Skip to main content

Advertisement

SpringerLink
Log in

Beyond HbA1c and Glucose: the Role of Nontraditional Glycemic Markers in Diabetes Diagnosis, Prognosis, and Management

  • Diabetes Epidemiology (NM Maruthur, Section Editor)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Fasting glucose and hemoglobin A1c (HbA1c) are the standard measures for diagnosis and monitoring of diabetes. There has been recent interest in nontraditional markers of hyperglycemia, including fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG), as alternatives or adjuncts to standard measures. There is a growing literature linking these nontraditional markers with microvascular and macrovascular complications. Fructosamine and glycated albumin have also been shown to improve identification of persons with diabetes. However, long-term prospective studies with clinical outcomes are lacking. Some modern laboratory assays for fructosamine, glycated albumin, and 1,5-AG have excellent performance. Expanded use of these tests has the potential to improve diabetes care as these measures may overcome limitations of HbA1c in certain patients, complement traditional measures by providing additional information on shorter-term glycemic control, and improve risk stratification for diabetes and its complications. Nonetheless, studies are needed to demonstrate if their routine use will benefit patients and improve outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Standards of medical care in diabetes–2014. Diabetes Care. 2014;37(Suppl 1):S14–80. doi:10.2337/dc14-S014.

  2. International A, Committee E, Diabe- A, Federation ID, Committee IE, International T. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32(7):1327–34.

    Article  Google Scholar 

  3. Rydén L, Grant PJ, Anker SD, et al. ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration. Eur Heart J. 2013;34(39):3035–87. doi:10.1093/eurheartj/eht108.

    Article  PubMed  Google Scholar 

  4. Consultation IDF. WHO IRIS: definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia: report of a WHO/IDF consultation. 2006. Available at: http://apps.who.int/iris/handle/10665/43588. Accessed 29 Mar 2014.

  5. World Health Organization. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus: abbreviated report of a WHO consultation. 2011;1–25.

  6. International Diabetes Federation Clinical Guidelines Task Force. Global guideline for type 2 diabetes. 2012;1–52. doi:10.1016/j.diabres.2012.10.001.

  7. Sacks DB. A1C versus glucose testing: a comparison. Diabetes Care. 2011;34(2):518–23. doi:10.2337/dc10-1546. This commentary discusses the current clinical utility of HbA1c, as well as its limitations. The author mentions fructosamine and glycated albumin as potential alternatives to HbA1c and , however, also notes the need for additional studies since there is a lack of data linking these markers to clinical outcomes from clinical trials and prospective studies, as well as no established clinical cut-points for use in persons with diabetes.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Inzucchi SE. Clinical practice. Diagnosis of diabetes. N Engl J Med. 2012;367(6):542–50. doi:10.1056/NEJMcp1103643.

    Article  CAS  PubMed  Google Scholar 

  9. Sacks DB. Hemoglobin A1c in diabetes: panacea or pointless? Diabetes. 2013;62(1):41–3. doi:10.2337/db12-1485.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. True MW. Circulating biomarkers of glycemia in diabetes management and implications for personalized medicine. J Diabetes Sci Technol. 2009;3(4):743–7. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2769973&tool=pmcentrez&rendertype=abstract.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Johns Hopkins POC-IT Guides: alternative markers of glycemia: fructosamine, glycated albumin, 1,5-AG. Available at: http://www.hopkinsguides.com/hopkins/ub/view/Johns_Hopkins_Diabetes_Guide/547055/all/Alternative_markers_of_glycemia:_fructosamine__glycated_albumin__1_5_AG. Accessed 20 June 2014.

  12. Joslin Diabetes Center: Home blood glucose (sugar) monitoring, hemoglobin A1C testing, and fructosamine tests. Available at: http://www.joslin.org/info/home_blood_glucose_sugar_monitoring_hemoglobin_a1c_testing_and_fructosamine_tests.html. Accessed 20 June 2014.

