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

Abstract

Background: We investigated whether residual insulin secretion and metabolic derangement at diagnosis of type 1 diabetes (T1DM) are influenced by human leukocyte antigens (HLA) class II genes.

Methods: Eight hundred and seventy-one T1DM consecutive Caucasian patients were typed for HLA class II genes. In 300 of these patients, glycated haemoglobin, insulin requirement, baseline C-peptide and body mass index (BMI) Z-score were measured at clinical diagnosis. The effect of the HLA genotypes on the quantitative variables was investigated using multiple linear regression. The beta coefficient regression of the age at onset and HLA genotypes were standardized to compare their specific importance for C-peptide levels.

Results: The HLA genotypes were divided in high-, moderate- and low-risk categories. The frequency of high-risk genotype, DRB1*03-DQB1*0201/DRB1*04-DQB1*0302, decreased with increasing age of onset (p < 0.0001, chi(2) linear trend). The presence of the high-risk genotype was independently associated with lower C-peptide levels at diagnosis (p = 0.002). In the regression analysis of C-peptide levels, the standardized beta coefficient for age of onset and high risk compared to low-risk genotypes showed similar results (0.27 and 0.24 respectively). There was a positive association between age of onset and C-peptide (p < 0.0001) and a negative association between age of onset and insulin requirement (p < 0.0001).

Conclusions: The degree of beta-cell destruction at diagnosis of T1DM is independently associated with both, age of onset and HLA genotypes, the two variables exert a similar quantitative effect on residual beta-cell function at diagnosis.