From Type 1, through LADA, to Type 2 Diabetes: A Continuous Spectrum?

Abstract

This study aims to explore whether diabetes mellitus from T1DM, through LADA, to T2DM presents a continuous spectrum in terms of HLA-DQ genetic background. We recruited 223 patients with autoimmune T1DM, 215 with LADA, 206 with T2DM, and 228 nondiabetic controls, and then defined their HLA-DQA1 and -DQB1 genotypes and haplotypes. T1DM patients were divided into two groups depending on age of onset of disease: juvenile-onset (JO; before the age of 20) and adult-onset (AO; after the age of 20). LADA patients were sorted according to the GADA titer: the LADA1 group had titers higher than 175 U/mL, whereas the LADA2 group had lower titers. The susceptible haplotypes of T1DM were DQA1*03-DQB1*0303, DQA1*03-DQB1*0401, and DQA1*05-DQB1*0201. The protective haplotype was DQA1*0102-DQB1*0602. The frequency of DQA1*03-DQB1*0303 in JO, AO, LADA1, LADA2, T2DM, and control groups were 38.2%, 34.2%, 25.3%, 18.9%, 17.5%, and 16.5%, respectively. The frequencies of DQA1*05-DQB1*0201 were 21.2%, 15.0%, 12.7%, 4.6%, 3.6% and 3.3%; the frequencies of DQA1*03-DQB1*0401 were 11.3%, 9.4%, 11.3%, 5.4%, 4.4% and 3.3%; and the frequencies of DQA1*0102-DQB1*0602 were 1.4%, 1.7%, 0.7%, 4.6%, 7.0%, and 5.3%. The linear-by-linear association showed that the frequency of DQA1*03-DQB1*0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 presented a decremental tendency in JO, AO, LADA1, LADA2, T2DM, and control groups. The preliminary data demonstrated that the susceptible haplotypes of the HLA-DQ gene present a continuous spectrum from typical T1DM, through LADA, to T2DM, which deserves further investigation.