Inflammation Research

, Volume 67, Issue 1, pp 21–30 | Cite as

Glycated albumin (GA) and inflammation: role of GA as a potential marker of inflammation

  • H. Vernon Roohk
  • Asad R. Zaidi
  • Dimple PatelEmail author



Abnormal levels of glycated albumin (GA) are associated with the onset of both diabetes and inflammation. Although inflammation has long been associated with diabetes, this article aims to explore the underlying mechanisms of this relationship as it pertains to the role of GA.


We have reviewed 52 research articles since the year 2000. Common search terms used were “(inflammatory mediator) and GA” or “inflammation and GA”. The findings have been organized according to diabetic complications with respect to the interactions of GA and inflammatory mediators. Glycated albumin and specific inflammatory mediators have been reported to play various roles in the pathogenesis of insulin resistance, atherosclerosis, coronary artery disease, retinopathy, and nephropathy. In the case of nephropathy and recently retinopathy, there is considerable evidence for GA in concert with inflammation playing a direct role in organ pathology. There is copious literature detailing GA’s involvement in stimulating inflammatory markers and certain pro-inflammatory cytokines. A recent clinical study has shown GA to be a marker for inflammation in non-diabetic rheumatoid arthritis patients with the significance of standard inflammatory markers.


The clinical utility of GA measurement may likely reside in its versatility as both a mediator of inflammation as well as a marker to track hyperglycemia and other diabetes complications. Further understanding of the role GA plays in glycemic and inflammatory diseases could lead to its acceptance as an independent bio-inflammatory marker.


Inflammation Glycated albumin Inflammatory marker Glycated albumin point-of-care test 



Dr. David Horwitz, Dr. Tessa Lebinger, Dr. Omar Ali, Dr. Salim Aziz, Dr. Saul Ship, and Dr. Alan Carter of the Epinex Diagnostics Inc. Science Advisory Board; Dr. David Trasoff, Tasnim Ahmed, and Kajal Bains of Epinex Diagnostics Inc.


