Wang, TiangeHuang, TaoZheng, YanRood, JenniferBray, George A.Sacks, FrankQi, Lu2016-11-182016Wang, Tiange, Tao Huang, Yan Zheng, Jennifer Rood, George A. Bray, Frank M. Sacks, and Lu Qi. 2016. “Genetic variation of fasting glucose and changes in glycemia in response to 2-year weight-loss diet intervention: the POUNDS Lost trial.” International journal of obesity (2005) 40 (7): 1164-1169. doi:10.1038/ijo.2016.41. http://dx.doi.org/10.1038/ijo.2016.41.0307-0565http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407874Objective: Weight loss intervention through diet modification has been widely used to improve obesity-related hyperglycemia; however, little is known about whether genetic variation modifies the intervention effect. We examined the interaction between weight-loss diets and genetic variation of fasting glucose on changes in glycemic traits in a dietary intervention trial. Research Design and Methods The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial is a randomized, controlled 2-year weight-loss trial. We assessed overall genetic variation of fasting glucose by calculating a genetic risk score (GRS) based on 14 fasting glucose-associated single nucleotide polymorphisms, and examined the progression in fasting glucose and insulin levels, and insulin resistance and insulin sensitivity in 733 adults from this trial. Results: The GRS was associated with 6-month changes in fasting glucose (P<0.001), fasting insulin (P=0.042), homeostasis model assessment of insulin resistance (HOMA-IR, P=0.009) and insulin sensitivity (HOMA-S, P=0.043). We observed significant interaction between the GRS and dietary fat on 6-month changes in fasting glucose, HOMA-IR and HOMA-S after multivariable adjustment (P-interaction=0.007, 0.045, and 0.028, respectively). After further adjustment for weight loss, the interaction remained significant on change in fasting glucose (P=0.015). In the high-fat diet group, participants in the highest GRS tertile showed increased fasting glucose, whereas participants in the lowest tertile showed decreased fasting glucose (P-trend<0.001); in contrast, the genetic association was not significant in the low-fat diet group (P-trend=0.087). Conclusions: Our data suggest that participants with a higher genetic risk may benefit more by eating a low-fat diet to improve glucose metabolism.en-USJournal Article2016-11-1810.1038/ijo.2016.41