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

Abstract

Abstract. 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 DQB1*0302/0201, DQB1*0302/x, DQB1*0201/x, or other DQBl 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 DQBl*O302/0201 heterozygotes ( P < 0.001 vs. DQB1*0201/x; P < 0.01 vs. DQB1*0302/x; P = 0.05 vs. others). On the other hand, the subjects with the DQB1*0201 genotype had the highest serum C-peptide concentrations, the levels being even higher than those of the patients carrying neutral or protective DQB 1 genotypes ( P < 0.01). These subjects also had lower daily insulin doses and blood glycated haemoglobin A, (HbA,) 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 *0302/020 1 heterozygous individuals with the greatest genetic risk of IDDM lack the capacity for recovery of @-cell function commonly seen in other subjects after starting exogenous insulin treatment. Our results also suggest that the 106 DQB1*0201/x genotype is associated with a milder form of the disease, since these subjects were characterized by a transient recovery of @-cell function accompanied by lower requirement of exogenous insulin and better metabolic control over the initial 2 years of IDDM.

Frequency of partial remission and related factors in children and adolescents diagnosed with type 1 diabetes mellitus

“…We observed a different correlation between remission rate and age at diagnosis in that partial remission occurred in 7 out of 12 patients aged below 3.5 years. There are also two studies reporting that age at diagnosis does not affect the remission rate [35,36]. Our results show disparity to other studies in some aspects.…”

Sex- and season-dependent differences in C-peptide levels at diagnosis of immune-mediated type 1 diabetes

“…Furthermore, at variance with a study in children [12], but in agreement with findings in nondiabetic subjects [13], C-peptide levels were higher in the high-incidence period (October to March) as compared with the low-incidence period (April to September) [7]. The lack of association between C-peptide levels around diagnosis and HLA-DQ risk status confirms our previous finding in adult-onset patients [10], but contrasts with grading of inaugural disease severity according to HLA-DQ-linked risk in Finnish children [14]. We believe that these discrepancies with previous studies may be due to our use of multivariate analysis and/or a larger sample size, including a wider age range.…”

Residual insulin secretion at diagnosis of type 1 diabetes is independently associated with both, age of onset and HLA genotype

“…T1DM subjects carrying HLA DQB1 * 0201/0302 high risk genotype show lower C-peptide levels in the initial years of T1DM compared to low risk (19)(20). This suggests that the aforesaid individuals lack the capacity for recovery of betacell function commonly observed in some patients after starting the introduction of insulin treatment (20), even though these interpretation could be biased by multiple factors such as subjects and physician behaviour.…”

“…Although previous studies demonstrate that HLA susceptible genotypes are important determinants of earlier disease onset, and that young age at diagnosis is associated with lower C-peptide levels, the relationship between HLA class II and beta-cell function did not lead to conclusive reports [16,19,20]. This is an interesting aspect as it may clarify the pathogenic processes of betacell destruction.…”