Table 1.
Summary of selected studies analyzing levels of AGEs in association with presence of varying stages of diabetic retinopathy.
| Subtance(s) analyzed | Reference/study design | Patient population | Key findings | Method of analysis |
|---|---|---|---|---|
| AGEs, sRAGE, and pentosidine (serum) | Kerkeni et al., 2012/cross sectional | N = 130 (40 NPDR, 60 PDR, 30 healthy controls) | Serum AGEs, sRAGE, and pentosidine levels significantly higher in patients with PDR vs. NPDR (p = 0.001, p = 0.01, and p = 0.005) | ELISA (Abo Switzerland Co. Ltd) |
| no comparison against diabetics with no eye disease | ||||
| Furosine (glycated collaged) and CML (skin biopsy) | Genuth et al., 2005/prospective | N = 216 (65 NDR baseline, 57 with baseline mild to mod DR or microalbuminuria) + 40 age matched healthy controls | Furosine + CML predicted progression of retinopathy independent of HbA1c (χ2 = 59.4, p < 0.0001) | HPLC of prepared skin biopsy specimens |
| hydroimidazole (methylglyoxal derived AGE) (serum) | Fosmark et al., 2006/cross sectional | N = 227 (89 NPDR, 52 PDR, 86 no DR) | Serum levels of hydroimidizole higher in PDR vs. NDR (p = 0.002); significant increase in NPDR vs. NDR (p = 0.008) | Specific solid-phase, time-resolved competitive immunoassays (Delfia Wallac, Turku, Finland) |
| Nε-CML (serum) | Boehm et al., 2004/case control | N = 929 (81 NDR, 56 NPDR, 792 healthy controls) | Serum CML provided progressive risk marker for PDR (OR 24.5)independent of HbA1c; serum CML >1000 ng/ml strongly related to presence of clinically significant | Competition based ELISA (mouse monoclonal 4G9; Alteon, ramsey, NJ, USA) |
| macular edema; serum CML levels elevated in DR vs. controls (p < 0.0001) | ||||
| N-epsilon-CML (Nε-CML) (serum) | Mishra et al., 2015/cross sectional | N = 80 (20 NDR, 20 NPDR, and 20 PDR, 20 healthy controls) | Mean levels of Nε-CML increased significantly with increasing severity of DR (p < 0.001 between controls, diabetics with no eye disease, NPDR, and PDR, respectively) | ELISA (Human Nε-CML ELISA kit from Uscn, Life Science Inc, USA) |
| N-epsilon-CML (Nε-CML) (serum) | Choudhuri et al., 2013/cross sectional | N = 379 (102 NDR, 77 NPDR, 105 PDR, 95 healthy controls) | Significant elevation of serum AGEs and Nε-CML in subjects with PDR (0 < 0.0001) and NPDR (p < 0.0001) compared to NDR | Nε-CML: ELISA (Cell Biolabs kit(catalog No STA 316) |
| AGEs (serum) | AGEs: ELISA(Cell Biolabs, SanDiego, CA) (kit no STA 317) | |||
| N-CML and pentosidine (serum) | Hirata and Kubo, 2004/cross sectional | N = 97 diabetic patients (42 NDR, 18 NPDR, 37 PDR) | Significantly higher blood levels of CML and pentosodine in PDR group compared to NDR (p < 0.01 and p < 0.05, respectively), no significant difference in CML or pentosidine levels between no DR and NPDR or between NPDR and PDR. | ELISA (assays prepared in own lab) |
| sRAGE and pentosidine (plasma) | Ng et al., 2013/cross sectional | N = 606 (171 NDR, 200 with DR (125 with NPDR; 75 with PDR), 235 healthy controls) | sRAGE/pentosidine ratio in DR patients was significantly lower than the ratio in diabetics without DR (p < 0.001); l higher levels of pentosidine, sRAGE, and sRAGE/pentosidine ratio in PDR compared to NPDR (p < 0.05, 0 < 0.01, and P < 0.01, respectively) | Standard ELISA sandwich kit: pentosidine (USCNK Life Scinece Inc, Wu Han, China); sRAGE (Biovendor Laboratorni Medicina akciova spolecnost, Brno, Reckovice, Czech Republic) |
CML, carboxymethyl-lysine; sRAGE, soluble receptors for advanced glycation end-products; NDR, diabetic with no retinopathy, NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy.