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Screening for preclinical type 1 diabetes in a discrete population with an apparent increased disease incidence
Author(s) -
Colman Peter G,
McNair Peter,
King Jenny,
Caudwell Jan,
Jankulovski Connie,
Tait Brian D,
Honeyman Margo C,
Harrison Leonard C
Publication year - 2000
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1034/j.1399-5448.2000.001004193.x
Subject(s) - medicine , population , subclinical infection , diabetes mellitus , type 1 diabetes , type 2 diabetes , incidence (geometry) , glutamate decarboxylase , human leukocyte antigen , immunology , antibody , disease , endocrinology , antigen , biology , biochemistry , physics , enzyme , environmental health , optics
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 (≥ 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.