  1. 1.
    Anguizola J, Matsuda R, Barnaby OS. Review: glycation of human serum albumin. Clin Chim Acta. 2013;425:64–76. doi: 10.1016/j.cca.2013.07.013.CrossRefPubMedGoogle Scholar
  2. 2.
    Furusyo N, Hayashi J. Glycated albumin and diabetes mellitus. Biochim et Biophys Acta (BBA) Gen Subj. 2013. doi: 10.1016/j.bbagen.2013.05.010.Google Scholar
  3. 3.
    Yajima T, Yajima K, Hayashi M, Yasuda K, Takahashi H, Yamakita N. Serum albumin-adjusted glycated albumin is a better predictor of mortality in diabetic patients with end-stage renal disease on hemodialysis. J Diabetes Complicat. 2016. doi: 10.1016/j.jdiacomp.2016.02.021.PubMedGoogle Scholar
  4. 4.
    Kobayashi H, Abe M, Yoshida Y, Suzuki H, Maruyama N, Okada K. Glycated albumin versus glycated hemoglobin as a glycemic indicator in diabetic patients on peritoneal dialysis. IJMS. 2016. doi: 10.3390/ijms17050619.Google Scholar
  5. 5.
    Roohk VH, Zaidi A. A review of glycated albumin as an intermediate glycation index for controlling diabetes. J Diabetes Sci Technol. 2008;2(6):1114–21.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Arroyo V, García-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol. 2014. doi: 10.1016/j.jhep.2014.04.012.Google Scholar
  7. 7.
    Chen S, Cohen MP, Ziyadeh FN. Amadori-glycated albumin in diabetic nephropathy: pathophysiologic connections. Kidney Int. 2000;58:S40–4. doi: 10.1046/j.1523-1755.2000.07707.x.CrossRefGoogle Scholar
  8. 8.
    Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Investig. 2006. doi: 10.1172/JCI29069.PubMedGoogle Scholar
  9. 9.
    Esser N, Legrand-Poels S, Piette J, Scheen A, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014. doi: 10.1016/j.diabres.2014.04/006.PubMedGoogle Scholar
  10. 10.
    Su D, Coudriet G, Hyun Kim D, Lu Y, Perdomo G, Qu S, et al. FoxO1 links insulin resistance to proinflammatory cytokine IL-1 production in macrophages. Diabetes. 2009. doi: 10.2337/db09-0232.Google Scholar
  11. 11.
    Lu L, Pu L, Xu X, Zhang Q, Zhang R, Zhang J, et al. Association of serum levels of glycated albumin, C-reactive protein and tumor necrosis factor-α with the severity of coronary artery disease and renal impairment in patients with type 2 diabetes mellitus. Clin Biochem. 2007. doi: 10.1016/j.clinbiochem.2007.03.022.Google Scholar
  12. 12.
    Nathan D, McGee P, Steffes M, Lachin J. Relationship of glycated albumin to blood glucose and HbA1c values and to retinopathy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study. Diabetes. 2013. doi: 10.2337/db13-0782.Google Scholar
  13. 13.
    Pu L, Lu L, Shen W, Zhang Q, Zhang R, Zhang J, et al. Increased serum glycated albumin level is associated with the presence and severity of coronary artery disease in type 2 diabetic patients. Circ J. 2007. doi: 10.1253/circj.71.1067.PubMedGoogle Scholar
  14. 14.
    Wang H, Lo W, Lin L. Angiotensin-(1–7) decreases glycated albumin-induced endothelial interleukin-6 expression via modulation of miR-146a. Biochem Biophys Res Commun. 2013. doi: 10.1016/j.bbrc.2012.12.018.Google Scholar
  15. 15.
    Bian Z. Signaling pathways for glycated human serum albumin-induced IL-8 and MCP-1 secretion in human RPE cells. Investig Ophthalmol Vis Sci. 2001;42(7):1660–8.Google Scholar
  16. 16.
    Pollack RM, Donath MY, LeRoith D, Leibowitz F. Anti-inflammatory agents in the treatment of diabetes and its vascular complications. Diabetes Care. 2016. doi: 10.2337/dc513-3015.Google Scholar
  17. 17.
    Chen L, Chen R, Wang H, Liang F. Mechanisms linking inflammation to insulin resistance. Int J Endocrinol. 2015. doi: 10.1155/2015/508409.Google Scholar
  18. 18.
    Song F, Schmidt AM. Glycation and insulin resistance: novel mechanisms and unique targets? Arerioscler Thromb Vasc Biol. 2012. doi: 10.1161/ATVBAHA.111.241877.Google Scholar
  19. 19.
    Hattori Y, Suzuki M, Hattori S, Kasai K. Vascular smooth muscle cell activation by glycated albumin (Amadori adducts). Hypertension. 2002. doi: 10.1161/hy1201.097300.PubMedGoogle Scholar
