Table of Contents
To view the fulltext, log-in or choose pay-per-view options:
Get Access

The Effect of Type 2 Diabetes Risk Loci on Insulin Requirements in Type 1 Diabetes

Moosavi M. · Séguin J. · Li Q. · Polychronakos C.
Departments of Paediatrics and Human Genetics, McGill University Health Centre, Montreal, Que., Canada Horm Res Paediatr 2012;77:305–308 (DOI:10.1159/000338665)

Abstract

Objective: To analyze the correlation between insulin requirements of type 1 diabetic (T1D) patients and genotype at type 2 diabetes (T2D) risk loci, obtained in our genome-wide association study. Methods: From a database of detailed insulin dosing of 567 patients, we selected 177 for whom we also had genome-wide genotyping data. Using PLINK software, we examined the association between insulin requirement as a quantitative trait and nineteen T2D risk loci. Results: Out of 19 single-nucleotide polymorphisms (SNPs), rs13266634 on chromosome 8 and rs7901695 on chromosome 10 showed nominal significance of association (p < 0.05). The first SNP is nonsynonymous (325 Arg>Trp) and maps to the SLC30A8 gene encoding the β-cell-specific ZnT8 zinc transporter, while the second is an intronic SNP in TCF7L2, the strongest known T2D association. Both loci exert their effect on β-cells and, in both, the T2D risk allele is associated with lower insulin requirements. Conclusion: We identified two T2D susceptibility loci that modulate insulin requirements in T1D patients. Our results are consistent with the association of lower insulin secretion with higher insulin sensitivity. To explain the continuation of this correlation after β-cell destruction, we hypothesize an epigenetic mechanism that alters insulin responsiveness in T1D patients based on β-cell function in early life. Such knowledge may allow a more precise approach to treatment.

 

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.


Pay-per-View Options
Direct payment This item at the regular price: USD 33.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 23.00