Radioassay determination of insulin autoantibodies in NOD mice. Correlation with increased risk of progression to overt diabetes.
In an initial cross-sectional study, 29 female and 25 male nondiabetic weaned nonobese diabetic (NOD) mice of various ages (age range 30-300 days, mean 108 +/- 10 days) and 11 unweaned NOD pups were evaluated for competitive insulin autoantibodies (CIAAs) with a fluid-phase radioassay. Eleven of 54 (20%) weaned NOD mice had CIAA levels above the range (greater than 39 nU/ml) of 81 control mice. The group of NOD mice that progressed to diabetes had a significantly higher level of CIAAs than NOD mice that did not progress to diabetes (NOD mice progressing to diabetes: CIAA 63 +/- 12 nU/ml; NOD mice not progressing to diabetes: CIAA 8 +/- 4 nU/ml; P less than .02). Seven of 11 (64%) NOD mice having CIAA concentrations exceeding the normal range progressed to diabetes, whereas only 4 of 43 (9%) NOD mice progressed to diabetes without detection of elevated CIAAs (Fisher's exact test, P less than .0005). The relative risk of progressing to overt diabetes with CIAA levels greater than 39 nU/ml was therefore 17 (P less than .005), giving a positive predictive value of 64%, a negative predictive value of 91%, and an overall accuracy of 85%. None of 11 unweaned NOD pups had CIAA levels above the normal range (mean -9.4 +/- 4.9 nU/ml). At 6 wk of age, 37% of female NOD mice were CIAA+, whereas none of the male animals exceeded the normal range at this age (38 +/- 13 vs. 5 +/- 6 nU/ml, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Ziegler
A G
AG
Joslin Diabetes Center, Boston, MA 02215.
Vardi
P
P
Ricker
A T
AT
Hattori
M
M
Soeldner
J S
JS
Eisenbarth
G S
GS
D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D005260:Female; D007330:Insulin Antibodies / Q000032:analysis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011446:Prospective Studies; D011863:Radioimmunoassay
D001323:Autoantibodies; D007330:Insulin Antibodies