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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)
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author
organization
publishing date
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
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
2008-12-04 16:28:08
date last changed
2017-09-03 04:48:14
@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},
  volume       = {359},
  year         = {2008},
}