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Abstract Background In this study, we investigated whether serum levels of advanced glycation end products (AGEs) independently correlated with relative muscle strength after adjustment for clinical variables including diabetic peripheral neuropathy in patients with type 2 diabetes. Relative muscle strength was defined as muscle strength (in decinewtons, dN) divided by total muscle mass (in kg). Methods We enrolled 152 ambulatory patients with type 2 diabetes. Each participant underwent measurements of muscle strength and total muscle mass. Serum levels of AGEs were determined. The Michigan Neuropathy Screening Instrument Physical Examination (MNSI-PE) was performed to assess diabetic peripheral neuropathy. Results The participants were divided into three groups on the basis of tertiles of serum AGEs levels. Significant differences were observed among the three groups in relative handgrip strength (71.03 ± 18.22, 63.17 ± 13.82, and 61.47 ± 13.95 dN/kg in the low-tertile, mid-tertile, and high-tertile groups, respectively, P = 0.005). The relative muscle strength of the ankle plantar flexors was higher in the low-tertile group than in the mid-tertile and high-tertile groups (107.60 ± 26.53, 94.97 ± 19.72, and 94.18 ± 16.09 dN/kg in the low-tertile, mid-tertile, and high-tertile groups, respectively, P = 0.002). After adjustment for MNSI-PE score and other clinical variables in partial correlation analysis, the correlations between serum levels of AGEs and the relative muscle strength of handgrip, ankle dorsiflexor, and ankle plantar flexor remained significant. Serum AGEs level was the only variable that remained significantly related to the relative muscle strength of handgrip, ankle dorsiflexor, and ankle plantar flexor when AGEs level, fasting plasma glucose, and glycated hemoglobin (HbA1c) were entered into multiple regression models simultaneously. Conclusions After adjustment for multiple factors including diabetic peripheral neuropathy, this study demonstrated that increased serum levels of AGEs were independently associated with decreased relative muscle strength in patients with type 2 diabetes. Compared with fasting plasma glucose and HbA1c, serum level of AGEs is more strongly associated with relative muscle strength.