Linked Life Data

11030756

Source:http://linkedlifedata.com/resource/pubmed/id/11030756

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2000-11-3
pubmed:abstractText
The insulin receptor substrate-2 (IRS-2) is a major insulin signalling molecule. IRS-2 inactivation in mice induces a form of diabetes characterized by peripheral insulin resistance and reduced beta cell mass. We tested the hypothesis that a common non-conservative amino acid substitution of IRS-2 (G1057D) might interact with overweight in the pathogenesis of type 2 diabetes. The variant was genotyped in 193 Italian patients with type 2 diabetes and 206 control subjects. In the absence of overweight, the risk of type 2 diabetes decreased according to the dosage of the D1057 allele (odds ratio for GD genotype 0.46 [95% CI 0.25-0.86]; DD genotype 0.18 [0.04-0.68]; P for trend = 0.0012). Conversely, the interaction between overweight and genotype increased the risk of type 2 diabetes according to the dosage of the D1057 allele (odds ratio for GD genotype 2.50 [1.11-5.65]; DD genotype 5.74 [1.11-29. 78]; P for trend = 0.0047). Among controls, fasting C-peptide levels, after adjustment for plasma glucose, were inversely related to the dosage of the D1057 allele (P = 0.020). This finding suggested that carriers of the D1057 allele may have higher insulin sensitivity and supported the protective effect of this allele. Conversely, among overweight patients there was a parallel increase in fasting plasma glucose (P for trend = 0.037) and fasting C-peptide according to the dosage of the D1057 allele, suggesting that higher insulin resistance and relative beta cell failure contributed to the increased risk of type 2 diabetes in overweight carriers of this allele. These data provide evidence for a strong association between type 2 diabetes and the G1057D common genetic variant of IRS-2, which appears to be protective against type 2 diabetes in a codominant fashion. Overweight appears to modify the effect of this polymorphism toward a higher risk of type 2 diabetes. Carriers of this polymorphism may represent an elective target for prevention of type 2 diabetes through preventing or treating excessive weight.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2517-21
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11030756-Adult, pubmed-meshheading:11030756-Aged, pubmed-meshheading:11030756-Alleles, pubmed-meshheading:11030756-Blood Glucose, pubmed-meshheading:11030756-Body Mass Index, pubmed-meshheading:11030756-C-Peptide, pubmed-meshheading:11030756-Case-Control Studies, pubmed-meshheading:11030756-Diabetes Mellitus, Type 2, pubmed-meshheading:11030756-Female, pubmed-meshheading:11030756-Gene Dosage, pubmed-meshheading:11030756-Genetic Predisposition to Disease, pubmed-meshheading:11030756-Genetic Variation, pubmed-meshheading:11030756-Genotype, pubmed-meshheading:11030756-Humans, pubmed-meshheading:11030756-Insulin Receptor Substrate Proteins, pubmed-meshheading:11030756-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11030756-Male, pubmed-meshheading:11030756-Middle Aged, pubmed-meshheading:11030756-Obesity, pubmed-meshheading:11030756-Odds Ratio, pubmed-meshheading:11030756-Phosphoproteins, pubmed-meshheading:11030756-Polymorphism, Genetic, pubmed-meshheading:11030756-Regression Analysis
pubmed:year
2000
pubmed:articleTitle
Interaction between the G1057D variant of IRS-2 and overweight in the pathogenesis of type 2 diabetes.
pubmed:affiliation
Department of Oncology and Neurosciences, Section of Molecular Pathology, University Gabriele D'Annunzio, Chieti, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't