Diabetes mellitus has reached epidemic proportions worldwide, with the global figure of people with diabetes projected to increase from 246 million in 2007 to 370 million by 2030. As the prevalence of diabetes continues to rise, diabetic complications have become one of the most challenging health problems of the 21st century. Among these complications, diabetic nephropathy and diabetic retinopathy represent the most devastating microvascular consequences, accounting for substantial disability, blindness, and end-stage renal disease.

Diabetic nephropathy is the most common cause of end-stage renal disease worldwide, with approximately 25–40% of type 1 or type 2 diabetic patients developing this complication within 20–25 years of diabetes onset. Similarly, diabetic retinopathy remains the prevailing cause of registerable blindness in the working population of developed countries. Despite advances in glycemic and blood pressure control, the burden of these complications continues to grow, highlighting the urgent need for a deeper understanding of their underlying biochemical mechanisms.

Chronic hyperglycemia triggers a cascade of metabolic and hemodynamic derangements, including increased formation of advanced glycation end products (AGEs), enhanced reactive oxygen species (ROS) generation, activation of protein kinase C (PKC), the polyol pathway, and the renin-angiotensin system (RAS). Among these, the AGE-RAGE-oxidative stress axis has emerged as a particularly important pathogenic pathway.

Advanced glycation end products are a complex and heterogeneous group of compounds formed through non-enzymatic glycation reactions between reducing sugars and the amino groups of proteins, lipids, and nucleic acids. Under hyperglycemic conditions, the formation of AGEs is markedly accelerated. These reactions not only modify the structure and function of proteins but also cause intramolecular and intermolecular cross-link formation. AGEs can form on the amino groups of proteins, lipids, and DNA through a number of complex pathways, including nonenzymatic glycation by glucose and reaction with metabolic intermediates and reactive dicarbonyl intermediates.

The pathogenic effects of AGEs are mediated through two principal mechanisms. First, AGE modification of proteins may produce changes in charge, solubility, and conformation, leading to molecular dysfunction as well as disrupting interactions with other proteins. Second, AGEs interact with specific receptors, most notably the receptor for advanced glycation end products (RAGE), to influence the expression of growth factors and cytokines implicated in the progression of diabetic complications.

RAGE is a multiligand receptor of the immunoglobulin superfamily that binds not only to AGEs but also to high-mobility group box-1, S100/calgranulins, and other ligands. Engagement of AGEs with RAGE triggers various downstream signaling pathways, including activation of NADPH oxidase, nuclear factor-κB (NF-κB), and mitogen-activated protein kinases, leading to oxidative stress generation, inflammatory mediator release, and extracellular matrix deposition.

Oxidative stress plays a central role in this pathogenic cascade. The AGE-RAGE interaction generates reactive oxygen species, which in turn promotes further AGE formation, creating a vicious cycle of progressive tissue damage. As shown by recent studies, AGEs seem to be not merely "actors" but "directors" of processes leading to diabetic complications, serving as a bridge between intracellular and extracellular damage.

In the kidney, AGEs accumulate in the glomerular basement membrane, mesangial cells, endothelial cells, and podocytes. They contribute to the pathogenesis of diabetic nephropathy via multifactorial mechanisms including oxidative stress generation and overproduction of various growth factors and cytokines. Furthermore, cross-talk between AGEs and the renin-angiotensin system has been proposed to participate in diabetic nephropathy.

In the retina, AGEs accumulate in the diabetic retina where they have important effects on retinal vascular cell function in vitro and in vivo. The biochemical damages are induced by both RAGE-dependent and RAGE-independent mechanisms. AGEs induce the breakdown of redox balance and cause oxidative stress in retinal cells, exerting cytopathic effects in the progression of diabetic retinopathy.

This study aimed to investigate the biochemical relationships between circulating AGE levels, oxidative stress markers, and the development and progression of diabetic nephropathy and retinopathy in patients with type 2 diabetes mellitus.

