Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study.
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 Swe...
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Format: | Article in Journal/Newspaper |
Language: | English |
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American Diabetes Association Inc.
2011
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Online Access: | https://lup.lub.lu.se/record/1715808 https://doi.org/10.2337/db10-0933 https://portal.research.lu.se/files/3994492/1858273.pdf |
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ftulundlup:oai:lup.lub.lu.se:4d338a7c-d461-4883-b0cc-164635a7edae 2024-05-12T08:08:57+00:00 Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study. Renström, F Shungin, Dmitry Johansson, I Florez, JC Hallmans, G Hu, FB Franks, Paul 2011 application/pdf https://lup.lub.lu.se/record/1715808 https://doi.org/10.2337/db10-0933 https://portal.research.lu.se/files/3994492/1858273.pdf eng eng American Diabetes Association Inc. https://lup.lub.lu.se/record/1715808 http://dx.doi.org/10.2337/db10-0933 https://portal.research.lu.se/files/3994492/1858273.pdf wos:000286017300042 scopus:78751535877 pmid:20870969 info:eu-repo/semantics/openAccess Diabetes; 60(1), pp 54-345 (2011) ISSN: 1939-327X Endocrinology and Diabetes contributiontojournal/article info:eu-repo/semantics/article text 2011 ftulundlup https://doi.org/10.2337/db10-0933 2024-04-17T14:03:32Z 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. Article in Journal/Newspaper Northern Sweden Lund University Publications (LUP) Diabetes 60 1 345 354 |
institution |
Open Polar |
collection |
Lund University Publications (LUP) |
op_collection_id |
ftulundlup |
language |
English |
topic |
Endocrinology and Diabetes |
spellingShingle |
Endocrinology and Diabetes Renström, F Shungin, Dmitry Johansson, I Florez, JC Hallmans, G Hu, FB Franks, Paul Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study. |
topic_facet |
Endocrinology and Diabetes |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Renström, F Shungin, Dmitry Johansson, I Florez, JC Hallmans, G Hu, FB Franks, Paul |
author_facet |
Renström, F Shungin, Dmitry Johansson, I Florez, JC Hallmans, G Hu, FB Franks, Paul |
author_sort |
Renström, F |
title |
Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study. |
title_short |
Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study. |
title_full |
Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study. |
title_fullStr |
Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study. |
title_full_unstemmed |
Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study. |
title_sort |
genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the glacier study. |
publisher |
American Diabetes Association Inc. |
publishDate |
2011 |
url |
https://lup.lub.lu.se/record/1715808 https://doi.org/10.2337/db10-0933 https://portal.research.lu.se/files/3994492/1858273.pdf |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_source |
Diabetes; 60(1), pp 54-345 (2011) ISSN: 1939-327X |
op_relation |
https://lup.lub.lu.se/record/1715808 http://dx.doi.org/10.2337/db10-0933 https://portal.research.lu.se/files/3994492/1858273.pdf wos:000286017300042 scopus:78751535877 pmid:20870969 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.2337/db10-0933 |
container_title |
Diabetes |
container_volume |
60 |
container_issue |
1 |
container_start_page |
345 |
op_container_end_page |
354 |
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1798852100651745280 |