IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71).
OBJECTIVE
Established autoimmune markers of type 1 diabetes, including islet cell autoantibodies (ICA) and autoantibodies to glutamic acid decarboxylase (GADA) have been used to screen people presenting with type 2 diabetes for latent autoimmune diabetes in adults. We have examined the prevalence of autoantibodies to protein tyrosine phosphatase isoforms IA-2 (IA-2A) and IA-2beta/phogrin (IA-2betaA) in a cohort of adult UKPDS patients thought to have type 2 diabetes, and investigated the possible role of these autoantibodies in predicting requirement for insulin therapy.


METHODS
IA-2A and IA-2betaA were measured by a validated radioimmunoassay with human recombinant autoantigens in 4,169 white Caucasian patients aged 25-65 years and newly diagnosed with type 2 diabetes. The clinical requirement for insulin therapy within 6 years was examined in 2,556 patients not randomised to insulin.


RESULTS
IA-2A and IA-2betaA were present in 2.2 and 1.4%, respectively, of these patients. IA-2A were more prevalent in younger patients (p for trend <0.00001), more often associated with the HLA-DR4 allele (26.3 vs 8.0%, p<0.0001), and their presence increased the likelihood of insulin therapy requirement within 6 years from diagnosis [relative risk (95%CI) 12.2 (9.8-15.3)]. The presence of IA-2A together with GADA increased the relative risk of requiring insulin therapy from 5.4 (4.1-7.1) for GADA alone to 8.3 (3.7-18.8) and the corresponding positive predictive value from 33 to 50%.


CONCLUSIONS
In type 2 diabetes, the presence of IA-2A is infrequent, associated with the HLA-DR4 haplotype, and highly predictive of future need for insulin therapy. The measurement of IA-2betaA does not provide additional information.
Bottazzo
G F
GF
Scientific Directorate, Bambino Gesù Paediatric Hospital, Scientific Institute, Rome, Italy.
Bosi
E
E
Cull
C A
CA
Bonifacio
E
E
Locatelli
M
M
Zimmet
P
P
Mackay
I R
IR
Holman
R R
RR
D000328:Adult; D000367:Age Factors; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D011446:Prospective Studies; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D018570:Risk Assessment / Q000379:methods
D001323:Autoantibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C096322:ICA512 autoantibody; D007328:Insulin; D008565:Membrane Proteins; C024211:islet cell antibody; C516862:PTPRN protein, human; C102889:PTPRN2 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase