Fluorescent advanced glycation end-products (ages) detected by spectro-photofluorimetry, as a screening tool to detect diabetic microvascular complications

Abstract

BACKGROUND: Advanced glycation end-products (AGEs) are one of the mechanisms related to diabetic vascular complications. However, since AGEs are multiple and heterogeneous moieties, there is no universally accepted method to measure them for clinical purposes. The aim of this work was to study the utility of a simple fluorimetric assay as predictor of complications. METHODS: Blood samples from 102 type 2 diabetic patients were obtained to assess glucose, glycosylated haemoglobin, creatinine, lipoproteins and C Reactive Protein (CRP), fluorescent AGES by spectrophotofluorimetry and non-fluorescent AGEs by measurement of N(ε)-carboxymethyl-Lysine (CML) using an ELISA kit in a subsample of 82 patients. Urinary fluorescent AGEs, albumin and creatinine were also measured in a morning urine sample. Microvascular complications were studied by ophthalmologic examination, albuminuria and peripheral nerve conduction velocity. RESULTS: Patients without microvascular complications had significantly lower levels of both serum and urinary AGEs. CML was associated with retinopathy. Multiple regression analysis confirmed that AGEs, length of diabetes and glycosylated haemoglobin were all variables associated with diabetic complications, in this sample. CONCLUSIONS: A simple fluorimetric assay to measure low molecular weight fluorescent AGEs, and CML could be employed as screening tools to predict diabetic complications, at a primary care setting. AGEs should probably be considered as another therapeutic target in diabetes management.

