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Vol. 77, No. 5, 2012
Issue release date: June 2012
Section title: Original Paper
Horm Res Paediatr 2012;77:305–308
(DOI:10.1159/000338665)

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

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 12/13/2011 9:45:52 AM
Accepted: 4/3/2012
Published online: 5/15/2012

Number of Print Pages: 4
Number of Figures: 1
Number of Tables: 1

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: http://www.karger.com/HRP

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.


  

Author Contacts

Constantin Polychronakos, MD
The McGill University Health Centre
Children’s Hospital Site, 2300 Tupper, Suite C244
Montreal, QC H3H 1P3 (Canada)
Tel. +1 514 412 4315, E-Mail Constantin.Polychronakos@McGill.ca

  

Article Information

Received: December 13, 2011
Accepted: April 3, 2012
Published online: May 15, 2012
Number of Print Pages : 4
Number of Figures : 1, Number of Tables : 1, Number of References : 17

  

Publication Details

Hormone Research in Paediatrics (From Developmental Endocrinology to Clinical Research)

Vol. 77, No. 5, Year 2012 (Cover Date: June 2012)

Journal Editor: Czernichow P. (Paris)
ISSN: 1663-2818 (Print), eISSN: 1663-2826 (Online)

For additional information: http://www.karger.com/HRP


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 12/13/2011 9:45:52 AM
Accepted: 4/3/2012
Published online: 5/15/2012

Number of Print Pages: 4
Number of Figures: 1
Number of Tables: 1

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: http://www.karger.com/HRP


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