  20. 20.
    Mukai N, Ninomiya T, Hata J, Hirakawa Y, Ikeda F, Fukuhara M, et al. Association of hemoglobin A1c and glycated albumin with carotid atherosclerosis in community-dwelling Japanese subjects: the Hisayama study. Cardiovasc Diabetol. 2015. doi: 10.1186/s12933-015-0247-7.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Auer J, Berent R, Lassnig E, Eber B. C-reactive protein and coronary artery disease. Jpn Heart J. 2002. doi: 10.1016/j.ehj.2014.11.005.PubMedGoogle Scholar
  22. 22.
    Pu LJ, Lu L, Xu XW, Zhang RY, Zhang Q, Zhang JS. Value of serum glycated albumin and high-sensitivity-C-reactive protein levels in the prediction of presence of coronary artery disease in patients with type 2 diabetes. Cardiovasc Diabetol. 2006. doi: 10.1186/1475-2840-5-27.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Ma X, Hu X, Zhou J, Hao Y, Luo Y, Lu Z, et al. Glycated albumin is more closely correlated with coronary artery disease than 1,5-anhydroglucitol and glycated hemoglobin A1c. Cardiovasc Diabetol. 2015. doi: 10.1186/s12933-014-0166-z.Google Scholar
  24. 24.
    Rubenstein D, Maria Z, Yin W. Glycated albumin modulates endothelial cell thrombogenic and inflammatory responses. J Diabetes Sci Technol. 2011;5(3):703–13.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kolluru G, Bir S, Kevil C. Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med. 2012. doi: 10.1155/2012/918267.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Schalkwijk C, Lieuw-a-Fa M, van Hinsbergh V, Stehouwer C. Pathophysiological role of amadori-glycated proteins in diabetic microangiopathy. Semin Vasc Med. 2002. doi: 10.1055/s-2002-32042.PubMedGoogle Scholar
  27. 27.
    Pan J, Li Q, Zhang L, Jia L, Tang J, Bao Y, et al. Serum glycated albumin predicts the progression of diabetic retinopathy—a five year retrospective longitudinal study. J Diabetes Complicat. 2014. doi: 10.1016/j.jdiacomp.2014.06.015.PubMedCentralGoogle Scholar
  28. 28.
    Loukovaara S, Immonen I, Koistinen R, Hiilesmaa V, Kaaja R. Inflammatory markers and retinopathy in pregnancies complicated with type I diabetes. Eye. 2004. doi: 10.1038/sj.eye.6701499.Google Scholar
  29. 29.
    Semeraro F, Cancarini A, dell’Omo R, Rezzola S, Romano M, Costagliola C. Diabetic retinopathy: vascular and inflammatory disease. J Diabetes Res. 2015. doi: 10.1155/2015/582060.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Abcouwer S. Angiogenic factors and cytokines in diabetic retinopathy. J Clin Cell Immunol. 2011. doi: 10.4172/2155-9899.Google Scholar
  31. 31.
    Ibrahim A, El-Remessy A, Matragoon S, Zhang W, Patel Y, Khan S, et al. Retinal microglial activation and inflammation induced by amadori-glycated albumin in a rat model of diabetes. Diabetes. 2011. doi: 10.2337/db10-1160.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Dong N, Xu B, Shi H, Lu Y. miR-124 regulates Amadori-glycated albumin-induced retinal microglial activation and inflammation by targeting Rac1. Retinal Cell Biol. 2016. doi: 10.1167/iovs.15-18224.Google Scholar
  33. 33.
    Li Y, Wang S. Glycated albumin activates NADPH oxidase in rat mesangial cells through up-regulation of p47phox. Biochem Biophys Res Commun. 2010. doi: 10.1016/j.bbrc.2010.04.084.Google Scholar
  34. 34.
    Vos FE, Schollum JB, Walker RJ. Glycated albumin is the preferred marker for assessing glycemic control in advanced chronic kidney disease. NTD Plus. 2011. doi: 10.1093/ndtplus/sfr140.Google Scholar
  35. 35.
    Cohen M, Lautenslager G, Hud E, Shea E, Wang A, Chen S, et al. Inhibiting albumin glycation attenuates dysregulation of VEGFR-1 and collagen IV subchain production and the development of renal insufficiency. AJP Renal Physiol. 2006. doi: 10.1152/ajprenal.00201.2006.Google Scholar
  36. 36.
    Cohen M, Chen S, Ziyadeh F, Shea E, Hud E, Lautenslager G, et al. Evidence linking glycated albumin to altered glomerular nephrin and VEGF expression, proteinuria, and diabetic nephropathy. Kidney Int. 2005. doi: 10.1111/j.1523-1755.2005.00567.x.Google Scholar
