Increased serum levels of advanced glycation end products are negatively associated with relative muscle strength in patients with type 2 diabetes mellitus

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.

Osteosarcopenia in the Spine Beyond Bone Mineral Density

“…Although we did not obtain a direct muscle strength measurement, there is evidence that elevated serum AGE is associated with decreased muscle strength. 61 This suggests a possible link between increased fAGE cross-link density in the bone and intramuscular fat in paraspinal muscles reported in our investigation. Also, our study was based on a cross-sectional observation, and causal relationships cannot be determined.…”

“…Nevertheless, our patient population can be well-characterized using ambulation status, recreational activity status, and the modified 5-item frailty index. Although we did not obtain a direct muscle strength measurement, there is evidence that elevated serum AGE is associated with decreased muscle strength 61 . This suggests a possible link between increased fAGE cross-link density in the bone and intramuscular fat in paraspinal muscles reported in our investigation.…”

Endogenous advanced glycation end products in the pathogenesis of chronic diabetic complications

“…AGEs are elevated in the presence of distal sensorimotor polyneuropathy (DSPN) among T2 DM patients, and AGEs are linked with the severity of DSPN, according to observational studies ( Papachristou et al, 2021 ). Decreased relative muscle strength was also observed in patients with T2 DM with elevated serum levels of AGEs ( Wu et al, 2022 ).…”

The impact of grip strength, waist circumference, and body mass index on Hemoglobin A1c value: Cross‐sectional study using outpatient clinical data in Japanese elderly patients with type 2 diabetes mellitus

“…High serum levels of advanced glycation end products (AGEs) were reported to have a negative association with relative muscular strength in patients with T2DM after adjustment was made for certain clinical factors. 17 Serum AGEs Figure 1 Adjusted odds ratio for controlled hemoglobin A 1c among elderly participants with T2DM who were categorized into the tertiles of grip strength (GS) (a), waist circumference (WC) (b), and body mass index (BMI) (c). Values are presented as odds ratios and 95% confidence intervals.…”

“…Accordingly, GS and its potential association with skeletal muscular strength and muscle mass, a significant site of glucose disposal and insulin action, might be indirectly related to the management of T2DM in the elderly. High serum levels of advanced glycation end products (AGEs) were reported to have a negative association with relative muscular strength in patients with T2DM after adjustment was made for certain clinical factors 17 . Serum AGEs were strongly associated with HbA 1c 18 because HbA 1c is an Amadori rearrangement substance produced by the same process as that in AGEs 19 .…”