The aim of the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial was to investigate whether the rs2943641 variant in the IRS1 gene, which has recently been linked to insulin resistance and hyperinsulinemia, modifies the long-term changes in insulin resistance and body weight in response to weight-loss diets.
Researchers from several sites in the United States genotyped this variant in 738 overweight adults. Eligible participants had been randomly assigned to one of four diets varying in macronutrient contents. The diet lasted 2 years, during which progress in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and weight loss by genotypes were assessed.
Among patients in the high-carbohydrate diet group, 6-month results indicated that participants with the risk-conferring CC genotype experienced greater decreases in insulin (P=.009), HOMA-IR (P=.015) and weight loss (P=.018) than those without this genotype. Among patients in the low-carbohydrate diet group, an opposite genotype effect on changes in insulin and HOMA-IR (P≤.05) was observed.
The other two diet groups did not experience significant differences across genotypes. "The tests for genotype by intervention interactions were all significant (P<.05)," the researchers said.
The genotype effect on changes in insulin and HOMA-IR continued to be significant at 2 years among those on the diet with the highest carbohydrate content (P<.05). The 2-year results also indicated that the high-carbohydrate diet yielded greater improvements in insulin and HOMA-IR (P for genotype-time interaction ≤.009) in participants with the CC genotype than those without this genotype.
"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," the researchers wrote.
Qi Q. Circulation. 2011;124:563-571