Linked Life Data

17624939

Source:http://linkedlifedata.com/resource/pubmed/id/17624939

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2007-11-9
pubmed:abstractText
There is strong evidence for the presence of a functional renin-angiotensin system in diabetogenic tissues, and ACE (angiotensin-converting enzyme) inhibitors may improve glucose metabolism in those individuals at high risk of developing T2DM (Type 2 diabetes). In the present study, we tested the hypothesis that subjects with genetically lower plasma and tissue ACE activity, because of their ACE [I/D (insertion/deletion)] genotype, would have a lower risk of T2DM in 2642 healthy middle-aged Caucasian men (mean age, 56 years) followed-up for 15 years. Obesity was the strongest predictor of T2DM, with an HR (95% CI) [hazard ratio (95% confidence interval)] of 3.74 (2.66-5.26) (P<0.0001). Overall there was no association between ACE genotype (II homozygotes, n=623; and D allele carriers, n=2019) and risk of T2DM, and although in lean men there was no genotype difference in risk in D allele carriers compared with II homozygotes [adjusted HR=0.75 (95% CI, 0.46-1.22)], in obese (body mass index >30 kg/m(2)) men the risk of T2DM was higher [adjusted HR=4.26 (95% CI, 1.30-13.93)] with a genotype-obesity interaction of P=0.01. A similar pattern of risk was seen by re-analysis of a previously published case-control study, where D allele carriers had a non-significant 1.30 (0.97-1.74)-fold higher risk of developing T2DM than II homozygotes when non-obese, but a 1.79 (1.17-2.72) (P=0.007)-fold higher risk when obese. Further prospective studies are needed to confirm these findings. The ACE D allele may worsen glucose metabolism, which could raise the prospective T2DM risk in obese men, but not in lean men. In obesity, adipose tissue undergoes inflammatory infiltration and the subsequent higher levels of pro-inflammatory angiotensin II may explain this association.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1470-8736
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
467-72
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Is the influence of variation in the ACE gene on the prospective risk of Type 2 diabetes in middle-aged men modified by obesity?
pubmed:affiliation
Centre For Cardiovascular Genetics, Royal Free and UCL Medical School, The Rayne Institute, 5 University Street, London WC1E 6JF, UK. a.muthumala@ucl.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural