HIGH GENETIC RISK FOR IDDM IN THE PACIFIC-NORTHWEST - FIRST REPORT FROM THE WASHINGTON-STATE DIABETES PREDICTION STUDY

A combination of immune, genetic, and metabolic markers potentially im plicated in the development of insulin-dependent diabetes mellitus (ID DM) was studied in the general population. We screened 3,992 healthy s choolchildren, 12-18 years of age with no family history of IDDM, for islet cell antibodies (ICAs). Of the children, 69 (1.7%) were found to be ICA positive (ICA(+)), of whom 7 (0.17%) also were positive for in sulin autoantibodies (IAAs). ICA(+) children (group 1) were human leuk ocyte antigen (HLA) typed at the DQ locus along with 123 matched (grou p 2) and 235 random (group 3) control subjects (from the original coho rt of 3,992). Of the ICA(+) children, 28 underwent beta-cell function (beta-CF) studies. High-risk DQ types were surprisingly prevalent in a ll groups with 35.8% of random control subjects carrying DQB10302 and 8.9% carrying the highest risk HLA type for IDDM, DQB10302/*0201. Th ose individuals with higher ICA titer (>19 Juvenile Diabetes Foundatio n units [JDF U]) had a significantly higher prevalence of DQB10302 th an those with lower titer ICA or normal control subjects. Six of 7 ind ividuals positive for both ICA and IAA and typed at the DQ locus were DQB10302/*0201 heterozygotes or DQB1*0302 or DQB1*0201 homozygotes, r epresenting three of the highest risk genotypes for IDDM. No correlati on was observed between ICA titer or DQ type and B-CF except that all those with p-CF below the 5th percentile carried either DQB10302 or D QB10201. Prospective follow-up is underway to determine if any combin ation of DQ type and immune markers predicts decline in beta-CF and th e development of IDDM.