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Exp Clin Endocrinol Diabetes 2013; 121(06): 361-367
DOI: 10.1055/s-0033-1345122
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

IGF2 Gene Polymorphisms and IGF-II Concentration are Determinants of Longitudinal Weight Trends in Type 2 Diabetes

R. P. Narayanan
1   Vascular Research Group
,
B. Fu
2   School of Community-based Medicine
,
A. Payton
3   Centre for Integrated Genomic Medical Research
,
J. E. Hudson
1   Vascular Research Group
,
R. L. Oliver
1   Vascular Research Group
,
S. G. Anderson
4   Cardiovascular Research Group
,
K. W. Siddals
1   Vascular Research Group
,
A. White
5   Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester, United Kingdom
,
W.E. R. Ollier
3   Centre for Integrated Genomic Medical Research
6   Salford R&D, Salford Royal Hospital NHS Foundation Trust, Salford, United Kingdom
,
A. H. Heald
1   Vascular Research Group
,
J. M. Gibson
1   Vascular Research Group
› Author Affiliations
Further Information

Publication History

received 21 August 2012
first decision 10 March 2013

accepted 12 April 2013

Publication Date:
06 June 2013 (online)

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Abstract

Objective:

The hypothesis of the study was that IGF2 gene polymorphisms were associated with longitudinal trends in weight through modification of IGF-II concentration.

Design:

Observational study that explored associations of the IGF2 gene and baseline circulating IGF-II concentration with ‘real-world’ longitudinal trends in body-mass index in a type 2 diabetes population.

Methods:

26 haplotype tagging single nucleotide polymorphisms (SNPs) from the IGF2 and H19 genes were studied in 485 Caucasian individuals in the Salford Longitudinal Diabetes Cohort. A generalised-estimating equation (GEE) model was used to separately study the association of SNPs and IGF-II concentration with 8-year longitudinal trends in body-mass index.

Results:

High serum IGF-II concentration at baseline was associated with weight loss over the study period (β=−0.006, 95% CI −0.009 to −0.002, p<0.001). 8 SNPs were associated with longitudinal body-mass index trends, of which 4 retained significance after multiple ­testing correction. 2 SNPs rs10770063 and rs3842767 were associated with both IGF-II concentration as well as longitudinal weight changes.

Conclusion:

We report novel associations between polymorphisms in the IGF2 gene, with concentration of circulating IGF-II and also with longitudinal weight change in type 2 diabetes. Our data indicate that the IGF2 gene and its gene product may be important determinants of longitudinal weight trends in type 2 diabetes.

Key words

IGF-II - polymorphisms - body-mass index - real-world data - longitudinal associations - type 2 diabetes
 

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