Biomedical papers, 2016 (vol. 160), issue 1

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016, 160(1):70-75 | 10.5507/bp.2015.045

Serum carboxymethyl-lysine, a dominant advanced glycation end product, is increased in women with gestational diabetes mellitus

Vendula Bartakovaa, Radana Kollarovab, Katarina Kuricovaa, Katarina Sebekovab, Jana Belobradkovac, Katerina Kankovaa
a Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5/A18, 625 00 Brno, Czech Republic
b Institute of Molecular BioMedicine, Medical Faculty, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovak Republic
c Diabetes Centre of the Department of Internal Medicine - Gastroenterology, University Hospital Brno, Czech Republic

Aims: The objective of the study was to measure one of the circulating Advanced Glycation End Products (AGEs) - Nε-(carboxymethyl)lysine (CML) - in a case-control study (n = 307) of pregnant women with gestational diabetes mellitus (GDM) and physiological pregnancies and to ascertain the factors contributing to CML levels and the potential relevance of CML for selected perinatal and postpartum outcomes.

Methods: All subjects underwent oGTT between 24th and 30th week of gestation and GDM was diagnosed according to WHO criteria. CML was determined by ELISA using commercial kit.

Results: Unadjusted and plasma protein adjusted CML levels were significantly higher in women with GDM compared to healthy controls (P = 0.00043 and P = 1x10-5, respectively, Mann-Whitney). CML was significantly inversely correlated with both pre- and mid-gestational BMI, however, differences between GDM and control group remained significant even after adjustment for BMI. CML levels correlated with 1-h and 2-h post-load glycaemia during oGTT.

Conclusion: In conclusion, we found statistically significantly higher protein- and BMI-normalised CML levels measured during 24-30th week of gestation in women with GDM compared to healthy pregnant controls. Further studies are warranted to comprehensively asses the spectrum of AGEs in GDM and their relevance to future metabolic health of mother and offspring.

Keywords: gestational diabetes, CML, BMI, oral glucose tolerance test, postpartum glucose intolerance

Received: April 23, 2015; Accepted: September 10, 2015; Prepublished online: November 24, 2015; Published: March 30, 2016


