Abstract 14433: Dietary Protein Intake Modifies the Genetic Risk on Insulin Resistance in the Pounds Lost Trial
Introduction: Genome-wide association studies have identified a group of genetic variants associated with insulin resistance (IR).
Hypothesis: Participants with genetic risk of IR may respond differently to diet interventions on weight loss and improvement of insulin sensitivity.
Methods: The Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial is a randomized, controlled 2-year weight-loss trial. We assessed the genetic risk of IR by a genetic risk score (GRS) based on 17 IR variants, and examined the genetic effect on changes in body weight and insulin sensitivity according to diet intervention groups in 692 overweight or obese adults. All models were adjusted for age, sex, ethnicity, and the baseline value for the respective outcome trait.
Results: We observed significant interactions between the GRS and dietary protein on 6-month changes in weight, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) and HOMA-insulin sensitivity (HOMA-S) (P for interaction=0.03, 0.02, 0.02, and 0.03, respectively). In the low-protein diet group, participants with higher GRS showed less reduction in insulin (P=0.03) and HOMA-IR (P=0.03); whereas in the high-protein group, changes in insulin and HOMA-IR were not statistically different across the GRS tertiles (Figure). Fasting insulin levels rebounded in parallel with weight regain after 6 months, and the interactions between the GRS and diet interventions on weight change and improvement in insulin sensitivity were attenuated.
Conclusions: Individuals with higher genetic risk of IR may benefit less in improvement of insulin sensitivity than those with lower genetic risk when choosing an energy-restricted low-protein weight-loss diet.
Author Disclosures: T. Wang: None. Y. Heianza: None. D. Sun: None. J. Rood: None. G.A. Bray: None. F.M. Sacks: None. L. Qi: None.
- © 2016 by American Heart Association, Inc.