Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter August 12, 2014

Skin advanced glycation endproducts are elevated at onset of type 1 diabetes in youth

  • Eileen A. Báez , Shreepal Shah , Dania Felipe , John Maynard , Suzanne Lefevre and Stuart A. Chalew EMAIL logo

Abstract

Objectives: To compare skin advanced glycation endproducts (AGEs) in children at onset of type 1 diabetes with children without diabetes.

Study design: Skin AGEs (sAGEs) were estimated by measurement of skin intrinsic fluorescence (SIF) at diagnosis of type 1 diabetes (NewD; n=47, F=45%, M=55%, Age=10±3.7) and in youth without diabetes (NoD; n=112, F=53%, M=47%, Age=10.4±4.8). HCO3, pH, pCO2, glucose level, and HbA1c effect on SIF was evaluated in NewD patients.

Results: SIF at 405 nm and 420 nm excitation were higher (p=0.03) in NewD children compared to NoD. HCO3, pH, pCO2, glucose, and HbA1c were not associated with SIF levels.

Conclusions: Despite the short duration of untreated diabetes, sAGEs were higher in children with NewD compared to children with NoD. Further study will be needed to determine whether early accumulation of sAGEs is associated with higher risk for development and progression of complications.


Corresponding author: Stuart A. Chalew, MD, Children’s Hospital, New Orleans, LA, USA, Phone: +504-896-9441, Fax: +504-894-5139, E-mail: ; and Pediatric Endocrinology/Diabetes, Louisiana State University - Health Sciences Center, New Orleans, LA, USA

Acknowledgments

Our group would like to acknowledge Dr. Stephen D. Heinrich and Gretchen Dondis for facilitating recruitment of individuals without diabetes for this study.

References

1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86.10.1056/NEJM199309303291401Search in Google Scholar

2. Ahmed N, Thornalley PJ. Advanced glycation endproducts: what is their relevance to diabetic complications? Diabetes Obes Metab 2007;9:233–45.10.1111/j.1463-1326.2006.00595.xSearch in Google Scholar

3. King GL, Brownlee M. The cellular and molecular mechanisms of diabetic complications. Endocrinol Metab Clin North Am 1996;25:255–70.10.1016/S0889-8529(05)70324-8Search in Google Scholar

4. Monnier VM, Vishwanath V, Frank KE, Elmets CA, Dauchot P, et al. Relation between complications of type I diabetes mellitus and collagen-linked fluorescence. N Engl J Med 1986;314:403–8.10.1056/NEJM198602133140702Search in Google Scholar

5. Goh SY, Cooper ME. Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 2008;93:1143–52.10.1210/jc.2007-1817Search in Google Scholar

6. Huebschmann AG, Regensteiner JG, Vlassara H, Reusch JE. Diabetes and advanced glycoxidation end products. Diabetes Care 2006;29:1420–32.10.2337/dc05-2096Search in Google Scholar

7. Berg TJ, Dahl-Jorgensen K, Torjesen PA, Hanssen KF. Increased serum levels of advanced glycation end products (AGEs) in children and adolescents with IDDM. Diabetes Care 1997;20:1006–8.10.2337/diacare.20.6.1006Search in Google Scholar

8. Chiarelli F, de Martino M, Mezzetti A, Catino M, Morgese G, et al. Advanced glycation end products in children and adolescents with diabetes: relation to glycemic control and early microvascular complications. J Pediatr 1999;134:486–91.10.1016/S0022-3476(99)70208-8Search in Google Scholar

9. Jakus V, Bauerova K, Michalkova D, Carsky J. Values of markers of early and advanced glycation and lipoxidation in serum proteins of children with diabetes mellitus. Bratisl Lek Listy 2000;101:484–9.Search in Google Scholar

10. Cerami A. The unexpected pathway to the creation of the HbA1c test and the discovery of AGE’s. J Intern Med 2012;271:219–26.10.1111/j.1365-2796.2012.02514.xSearch in Google Scholar PubMed

11. Dyer DG, Dunn JA, Thorpe SR, Bailie KE, Lyons TJ, et al. Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest 1993;91:2463–9.10.1172/JCI116481Search in Google Scholar PubMed PubMed Central

12. Genuth S, Sun W, Cleary P, Sell DR, Dahms W, et al. 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 2005;54:3103–11.10.2337/diabetes.54.11.3103Search in Google Scholar PubMed PubMed Central

13. Monnier VM, Bautista O, Kenny D, Sell DR, Fogarty J, et al. Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial. Diabetes 1999;48:870–80.10.2337/diabetes.48.4.870Search in Google Scholar PubMed PubMed Central

14. Monnier VM. Nonenzymatic glycosylation, the Maillard reaction and the aging process. J Gerontol 1990;45:B105–11.10.1093/geronj/45.4.B105Search in Google Scholar PubMed

15. Hull, EL, Ediger MN, Brown CD, Maynard JD, Johnson RD. Determination of a measure of a glycation end-product or disease state using tissue fluorescence. 2006. US Patent 7139598.Search in Google Scholar

16. Meerwaldt R, Graaff R, Oomen PH, LinksTP, Jager JJ, et al. Simple non-invasive assessment of advanced glycation endproduct accumulation. Diabetologia 2004;47:1324–30.10.1007/s00125-004-1451-2Search in Google Scholar PubMed

17. Mulder DJ, Water TV, Lutgers HL, Graaff R, GansRO, et al. Skin autofluorescence, a novel marker for glycemic and oxidative stress-derived advanced glycation endproducts: an overview of current clinical studies, evidence, and limitations. Diabetes Technol Ther 2006;8:523–35.10.1089/dia.2006.8.523Search in Google Scholar PubMed

18. Cleary PA, Braffett BH, Orchard T, Lyons TJ, Maynard J, et al. Clinical and technical factors associated with skin intrinsic fluorescence in subjects with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Diabetes Technol Ther 2013;15:466–74.10.1089/dia.2012.0316Search in Google Scholar PubMed PubMed Central

19. Felipe DL, Hempe JM, Liu S, Matter N, Maynard J, et al. Skin Intrinsic Fluorescence Is Associated With Hemoglobin A1c and Hemoglobin Glycation Index but Not Mean Blood Glucose in Children With Type 1 Diabetes. Diabetes Care 2011;34:1816–20.10.2337/dc11-0049Search in Google Scholar PubMed PubMed Central

20. Noordzij MJ, Lefrandt JD, Graaff R, Smit AJ. Skin autofluorescence and glycemic variability. Diabetes Technol Ther 2010;12:581–5.10.1089/dia.2010.0014Search in Google Scholar PubMed

21. Shah S, Baez EA, Felipe DL, Maynard JD, Hempe JM, et al. Advanced Glycation Endproducts in Children with Diabetes. J Pediatr 2013;163:1427–31.10.1016/j.jpeds.2013.06.044Search in Google Scholar PubMed

22. Araszkiewicz A, Naskret D, Niedzwiecki P, Samborski P, Wierusz-Wysocka B, et al. Increased accumulation of skin advanced glycation end products is associated with microvascular complications in type 1 diabetes. Diabetes Technol Ther 2011;13:837–42.10.1089/dia.2011.0043Search in Google Scholar PubMed

23. Genevieve M, Vivot A, Gonzalez C, Raffaitin C, Barberger-Gateau P, et al. Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus. Diabetes Metab 2013;39:349–54.10.1016/j.diabet.2013.03.003Search in Google Scholar

24. Meerwaldt R, Links TP, Graaff R, Hoogenberg K, Lefrandt JD, et al. Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy. Diabetologia 2005;48:1637–44.10.1007/s00125-005-1828-xSearch in Google Scholar

25. Meerwaldt R, Lutgers HL, Links TP, Graaff R, Baynes JW, et al. Skin autofluorescence is a strong predictor of cardiac mortality in diabetes. Diabetes Care 2007;30:107–12.10.2337/dc06-1391Search in Google Scholar

26. Nicholl ID, Bucala R. Advanced glycation endproducts and cigarette smoking. Cell Mol Biol (Noisy-le-grand) 1998;44:1025–33.Search in Google Scholar

27. Bos DC, de Ranitz-Greven WL, de Valk HW. Advanced glycation end products, measured as skin autofluorescence and diabetes complications: a systematic review. Diabetes Technol Ther 2011;13:773–9.10.1089/dia.2011.0034Search in Google Scholar

28. Januszewski AS, Sachithanandan N, Karschimkus C, O’Neal DN, Yeung CK, et al. Non-invasive measures of tissue autofluorescence are increased in Type 1 diabetes complications and correlate with a non-invasive measure of vascular dysfunction. Diabet Med 2012;29:726–33.10.1111/j.1464-5491.2011.03562.xSearch in Google Scholar

29. Orchard TJ, Lyons TJ, Cleary PA, Braffett BH, Maynard J, et al. The association of skin intrinsic fluorescence with type 1 diabetes complications in the DCCT/EDIC study. Diabetes Care 2013;36:3146–53.10.2337/dc12-2661Search in Google Scholar

30. Hempe JM, Gomez R, McCarter RJ Jr., Chalew SA. High and low hemoglobin glycation phenotypes in type 1 diabetes: a challenge for interpretation of glycemic control. J Diabetes Complications 2002;16:313–20.10.1016/S1056-8727(01)00227-6Search in Google Scholar

31. Hempe JM, McGehee AM, Chalew SA. Two-dimensional analysis of glycated hemoglobin heterogeneity in pediatric type 1 diabetes patients. Anal Biochem 2013;442:205–12.10.1016/j.ab.2013.07.016Search in Google Scholar PubMed

Received: 2013-12-25
Accepted: 2014-7-14
Published Online: 2014-8-12
Published in Print: 2015-1-1

©2015 by De Gruyter

Downloaded on 19.5.2024 from https://www.degruyter.com/document/doi/10.1515/jpem-2014-0086/html
Scroll to top button