Expression of GAD65 and Islet Cell Antibody (ICA512) Autoantibodies Among Cytoplasmic ICA+ Relatives Is Associated With Eligibility for the Diabetes Prevention Trial−Type 1
- Liping Yu1,
- David D. Cuthbertson2,
- Noel Maclaren3,
- Richard Jackson4,
- Jerry P. Palmer5,
- Tihamer Orban4,
- George S. Eisenbarth1,
- Jeffrey P. Krischer2 and
- and the DPT-1 Participating Investigators
- 1Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, Colorado
- 2H. Lee Moffitt Cancer Research Center, University of South Florida, Tampa, Florida
- 3Juvenile Diabetes Program, Weill Medical College, Cornell University, New York, New York
- 4Joslin Diabetes Center, Harvard University, Boston, Massachusetts
- 5Seattle Veterans Affairs Medical Center, University of Washington, Seattle, Washington
Abstract
More than 71,000 relatives of type 1 diabetic patients have been screened for cytoplasmic islet cell antibodies (ICAs), GAD65 autoantibodies (GAAs), and ICA512 autoantibodies (ICA512AAs). Among those 71,148 relatives, 2,448 were cytoplasmic ICA+, and the remainder were ICA−. Of the ICA+ group, 1,229 (50.2%) were positive for GAAs and/or ICA512AAs. Among ICA− relatives, 1,897 (2.76%) were positive for GAAs and/or ICA512AAs. Given the large number of relatives positive for cytoplasmic ICA and negative for “biochemically” determined autoantibodies, and the converse, we analyzed the proportion of ICA+ relatives found eligible to participate in the intervention phase of Diabetes Prevention Trial−Type 1 (DPT-1). To be eligible for the parenteral insulin DPT-1 trial, a relative had to have first-phase insulin secretion below the 1st percentile of cut-points (for parents) or below the 10th percentile (for siblings and offspring). To be eligible for the oral insulin trial, a relative had to have first-phase insulin secretion above cut-points (>1st percentile for parents, >10th percentile for siblings/offspring) and be positive for anti-insulin autoantibodies. For both trials, DQB1*0602 was an exclusion criteria, cytoplasmic ICA positivity had to be confirmed, and an oral glucose tolerance test had to result in nondiabetic levels. Of 572 relatives found to be eligible for trial entry, 442 (77.3%) were positive for GAAs and/or ICA512AAs, although overall only 50.2% of ICA+ relatives were positive for GAAs and/or ICA512AAs. The positive predictive value for trial eligibility for ICA+ relatives with GAAs or ICA512AAs who completed staging was 51.0%. In contrast, only 11.9% of ICA+ but GAA− and ICA512AA− relatives were found to be eligible by DPT criteria for trial entry. Positivity for biochemically determined autoantibodies among cytoplasmic antibody–positive relatives is associated with eligibility for the DPT-1 study.
Footnotes
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Address correspondence and reprint requests to George S. Eisenbarth, MD, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 E. 9th Ave., B-140, Denver, CO 80262. E-mail: george.eisenbarth{at}uchsc.edu.
G.S.E. has received consulting fees from Quest diagnostics. N.M. has received research support from Eli Lilly.
Received for publication 5 September 2000 and accepted in revised form 25 April 2001.
DPT-1, Diabetes Prevention Trial−Type 1; FPIR, first-phase insulin release; GAA, GAD65 autoantibody; IAA, insulin autoantibody; ICA, islet cell antibody; ICA512AA, ICA512 autoantibody; IDS, Immunology of Diabetes Society; IVGTT, intravenous glucose tolerance test; JDFU, Juvenile Diabetes Foundation Units; mIAA, microinsulin autoantibody.
