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Insulin receptor substrate 1 gene variation modifies insulin resistance response to weight-loss diets in a 2-year randomized trial: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Qi, Qibin Bray, George A. Smith, Steven R. Hu, Frank B. Sacks, Frank M. |
| Copyright Year | 2011 |
| Abstract | BACKGROUND Common genetic variants in the insulin receptor substrate 1 (IRS1) gene have been recently associated with insulin resistance and hyperinsulinemia. We examined whether the best-associated variant modifies the long-term changes in insulin resistance and body weight in response to weight-loss diets in Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. METHODS AND RESULTS We genotyped IRS1 rs2943641 in 738 overweight adults (61% were women) who were randomly assigned to 1 of 4 diets varying in macronutrient contents for 2 years. We assessed the progress in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and weight loss by genotypes. At 6 months, participants with the risk-conferring CC genotype had greater decreases in insulin (P=0.009), HOMA-IR (P=0.015), and weight loss (P=0.018) than those without this genotype in the highest-carbohydrate diet group whereas an opposite genotype effect on changes in insulin and HOMA-IR (P≤0.05) was observed in participants assigned to the lowest-carbohydrate diet group. No significant differences were observed across genotypes in the other 2 diet groups. The tests for genotype by intervention interactions were all significant (P<0.05). At 2 years, the genotype effect on changes in insulin and HOMA-IR remained significant in the highest-carbohydrate diet group (P<0.05). The highest carbohydrate diet led to a greater improvement of insulin and HOMA-IR (P for genotype-time interaction ≤0.009) in participants with the CC genotype than those without this genotype across 2-year intervention. CONCLUSIONS Individuals with the IRS1 rs2943641 CC genotype might obtain more benefits in weight loss and improvement of insulin resistance than those without this genotype by choosing a high-carbohydrate and low-fat diet. CLINICAL TRIAL REGISTRATION http:www.clinicaltrials.gov. Unique identifier: NCT00072995. |
| File Format | PDF HTM / HTML |
| DOI | 10.1161/CIRCULATIONAHA.111.025767 |
| PubMed reference number | 21747052 |
| Journal | Medline |
| Volume Number | 124 |
| Issue Number | 5 |
| Alternate Webpage(s) | http://circ.ahajournals.org/content/circulationaha/124/5/563.full.pdf?download=true |
| Alternate Webpage(s) | http://circ.ahajournals.org/content/circulationaha/early/2011/07/11/CIRCULATIONAHA.111.025767.full.pdf |
| Alternate Webpage(s) | http://circ.ahajournals.org/content/circulationaha/early/2011/07/11/CIRCULATIONAHA.111.025767.full.pdf?download=true |
| Alternate Webpage(s) | https://doi.org/10.1161/CIRCULATIONAHA.111.025767 |
| Journal | Circulation |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