References

  1. Reece EA, Leguizamón G, Wiznitzer A. Gestational diabetes: The need for a common ground. Lancet 2009;373:1789-1797. Go to original source... Go to PubMed...
  2. Lacroix M, Kina E, Hivert MF. Maternal/fetal determinants of insulin resistance in women during pregnancy and in offspring over life. Curr Diab Rep 2013;13:238-244. Go to original source... Go to PubMed...
  3. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988;318:1315-1321. Go to original source... Go to PubMed...
  4. Uribarri J, Cai W, Ramdas M, Goodman S, Pyzik R, Chen X, Zhu L, Striker GE, Vlassara H. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: Potential role of ager1 and sirt1. Diabetes Care 2011;34:1610-1616. Go to original source... Go to PubMed...
  5. Kalousová M, Skrha J, Zima T. Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res 2002;51:597-604. Go to PubMed...
  6. Boehm BO, Schilling S, Rosinger S, Lang GE, Lang GK, Kientsch-Engel R, Stahl P. Elevated serum levels of n(epsilon)-carboxymethyl-lysine, an advanced glycation end product, are associated with proliferative diabetic retinopathy and macular oedema. Diabetologia 2004;47:1376-1379. Go to original source... Go to PubMed...
  7. Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product n(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest 1997;99:457-468. Go to original source... Go to PubMed...
  8. Harsem NK, Braekke K, Torjussen T, Hanssen K, Staff AC. Advanced glycation end products in pregnancies complicated with diabetes mellitus or preeclampsia. Hypertens Pregnancy 2008;27:374-386. Go to original source... Go to PubMed...
  9. Guosheng L, Hongmei S, Chuan N, Haiying L, Xiaopeng Z, Xianqiong L. The relationship of serum age levels in diabetic mothers with adverse fetal outcome. J Perinatol 2009;29:483-488. Go to original source... Go to PubMed...
  10. Buongiorno AM, Morelli S, Sagratella E, Castaldo P, Di Virgilio A, Maroccia E, Ricciardi G, Sciullo E, Cardellini G, Fallucca F, Sensi M. Levels of advanced glycosylation end-products (age) in sera of pregnant diabetic women: Comparison between type 1, type 2 and gestational diabetes mellitus. Ann Ist Super Sanita 1997;33:375-378. Go to PubMed...
  11. de Ranitz-Greven WL, Bos DC, Poucki WK, Visser GH, Beulens JW, Biesma DH, de Valk HW. Advanced glycation end products, measured as skin autofluorescence, at diagnosis in gestational diabetes mellitus compared with normal pregnancy. Diabetes Technol Ther 2012;14:43-49. Go to original source... Go to PubMed...
  12. de Ranitz-Greven WL, Kaasenbrood L, Poucki WK, Hamerling J, Bos DC, Visser GH, Biesma DH, Beulens JW, de Valk HW. Advanced glycation end products, measured as skin autofluorescence, during normal pregnancy and pregnancy complicated by diabetes mellitus. Diabetes Technol Ther 2012;14:1134-1139. Go to original source... Go to PubMed...
  13. Sacks DA, Hadden DR, Maresh M, Deerochanawong C, Dyer AR, Metzger BE, Lowe LP, Coustan DR, Hod M, Oats JJ, Persson B, Trimble ER, Group HSCR. Frequency of gestational diabetes mellitus at collaborating centers based on iadpsg consensus panel-recommended criteria: The hyperglycemia and adverse pregnancy outcome (hapo) study. Diabetes Care 2012;35:526-528. Go to original source... Go to PubMed...
  14. Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. BMJ 1990;300:230-235. Go to original source... Go to PubMed...
  15. Sebeková K, Somoza V, Jarcusková M, Heidland A, Podracká L. Plasma advanced glycation end products are decreased in obese children compared with lean controls. Int J Pediatr Obes 2009;4:112-118. Go to original source... Go to PubMed...
  16. Sebeková K, Krivošíková Z, Gajdoš M. Total plasma nε-(carboxymethyl)lysine and srage levels are inversely associated with a number of metabolic syndrome risk factors in non-diabetic young-to-middle-aged medication-free subjects. Clin Chem Lab Med 2014;52:139-149. Go to PubMed...
  17. Semba RD, Arab L, Sun K, Nicklett EJ, Ferrucci L. Fat mass is inversely associated with serum carboxymethyl-lysine, an advanced glycation end product, in adults. J Nutr 2011;141:1726-1730. Go to original source... Go to PubMed...
  18. Gaens KH, Goossens GH, Niessen PM, van Greevenbroek MM, van der Kallen CJ, Niessen HW, Rensen SS, Buurman WA, Greve JW, Blaak EE, van Zandvoort MA, Bierhaus A, Stehouwer CD, Schalkwijk CG. Nε-(carboxymethyl)lysine-receptor for advanced glycation end product axis is a key modulator of obesity-induced dysregulation of adipokine expression and insulin resistance. Arterioscler Thromb Vasc Biol 2014;34:1199-1208. Go to original source... Go to PubMed...
  19. Semba RD, Beck J, Sun K, Egan JM, Carlson OD, Varadhan R, Ferrucci L. Relationship of a dominant advanced glycation end product, serum carboxymethyl-lysine, and abnormal glucose metabolism in adults: The baltimore longitudinal study of aging. J Nutr Health Aging 2010;14:507-513. Go to original source... Go to PubMed...
  20. Fu MX, Requena JR, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SROV. The advanced glycation end product, nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. J Biol Chem 1996;271:9982-9986. Go to original source... Go to PubMed...
  21. Ohgami N, Nagai R, Ikemoto M, Arai H, Miyazaki A, Hakamata H, Horiuchi S, Nakayama H. Cd36, serves as a receptor for advanced glycation endproducts (age). J Diabetes Complications 2002;16:56-59. Go to original source... Go to PubMed...
  22. Kuniyasu A, Ohgami N, Hayashi S, Miyazaki A, Horiuchi S, Nakayama H. Cd36-mediated endocytic uptake of advanced glycation end products (age) in mouse 3t3-l1 and human subcutaneous adipocytes. FEBS Lett 2003;537:85-90. Go to original source... Go to PubMed...