Association between the longitudinal plasma AGEs at the three time points and outcomes in Cox PH models adjusted for age, duration of T1D, sex, BP, BMI and mean updated HbA1c, with the pAGEs and the risk factors included as time-varying covariates
| AGEs | PDR (n=141) | CSME (n=160) | Sustained eGFR <60 (n=48) | Sustained microalbuminuria (n=149) | Cardiac autonomic neuropathy (n=196) | Confirmed clinical neuropathy (n=142) | ||||||
| HR* | P value | HR* | P value | HR* | P value | HR* | P value | HR* | P value | HR* | P value | |
| Fructose-lysine | 2.03 (1.30 to 3.19) | 0.0019 | 1.38 (0.90 to 2.10) | 0.1388 | 1.79 (0.86 to 3.71) | 0.1176 | 1.75 (1.14 to 2.70) | 0.0113 | 1.20 (0.80 to 1.79) | 0.3753 | 1.93 (1.22 to 3.03) | 0.0047 |
| Glucosepane | 1.53 (1.09 to 2.15) | 0.0147 | 1.14 (0.81 to 1.59) | 0.4529 | 1.02 (0.68 to 1.53) | 0.9238 | 1.36 (0.96 to 1.93) | 0.0878 | 1.02 (0.76 to 1.37) | 0.9025 | 1.77 (1.22 to 2.56) | 0.0027 |
| CML | 2.03 (1.28 to 3.20) | 0.0024 | 1.61 (1.07 to 2.43) | 0.0230 | 1.79 (0.85 to 3.76) | 0.1267 | 1.61 (1.06 to 2.44) | 0.0268 | 0.93 (0.71 to 1.22) | 0.6026 | 1.16 (0.78 to 1.74) | 0.4600 |
| MG-H1 | 1.20 (0.94 to 1.55) | 0.1497 | 0.96 (0.76 to 1.20) | 0.7179 | 0.71 (0.47 to 1.08) | 0.1083 | 0.97 (0.75 to 1.25) | 0.8165 | 0.97 (0.80 to 1.19) | 0.7834 | 0.91 (0.72 to 1.16) | 0.4342 |
| CEL | 1.15 (0.91 to 1.44) | 0.2364 | 1.10 (0.90 to 1.34) | 0.3545 | 1.35 (0.89 to 2.04) | 0.1635 | 0.99 (0.82 to 1.20) | 0.9505 | 0.95 (0.81 to 1.12) | 0.5565 | 1.08 (0.87 to 1.34) | 0.4876 |
| G-H1 | 0.91 (0.62 to 1.34) | 0.6383 | 0.76 (0.54 to 1.07) | 0.1167 | 0.71 (0.38 to 1.35) | 0.2960 | 1.15 (0.76 to 1.76) | 0.5090 | 0.97 (0.68 to 1.38) | 0.8543 | 1.13 (0.74 to 1.72) | 0.5725 |
| Pentosidine | 1.20 (1.04 to 1.38) | 0.0150 | 1.11 (0.97 to 1.26) | 0.1287 | 0.94 (0.76 to 1.16) | 0.5498 | 0.98 (0.85 to 1.11) | 0.7055 | 0.97 (0.87 to 1.09) | 0.6552 | 0.96 (0.84 to 1.09) | 0.5190 |
| MOLD | 1.10 (0.99 to 1.21) | 0.0807 | 1.07 (0.97 to 1.17) | 0.1758 | 1.01 (0.85 to 1.20) | 0.8917 | 0.99 (0.90 to 1.09) | 0.8426 | 1.04 (0.96 to 1.13) | 0.3724 | 0.99 (0.90 to 1.08) | 0.7854 |
| o-Tyrosine | 1.01 (0.79 to 1.29) | 0.9344 | 1.25 (0.96 to 1.62) | 0.0988 | 0.73 (0.50 to 1.08) | 0.1142 | 1.24 (0.93 to 1.64) | 0.1394 | 0.98 (0.78 to 1.23) | 0.8623 | 1.11 (0.84 to 1.47) | 0.4567 |
| 3-Nitrotyrosine | 1.02 (0.91 to 1.14) | 0.7445 | 0.96 (0.87 to 1.06) | 0.4335 | 0.98 (0.81 to 1.19) | 0.8595 | 0.98 (0.88 to 1.10) | 0.7577 | 0.99 (0.90 to 1.09) | 0.8563 | 1.00 (0.90 to 1.12) | 0.9784 |
| MetSOX | 1.41 (0.92 to 2.17) | 0.1159 | 0.91 (0.64 to 1.28) | 0.5718 | 1.93 (0.90 to 4.15) | 0.0918 | 1.49 (1.00 to 2.21) | 0.0511 | 1.36 (0.97 to 1.92) | 0.0763 | 1.05 (0.73 to 1.51) | 0.8145 |
*HRs are generated using a Cox proportional hazards model. HRs and the 95% CIs are per unit increase in log AGE. Associations with p values <0.05 are in bold. For units see figure 1.
AGE, advanced glycation end product; BMI, body mass index; BP, blood pressure; CEL, carboxyethyl-lysine; CML, carboxymethyl-lysine; CSME, clinically significant macular edema; eGFR, estimated glomerular filtration rate; G-H1, glyoxal hydroimidazolone 1; HbA1c, hemoglobin A1c; MetSOX, methionine sulfoxide; MG-H1, methylglyoxal hydroimidazolone 1; MOLD, methylglyoxal lysine dimer; pAGEs, protein-bound AGEs; PDR, proliferative diabetic retinopathy; PH, proportional hazard; T1D, type 1 diabetes.