This cross-sectional study was conducted in the Department of Biochemistry at a tertiary care center over a period of 6 months. A total of 280 patients with type 2 diabetes mellitus and 120 age- and sex-matched healthy controls were enrolled. Type 2 diabetes was diagnosed according to the American Diabetes Association criteria: fasting plasma glucose ≥126 mg/dL (7.0 mmol/L), 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during oral glucose tolerance test, HbA1c ≥6.5% (48 mmol/mol), or classic symptoms of hyperglycemia with random plasma glucose ≥200 mg/dL (11.1 mmol/L). Inclusion criteria for diabetic patients were: (1) age ≥30 years, (2) established diagnosis of type 2 diabetes for at least 5 years, (3) stable glycemic control (no change in antidiabetic medication in the preceding 3 months), and (4) provision of written informed consent. Exclusion criteria included: (1) type 1 diabetes mellitus, (2) acute diabetic complications (diabetic ketoacidosis, hyperosmolar hyperglycemic state), (3) acute infections or inflammatory conditions, (4) active malignancy, (5) pregnancy or lactation, (6) chronic kidney disease stage 5, and (7) use of antioxidant supplements within the preceding 3 months. Healthy controls were recruited from individuals undergoing routine health check-ups and had no history of diabetes, prediabetes, or any chronic disease. They were matched to the patient group for age (±5 years) and sex. All participants provided written informed consent, and the study was approved by the institutional ethics committee in accordance with the Declaration of Helsinki. The study cohort comprised 152 males (54.3%) and 128 females (45.7%) in the diabetic group, with a mean age of 58.7 ± 12.4 years. The mean duration of diabetes was 10.2 ± 6.8 years. Among diabetic patients, 132 (47.1%) were on metformin monotherapy, 84 (30.0%) on metformin plus sulfonylurea, 38 (13.6%) on insulin-based regimens, and 26 (9.3%) on other combinations. Biochemical Measurements Fasting blood samples (10 mL) were collected from all participants after an overnight fast of 10–12 hours. Samples were centrifuged at 3,000 rpm for 15 minutes within 2 hours of collection, and serum/plasma was aliquoted and stored at -80°C until analysis. Fasting blood glucose was measured by the glucose oxidase method (Roche Diagnostics, Basel, Switzerland). HbA1c was measured by high-performance liquid chromatography (HPLC) using the Bio-Rad Variant II Turbo system (Bio-Rad Laboratories, Hercules, CA, USA). Serum creatinine was measured by enzymatic method, and eGFR was calculated using the CKD-EPI equation. Serum AGEs: Serum AGE levels were measured using a competitive enzyme-linked immunosorbent assay (ELISA) with an anti-AGE monoclonal antibody (Trans Genic Inc., Kumamoto, Japan). The assay specifically recognizes AGE structures, with a detection range of 0.5–50 U/mL and intra- and inter-assay coefficients of variation <10%. Results were expressed as U/mL. Serum Malondialdehyde (MDA): Serum MDA levels were measured using the thiobarbituric acid reactive substances (TBARS) assay. Briefly, 0.5 mL of serum was mixed with 1.0 mL of 20% trichloroacetic acid and 1.0 mL of 0.67% thiobarbituric acid, heated in a boiling water bath for 30 minutes, and cooled. The resulting chromogen was extracted with n-butanol and measured spectrophotometrically at 532 nm. MDA concentration was calculated using a standard curve prepared with 1,1,3,3-tetramethoxypropane and expressed as μmol/L. Urinary 8-Hydroxy-2'-deoxyguanosine (8-OHdG): Urinary 8-OHdG levels were measured using a competitive ELISA kit (Highly Sensitive 8-OHdG Check ELISA, Japan Institute for the Control of Aging, Fukuroi, Japan). The assay employed a monoclonal antibody specific for 8-OHdG, with a detection range of 0.5–200 ng/mL and intra- and inter-assay coefficients of variation <8%. Results were normalized to urinary creatinine concentration and expressed as ng/mg creatinine. Urinary Albumin-to-Creatinine Ratio (UACR): Spot urine samples were collected for measurement of urinary albumin by immunoturbidimetric method and urinary creatinine by enzymatic method. UACR was calculated and expressed as mg/g. Microalbuminuria was defined as UACR 30–300 mg/g, and macroalbuminuria as UACR >300 mg/g. Assessment of Diabetic Complications Diabetic Nephropathy: Diabetic nephropathy was defined as persistent albuminuria (UACR ≥30 mg/g) or eGFR <60 mL/min/1.73 m² in the absence of other causes of kidney disease. Patients were classified into stages according to the KDIGO guidelines. Diabetic Retinopathy: All diabetic patients underwent comprehensive ophthalmic examination including fundus photography and optical coherence tomography performed by a trained ophthalmologist. Diabetic retinopathy was classified as non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria. Statistical Analysis Statistical analyses were performed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range (IQR) for non-normally distributed data. Categorical variables were presented as frequencies and percentages. Comparisons between diabetic patients and healthy controls were performed using independent Student's t-test for normally distributed variables and Mann-Whitney U test for non-normally distributed variables. Chi-square test was used for categorical variables. Correlations between biomarkers and clinical parameters were assessed using Pearson's or Spearman's correlation coefficients as appropriate. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of AGEs and oxidative stress markers for predicting diabetic complications. Area under the curve (AUC) values were calculated with 95% confidence intervals (CI). Multivariate logistic regression analysis was performed to identify independent predictors of diabetic nephropathy and retinopathy, adjusting for potential confounders including age, sex, diabetes duration, HbA1c, and BMI. A two-sided p-value <0.05 was considered statistically significant.

