Multiple genes are implicated as markers in Type 1 diabetes (T1DM). Although previous studies demonstrated 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-cells function did not lead to conclusive reports. We investigated whether residual insulin secretion and metabolic derangement at diagnosis of T1DM are influenced by HLA markers. 871 T1DM consecutive Caucasian patients were typed for HLA class II genes. In 300 of these patients, HbA1c, insulin requirement, baseline C-peptide and BMI were measured at diagnosis. The effect of the HLA genotypes on the quantitative variables was investigated using multiple linear regression. The beta coefficient regression of age at onset and HLA genotypes were standardized to compare their specific importance for C-peptide levels. HLA-DRB1 and DQB1 class II genes were determined using SSOP technique. 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, c2 linear trend). The presence of the high risk genotype was independently associated with lower C-peptide levels at diagnosis (p=0.004). 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 (0.26 and 0.22 respectively). There was a positive association between age of onset and the following biochemical parameters: C-peptide (p=0.0001), BMI (p<0.0001) and a negative association between age of onset and insulin requirement (p<0.0001). 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.

Insulin Secretion at Diagnosis of Type 1 Diabetes Is Associated with Both Age of Onset and HLA Class II

PICARDI A;MANFRINI S;
2005-01-01

Abstract

Multiple genes are implicated as markers in Type 1 diabetes (T1DM). Although previous studies demonstrated 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-cells function did not lead to conclusive reports. We investigated whether residual insulin secretion and metabolic derangement at diagnosis of T1DM are influenced by HLA markers. 871 T1DM consecutive Caucasian patients were typed for HLA class II genes. In 300 of these patients, HbA1c, insulin requirement, baseline C-peptide and BMI were measured at diagnosis. The effect of the HLA genotypes on the quantitative variables was investigated using multiple linear regression. The beta coefficient regression of age at onset and HLA genotypes were standardized to compare their specific importance for C-peptide levels. HLA-DRB1 and DQB1 class II genes were determined using SSOP technique. 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, c2 linear trend). The presence of the high risk genotype was independently associated with lower C-peptide levels at diagnosis (p=0.004). 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 (0.26 and 0.22 respectively). There was a positive association between age of onset and the following biochemical parameters: C-peptide (p=0.0001), BMI (p<0.0001) and a negative association between age of onset and insulin requirement (p<0.0001). 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/14390
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