Diabetes, Vol 45, Issue 12 1706-1710, Copyright © 1996 by American Diabetes Association
Disease-associated antibodies in offspring of mothers with IDDM
A Martikainen, T Saukkonen, PK Kulmala, H Reijonen, J Ilonen, K Teramo, P Koskela, M Knip and HK Akerblom
Department of Pediatrics, University of Oulu, Finland.
We studied 20 infants of mothers with IDDM participating in a pilot study
for a dietary intervention trial, testing the hypothesis that avoidance of
cow's milk proteins early in life will reduce the risk of subsequent IDDM.
The aim was to evaluate the elimination of IDDM-associated antibodies from
the peripheral circulation of the infants, the possible emergence of
autoantibodies indicating beta-cell destruction, and the influence of the
dietary intervention and genetic disease susceptibility on the development
of these autoantibodies. Transplacentally transferred islet cell antibodies
(ICAs) and antibodies to the 65-kDa isoform of glutamic acid decarboxylase
(GAD65As) disappeared from the peripheral circulation of most infants over
the first few months of life and in all infants before the age of 9 months.
Insulin antibodies were eliminated before the same age in all cases but
one. The higher the initial antibody level was, the longer the time
required for elimination. Four infants tested positive for insulin
autoantibodies (IAAs) on at least one occasion during the first year of
life, and 5 out of 16 unaffected subjects (31%) had IAAs at the age of 2
years. One infant became positive for IAA before the age of 6 months, with
increasing levels later, seroconverted to positivity for ICAs and GAD65As
between 6 and 9 months and presented with clinical IDDM at the age of 14
months. He had the HLA DQB1*0302/x genotype, which predisposes carriers to
IDDM, and had been given the casein hydrolysate formula as supplementary
milk. There were no significant differences in the levels of various
autoantibodies between two groups of subjects defined either on the type of
dietary intervention or the degree of genetic susceptibility. The findings
indicate that transplacentally transferred antibodies related to IDDM are
usually eliminated from the peripheral circulation of infants before 9
months of age and that IDDM-associated autoantibodies may emerge before the
age of 6 months. Our results also illustrate that avoidance of cow's milk
proteins over the first 9 months of life does not provide total protection
against IDDM.