  13. Goldstein DE, Little RR, Lorenz RA, et al. Tests of glycemia in diabetes. Diabetes Care. 2004;27(7):1761–73. doi:10.2337/diacare.27.7.1761.

    Article  PubMed  Google Scholar 

  14. Selvin E, Crainiceanu CM, Brancati FL, Coresh J. Short-term variability in measures of glycemia and implications for the classification of diabetes. Arch Intern Med. 2007;167(14):1545–51. doi:10.1001/archinte.167.14.1545.

    Article  CAS  PubMed  Google Scholar 

  15. Meigs JB, Nathan DM, Cupples LA, Wilson PWF, Singer DE. Tracking of glycated hemoglobin in the original cohort of the Framingham Heart Study. J Clin Epidemiol. 1996;49(4):411–7. doi:10.1016/0895-4356(95)00513-7.

    Article  CAS  PubMed  Google Scholar 

  16. Little RR, Rohlfing CL. The long and winding road to optimal HbA1c measurement. Clin Chim Acta. 2013;418:63–71. doi:10.1016/j.cca.2012.12.026.

    Article  CAS  PubMed  Google Scholar 

  17. Little RR, Rohlfing CL, Sacks DB. Status of hemoglobin A1c measurement and goals for improvement: from chaos to order for improving diabetes care. Clin Chem. 2011;57(2):205–14. doi:10.1373/clinchem.2010.148841.

    Article  CAS  PubMed  Google Scholar 

  18. Rohlfing CL, Parvin CA, Sacks DB, Little RR. Comparing analytic performance criteria: evaluation of HbA1c certification criteria as an example. Clin Chim Acta. 2014;433:259–63.

    Article  CAS  PubMed  Google Scholar 

  19. Sacks DB, John WG. Interpretation of hemoglobin a1c values. JAMA. 2014;311(22):2271–2. doi:10.1001/jama.2014.6342.

    Article  CAS  PubMed  Google Scholar 

  20. Armbruster DA. Fructosamine: structure, analysis, and clinical usefulness. Clin Chem. 1987;33(12):2153–63. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3319287. Accessed 5 Apr 2014.

    CAS  PubMed  Google Scholar 

  21. Buse JB, Freeman JLR, Edelman SV, Jovanovic L, McGill JB. Serum 1,5-anhydroglucitol (GlycoMark): a short-term glycemic marker. Diabetes Technol Ther. 2003;5(3):355–63. doi:10.1089/152091503765691839.

    Article  CAS  PubMed  Google Scholar 

  22. Dungan KM. (GlycoMark ™) as a marker of short-term glycemic control and glycemic excursions. 2008;9–19.

  23. Kim WJ, Park C-Y. 1,5-Anhydroglucitol in diabetes mellitus. Endocrine. 2013;43(1):33–40. doi:10.1007/s12020-012-9760-6.

    Article  CAS  PubMed  Google Scholar 

  24. Yamanouchi T, Akanuma Y. Serum 1,5-anhydroglucitol (1,5 AG): new clinical marker for glycemic control. Diabetes Res Clin Pract. 1994;24(Suppl):S261–8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7859616. Accessed 25 Jul 2014.

    Article  PubMed  Google Scholar 

  25. Yamanouchi T. Clinical usefulness of glycaemic control. Lancet. 1994;347:1514–8.

    Article  Google Scholar 

  26. Ai M, Otokozawa S, Schaefer EJ, et al. Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus. Clin Chim Acta. 2009;406(1–2):71–4. doi:10.1016/j.cca.2009.05.015.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Juraschek SP, Steffes MW, Selvin E. Associations of alternative markers of glycemia with hemoglobin A(1c) and fasting glucose. Clin Chem. 2012;58(12):1648–55. doi:10.1373/clinchem.2012.188367.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Nathan DM, McGee P, Steffes MW, Lachin JM. Relationship of glycated albumin to blood glucose and HbA1c values and to retinopathy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study. Diabetes. 2014;63(1):282–90. doi:10.2337/db13-0782. This was an important study conducted in a subsample of participants from the Diabetes Control and Complications Trial (DCCT), to assess the association of short-term and intermediate glycemia on microvascular and macrovascular complications in persons with type 1 diabetes. Over a mean of 6.5 years of follow-up, this paper reported similar associations of HbA1c and glycated albumin with microvascular complications.

