Clinical risk factors, DNA variants, and the development of type 2 diabetes.
Lyssenko, Valeriya LU ; Jonsson, Anna LU ; Almgren, Peter LU ; Pulizzi, Nicolo LU ; Isomaa, Bo ; Tuomi, Tiinamaija LU
; Berglund, Göran
LU
; Altshuler, David
; Nilsson, Peter
LU
and Groop, Leif
LU
(2008)
In New England Journal of Medicine
359(21).
p.2220-2232
- Abstract
- BACKGROUND: Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts. METHODS: We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time. RESULTS: Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking... (More)
- BACKGROUND: Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts. METHODS: We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time. RESULTS: Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking status, and reduced measures of insulin secretion and action. Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta-cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P=1.0x10(-4)). The discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased. CONCLUSIONS: As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1271300
- author
- Lyssenko, Valeriya
LU
; Jonsson, Anna
LU
; Almgren, Peter
LU
; Pulizzi, Nicolo
LU
; Isomaa, Bo
; Tuomi, Tiinamaija
LU
; Berglund, Göran
LU
; Altshuler, David
; Nilsson, Peter
LU
and Groop, Leif
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- New England Journal of Medicine
- volume
- 359
- issue
- 21
- pages
- 2220 - 2232
- publisher
- Massachusetts Medical Society
- external identifiers
-
- wos:000260994000005
- pmid:19020324
- scopus:55649105963
- pmid:19020324
- ISSN
- 0028-4793
- DOI
- 10.1056/NEJMoa0801869
- language
- English
- LU publication?
- yes
- id
- 7f9ef5c7-7803-4adc-a3bb-7fe395834ee0 (old id 1271300)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19020324?dopt=Abstract
- date added to LUP
- 2016-04-04 07:45:45
- date last changed
- 2024-05-10 21:25:13
@article{7f9ef5c7-7803-4adc-a3bb-7fe395834ee0,
abstract = {{BACKGROUND: Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts. METHODS: We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time. RESULTS: Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking status, and reduced measures of insulin secretion and action. Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta-cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P=1.0x10(-4)). The discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased. CONCLUSIONS: As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up.}},
author = {{Lyssenko, Valeriya and Jonsson, Anna and Almgren, Peter and Pulizzi, Nicolo and Isomaa, Bo and Tuomi, Tiinamaija and Berglund, Göran and Altshuler, David and Nilsson, Peter and Groop, Leif}},
issn = {{0028-4793}},
language = {{eng}},
number = {{21}},
pages = {{2220--2232}},
publisher = {{Massachusetts Medical Society}},
series = {{New England Journal of Medicine}},
title = {{Clinical risk factors, DNA variants, and the development of type 2 diabetes.}},
url = {{http://dx.doi.org/10.1056/NEJMoa0801869}},
doi = {{10.1056/NEJMoa0801869}},
volume = {{359}},
year = {{2008}},
}