Whole-Grain Staple Replacement and Cardiometabolic Phenotypes in Adults at High Risk of Type 2 Diabetes: An Extended Randomized-Trial Analysis with NHANES and Country-Level Context.

Adults at high risk of type 2 diabetes frequently show concurrent dyslipidemia, insulin resistance, and central adiposity before overt diabetes develops. We evaluated cardiometabolic responses to standardized whole-grain staple replacement and examined grain-quality patterns in free-living and country-level settings. This secondary exploratory analysis included 144 participants (48 per group) from a 12-week, three-arm randomized dietary trial. Participants were analyzed according to their randomized assignments to 100 g/day, 50 g/day, or control. Lipid, anthropometric, body composition, and composite cardiometabolic phenotypes were evaluated. Longitudinal and time-weighted cumulative effects were estimated using linear mixed-effects and regression models, with Benjamini-Hochberg false discovery rate (FDR) correction applied within the corresponding multiplicity domains. Complementary analyses included 30,769 NHANES adults without diabetes, including 12,169 with prediabetes, and descriptive country-level data on whole-grain intake, high-FPG-attributable diabetes burden, and cereal supply. Within the extended phenotype panel, HWG versus control time-weighted cumulative effects included triglycerides (β = -0.220, 95% CI -0.397 to -0.043; FDR-adjusted p = 0.047), the atherogenic index of plasma (β = -0.125, -0.191 to -0.060; FDR-adjusted p = 0.002), and the triglyceride-glucose index (β = -0.301, -0.429 to -0.173; FDR-adjusted p < 0.001). Conventional lipid components showed distinct temporal responses. In NHANES, higher whole-grain exposure and more favorable grain-quality ratios were associated with lower adiposity- and insulin resistance-related phenotypes, whereas refined-grain exposure generally showed the opposite pattern. Country-level analyses showed marked heterogeneity in whole-grain intake, diabetes burden, and cereal supply context. Standardized whole-grain staple replacement was associated with short-term changes across several cardiometabolic dimensions in adults at high risk of type 2 diabetes, with the clearest extended-phenotype signals involving triglyceride-related and glucose-triglyceride coupling measures. NHANES identified cross-sectional grain-quality associations in free-living adults; country-level analyses described heterogeneity in whole-grain intake, diabetes burden, and cereal supply context.