Background We investigated whether residual insulin secretion andmetabolic derangement at diagnosis of type 1 diabetes (T1DM) are influencedby human leukocyte antigens (HLA) class II genes.Methods Eight hundred and seventy-one T1DM consecutive Caucasianpatients were typed for HLA class II genes. In 300 of these patients, glycatedhaemoglobin, insulin requirement, baseline C-peptide and body mass index(BMI) Z-score were measured at clinical diagnosis. The effect of the HLAgenotypes on the quantitative variables was investigated using multiplelinear regression. The beta coefficient regression of the age at onset andHLA genotypes were standardized to compare their specific importance forC-peptide levels.Results The HLA genotypes were divided in high-, moderate- andlow-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, χ2 linear trend). The presence of the high-risk genotypewas independently associated with lower C-peptide levels at diagnosis(p = 0.002). In the regression analysis of C-peptide levels, the standardizedbeta coefficient for age of onset and high risk compared to low-risk genotypesshowed similar results (0.27 and 0.24 respectively). There was a positiveassociation between age of onset and C-peptide (p < 0.0001) and a negativeassociation between age of onset and insulin requirement (p < 0.0001).Conclusions The degree of beta-cell destruction at diagnosis of T1DM isindependently associated with both, age of onset and HLA genotypes, the twovariables exert a similar quantitative effect on residual beta-cell function atdiagnosis.
Residual insulin secretion at diagnosis of type 1 diabetes is independently associated with both, age of onset and HLA genotype
Picardi A;Manfrini S;Pozzilli P;
2005-01-01
Abstract
Background We investigated whether residual insulin secretion andmetabolic derangement at diagnosis of type 1 diabetes (T1DM) are influencedby human leukocyte antigens (HLA) class II genes.Methods Eight hundred and seventy-one T1DM consecutive Caucasianpatients were typed for HLA class II genes. In 300 of these patients, glycatedhaemoglobin, insulin requirement, baseline C-peptide and body mass index(BMI) Z-score were measured at clinical diagnosis. The effect of the HLAgenotypes on the quantitative variables was investigated using multiplelinear regression. The beta coefficient regression of the age at onset andHLA genotypes were standardized to compare their specific importance forC-peptide levels.Results The HLA genotypes were divided in high-, moderate- andlow-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, χ2 linear trend). The presence of the high-risk genotypewas independently associated with lower C-peptide levels at diagnosis(p = 0.002). In the regression analysis of C-peptide levels, the standardizedbeta coefficient for age of onset and high risk compared to low-risk genotypesshowed similar results (0.27 and 0.24 respectively). There was a positiveassociation between age of onset and C-peptide (p < 0.0001) and a negativeassociation between age of onset and insulin requirement (p < 0.0001).Conclusions The degree of beta-cell destruction at diagnosis of T1DM isindependently associated with both, age of onset and HLA genotypes, the twovariables exert a similar quantitative effect on residual beta-cell function atdiagnosis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.