Effects of High-Protein Nutritional Guidance on Sarcopenia-Related Parameters in Individuals Aged ≥ 75 Years with Type 2 Diabetes: An Exploratory Single-Arm Pre–Post Intervention Study

Background: Sarcopenia and metabolic deterioration are major health concerns in adults aged ≥ 75 years with type 2 diabetes (T2DM), a population characterized by anabolic resistance, reduced dietary intake, and limited renal reserve. Optimizing protein nutrition may support muscle maintenance in this high-risk group, but clinical evidence for individualized high-protein guidance in the oldest-old population remains limited. Objective: We investigated whether an 18-month dietary intervention improves muscle mass and strength in adults aged ≥ 75 years with T2DM and whether serum amino acid (AA) and hormonal profiles reflect these changes. Methods: In this 18-month, single-arm, prospective intervention study, 44 community-dwelling adults aged ≥ 75 years with T2DM received individualized, dietitian-led nutritional guidance targeting a protein intake of approximately 1.4 g/kg ideal body weight (IBW)/day. Assessments at baseline and every 6 months included body composition, muscle strength, renal function, and fasting serum amino acid and hormonal profiles. Longitudinal changes were analyzed using paired t-tests and linear mixed-effects models. This trial was registered in the UMIN Clinical Trials Registry (UMIN000044687). Results: Skeletal muscle index and grip strength showed significant improvements at specific time points during follow-up (both p < 0.05), while gait speed improved at 6 months. Renal function remained clinically stable (eGFRcreat slope: +0.18 mL/min/1.73 m2/year; eGFRcys slope: −2.97 mL/min/1.73 m2/year), with no significant increase in CKD stage. Changes in glucagon correlated positively and C-peptide negatively with changes in skeletal muscle index, whereas glucagon was inversely associated with grip strength. Serum fibroblast growth factor 21 (FGF21) levels decreased over time, suggesting metabolic adaptation to the intervention. Conclusions: Individualized high-protein nutritional guidance for 18 months improved sarcopenia-related parameters, including skeletal muscle index and grip strength, without clinically significant deterioration of renal function in adults aged ≥ 75 years with T2DM. These findings support the feasibility and safety of protein-focused dietary counseling as a strategy to preserve muscle health in advanced age.