INSULIN RECEPTOR SUBSTRATE 1 GENE VARIATION MODIFIES INSULIN RESISTANCE RESPONSE TO VARIOUS TYPES OF DIETARY STRATEGIES: RESULTS FROM THE DIRECT INTERVENTION TRIAL

Ronen Durst, Shoshi Shpitzen, Vardialla Meiner, Dan Schwarzfuchs, Meir J. Stampfer, Daniel Schurr, Osnat Eliav, Eran Leitersdorf, Iris Shai

Research output: Contribution to journalMeeting Abstract

Abstract

Background
Common genetic variants in the Insulin receptor substrate 1 (IRS1) gene have been recently associated with insulin resistance and hyperinsulinemia. It is currently unknown whether genetic variants influence insulin resistance by dietary response.

Methods and Results
We genotyped IRS1 rs2943641 in 263 overweight adults randomly assigned to either low fat, low carbohydrate or Mediterranean diets in the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT) study. We assessed the progress in fasting insulin, insulin resistance (HOMA-IR) and weight loss by genotypes. There was significant interactions between IRS1 rs2943641 genotype and type of dietary intervention on changes in fasting insulin (P=0.004 for interaction) and HOMA-IR (P=0.013 for interaction) at 2 years. For example: participants with CC wildtype genotype had greater decreases in insulin resistance (HOMA-IR) than those without this genotype in the low-fat diet group, while an opposite effect was observed on the non-wild type allele carriers (CT+TT) (P=0.01). Our results recapitulated the recently published results of the Pound Loss study [1]

Conclusions
In this generic – intervention trial, we found a genetic predisposition affecting insulin levels and insulin resistance after dietary intervention. This is demonstrated by different response to various types of diet among carriers of the wild type and non-wild type IRS1 rs2943641 allele.
Original languageEnglish GB
Pages (from-to)E1664-E1664
JournalJournal of the American College of Cardiology
Volume59
Issue number13
StatePublished - 27 Mar 2012

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