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Original Articles

High Genetic Risk for IDDM in the Pacific Northwest: First Report From the Washington State Diabetes Prediction Study

  1. Rachel E Rowe,
  2. Nicola J Leech,
  3. Gerald T Nepom and
  4. David K McCulloch
  1. Virginia Mason Research Center and the University of Washington Seattle, Washington
  1. Address correspondence and reprint requests to Dr. David K. McCulloch, Diabetes Clinical Research Unit, Virginia Mason Medical Center (X2-END), 1100 Ninth Avenue South, P.O. Box 900, Seattle WA 98111.
Diabetes 1994 Jan; 43(1): 87-94. https://doi.org/10.2337/diab.43.1.87
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Abstract

A Combination Of Immune, genetic, and metabolic markers potentially implicated in the development of insulin-dependent diabetes mellitus (IDDM) was studied in the general population. We screened 3,992 healthy schoolchildren, 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 insulin autoantibodies (lAAs). ICA+ children (group 1) were human leukocyte antigen (HLA) typed at the DQ locus along with 123 matched (group 2) and 235 random (group 3) control subjects (from the original cohort of 3,992). Of the ICA+ children, 28 underwent β-cell function (β-CF) studies. High-risk DQ types were surprisingly prevalent in all groups with 35.8% of random control subjects carrying DQB1*0302 and 8.9% carrying the highest risk HLA type for IDDM, DQB1*0302/*0201. Those individuals with higher ICA titer (>19 Juvenile Diabetes Foundation units [JDF U]) had a significantly higher prevalence of DQB1*0302 than those with lower titer ICA or normal control subjects. Six of 7 individuals positive for both ICA and IAA and typed at the DQ locus were DQB1 *0302/*0201 heterozygotes or DQB1*0302 or DQB1*0201 homozygotes, representing three of the highest risk genotypes for IDDM. No correlation was observed between ICA titer or DQ type and β-CF except that all those with β-CF below the 5th percentile carried either DQB1*0302 or DQB1*0201. Prospective follow-up is underway to determine if any combination of DQ type and immune markers predicts decline in β-CF and the development of IDDM .

  • Received March 9, 1993.
  • Revision received August 12, 1993.
  • Accepted August 12, 1993.
  • Copyright © 1994 by the American Diabetes Association
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January 1994, 43(1)
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High Genetic Risk for IDDM in the Pacific Northwest: First Report From the Washington State Diabetes Prediction Study
Rachel E Rowe, Nicola J Leech, Gerald T Nepom, David K McCulloch
Diabetes Jan 1994, 43 (1) 87-94; DOI: 10.2337/diab.43.1.87

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High Genetic Risk for IDDM in the Pacific Northwest: First Report From the Washington State Diabetes Prediction Study
Rachel E Rowe, Nicola J Leech, Gerald T Nepom, David K McCulloch
Diabetes Jan 1994, 43 (1) 87-94; DOI: 10.2337/diab.43.1.87
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