MULTIPLE MARKERS OF AUTOIMMUNITY AMONG APPARENT NIDDM SUBJECTS IN THE 
FUSION STUDY. William A. Hagopian*1, Timo Valle2, Richard M. Watanabe3,4, 
Elizabeth R. Hauser4, Richard N. Bergman3, Eva Tuomilehto-Wolf2, Jaakko 
Tuomilehto2, Soumitra Ghosh5, Francis Collins5, Michael Boehnke4, and the 
Finland-United States Investigation of NIDDM Genetics (FUSION) Study 
Group. 1Dept. Medicine, Univ. Washington, Seattle WA, 2Dept. 
Epidemiology, National Public Health Institute, Helsinki FINLAND, 3Dept. 
Physiology, USC, Los Angeles CA, 4Dept. Biostatistics, Univ. Michigan, 
Ann Arbor MI, 5NCHGR, Bethesda MD.

Autoantibodies to the two major identified ICA antigens, glutamate 
decarboxylase (GAD) and the beta-cell protein tyrosine phosphatase 
ICA512, were measured in plasma samples from 1084 Finnish NIDDM patients 
(WHO criteria, aged 35-60 years) sampled a mean of 11 years after 
diagnosis.  A total of 59/1084 (5.4%) were positive for GADab (cutoff = 
mean + 3SD of 104 Swedish, Finnish and American controls).  Fifty-seven 
GADab positive samples, and 41 samples negative for GADab, were tested 
for antibodies to ICA512 (cutoff = mean + 3SD of 104 Swedish, Finnish and 
American controls).  Only 11/57 (19.3%) of the GADab positive samples, 
and 0/41 of the GADab negative samples, had autoantibodies to ICA512 
(p=0.001, Fisher's exact test).  Of subjects positive for both 
autoantibodies, ICA512ab levels were highly correlated to GADab levels 
(r=0.87, p<0.001).  No relationship between presence of either marker and 
subject age nor time of sampling after diagnosis was found, but fasting 
C-peptide and fasting insulin were both significantly lower in those with 
GADab (p<0.001 and p=0.008, respectively) and those with ICA512ab 
(p=0.007 and p=0.015, respectively) versus those without these 
autoantibodies.  We conclude that although ICA512ab may be less sensitive 
than GADab for detecting autoimmunity in NIDDM patients sampled long 
after onset, both autoantibodies are associated with low endogenous 
insulin secretion among these subjects.