  37. 37.
    Tang S, Leung J, Chan L, Tsang A, Lai KN. Activation of tubular epithelial cells in diabetic nephropathy and the role of peroxisome proligerator-activated receptor-γ agonist. JASN. 2006. doi: 10.1681/ASN.2005101113.Google Scholar
  38. 38.
    Park J, Song J, Park Y, Lee S, Lee S. Glycated albumin increases with disease activity in rheumatoid factor positive rheumatoid arthritis patients with normal fasting glucose and HbA1c. Jt Bone Spine. 2016. doi: 10.1016/j.jbspin.2016.01.011.Google Scholar
  39. 39.
    Shim E, Babu J. Glycated albumin produced in diabetic hyperglycemia promotes monocyte secretion of inflammatory cytokines and bacterial adherence to epithelial cells. J Periodontal Res. 2014. doi: 10.1111/jre.12194.PubMedGoogle Scholar
  40. 40.
    Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Investig. 2003;111(12):1805–12.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kennedy L, Pilar SM, Meneghini L, Lo M, Cohen MP. Anti-glycation and anti-albuminuric effects of GLY-230 in human diabetes. Am J Nephrol. 2010;31:110–6.CrossRefPubMedGoogle Scholar
  42. 42.
    Donath MY. Multiple benefits of targeting inflammation in the treatment of type 2 diabetes. Diabetologia. 2016. doi: 10.1007/s00125-016-3873-z.PubMedGoogle Scholar
  43. 43.
    Koga M, Hirata T, Kasayama S, Ishizaka Y, Yamakado M. Body mass index negatively regulates glycated albumin through insulin secretion in patients with type 2 diabetes mellitus. Clin Chim Acta. 2015. doi: 10.1016/j.ccs.2014.07.035.Google Scholar
  44. 44.
    Koga M, Otsuki M, Matsumoto S, Saito H, Mukai M, Kasayama S. Negative association of obesity and its related chronic inflammation with serum glycated albumin but not glycated hemoglobin levels. Clin Chim Acta. 2007. doi: 10.1016/j.cca.2006.10.013.PubMedGoogle Scholar
  45. 45.
    Varghese A, Asha NS, Celine TM, Prasanna D. Inflammatory markers in type II diabetes mellitus. Pharm J. 2015;4(7):64–6.Google Scholar
  46. 46.
    Gustavsson CG, Agardh CD. Markers of inflammation in patients with coronary artery disease are also associated with glycosylated haemoglobin A within the normal range. Eur Heart J. 2004. doi: 10.1016/j.ehj.2004.09.008.PubMedGoogle Scholar
  47. 47.
    Shafi T, Sozio S, Plantinga L, Jaar B, Kim E, Parekh R, et al. Serum fructosamine and glycated albumin and risk of mortality and clinical outcomes in hemodialysis patients. Diabetes Care. 2012. doi: 10.2337/dc12-1896.PubMedGoogle Scholar
  48. 48.
    DeCoux A, Tian Y, DeLeon-Pennell K, Nguyen N, de Castro Brás L, Flynn E, et al. Plasma glycoproteomics reveals sepsis outcomes linked to distinct proteins in common pathways*. Crit Care Med. 2015. doi: 10.1097/CCM.0000000000001134.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Kate C, Parhar RS, Saleh SS, Meyer BF, Kwaasi AA, Hammami MM, et al. RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). J Leukoc Biol. 2002;71(3):1122–33.Google Scholar
  50. 50.
    Neelofar K, Arif Z, Alam K, Ahmad J. Hyperglycemia induced structural and functional changes in human serum albumin of diabetic patients: a physico-chemical study. Mol Biosyst. 2016. doi: 10.1039/C6MB00324A.PubMedGoogle Scholar
  51. 51.
    Rondeau P, Bourdon E. The glycation of albumin: structural and functional impacts. Biochimie. 2011. doi: 10.1016/j.biochi.2010.003.PubMedGoogle Scholar
  52. 52.
    Arasteh A, Farahi S, Habibi-Rezaei M, Moosavi-Movahedi A. Glycated albumin: an overview of the In Vitro models of an In Vivo potential disease marker. J Diabetes Metab Disord. 2014. doi: 10.1186/2251-6581-13-49.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Surgery (Emeritus)University of California IrvineIrvineUSA
  2. 2.Epinex Diagnostics, Inc.TustinUSA
  3. 3.Undergraduate Student of Biomedical EngineeringUniversity of California IrvineIrvineUSA

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