compared to slow progressors. A lower prevalence of 4 HLA-DQ heterodimers (p=0.09 when comparing Group I to Group III), of the combination of 3 antibodies plus 4 high risk heterodimers, older age and their relative status may also be important factors in identifying those who will develop LADA. These results suggest that additional markers may be needed to improve the ability to differentiate the varying rates of progression to IDDM in first degree relatives.

Table 1 No caption available.
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