IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71)

• Published in: Diabetologia Vol. 48; no. 4; pp. 703 - 708
• Main Authors: BOTTAZZO, G. F, BOSI, E, CULL, C. A, BONIFACIO, E, LOCATELLI, M, ZIMMET, P, MACKAY, I. R, HOLMAN, R. R
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.04.2005; Springer Nature B.V
• Subjects: Adult; Age Factors; Aged; Autoantibodies - blood; Biological and medical sciences; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Glutamate Decarboxylase - immunology; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Insulin - therapeutic use; Logistic Models; Male; Medical sciences; Membrane Proteins - immunology; Middle Aged; Multivariate Analysis; Prevalence; Prospective Studies; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - immunology; Receptor-Like Protein Tyrosine Phosphatases, Class 8; Risk Assessment - methods; Endocrinopathy; Autoimmunity; Type 2 diabetes; Human; Pancreatic hormone; Prevalence; Antibody; IA2A; ICA; Langerhans islet; Autoantibody; Metabolic diseases; Insulin; Islet cell autoantibodies; GADA; Risk factor; UKPDS; Insulin requirement; Endocrine pancreas
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-005-1691-9

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. 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. 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%. 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.