    Article  CAS  PubMed  Google Scholar 

  29. Selvin E, Rawlings AM, Grams M, et al. Fructosamine and glycated albumin for risk stratification and prediction of incident diabetes and microvascular complications: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study. Lancet Diabetes Endocrinol. 2014;2(4):279–88. doi:10.1016/S2213-8587(13)70199-2. This has been the largest population-based study, with the longest follow-up, to assess prospective associations of fructosamine and glycated albumin with incident diabetes and microvascular outcomes in persons with and without diabetes. This study included more than 12,000 participants (nearly 1,000 with diabetes), who were followed for about 20 years.

    Article  PubMed  Google Scholar 

  30. Yang C, Li H, Wang Z, et al. Glycated albumin is a potential diagnostic tool for diabetes mellitus. Clin Med (Northfield Il). 2012;12(6):568–71. doi:10.7861/clinmedicine.12-6-568.

    Article  Google Scholar 

  31. Beck R, Steffes M, Xing D, et al. The interrelationships of glycemic control measures: HbA1c, glycated albumin, fructosamine, 1,5-anhydroglucitrol, and continuous glucose monitoring. Pediatr Diabetes. 2011;12(8):690–5. doi:10.1111/j.1399-5448.2011.00764.x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Jung CH, Hwang Y-C, Kim KJ, et al. Development of an HbA1c-based conversion equation for estimating glycated albumin in a Korean population with a wide range of glucose intolerance. PLoS One. 2014;9(4):e95729. doi:10.1371/journal.pone.0095729.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Inoue K, Tsujimoto T, Yamamoto-Honda R, et al. A newer conversion equation for the correlation between HbA1c and glycated albumin. Endocr J. 2014. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24681757. Accessed 4 May 2014.

  34. Tahara Y. Analysis of the method for conversion between levels of HbA1c and glycated albumin by linear regression analysis using a measurement error model. Diabetes Res Clin Pract. 2009;84(3):224–9. doi:10.1016/j.diabres.2009.03.014.

    Article  CAS  PubMed  Google Scholar 

  35. Selvin E, Rawlings AM, Grams M, Klein R, Steffes M, Coresh J. Association of 1,5-Anhydroglucitol with Diabetes and Microvascular Conditions. Clin Chem. 2014. doi:10.1373/clinchem.2014.229427

  36. Gambino R. Glucose. A simple molecule that is not simple to quantify. Clin Chem. 2007;53(12):2040–1. doi:10.1373/clinchem.2007.094466.

  37. Selvin E, Francis LM, Ballantyne CM, et al. Nontraditional markers of glycemia: associations with microvascular conditions. Diabetes Care. 2011;34(4):960–7. doi:10.2337/dc10-1945.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. He B-B, Wei L, Gu Y-J, et al. Factors associated with diabetic retinopathy in Chinese patients with type 2 diabetes mellitus. Int J Endocrinol. 2012;2012:157940. doi:10.1155/2012/157940.

    PubMed Central  PubMed  Google Scholar 

  39. Morita S, Kasayama S, Deguchi R, et al. Glycated albumin, rather than Hba1c, reflects diabetic retinopathy in patients with type 2 diabetes mellitus. J Diabetes Metab. 2013;4(6):4–7. doi:10.4172/2155-6156.1000278.