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Pia de la Maza, M. , Garrido, F. , Escalante, N. , Leiva, L. , Barrera, G. , Schnitzler, S. , Zanolli, M. , Verdaguer, J. , Hirsch, S. , Jara, N. and Bunout, D. (2012) Fluorescent advanced glycation end-products (ages) detected by spectro-photofluorimetry, as a screening tool to detect diabetic microvascular complications. Journal of Diabetes Mellitus, 2, 221-226. doi: 10.4236/jdm.2012.22035.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Singh, R., Barden, A., Mori, T. and Beilin, L. (2001) Advanced glycation end products: A review. Diabetologia, 44, 129-146. doi:10.1007/s001250051591
[2] Goldberg, T., Cai, W., Peppa, M., Dardane, V., Baliga, B.S., Uribarri, J. and Vlassara, H. (2004) Advanced glycoxidation end products in commonly consumed foods. Journal of the American Dietetic Association, 104, 1287-1291. doi:10.1016/j.jada.2004.05.214
[3] Thomas, M.C., Tsalamandris, C., MacIsaac, R., Medley, T., Kingwell, B., Cooper, M.E. and Jerums, G. (2004) Low-molecular-weight AGEs are associated with GFR and anemia in patients with type 2 diabetes. Kidney International, 66, 1167-1172. doi:10.1111/j.1523-1755.2004.00868.x
[4] Forbes, J.M., Soldatos, G., and Thomas, M.C. (2005) Below the radar: Advanced glycation end products that detour “around the side”. Is HbA1c not an accurate enough predictor of long term progression and glycaemic control in diabetes? Clinical of Biochemistry Reviews, 26, 123-134
[5] Genuth, S., Sun, W., Cleary, P., Sell, D.R., Dahms, W., Malone, J., Sivitz, W., and Monnier, V.M. (2005) Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes. Diabetes, 54, 3103-3111. doi:10.2337/diabetes.54.11.3103
[6] Sampathkumar, R., Balasubramanyam, M., Rema, M., Premanand, C. and Mohan, V. (2005) A novel advanced glycation index and its association with diabetes and microangiopathy. Metabolism, 54, 1002-1007. doi:10.1016/j.metabol.2005.02.017
[7] Grossin, N., Wautier, M.P., Meas, T., Guillausseau, P.J., Massin, P. and Wautier, J.L. (2008) Severity of diabetic microvascular complications is associated with a low soluble RAGE level. Diabetes Metabolism, 34, 392-395. doi:10.1016/j.diabet.2008.04.003
[8] Gerrits, E.G., Lutgers, H.L., Kleefstra, N., Graaff, R., Groenier, K.H., Smit, A.J., Gans, R.O. and Bilo, H.J. (2008) Skin autofluorescence: A tool to identify type 2 diabetic patients at risk for developing microvascular complications. Diabetes Care, 31, 517-521. doi:10.2337/dc07-1755
[9] Roberts, M.A., Thomas, M.C., Fernando, D., Macmillan, N., Power, D.A. and Ierino, F.L. (2006) Low molecular weight advanced glycation end products predict mortality in asymptomatic patients receiving chronic haemodialysis. Nephrology Dialysis Transplantation, 21, 1611-1617. doi:10.1093/ndt/gfl053
[10] Wróbel, K., Wróbel, K., Garay-Sevilla, M.E., Nava, L.E. and Malacara, J.M. (1997) Novel analytical approach to monitoring advanced glycosylation end products in human serum with on-line spectrophotometric and spectrofluorometric detection in a flow system. Clinical of Chemistry, 43, 1563-1569.
[11] Dumitru, D., Amato, A.A. and Zwarts, M.J. (2001) Electrodiagnostic medicine. 2nd Edition, Hanley & Belfus, San Antonio.
[12] De la Maza, M.P., Bravo, A., Leiva, L., Gattás, V., Barrera, G., Petermann, M., Garrido, F., Uribarri, J., Bunout, D. and Hirsch, S. (2008) Urinay excretion of fluorescent advanced glycation end products in the elderly. The Journal of Nutrition, Health & Ageing, 12, 222-225. doi:10.1007/BF02982625
[13] Sun, J.K., Keenan, H.A., Cavallerano, J.D., Asztalos, B.F., Schaefer, E.J., Sell, D.R., Strauch, C.M., Monnier, V.M., Doria, A., Aiello, L.P. and King, G.L. (2011) Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration: The Joslin 50-year medalist study. Diabetes Care, 34, 968-974. doi:10.2337/dc10-1675
[14] Uribarri, J., Peppa, M., Cai, W., Goldberg, T., Lu, M., Baliga, S., Vassalotti, J.A. and Vlassara, H. (2003) Dietary glycotoxins correlate with circulating advanced glycation end product levels in renal failure patients. American Journal of Kidney Disease, 42, 532-538. doi:10.1016/S0272-6386(03)00779-0
[15] Uribarri, J., Cai, W., Peppa, M., Goodman, S., Ferrucci, L., Striker, G. and Vlassara, H. (2007) Circulating glycotoxins and dietary advanced glycationendproducts: two links to inflammatory response, oxidative stress, and aging. The Journal of Gerontology Series A: Biology Science and Medicine Science, 62, 427-433. doi:10.1093/gerona/62.4.427
[16] Delgado-Andrade, C., Seiquer, I., Navarro, M.P. and Morales, F.J. (2007) Maillard reaction indicators in diets usually consumed by adolescent population. Molecular Nutrition Food Research, 51, 341-351. doi:10.1002/mnfr.200600070
[17] Delgado-Andrade, C., Tessier, F.J., Niquet-Leridon, C., Seiquer, I. and Navarro, M.P. (2001) Study of the urinary and faecal excretion of Nε-carboxymethyl-lysine in young human volunteers. Amino Acids, in press. doi:10.1007/s00726-011-1107-8
[18] Vallejo-Cordoba, B. and González-Córdova, A.F. (2007) CE: A useful analytical tool for the characterization of Maillard reaction products in foods. Electrophoresis, 28, 4063-4071. doi:10.1002/elps.200700314
[19] Uribarri, J., Cai, W., Ramdas, M., Goodman, S., Pyzik, R., Chen, X., Zhu, L., Striker, G.E. and Vlassara, H. (2011) Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: Potential role of AGER1 and SIRT1. Diabetes Care, 34, 1610-1616. doi:10.2337/dc11-0091

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