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Type
1 (insulin-dependent) diabetes mellitus (IDDM)
is one of the most common
chronic diseases in children and young adults.
The long-term complications of IDDM are debilitating
and often lead to premature death. Genetic
susceptibility, combined with as yet unknown
environmental exposures, have repeatedly been
implicated in the
etiology of IDDM. The appearant necessity of an
environmental trigger for the immune responses
which eventually destroy the insulin-producing
cells of pancreas indicates that IDDM may be preventable.
The childhood onset form of IDDM (i.e., ages < 15
years) has been studied extensively. In contrast,
the adult onset form of IDDM is poorly characterized
although there are reports claiming the majority
of occurrences take place in the ages > 15 years.
The onset of IDDM in adults is usually slower and
less acute. There are other differences, in incidence
rates, gender distribution (i.e., a male excess),
and the frequencies of genetic and immunological
markers. Hence, the adult and childhood onset forms
may differ aetiologically. Defining these differences
is problematic: a significant proportion of occurences
in adults represent gestational and Type 2 (non
insulin?dependent) diabetes mellitus. Classification
is difficult. Patients are treated in diabetes
wards, general practises, and sometimes even in
obstetrical units. Uniform objective classification
criteria suitable for epidemiological studies are
lacking.
We propose to investigate the epidemiology and
genetic epidemiology of adult onset IDDM. Specifically,
we will
1) develop uniform diagnostic criteria for classification
of the disease; 2) estimate the age? and gender?specific
incidence of adult onset IDDM; 3) relate incidence
to year (and month) of onset and geographical region
within Europe; 4) estimate the frequencies of genetic
(i.e., HLA and non?HLA genes) and immunological
markers in IDDM patients and normal subjects in
European populations; and, 5) relate marker frequencies
to IDDM incidence throughout Europe. The proposed
study, IDA, builds on an existing epidemiologic
network involving EURODIAB ACE, EURODIAB TIGER,
and PARADIGM. Specifically, EURODIAB ACE (Dr Anders
Green, Odense) was established as a Concerted Action
under the BIOMED I Programme to define the epidemiology
of IDDM. EURODIAB TIGER was then established under
the BIOMED II Programme and proposed work to relate
the frequencies of high risk genotypes and immune
markers to the incidence of IDDM has been funded.
The centralized laboratory facility for EURODIAB
TIGER (and subsequnetly IDA) involves PARADIGM
(Dr. Polly J. Bingley, London), also established
under the BIOMED II Programme. IDA originated within
EURODIAB ACE when problems related to classification
criteria, and a wider network of collaborators,
resulted in the need for splitting up coordination
and data management for studies of childhood and
adult IDDM. However, IDA and EURODIAB TIGER are
harmonized: they have coordinated study designs
and employ the same laboratory facility. This should
greatly facilitate comparisons between childhood
and adult onset IDDM. Note that the epidemiological
component of IDA began 1 January 1996. The proposed
study will deliver scientific information in an
area that has so far been more or less neglected
in the diabetes research world despite the evidence
that the majority of new IDDM cases arise in adulthood
rather than in children. The epidemiologic resources
involved are unique and cannot be delivered anywhere
else in the world. The application of uniform classification
criteria will provide doctors with accurate information,
needed to counsel patients on the risk of adults
onset IDDM. The epidemiologic and genetic epidemiologic
information generated by IDA is expected to facilitate
etiologic studies that might eventually lead to
preventive interventions.
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