Baseline Characteristics

Table 1 presents the baseline demographic and clinical characteristics of the study population. Diabetic patients and healthy controls were well-matched for age (58.7 ± 12.4 vs. 57.2 ± 13.0 years, p=0.258) and sex distribution (54.3% vs. 51.7% male, p=0.621). As expected, diabetic patients had significantly higher fasting blood glucose (162.8 ± 44.2 vs. 94.6 ± 11.2 mg/dL, p<0.001), HbA1c (8.4 ± 1.8% vs. 5.3 ± 0.4%, p<0.001), and triglyceride levels (182.4 ± 84.6 vs. 128.2 ± 50.4 mg/dL, p<0.001) compared to controls.

Among diabetic patients, 112 (40.0%) had diabetic nephropathy (UACR ≥30 mg/g or eGFR <60 mL/min/1.73 m²), and 94 (33.6%) had diabetic retinopathy. The mean diabetes duration was significantly longer in patients with complications compared to those without (13.8 ± 7.2 vs. 8.4 ± 5.6 years, p<0.001).

Table 1: Baseline Demographic and Clinical Characteristics

Data presented as mean ± SD or n (%). BMI: body mass index; HbA1c: glycated hemoglobin; HDL: high-density lipoprotein; LDL: low-density lipoprotein; eGFR: estimated glomerular filtration rate; UACR: urinary albumin-to-creatinine ratio; IQR: interquartile range.

AGEs and Oxidative Stress Marker Levels

Table 2 presents the levels of AGEs and oxidative stress markers in diabetic patients and healthy controls. Serum AGE levels were nearly three-fold higher in diabetic patients compared to controls (12.8 ± 4.2 vs. 4.6 ± 1.8 U/mL, p<0.001), representing a 178% increase. MDA levels were elevated by 137% (4.92 ± 1.58 vs. 2.08 ± 0.72 μmol/L, p<0.001), and urinary 8-OHdG levels were elevated by 178% (9.12 ± 3.34 vs. 3.28 ± 1.12 ng/mg creatinine, p<0.001).

These findings are consistent with the established understanding that chronic hyperglycemia and oxidative stress in diabetes result in the formation and accumulation of AGEs, which have a wide range of chemical, cellular, and tissue effects that contribute to the development of microvascular complications.

Table 2: AGEs and Oxidative Stress Marker Levels

Data presented as mean ± SD. AGEs: advanced glycation end products; MDA: malondialdehyde; 8-OhdG: 8-hydroxy-2’-deoxyguanosine.

Correlations with Diabetic Nephropathy

Table 3 presents the correlation coefficients between AGEs, oxidative stress markers, and parameters of diabetic nephropathy. Serum AGE levels showed the strongest positive correlation with UACR (r=0.72, p<0.001) and the strongest negative correlation with eGFR (r=-0.68, p<0.001). MDA also showed significant correlations with UACR (r=0.58, p<0.001) and eGFR (r=-0.52, p<0.001). 8-OHdG demonstrated similar correlation patterns, though with slightly lower magnitudes.

These findings are consistent with previous reports that AGEs accumulate in the glomerular basement membrane, mesangial cells, endothelial cells, and podocytes in patients with diabetes, and are involved in the pathogenesis of diabetic nephropathy via oxidative stress generation.

