Introduction
obesity, weight loss, WL
OBESITY, SEVERE OBESITY, INSULIN RESISTANCE, SECONDARY
The 2017–2018 National Health and Nutrition Examination Survey (NHANES) showed that almost 43% of US adults aged 20 and over have obesity, including 9.0% with severe obesity, and another 31% are overweightMany weight loss (WL) strategies emphasize either high-carbohydrate (and low-fat) or high-fat (low-carbohydrate) dietsThe present RCT tested the hypothesis that participants assigned to a diet corresponding to their a priori-determined (fat-responsive or carbohydrate-responsive) genotype would lose more weight over 12 weeks than those assigned to a diet discordant with their genotype. Further, we aimed to analyze those with a fat-responsive genotype (subsequently “fat-responders”) and carbohydrate-responsive genotype (subsequently “carbohydrate-responders”) separately. We hypothesized that (1) fat-responders would lose more weight on the high-fat vs. high-carbohydrate diet and conversely (2) carbohydrate-responders would lose more weight on the high-carbohydrate vs. high-fat diet. A secondary objective of the present RCT was to test the newly-developed genetic risk score to determine fat- and carbohydrate-responsive genotypes that was based on the current state-of-the-art in nutrigenomics. We also aimed to determine associations between baseline insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) and differential WL between the diets. These analyses were pursued as previous results were mixed with some studies finding that insulin resistance