Analysis of pathogenesis of juvenile new-onset diabetes.
BACKGROUND
Measurement of anti-islet autoantibodies at the time of disease onset contributes greatly to the differentiation of Type 1A diabetes with HLA Class II subtyping also contributing.


METHODS
Blood samples were obtained from 900 patients with age from 1 month to 25 years (median age 11.1 years) within 2 weeks of diabetes onset to test anti-islet autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma antigen (IA-2AA), the zinc transporter-8 (ZnT8AA), and islet-cell antibodies (ICA). Polymorphisms of the HLA Class II gene were typed in 547 randomly selected patients.


RESULTS
Of the 900 subjects analyzed, 145 (16.1%) were negative for all five anti-islet autoantibodies, and autoantibody negativity significantly increased with age: 10.2% (38/372) among children <10 years of age, 14.2% (46/325) in those 10-14 years of age, and 30.1% (61/203) in those >14 years of age (P < 0.001). The prevalence of IA-2AA was the highest among young children. The prevalence of GADA increased with age while the prevalence of IAA was inversely correlated with age. At diagnosis, the subjects with negative antibodies had a higher body mass index (P < 0.001) and less high risk HLA genotype DR3-DQ2/DR4-DQ8 (P < 0.01).


CONCLUSIONS
A large percentage of children and youths negative for all anti-islet autoantibodies at the onset of diabetes are likely to have the non-immune form, especially those without DR3/DR4 and obese patients. Among autoantibody-positive Type 1A patients, IAA and GADA showed a reciprocal prevalence, suggesting differential disease pathogenesis.
Department of Endocrinology, Nanjing Jinling Hospital, Nanjing, Jiangsu, China.
Jian
J
Wang
Dongmei
D
Miao
Yangtian
Y
Wang
Bin
B
Lu
Sunanda
S
Babu
Georgeanna
G
Klingensmith
Marian
M
Rewers
George S
GS
Eisenbarth
Liping
L
Yu
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000235:genetics / Q000276:immunology*; D027682:Cation Transport Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007223:Infant; D007328:Insulin / Q000097:blood / Q000235:genetics / Q000276:immunology; D007340:Insulinoma / Q000097:blood / Q000235:genetics / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D055815:Young Adult; D000075703:Zinc Transporter 8
D001323:Autoantibodies; D027682:Cation Transport Proteins; D000949:Histocompatibility Antigens Class II; D007328:Insulin; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; C024211:islet cell antibody; D004247:DNA; D005968:Glutamate Decarboxylase