Table 3: Correlations of AGEs and Oxidative Stress Markers with Nephropathy Parameters

*p<0.001 for all correlations. AGEs: advanced glycation end products; MDA: malondialdehyde; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; UACR: urinary albumin-to-creatinine ratio; eGFR: estimated glomerular filtration rate.

AGEs and Diabetic Retinopathy

Table 4 compares AGE and oxidative stress marker levels between diabetic patients with and without retinopathy. Patients with diabetic retinopathy (n=94, 33.6%) had significantly higher serum AGE levels compared to those without retinopathy (15.4 ± 4.6 vs. 11.2 ± 3.8 U/mL, p<0.001). MDA and 8-OHdG levels were also significantly elevated in patients with retinopathy.

Among patients with retinopathy, 62 (66.0%) had NPDR and 32 (34.0%) had PDR. Patients with PDR had the highest AGE levels (17.8 ± 4.2 U/mL), followed by NPDR (14.2 ± 4.0 U/mL) and no retinopathy (11.2 ± 3.8 U/mL), demonstrating a stepwise increase in AGE levels with retinopathy severity.

These findings support the role of AGEs in the pathogenesis of diabetic retinopathy, as AGEs are known to accumulate in the diabetic retina where they have important effects on retinal vascular cell function. Evidence points toward a pathogenic role for advanced glycation in the initiation and progression of diabetic retinopathy.

Table 4: AGEs and Oxidative Stress Markers by Retinopathy Status

Data presented as mean ± SD. AGEs: advanced glycation end products; MDA: malondialdehyde; 8-OHdG: 8-hydroxy-2'-deoxyguanosine.

Diagnostic Performance of AGEs

Table 5 presents the ROC curve analysis for predicting diabetic nephropathy and retinopathy. For diabetic nephropathy, serum AGEs demonstrated excellent diagnostic accuracy with an AUC of 0.912 (95% CI 0.876–0.948). At the optimal cut-off of 11.5 U/mL, AGEs showed a sensitivity of 84.8% and specificity of 87.5% for identifying diabetic nephropathy.

For diabetic retinopathy, serum AGEs achieved an AUC of 0.884 (95% CI 0.842–0.926), with a sensitivity of 81.9% and specificity of 83.3% at the cut-off of 13.2 U/mL. The combination of AGEs and MDA yielded higher AUC values for both nephropathy (0.934, 95% CI 0.904–0.964) and retinopathy (0.908, 95% CI 0.870–0.946).

Table 5: Diagnostic Performance of AGEs for Diabetic Complications

AUC: area under the curve; CI: confidence interval; AGEs: advanced glycation end products; MDA: malondialdehyde.

Multivariate Regression Analysis

Table 6 presents the results of multivariate logistic regression analysis for predictors of diabetic nephropathy. After adjusting for age, sex, BMI, diabetes duration, and HbA1c, elevated serum AGEs (OR 3.42, 95% CI 2.18–5.36, p<0.001) and elevated MDA (OR 2.68, 95% CI 1.72–4.18, p<0.001) remained independently associated with diabetic nephropathy. Diabetes duration (OR 1.52, 95% CI 1.18–1.96, p=0.002) and HbA1c (OR 1.64, 95% CI 1.28–2.10, p<0.001) also emerged as independent predictors.

These findings are consistent with the concept that AGEs are thought to be involved in the pathogenesis of diabetic nephropathy via multifactorial mechanisms such as oxidative stress generation and overproduction of various growth factors and cytokines. The cross-talk between AGEs and the renin-angiotensin system further participates in diabetic nephropathy.

Table 6: Multivariate Logistic Regression for Predictors of Diabetic Nephropathy

OR: odds ratio; CI: confidence interval; HbA1c: glycated hemoglobin; AGEs: advanced glycation end products; MDA: malondialdehyde; 8-OHdG: 8-hydroxy-2'-deoxyguanosine. Adjusted for age, sex, BMI, diabetes duration, and HbA1c.