    Article  Google Scholar 

  40. Mukai N, Yasuda M, Ninomiya T, et al. Thresholds of various glycemic measures for diagnosing diabetes based on prevalence of retinopathy in community-dwelling Japanese subjects: the Hisayama Study. Cardiovasc Diabetol. 2014;13(1):45. doi:10.1186/1475-2840-13-45.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Furusyo N, Koga T, Ai M, et al. Plasma glycated albumin level and atherosclerosis: results from the Kyushu and Okinawa Population Study (KOPS). Int J Cardiol. 2013;167(5):2066–72. doi:10.1016/j.ijcard.2012.05.045.

    Article  PubMed  Google Scholar 

  42. Kondaveeti SB, Kumaraswamy D, Mishra S, Kumar RA, Shaker IA. Evaluation of glycated albumin and microalbuminuria as early risk markers of nephropathy in type 2 diabetes mellitus. J Clin Diagn Res. 2013;7(7):1280–3. doi:10.7860/JCDR/2013/5145.3117.

    PubMed Central  PubMed  Google Scholar 

  43. Shen Y, Pu LJ, Lu L, Zhang Q, Zhang RY, Shen WF. Serum advanced glycation end-products and receptors as prognostic biomarkers in diabetics undergoing coronary artery stent implantation. Can J Cardiol. 2012;28(6):737–43. doi:10.1016/j.cjca.2012.08.015.

    Article  PubMed  Google Scholar 

  44. Lu L, Pu LJ, Xu XW, et al. Association of serum levels of glycated albumin, C-reactive protein and tumor necrosis factor-alpha with the severity of coronary artery disease and renal impairment in patients with type 2 diabetes mellitus. Clin Biochem. 2007;40(11):810–6. doi:10.1016/j.clinbiochem.2007.03.022.

    Article  CAS  PubMed  Google Scholar 

  45. Jin C, Lu L, Zhang RY, et al. Association of serum glycated albumin, C-reactive protein and ICAM-1 levels with diffuse coronary artery disease in patients with type 2 diabetes mellitus. Clin Chim Acta. 2009;408(1–2):45–9. doi:10.1016/j.cca.2009.07.003.

    Article  CAS  PubMed  Google Scholar 

  46. Lu L, Pu LJ, Zhang Q, et al. Increased glycated albumin and decreased esRAGE levels are related to angiographic severity and extent of coronary artery disease in patients with type 2 diabetes. Atherosclerosis. 2009;206(2):540–5. doi:10.1016/j.atherosclerosis.2008.12.045.

    Article  CAS  PubMed  Google Scholar 

  47. Lu L, Jin Pu L, Chen QJ, et al. Increased glycated albumin and decreased esRAGE concentrations are associated with in-stent restenosis in Chinese diabetic patients. Clin Chim Acta. 2008;396(1–2):33–7. doi:10.1016/j.cca.2008.06.019.

    Article  CAS  PubMed  Google Scholar 

  48. Song SO, Kim KJ, Lee B-W, Kang ES, Cha BS, Lee HC. Serum glycated albumin predicts the progression of carotid arterial atherosclerosis. Atherosclerosis. 2012;225(2):450–5. doi:10.1016/j.atherosclerosis.2012.09.005.

    Article  CAS  PubMed  Google Scholar 

  49. Moon JH, Chae MK, Kim KJ, et al. Decreased endothelial progenitor cells and increased serum glycated albumin are independently correlated with plaque-forming carotid artery atherosclerosis in type 2 diabetes patients without documented ischemic disease. Circ J. 2012;76(9):2273–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22664650. Accessed 4 May 2014.

    Article  CAS  PubMed  Google Scholar 

  50. Shen Y, Pu LJ, Lu L, Zhang Q, Zhang RY, Shen WF. Glycated albumin is superior to hemoglobin A1c for evaluating the presence and severity of coronary artery disease in type 2 diabetic patients. Cardiology. 2012;123(2):84–90. doi:10.1159/000342055.

