Clinical, autoimmune, and HLA characteristics of children diagnosed with type 1 diabetes before 5 years of age.
BACKGROUND
Little is known about auxologic, autoimmune, and HLA characteristics specific to children with early-onset diabetes (EOD). HLA subtypes have been shown to play an important part in the determination of islet-cell autoimmunity and in the pace and intensity of the beta-cell destructive process.


OBJECTIVE
Our goals were to: 1) outline auxologic, autoimmune, and HLA class II characteristics of children diagnosed with type 1 diabetes before 5 years of age (EOD); 2) evaluate differences between EOD and later-onset or non-age-stratified type 1 diabetes; and 3) investigate the relation between type 1 diabetes-related HLA subtypes and markers of diabetic autoimmunity in EOD.


METHODS
Forty children with EOD were studied. Auxologic and antibody radioimmunoassay data were obtained by retrospective analysis of records. HLA diabetes-related class II alleles were typed by polymerase chain reaction using sequence-specific primers.


RESULTS
At diagnosis, the average age of the EOD study patients was 2.6 years, body mass index was 16.9 kg/m2, and weight was 106% of average weight for height. When compared with a matched subgroup of children with later-onset type 1 diabetes, preschoolers did not significantly differ in terms of birth weight or body mass index. The frequency of positive islet cell antibodies 512 and glutamic acid decarboxylase 65 antibodies was significantly less in EOD (28.6% and 31.6%, respectively). There were significant differences in the frequencies of some diabetes-related HLA alleles and haplotypes between the early-onset group and a large non-age-stratified type 1 diabetes group. None of the patients with EOD had either of the protective DRB1*1501 or DQB1*0602 alleles. There was a negative correlation between glutamic acid decarboxylase and the predisposing haplotype DR3/DQ2.


CONCLUSIONS
Children diagnosed with type 1 diabetes before 5 years of age may have different diabetes-related autoimmune and genetic characteristics from those diagnosed at a later age.
Hathout
Eba H
EH
Pediatric Diabetes Center and Transplant Immunology Center, Loma Linda University Children's Hospital, Loma Linda, California 92354, USA. ehathout@ahs.llumc.edu
Hartwick
Noelle
N
Fagoaga
Omar R
OR
Colacino
Anna Rita
AR
Sharkey
Jeannine
J
Racine
Michael
M
Nelsen-Cannarella
Sandra
S
Mace
John W
JW
D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D001724:Birth Weight; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D005802:Genes, MHC Class II; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007330:Insulin Antibodies / Q000032:analysis; D007453:Iodide Peroxidase / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D012189:Retrospective Studies; D013954:Thyroglobulin / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D006680:HLA Antigens; D007330:Insulin Antibodies; D013954:Thyroglobulin; D007453:Iodide Peroxidase; D005968:Glutamate Decarboxylase