Low-risk HLA genotype in Type 1 diabetes is associated with less destruction of pancreatic B-cells 12 months after diagnosis.
OBJECTIVE
The role of human leukocyte antigen (HLA) genes in the susceptibility to Type 1 diabetes (T1DM) is well known. However, we do not know whether the degree of pancreatic B-cell destruction depends on different HLA genetic risk. The aim of this study was to analyse the influence of DRB1* and DQB1* genes on the rate of pancreatic B-cell loss in a prospective series of 120 consecutive newly diagnosed T1DM subjects in the first 12 months after diagnosis.


METHODS
Patients were typed for HLA-DRB1* and DQB1* loci by a reverse line blot assay using an array of immobilized sequence-specific oligonucleotide probes. C-peptide, insulin requirement and glycated haemoglobin (HbA(1c)) were determined at diagnosis and every 3 months for 12 months. The variance of C-peptide as evidence of B-cell loss during follow-up was analysed using the general linear model for repeated-measures procedure.


RESULTS
Fasting C-peptide in T1DM subjects with low HLA genetic risk was significantly higher when compared with subjects with moderate or high HLA genetic risk from time of diagnosis up to 12 months (P = 0.007 and P = 0.0002, respectively). Nonetheless, the changes in C-peptide levels over a 12-month period did not differ significantly between T1DM subjects with different HLA genetic risks.


CONCLUSIONS
Low-risk HLA genotype in T1DM is associated with less destruction of pancreatic B-cells up to 12 months after diagnosis. These results are useful when designing trials for therapies aimed to prevent the progression of B-cell destruction in recent-onset T1DM.
Spoletini
M
M
Endocrinology, Department of Clinical Science, Sapienza University, Rome, Italy.
Petrone
A
A
Zampetti
S
S
Capizzi
M
M
Zavarella
S
S
Osborn
J
J
Foffi
C
C
Tuccinardi
D
D
Pozzilli
P
P
Buzzetti
R
R
D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male
D002096:C-Peptide; D006442:Glycated Hemoglobin; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C069051:HLA-DQB1 antigen