    Article  CAS  PubMed  Google Scholar 

  51. Shen Y, Lu L, Ding FH, et al. Association of increased serum glycated albumin levels with low coronary collateralization in type 2 diabetic patients with stable angina and chronic total occlusion. Cardiovasc Diabetol. 2013;12(1):165. doi:10.1186/1475-2840-12-165.

    Article  PubMed  Google Scholar 

  52. Fujiwara T, Yoshida M, Yamada H, et al. Lower 1,5-anhydroglucitol is associated with denovo coronary artery disease in patients at high cardiovascular risk. Heart Vessels. 2014. doi:10.1007/s00380-014-0502-y.

  53. Kim WJ, Park CY, Park SE, et al. Serum 1,5-anhydroglucitol is associated with diabetic retinopathy in type 2 diabetes. Diabet Med. 2012;29(9):1184–90. doi:10.1111/j.1464-5491.2012.03613.x.

    Article  CAS  PubMed  Google Scholar 

  54. Watanabe K, Suzuki T, Ouchi M, et al. Relationship between postprandial glucose level and carotid artery stiffness in patients without diabetes or cardiovascular disease. BMC Cardiovasc Disord. 2013;13(1):11. doi:10.1186/1471-2261-13-11.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Cohen RM, LeCaire TJ, Lindsell CJ, Smith EP, D’Alessio DJ. Relationship of prospective GHb to glycated serum proteins in incident. Diabetes Care. 2008;31(1):151–3. doi:10.2337/dc07-1465.Additional.

    Article  CAS  PubMed  Google Scholar 

  56. Cardoso CRL, Salles GF. Predictors of development and progression of microvascular complications in a cohort of Brazilian type 2 diabetic patients. J Diabetes Complications. 2008;22(3):164–70. doi:10.1016/j.jdiacomp.2007.02.004.

    Article  PubMed  Google Scholar 

  57. Watanabe M, Kokubo Y, Higashiyama A, Ono Y, Miyamoto Y, Okamura T. Serum 1,5-anhydro-D-glucitol levels predict first-ever cardiovascular disease: an 11-year population-based cohort study in Japan, the Suita study. Atherosclerosis. 2011;216(2):477–83. doi:10.1016/j.atherosclerosis.2011.02.033. This was a large population-based prospective study with long-term follow-up. It included approximately 2,000 persons (only about 30 people with diabetes) and assessed the association of 1,5-AG with incident cardiovascular events over about 11 years.

    Article  CAS  PubMed  Google Scholar 

  58. Colagiuri S, Dickinson S, Girgis S, Colagiuri R. National evidence based guideline for blood glucose control in type 2 diabetes. Diabetes Aust NHMRC. 2009.

  59. Kesavadev J, Sadikot S, Wangnoo S, et al. Consensus guidelines for glycemic monitoring in type 1/type 2 & GDM. Diabetes Metab Syndr Clin Res Rev. 2014. doi:10.1016/j.dsx.2014.04.030.

    Google Scholar 

  60. Sacks DB, Arnold M, Bakris GL, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care. 2011;34(6):e61–99. doi:10.2337/dc11-9998.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Type 2 diabetes: National Clinical Guideline for management in primary and secondary care (update). London: 2008.

  62. Diabetes UK Guide to diabetes: testing. Available at: http://www.diabetes.org.uk/Guide-to-diabetes/Monitoring/Testing/. Accessed 20 June 2014.

  63. Association for clinical biochemistry: fructosamine (plasma, serum). Available at: http://www.acb.org.uk/docs/default-source/amalc/fructosamine-3.pdf. Accessed 20 June 2014.

  64. Araki T, Ishikawa Y, Okazaki H, et al. Introduction of glycated albumin measurement for all blood donors and the prevalence of a high glycated albumin level in Japan. J Diabetes Investig. 2012;3(6):492–7. doi:10.1111/j.2040-1124.2012.00224.x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Upton J, Lever M, Sadler WA, George PM, Boswell DR. The quality of performance of the fructosamine test. N Z Med J. 1988;101(854):606–8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3173855. Accessed 19 Apr 2014.

