"HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study

Aims/hypothesis: WHO considers an etiological classification of diabetes to be essential. To evaluate whether HLA-DQB1 genotypes facilitates the classification of diabetes as compared with islet antibodies, young adult diabetic patients were investigated. Methods: Blood samples were available at diagnosis from 1872 (90%) of the 2077 young adult patients (15-34 years old) during a five-year period in the nationwide Diabetes Incidence Study in Sweden (DISS). Islet antibodies were measured at diagnosis in 1869, fasting-plasmaC-peptide (F-P-C-peptide) after diagnosis in 1522, while HLA-DQB1genotypes were determined in 1743 patients. Results: Islet antibodies were found among 83% clinically considered to have type 1 diabetes, 23% with type 2 and 45% with unclassifiable diabetes. F-P-C-peptide concentrations after diagnosis were markedly lower in patients with than in those without islet antibodies (median 0.24 nmol/l vs. median 0.69 nmol/l; p<0.0001). Irrespective of clinical classification, patients with islet antibodies showed increased frequencies at least one of risk HLA-DQB1 genotypes compared with patients without. Antibody negative patients with risk HLA-DQB1 genotypes had significantly lower fasting P-C-peptide concentrations than those without risk genotypes (0.51 nmol/l vs. 0.74 nmol/l; p=0.0003). Conclusions/interpretation: Assessment of islet antibodies is necessary for an etiological classification of diabetic patients. HLA-DQB1 genotyping does not improve the classification in patients with islet antibodies. However, in patients without islet antibodies, HLA-DQB1 genotyping together with C-peptide measurement may be of value in the differentiation between idiopathic type 1 diabetes versus type 2 diabetes.