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Table 3 Study characteristics

From: The Contribution of Advanced Glycation End product (AGE) accumulation to the decline in motor function

First author/year of publication Design Population n =, age, gender and co-morbidity AGE/RAGE Circulating/Tissue levels, Tissue type Musculoskeletal outcome Physical performance and functioning outcome Main findings and Outcome statistics:
Semba et al. 2010 [45] Cross-sectional Community dwelling older adults N = 944 (416 M, 528 F), aged 75 ± 7 years Circulating plasma CML (cut-off value for high level = 424 ng/mL) - Walking speed (cut-off value for slow walking <0.79 m/s) Risk for slow walking speed with high AGE’s level: OR = 1.60 (95 % CI:1.02–2.52)*c OR = 1.87 (95 % CI:1.15–3.04)*c (+ adjusted for DM2)
Sun et al. 2012 [46] Longitudinal observational study with 30 month follow-up Moderately to severe disabled community dwelling F, N = 394, aged 76 ± 8 years Circulating serum CML (cut-off value for high level = 689.1 ng/mL) - Walking disability (inability or slow speed) (cut-off value for slow walking <0.4 m/s) Walking disability risk with high AGE’s level: HR = 1.68 (95 % CI: 1.11–2.52)* HR = 1.63 (95 % CI: 1.06–2.49)*c(1) HR = 1.56 (95 % CI: 1.04–2.36)*c(2) HR = 1.54 (95 % CI: 1.04–2.29)*c(3) HR = 1.46 (95 % CI: 0.95–2.23) NS.c(4)
Whitson et al., 2014 [47] Longitudinal observational study with 14 year follow-up for ADL disability. Cross-sectional for physical frailty components Community dwelling older adults N = 3373 (1344 M, 2029 F) aged 78.1 ± 4.8 years Circulating serum CML (cut-off value for high level = 620 ng/mL) ADL disability Physical frailty ≥3 of following characteristics: 1. Low handgrip strength 2. Unintentional weight loss 3. Low physical activity 4. Exhaustion 5. Slow walking speed ADL disability risk with high AGE’s level: HR = 1.08 (95 % CI: 1.03–1.13)*b HR = 1.10 (95 % CI: 1.05–1.15)*c HR = 1.05 (95 % CI: 1.01–1.11)*c (+ adjusted for arthritis, cognition, kidney disease) Physical frailty risk with high AGE’s level in men: HR = 1.30 (95 % CI: 1.14–1.48)*b HR = 1.24 (95 % CI: 1.07–1.45)*c HR = 1.10 (95 % CI: 0.92–1.32) NS.c (+ adjusted for arthritis, cognition, kidney disease) Physical frailty risk with high AGE’s level in women: HR = 1.06 (95 % CI: 0.91–1.23) NS.b HR = 1.06 (95 % CI: 0.90–1.24) NS.c HR = 0.91 (95 % CI: 0.77–1.07) NS.c (+ adjusted for arthritis, cognition, kidney disease)
Shah et al. 2015 [50] Cross-sectional DM2 patients N = 26 (13 M, 13 F) aged 64,5 ± 6,8 Non DM N = 26 (13 M, 13 F) aged 64,2 ± 5,8 AGE-type not defined (skin tissue auto fluorescent Crosslinking AGE’s) Shoulder flexor strength 1. Upper extremity disability 2. Upper extremity function Correlation flexor strength and AGE’s level: R = 0,07 NS Correlation Upper extremity disability and AGE’s level: R = 0,51* Correlation Upper extremity function and AGE’s level: − humerothoracic elevation R = −0.44* − glenohumeral external rotation R = −0.32 NS
Dalal et al. 2009 [43] Cross- sectional Moderately to severe disabled community dwelling F, N = 559, aged 76 ± 8 years Circulating serum CML (cut-off value for high level = 0.68 mg/mL) Handgrip strength - Group difference high vs. low AGE’s level: 18.2 (6.4) kg. vs. 20.1 (6.2) kg., Beta −1.88 (SE = 0.65)* 18.6 kg vs. 20.0 kg, Beta −1.31 (SE = 0.61)*c
De La Maza et al. 2008 [49] Cross-sectional Healthy M, N = 21 − Weight maintainers, N = 10, − aged 41 ± 4 years − Weight gainers, N = 7, aged 42 ± 5 years − Elderly, N = 4, aged 67 ± 2 years Skeletal muscle tissue CML/RAGE Handgrip strength - Correlation grip strength and AGE’s level: R = −0,54*
Momma et al. 2011 [44] Cross-sectional Healthy M, aged 46 years (37–56)a - Grip strength analysis, N = 232 - Leg extension analysis, N = 138 AGE-type not defined (skin tissue auto fluorescent Crosslinking AGE’s) (cut-off value for high level = 2.09–4.44 AF) 1. Handgrip strength 2. Leg extension power - Group difference high vs low AGE’s level: 1. Muscle (handgrip)strength: 41.7 (95 % CI: 40.3- 43.1) kg. vs. 44.5 (95 % CI: 43.2- 45.9) kg.*c ES = 0.45 2. Muscle (leg extension) power: 16.0 (95 % CI: 14.9- 17.1) W/kg. vs. 17.8 (95 % CI: 16.6- 19.1) W/kg.*c ES = 0.44
Tanaka et al. 2015 [48] Cross-sectional DM2 patients, F, N = 133, aged 66,8 ± 9,5 years Circulating serum Pentosidine 1. Upper extremity muscle mass 2. Lower extremity muscle mass 3. Relative skeletal muscle mass index   Association UMM and AGE’s level: R = −0.11 NS Beta −0.11 NS Association LMM and AGE’s level: R = −0.21* Beta −0.18* Association RSMI and AGE’s level: R = −0.18* Beta −0.27*
  1. M Male, F Female, yrs years, AGE Advanced Glycation End product, RAGE Receptor for Advanced Glycation End products, CML Carboxy-methyl-Lysine, DM2 Diabetes Mellitus type 2
  2. aMedian (interquartile range), ES Effect Size, OR Odds Ratio, HR Hazard Risk
  3. bmultivariate adjusted for demographics
  4. cidem + multivariate adjusted for potential confounders. NS Not significant. (1) All women with missing data had multiple simulations to impute walking disability status prior to death. (2) Inverse probability weighting method. (3) All women with missing data treated as developing walking disability prior to death. (4) All women with missing data treated as censored, that is, no walking disability prior to death, UMM Upper extremity Muscle Mass, LMM Lower extremity Muscle Mass, RSMI Relative Skeletal Muscle Mass Index
  5. * P < 0,05