This comprehensive cross-sectional study provides robust evidence for the central role of advanced glycation end products and oxidative stress in the pathogenesis of diabetic nephropathy and retinopathy. Our findings demonstrate that patients with type 2 diabetes mellitus have significantly elevated circulating AGE levels and oxidative stress markers compared to healthy controls, and that these biochemical abnormalities are strongly associated with the presence and severity of microvascular complications. The marked elevation of serum AGEs (178% increase) in diabetic patients compared to controls is consistent with the established understanding that chronic hyperglycemia and oxidative stress in diabetes result in the formation and accumulation of AGEs. AGEs are heterogeneous cross-linked sugar-derived proteins which accumulate in the glomerular basement membrane, mesangial cells, endothelial cells, and podocytes in patients with diabetes. The formation of AGEs occurs through a series of complex, non-enzymatic reactions between reducing sugars and the amino groups of proteins, lipids, and nucleic acids. The parallel elevation of oxidative stress markers (MDA and 8-OHdG) in our diabetic cohort underscores the intimate relationship between glycation and oxidation. Reactive oxygen species generation is both a consequence and a cause of AGE formation. As shown by recent studies, AGEs seem to be not merely "actors" but "directors" of processes conducting to diabetic complications, serving as a bridge between intracellular and extracellular damage. This glycoxidation-centric view suggests that AGEs have a dominant, hyperglycemia-independent role in the onset of microvascular complications. The strong correlations between serum AGE levels and parameters of diabetic nephropathy (UACR: r=0.72, eGFR: r=-0.68) observed in our study are particularly noteworthy. These findings align with the pathophysiological role of AGEs in diabetic nephropathy, where AGEs accumulate in renal tissues and contribute to disease progression via oxidative stress generation. AGE modification of proteins may produce changes in charge, solubility, and conformation, leading to molecular dysfunction as well as disrupting interactions with other proteins. Furthermore, AGEs interact with RAGE to influence the renal expression of growth factors and cytokines implicated in the progression of diabetic renal disease. The observation that patients with diabetic retinopathy had significantly higher AGE levels compared to those without retinopathy (15.4 ± 4.6 vs. 11.2 ± 3.8 U/mL, p<0.001) supports the pathogenic role of AGEs in retinal complications. AGEs are known to accumulate in the diabetic retina where they have important effects on retinal vascular cell function. The biochemical damages are induced by both RAGE-dependent and RAGE-independent mechanisms. AGEs induce the breakdown of redox balance and cause oxidative stress in retinal cells, exerting cytopathic effects in the progression of diabetic retinopathy. The stepwise increase in AGE levels with retinopathy severity (no retinopathy → NPDR → PDR) further supports a dose-response relationship between glycation burden and retinal damage. The excellent diagnostic performance of serum AGEs for predicting diabetic nephropathy (AUC 0.912) and retinopathy (AUC 0.884) suggests that AGEs may serve as valuable biomarkers for risk stratification. The combination of AGEs and MDA yielded even higher predictive accuracy, indicating that assessment of both glycation and oxidation provides complementary information. These findings are consistent with the concept that AGEs show potential as biomarkers of cumulative metabolic stress and predictors of diabetic end-organ damage. The independent association of AGEs with diabetic nephropathy in multivariate analysis (OR 3.42, 95% CI 2.18–5.36, p<0.001) after adjusting for traditional risk factors underscores the unique contribution of glycation to renal complications. This finding is consistent with the concept that AGEs are involved in the pathogenesis of diabetic nephropathy via multifactorial mechanisms such as oxidative stress generation and overproduction of various growth factors and cytokines. Furthermore, the cross-talk between AGEs and the renin-angiotensin system has been proposed to participate in diabetic nephropathy, with activation of the RAS eliciting ROS generation and subsequently stimulating growth factor and cytokine production by kidney cells. The clinical implications of our findings are substantial. First, the strong association between circulating AGE levels and diabetic complications suggests that AGEs could serve as valuable biomarkers for identifying patients at highest risk of developing nephropathy and retinopathy. Second, the AGE-RAGE-oxidative stress axis represents a critical therapeutic target. Therapeutic options such as strict blood glucose and blood pressure controls are effective for preventing diabetic nephropathy, but are far from satisfactory. Agents that inhibit the formation of AGEs or remove established AGE modifications may form an important component of future therapy in patients with diabetes. Third, the concept of carbonyl stress as a cause of AGE toxicity opens avenues for therapeutic interventions targeting reactive carbonyl species. Several limitations of this study should be acknowledged. First, the cross-sectional design precludes establishing causal relationships between AGEs and diabetic complications. Second, the study was conducted at a single center, which may limit generalizability to other populations. Third, we did not measure tissue AGE accumulation (e.g., skin autofluorescence), which may provide additional information beyond circulating levels. Fourth, the relatively modest sample size for subgroup analyses (particularly PDR) limits statistical power for some comparisons. Fifth, we did not evaluate all potential AGE species or all RAGE-mediated signaling pathways. Despite these limitations, our study provides robust evidence supporting the central role of the AGE-RAGE-oxidative stress axis in diabetic microvascular complications. The strong associations observed between circulating AGE levels and both nephropathy and retinopathy suggest that AGEs may serve as both biomarkers and therapeutic targets. Future research should focus on prospective validation of AGEs as predictors of complication development, evaluation of AGE-lowering therapies in clinical trials, and investigation of the molecular mechanisms linking specific AGE species to particular complications.

