Effect of genetic risk load defined by HLA‐DQB1 polymorphism on clinical characteristics of ID DM in children

Clinical and autoimmune characteristics of 150 diabetic children of mean age 7.8 years (SD 4.1 years) were recorded at clinical manifestation and during the first 2 years of IDDM in order to investigate whether subjects with high risk HLA‐DQB1 genotypes differ from those without these risk markers. When comparing subjects with the DQB 1*0302/0201, DQBl *0302/x, DQBl *0201/x, or other DQB1 genotypes (x = no protective allele), no differences were found in the age of the subjects at diagnosis, the duration of hyperglycaemic symptoms, or the length of clinical remission. The frequency of islet cell antibodies (ICA) and quantitative serum levels of these antibodies were of the same magnitude in all four groups. During the initial 2 years of IDDM serum C‐peptide concentrations were observed to be inversely related to the degree of genetic risk (P < 0.001 in two‐way analysis of variance for repeated measures), the lowest C‐peptide levels being observed in the group of DQB 1*0302/0201 hetero‐zygotes (P < 0.001 vs. DQBl *0201/x; P < 0.01 vs. DQBl *0302/x; P= 0.05 vs. others). On the other hand, the subjects with the DQB 1 *0201 genotype had the highest serum C‐peptide concentrations, the levels being even higher than those of the patients carrying neutral or protective DQB1 genotypes (P < 0.01). These subjects also had lower daily insulin doses and blood glycated haemoglobin A1 (HbA1) levels over the initial 2 years of the disease when compared with the DQB 1 *0302/0201 heterozygotes (P < 0.05 and P < 0.01, respectively). We conclude that the DQB 1 *0302/0201 heterozygous individuals with the greatest genetic risk of IDDM lack the capacity for recovery of β‐cell function commonly seen in other subjects after starting exogenous insulin treatment. Our results also suggest that the DQBl *0201/x genotype is associated with a milder form of the disease, since these subjects were characterized by a transient recovery of β‐cell function accompanied by lower requirement of exogenous insulin and better metabolic control over the initial 2 years of IDDM.