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. 2016 Jun 1;7:200. doi: 10.3389/fphys.2016.00200

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.