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Significant reductions in insulin resistance (IR) can be achieved by either calorie restriction or by the increase of lean mass. However, calorie restriction usually results in significant loss of lean mass. A 6-week randomized controlled feeding trial was conducted to determine if a calorie-restricted, high-protein diet (~125 g protein/day consumed evenly throughout the day) using novel functional foods would be more successful for reducing IR in comparison to a conventional diet (~80 g protein/day) with a similar level of calorie restriction. Healthy adults (age 20–75 years; body mass index, 20–42 kg/m) with raised triglyceride/high-density lipoprotein ratios were randomly assigned to the control group (CON: test foods prepared using gluten-free commercial pasta and cereal) or to the high-protein group (HPR: test foods prepared using novel high-protein pasta and cereal both rich in wheat gluten). Mean weight loss did not differ between groups (−2.7 ± 2.6 and −3.2 ± 3.0 kg for CON (= 11) and HPR (= 10) respectively,= 0.801); however, the 6-week change in fat-free mass (FFM) differed significantly between groups (−0.5 ± 1.5 and +1.5 ± 3.8 kg for CON and HPR respectively,= 0.008). IR improved in HPR vs. CON participants (homeostasis model assessment-estimated insulin resistance [HOMAIR] change: −1.7 ± 1.4 and −0.7 ± 0.7 respectively;= 0.020). The change in HOMA-IR was related to the change in FFM among participants (= −0.511,= 0.021). Thus, a high-protein diet using novel functional foods combined with modest calorie restriction was 140% more effective for reducing HOMA-IR in healthy adults compared to a lower protein, standard diet with an equal level of calorie restriction. View Full-Text