This study demonstrates that patients with type 2 diabetes mellitus have significantly elevated circulating advanced glycation end products and oxidative stress markers compared to healthy controls. Serum AGE levels correlate strongly with the presence and severity of diabetic nephropathy and retinopathy, and independently predict these complications after adjustment for traditional risk factors. The AGE-RAGE-oxidative stress axis represents a critical pathogenic pathway in diabetic microvascular complications. These findings support the potential utility of AGEs as biomarkers for risk stratification and highlight the need for therapeutic strategies targeting glycation and oxidative stress to prevent or retard the progression of diabetic nephropathy and retinopathy.

1. Yamagishi S, Matsui T. Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxid Med Cell Longev. 2010;3(2):101-8.
2. Thomas MC. Advanced glycation end products and diabetic nephropathy. Am J Ther. 2005;12(6):562-72.
3. Fukami K, Yamagishi S, Ueda S, Okuda S. Role of AGEs in diabetic nephropathy. Curr Pharm Des. 2008;14(10):946-52.
4. Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001;44(2):129-46.
5. Stitt AW. The role of advanced glycation in the pathogenesis of diabetic retinopathy. Exp Mol Pathol. 2003;75(1):95-108.
6. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058-70.
7. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414(6865):813-20.
8. Forbes JM, Cooper ME, Oldfield MD, Thomas MC. Role of advanced glycation end products in diabetic nephropathy. J Am Soc Nephrol. 2003;14(8 Suppl 3):S254-8.
9. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114(6):597-605.
10. Bierhaus A, Humpert PM, Morcos M, et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med. 2005;83(11):876-86.
11. Schmidt AM, Yan SD, Yan SF, Stern DM. The biology of the receptor for advanced glycation end products and its ligands. Biochim Biophys Acta. 2000;1498(2-3):99-111.
12. Thornalley PJ. Glyoxalase I—structure, function and a critical role in the enzymatic defence against glycation. Biochem Soc Trans. 2003;31(Pt 6):1343-8.
13. Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes. 1999;48(1):1-9.
14. Nishikawa T, Edelstein D, Du XL, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000;404(6779):787-90.
15. Yamagishi S, Nakamura K, Matsui T, Noda Y, Imaizumi T. Receptor for advanced glycation end products (RAGE): a novel therapeutic target for diabetic vascular complication. Curr Pharm Des. 2008;14(5):487-95.
16. Stitt AW, Jenkins AJ, Cooper ME. Advanced glycation end products and diabetic complications. Expert Opin Investig Drugs. 2002;11(9):1205-23.
17. Vlassara H, Palace MR. Diabetes and advanced glycation endproducts. J Intern Med. 2002;251(2):87-101.
18. Wendt T, Harja E, Bucciarelli L, et al. RAGE modulates vascular inflammation and atherosclerosis in a murine model of type 2 diabetes. Atherosclerosis. 2006;185(1):70-7.
19. Ramasamy R, Yan SF, Schmidt AM. RAGE: therapeutic target and biomarker of the inflammatory response—the evidence mounts. J Leukoc Biol. 2009;86(3):505-12.
20. Ahmed N. Advanced glycation endproducts—role in pathology of diabetic complications. Diabetes Res Clin Pract. 2005;67(1):3-21.