AGEs – Advanced Glycation Endproducts

AGEs play a pivotal role in the development of chronic metabolism and age related diseases such as diabetes, renal failure and cardio-vascular disease.

The level of AGEs in long-lived tissue – not in blood – serves as a memory of glyco-metabolic and oxidative stress. Hence AGEs mirror the process in disease advancement and act as strong predictors, in particular of cardio-vascular complications. Gradually accumulating over a human lifetime this progression is enhanced in patients with conditions such as diabetes mellitus, renal failure, or cardio-vascular disease¹.
Accumulation of tissue AGEs is also indicative in metabolic disease related complications such as early kidney, eye, and nerve impairments. Clinically AGEs can be used in the risk assessment of future cardio-vascular morbidity and mortality². New drugs, aimed at preventing formation of AGEs or braking AGEs, are under development and may be available in the near future.

Clinical Applications

• Assessment of individual cardio-vascular risk
• Identification of high risk patients
• Therapy follow-up and optimization
• Reduction of cost and side effects of drugs
• Monitoring of intensive care patients
• Monitoring of dialysis and transplant patients
• Risk profiling in public and corporate health programs

Comprehensive Validation

AGE reader has been validated against skin biopsy, still serving as a gold standard, in clinical settings¹³. Its clinical value has been proven in several large scale studies involving thousands of patients with diabetes, cardio-vascular disease and renal failure³⁴⁵⁶. AGE Reader is backed by broad scientific literature, a knowledge base covering more than ten years.

AGEs Reader in Research

• Clinical studies
1. Diabetes
2. Renal failure and kidney disease
3. Cardio-vascular disease

• Drug studies
• Nutritional research
• Ageing research
• Skin care research
• Epidemiological studies
• Screening programs

AGE Reader for Individual Risk Stratification

Diabetes

• Best single predictor of cardio-vascular risk in combination with the UKPDS risk score, except age².
• Independent predictor of micro-vascular complications in type 2 diabetes⁷.
• Reflects vascular damage in diabetes outpatients and identifies diabetic patients at risk of developing complications³.

Renal Disease

• Independent predictor of cardio-vascular disease related mortality in dialysis patients⁴.
• Strong independent predictor of mortality and craft loss in renal transplant recipients⁸.
• AGEs correlate with arterial stiffness and diastolic function in both, hemodialysis and peritoneal dialysis patients⁹¹⁴.

Cardio-Vascular Disease

• Independent marker of acute myocardial infarction¹⁰.
• Non-invasive marker for inflammatory stress in stable coronary artery disease¹¹.
• Predictor of future cardio-vascular morbidity and mortality in STEMI patients¹¹¹².

Enhancing Risk Prediction of SCORE, Framingham, UKPDS, IMT

• Viable and economical assessment tool enhancing conventional risk engines².
• Related to early IMT increase and atherosclerosis (cardio-vascular morbidity and mortality), independent of conventional risk scores and engines¹²¹⁵.
• AGEs are indicative of pathogenic pathways not covered by conventional risk scores¹⁶.

Literature:

¹ Meerwaldt R et al. Cardiovascular Diabetology 2008; 7: 29

² Lutgers HL et al. Diabetologia 2009; 52(5): 789-797

³ Lutgers HL et al. Diabetes Care 2006; 29(12): 2654-2659

⁴ Meerwaldt R et al. J Am Soc Nephrol 2005; 16: 3687-3693

⁵ Meerwaldt R et al. Diabetologia 2005; 48: 1637-1644

⁶ Meerwaldt R et al. Ann N Y Acad Sci 2005; 1043: 299-307

⁷ Gerrits E et al. Diabetes Care 2008; 31(3): 517-521

⁸ Hartog J et al. Transplantation 2009; 87: 1069-1077

⁹ Ueno H et al. Metabolism Clin Exp 2008; 57(10): 1452-1457

¹⁰ Mulder DJ et al. Circulation 2005; 112:II-371

¹¹ Mulder DJ et al. Netherlands Heart J 2009; 17(4); 162-168

¹² Meerwaldt R et al. Eur J Vasc Endovasc Surg 2008; 36(2) 125-131

¹³ Meerwaldt R et al. Diabetologia 2004; 47: 1324-1330

¹⁴ Hartog J et al. J Card Failure 2008; 14(17): 596-602

¹⁵ Mulder DJ et al. Artherosclerosis 2008; 197(1): 217-223

¹⁶ Smit AJ at al. Cur Med Chem 2004;11: 1241-1253