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.

Background: Sarcopenia is a major cause of physical decline in older adults with type 2 diabetes (T2DM). Nutritional interven-tions, especially high-protein diets, are clinically recommended, but their long-term effectiveness and tolerability in very elderly diabetes patients remain unclear. Objective: We investigated whether an 18-month dietary intervention improves muscle mass and strength in patients aged ≥75 years with T2DM, and whether serum amino acids (AAs) and hormonal profiles reflect these changes. Methods: We enrolled 44 subjects aged ≥75 years with T2DM. Nutritional counseling was provided at baseline, 6, 12, and 18 months. Skeletal muscle index (SMI), grip strength, and gait speed as well as fasting plasma hormones and AAs were assessed at each visit. Sex-normalized SMI (nSMI) and grip strength (nGrip) were calculated, and multiple linear regression analysis was per-formed. Results: SMI improved at 6 and 12 months; gait speed improved at 6 months. Grip strength showed a significant increase at 12 months. Changes in ΔnSMI were independently associated with Δglucagon (positive) and ΔC-peptide (CPR)(negative), while Δn-Grip was inversely associated with Δglucagon at 6 months. Increases in two AAs were linked to reduced ΔnSMI and increases in 16 AAs were linked to reduced ΔnGrip. Renal and hepatic function remained stable over 18 months. Conclusion: Long-term dietary intervention is effective for improving sarcopenia-related outcomes in very elderly patients with T2DM while maintaining general metabolic stability. Early changes in glucagon, CPR, and AAs levels may contribute to these improvements.