Impact of IDDM2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes: reduced insulin antibody titres and preserved beta cell function.

Abstract

AIMS/HYPOTHESIS:

The insulin-dependent diabetes mellitus 2 gene (IDDM2) is a type 1 diabetes susceptibility locus contributed to by the variable number of tandem repeats (VNTR) upstream of the insulin gene (INS). We investigated the association between INS VNTR class III alleles (-23HphIA/T) and both insulin antibody presentation and residual beta cell function during the first year after diagnosis in 257 children with type 1 diabetes.

MATERIALS AND METHODS:

To estimate C-peptide levels and autoantibody presentation, patients underwent a meal-stimulated C-peptide test 1, 6, and 12 months after diagnosis. The insulin -23HphIA/T variant was used as a marker of class III alleles and genotyped by PCR-RFLP.

RESULTS:

The insulin antibody titres at 1 and 6 months were significantly lower in the class III/III and class I/III genotype groups than in the class I/I genotype group (p = 0.01). Class III alleles were also associated with residual beta cell function 12 months after diagnosis and independently of age, sex, BMI, insulin antibody titres, and HLA-risk genotype group (p = 0.03). The C-peptide level was twice as high among class III/III genotypes as in class I/I and class I/III genotypes (319 vs 131 and 166 pmol/l, p=0.01). Furthermore, the class III/III genotype had a 1.1% reduction in HbA(1)c after adjustment for insulin dose (p = 0.04).

CONCLUSIONS/INTERPRETATION:

These findings suggest a direct connection in vivo between INS VNTR class III alleles, a decreased humoral immune response to insulin, and preservation of beta cell function in recent-onset type 1 diabetes.

• Authors: L B Nielsen, H B Mortensen, F Chiarelli, R Holl, P Swift, C de Beaufort, F Pociot, P Hougaard, S Gammeltoft, M Knip, L Hansen, Hvidøre Study Group
• Journal: Diabetologia (Diabetologia) Vol. 49 Issue 1 Pg. 71-4 (Jan 2006) ISSN: 0012-186X [Print] Germany
• PMID: 16307231 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• C-Peptide
• Insulin
• Insulin Antibodies

Topics

• C-Peptide (blood)
• Child
• Diabetes Mellitus, Type 1 (genetics, immunology)
• Follow-Up Studies
• Genetic Predisposition to Disease
• Humans
• Insulin (genetics)
• Insulin Antibodies (blood)
• Insulin-Secreting Cells (metabolism)
• Minisatellite Repeats (genetics)
• Polymorphism, Single Nucleotide
• Time Factors