PMID- 15016215
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20040630
LR  - 20040312
IS  - 1399-543X (Print)
IS  - 1399-543X (Linking)
VI  - 1
IP  - 4
DP  - 2000 Dec
TI  - Screening for preclinical type 1 diabetes in a discrete population with an 
      apparent increased disease incidence.
PG  - 193-8
AB  - Environmental agents are proposed to play a role in triggering or exacerbating 
      pancreatic islet autoimmunity in people genetically predisposed to type 1 
      diabetes. However, with few exceptions, these agents remain enigmatic. Clues to 
      environmental agents may be found by investigating population/geographic clusters 
      or 'hotspots' of high disease incidence. We were alerted to a small community 
      where the incidence of type 1 diabetes appeared to be five-fold higher than 
      expected. Because type 1 diabetes is now recognized to have a subclinical phase 
      during which anti-islet antibodies can be detected, we aimed to identify and 
      characterize a reservoir of children with subclinical disease in this community. 
      Venous blood samples were collected from 1906/2347 (81%) local school children 
      during one week. Islet cell antibodies (ICAs) were detected in 122 (6.4%) 
      children, 18 (0.9%) being high titer (> or = 20 Juvenile Diabetes Foundation 
      units (JDFu)). On retest, 15 months later, the majority of low titer ICAs were 
      undetectable, whereas high-titer ICAs persisted. The latter were found in two 
      distinct age-related, ethnically similar groups. The younger group, aged 6-9 yr, 
      had antibodies to insulin (IAAs), glutamic acid decarboxylase (GAD) and tyrosine 
      phosphatase IA2 in addition to ICA, human leukocyte antigen (HLA) genes 
      associated with susceptibility to type 1 diabetes, and lower first-phase insulin 
      responses (FPIRs) to intravenous glucose. The older group, aged 13-16 yr, the age 
      cohort of the index clinical cases, had few antibodies other than ICA, 
      non-susceptibility HLA genes and normal FPIRs. During follow-up, three children, 
      all from the younger group with multiple antibodies and FPIRs less than the first 
      percentile, developed diabetes 4, 6 and 7 yr after screening. The finding of two 
      age groups of subclinical disease suggests that if environmental agents triggered 
      islet autoimmunity they did not act constantly on the community. Furthermore, the 
      absence of multiple autoantibodies and/or HLA susceptibility genes in the older 
      group, the source of index clinical cases, implies they are a residual subgroup 
      with slow or absent progressive beta-cell destruction. This study illustrates 
      that the natural history of type 1 diabetes may be elucidated by analyzing 
      age-related subclinical disease in the general population.
FAU - Colman, P G
AU  - Colman PG
AD  - Department of Diabetes and Endocrinology, Walter and Eliza Hall Institute of 
      Medical Research, Royal Melbourne Hospital, Victoria, Australia. 
      peter.colman@mh.org.au
FAU - McNair, P
AU  - McNair P
FAU - King, J
AU  - King J
FAU - Caudwell, J
AU  - Caudwell J
FAU - Jankulovski, C
AU  - Jankulovski C
FAU - Tait, B D
AU  - Tait BD
FAU - Honeyman, M C
AU  - Honeyman MC
FAU - Harrison, L C
AU  - Harrison LC
LA  - eng
PT  - Journal Article
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
EDAT- 2004/03/16 05:00
MHDA- 2004/03/16 05:01
CRDT- 2004/03/16 05:00
PHST- 2004/03/16 05:00 [pubmed]
PHST- 2004/03/16 05:01 [medline]
PHST- 2004/03/16 05:00 [entrez]
AID - PDIpdi0o018 [pii]
AID - 10.1034/j.1399-5448.2000.001004193.x [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2000 Dec;1(4):193-8. doi: 10.1034/j.1399-5448.2000.001004193.x.