Islet Autoantibodies And Hla Gene Heterogeneity Of Type 1 Diabetes Onset At Different Ages

Objective To characterize the clinical phenotypes, islet autoantibodies and HLA gene heterogeneity of type 1 diabetes (TIDM) onset at different ages.Methods Five hundred and thirty nine type 1 diabetic patients were recruited from Xiangya 2nd Hospital of Central South University and Hunan Province T1DM Cooperative Study Group between Oct 1999 and Dec 2009. They were divided into the adolescent and adult groups according to the onset age of boundary point 20 years. The average age at diagnosis was 12.8 years (range 1-20 years) with 97 males and 135 females in the adolescent group. While in the adult group the average age at diagnosis was 34.1 years (range 21-62 years) with 196 males and 111 females. The measurements of glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A) and zinc transporter 8 antibody (ZnT8A) were carried out by radioligand binding assays. Human leukocyte antigen HLA-DQ gene was determined by polymerase chain reaction (PCR) and sequencing-based typing.Resultsâ‘ The proportion of male in the adolescent group patients of 41.8%(97/232) was markedly lower than that in the adult group of 63.8%(196/307) (P=0.000). Compared with the adolescent patients, the adult patients had longer disease duration, higher body mass index (BMI) and waist-to-hip ratio (WHR), higher systolic pressure and diastolic pressure, higher triglyceride (allP<0.05), higher fasting C peptide and 2-hour postprandial C peptide (FCP, PCP) (P<0.01).â‘¡The prevalence of IA-2A in the adolescent patients was 36.6%(85/232), obviously higher than that of the adult patients which was 17.6%(54/307) (P=0.000). There was no significant difference in the prevalence of GAD A and ZnT8A between the adolescent and thte adult group (P> 0.05). Similarly, the antibody level of IA-2A in the adolescent patients was 0.0026(-0.0300-2.7846), higher than that of the adult patients which was 0.0008(-0.0410-5.5700) (P=0.007). There was no significant difference in the antibody levels of GADA and ZnT8A between the adolescent and the adult group (P>0.05).â‘¢The frequency of allele in the adolescent patients with HLA-DQA1*03 was significantly higher than that of the adults (68% vs 48.9%, P=0.000). There was no significant difference in other HLA-DQA1 allele between the adults and adolescents (P>0.05). And There was no significant difference in HLA-DQB1 allele between the adults and adolescents (P>0.05). The frequency of haplotype in the the adolescent patients with DQA1*05-DQB 1*0201, DQA1*03-DQB 1*0302 was significantly higher than that of the adults (44.4% vs 28.2%, P=0.003,18.3% vs 9.8%, P=0.028), respectively. And the frequency of haplotype in the adolescent patients with DQA1*0102-DQB 1*0601 was significantly lower than that of the adults(0.0% vs 3.4%, P=0.025).Conclusionsâ‘ The adults onset type 1 diabetes that have a stronger tendency to type 2 diabetes has different clinical phenotypes compared with the adolescent onset one.â‘¡The prevalence and level of IA-2A are different between the adolescents and the adults, but not for that of GADA and ZnT8A.â‘¢HLA-DQ gene background is discrepant between the adolescents and the adults, and the main different haplotypes are DQA1*05-DQB1*0201, DQA1*03-DQB1*0302 and DQA1*0102-DQB1 *0601.