Diabetes, Vol 44, Issue 9 1029-1032, Copyright © 1995 by American Diabetes Association
Immunogenetic determinants and prediction of IDDM in French schoolchildren
C Levy-Marchal, F Dubois, M Noel, J Tichet and P Czernichow
INSERM, CJF 93-13, Hopital Robert Debre, Paris, France.
Islet cell antibodies (ICAs) are predictive markers of the disease in
first-degree relatives of patients with insulin-dependent diabetes mellitus
(IDDM). The large majority of newly diagnosed cases, however, will develop
in children with no family history of diabetes. In France, the risk for
development of IDDM up to the age of 20 years is 60 times higher in
first-degree relatives than in the general population. The aim of this
study was to test whether data collected in the first-degree relatives of
IDDM patients could be transferred to children for the prediction of overt
diabetes. A large population-based cohort of French school-aged children (n
= 13,380; ages 6-17 years) were screened for ICAs, and results were
compared with those of 1,185 first-degree relatives of IDDM patients. ICA
prevalence rates were significantly different in the two populations (5.5%
vs. 1.5%; P < 0.0001), with a significantly higher proportion of high
ICA titers in first-degree relatives (37%) than in schoolchildren (14%) (P
= 0.0005). ICA titers remained remarkably stable in children over 4 years.
Insulin autoantibodies (IAAs) were found in 3.4 and 15.4% of ICA+ children
and first-degree relatives, respectively. Susceptibility alleles at the
human leukocyte antigen (HLA)-DQB1 locus were observed significantly more
frequently in children in whom ICA titers > or = 20 Juvenile Diabetes
Foundation units (JDF U) were found on two separate occasions (67%) than in
ICA- children (52%) (P = 0.05). Five subjects developed overt diabetes
during follow-up. ICA titers of > 20 JDF U were found in all of them on
the first sample and at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)