Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study.
(2011) In Diabetes 60(1). p.54-345- Abstract
- To assess whether recently discovered genetic loci associated with hyperglycemia also predict long-term changes in glycemic traits. Methods: Sixteen fasting glucose-raising loci were genotyped in middle-aged adults from the GLACIER Study, a population-based prospective cohort study from Northern Sweden. Genotypes were tested for association with baseline fasting and 2-hr post-challenge glycemia (N=16,398), and with change in glycemic traits during a 10 year follow-up period (N=4,059). Results: Cross-sectional directionally consistent replication with fasting glucose concentrations was achieved for 12/16 variants; nine variants also associated with impaired fasting glucose (IFG) and seven were independently associated with 2-hr... (More)
- To assess whether recently discovered genetic loci associated with hyperglycemia also predict long-term changes in glycemic traits. Methods: Sixteen fasting glucose-raising loci were genotyped in middle-aged adults from the GLACIER Study, a population-based prospective cohort study from Northern Sweden. Genotypes were tested for association with baseline fasting and 2-hr post-challenge glycemia (N=16,398), and with change in glycemic traits during a 10 year follow-up period (N=4,059). Results: Cross-sectional directionally consistent replication with fasting glucose concentrations was achieved for 12/16 variants; nine variants also associated with impaired fasting glucose (IFG) and seven were independently associated with 2-hr post-challenge glucose concentrations. In prospective analyses corrected for multiple testing, the effect alleles at four loci (GCK rs4607517, ADRA2A rs10885122, DGKB-TMEM195 rs2191349, G6PC2 rs560887) were statistically associated with worsening fasting glucose concentrations during 10-years follow-up. MTNR1B rs10830963, which was predictive of elevated fasting glucose concentrations in cross-sectional analyses, was associated with a protective effect on post-challenge glucose concentrations during follow-up; however, this was only when baseline fasting and 2-hr glucoses were adjusted for. An additive effect of multiple risk alleles on glycemic traits was observed: a weighted genetic risk score (80(th) vs. 20(th) centiles) was associated with a 0.16mmol/l (P=2.4×10(-6)) greater elevation in fasting glucose and a 64% (95% CI:33-201%) higher risk of developing IFG during 10-years follow-up. Conclusions: Our findings imply that genetic profiling might facilitate the early detection of persons who are genetically susceptible to deteriorating glucose control; studies of incident type 2 diabetes and discrete cardiovascular endpoints will help establish whether the magnitude of these changes is clinically relevant. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1715808
- author
- Renström, F ; Shungin, Dmitry LU ; Johansson, I ; Florez, JC ; Hallmans, G ; Hu, FB and Franks, Paul LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 60
- issue
- 1
- pages
- 54 - 345
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- wos:000286017300042
- scopus:78751535877
- pmid:20870969
- ISSN
- 1939-327X
- DOI
- 10.2337/db10-0933
- language
- English
- LU publication?
- yes
- id
- 4d338a7c-d461-4883-b0cc-164635a7edae (old id 1715808)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20870969
- date added to LUP
- 2016-04-01 14:28:23
- date last changed
- 2024-04-10 20:20:33
@article{4d338a7c-d461-4883-b0cc-164635a7edae,
abstract = {{To assess whether recently discovered genetic loci associated with hyperglycemia also predict long-term changes in glycemic traits. Methods: Sixteen fasting glucose-raising loci were genotyped in middle-aged adults from the GLACIER Study, a population-based prospective cohort study from Northern Sweden. Genotypes were tested for association with baseline fasting and 2-hr post-challenge glycemia (N=16,398), and with change in glycemic traits during a 10 year follow-up period (N=4,059). Results: Cross-sectional directionally consistent replication with fasting glucose concentrations was achieved for 12/16 variants; nine variants also associated with impaired fasting glucose (IFG) and seven were independently associated with 2-hr post-challenge glucose concentrations. In prospective analyses corrected for multiple testing, the effect alleles at four loci (GCK rs4607517, ADRA2A rs10885122, DGKB-TMEM195 rs2191349, G6PC2 rs560887) were statistically associated with worsening fasting glucose concentrations during 10-years follow-up. MTNR1B rs10830963, which was predictive of elevated fasting glucose concentrations in cross-sectional analyses, was associated with a protective effect on post-challenge glucose concentrations during follow-up; however, this was only when baseline fasting and 2-hr glucoses were adjusted for. An additive effect of multiple risk alleles on glycemic traits was observed: a weighted genetic risk score (80(th) vs. 20(th) centiles) was associated with a 0.16mmol/l (P=2.4×10(-6)) greater elevation in fasting glucose and a 64% (95% CI:33-201%) higher risk of developing IFG during 10-years follow-up. Conclusions: Our findings imply that genetic profiling might facilitate the early detection of persons who are genetically susceptible to deteriorating glucose control; studies of incident type 2 diabetes and discrete cardiovascular endpoints will help establish whether the magnitude of these changes is clinically relevant.}},
author = {{Renström, F and Shungin, Dmitry and Johansson, I and Florez, JC and Hallmans, G and Hu, FB and Franks, Paul}},
issn = {{1939-327X}},
language = {{eng}},
number = {{1}},
pages = {{54--345}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study.}},
url = {{https://lup.lub.lu.se/search/files/3994492/1858273.pdf}},
doi = {{10.2337/db10-0933}},
volume = {{60}},
year = {{2011}},
}