    CAS  PubMed  Google Scholar 

  66. Cefalu WT, Bell-Farrow AD, Petty M, Izlar C, Smith JA. Clinical validation of a second-generation fructosamine assay. Clin Chem. 1991;37(7):1252–6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1855298. Accessed 29 Jul 2014.

    CAS  PubMed  Google Scholar 

  67. Shafi T, Sozio SM, Plantinga LC, et al. Serum fructosamine and glycated albumin and risk of mortality and clinical outcomes in hemodialysis patients. Diabetes Care. 2013;36(6):1522–33. doi:10.2337/dc12-1896. This was a large prospective cohort study of persons on hemodialysis over a median follow-up of 3.5 years, and describes associations of fructosamine and glycated albumin with clinical outcomes, which had not been previously described in this population.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Executive summary: standards of medical care in diabetes–2014. Diabetes Care. 2014;37 Suppl 1(January):S5–13. doi:10.2337/dc14-S005.

  69. Shima K, Komatsu M, Noma Y, Miya K. Glycated albumin (GA) is more advantageous than hemoglobin A1c for evaluating the efficacy of sitagliptin in achieving glycemic control in patients with type 2 diabetes. Intern Med. 2014;53(8):829–35. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24739602. Accessed 4 May 2014.

    Article  CAS  PubMed  Google Scholar 

  70. Moura BP, Amorim PR, Silva BP, Franceschini SC, Reis JS, Marins JC. Effect of a short-term exercise program on glycemic control measured by fructosamine test in type 2 diabetes patients. Diabetol Metab Syndr. 2014;6(1):16. doi:10.1186/1758-5996-6-16.

    Article  PubMed Central  PubMed  Google Scholar 

  71. Yoshiuchi K, Matsuhisa M, Katakami N, et al. Glycated albumin is a better indicator for glucose excursion than glycated hemoglobin in type 1 and type 2 diabetes. Endocr J. 2008;55(3):503–7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18445997. Accessed 20 May 2014.

    Article  CAS  PubMed  Google Scholar 

  72. Suwa T, Ohta A, Matsui T, et al. Relationship between clinical markers of glycemia and glucose excursion evaluated by continuous glucose monitoring (CGM). Endocr J. 2010;57(2):135–40. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19926921. Accessed 19 May 2014.

    Article  CAS  PubMed  Google Scholar 

  73. Koga M, Murai J, Morita S, Saito H, Kasayama S. Comparison of annual variability in HbA1c and glycated albumin in patients with type 1 vs. type 2 diabetes mellitus. J Diabetes Complications. 2013;27(3):211–3. doi:10.1016/j.jdiacomp.2012.12.001.

    Article  PubMed  Google Scholar 

  74. Hirsch IB, Brownlee M. Beyond hemoglobin A1c—need for additional markers of risk for diabetic microvascular complications. JAMA. 2010;303(22):2291–2. doi:10.1001/jama.2010.785.

    Article  CAS  PubMed  Google Scholar 

  75. Clinical Guide: 1,5-Anhydroglucitol (1,5-AG) blood test. Available at: http://www.glycomark.com/docs/default-source/downloads/glycomarkclinicalguide.pdf?sfvrsn=8. Accessed 20 June 2014.

  76. Rubinow KB, Hirsch IB. Reexamining metrics for glucose control. JAMA. 2014;305(11):1132–3.

    Article  Google Scholar 

  77. Won JC, Park C-Y, Park H-S, et al. 1,5-Anhydroglucitol reflects postprandial hyperglycemia and a decreased insulinogenic index, even in subjects with prediabetes and well-controlled type 2 diabetes. Diabetes Res Clin Pract. 2009;84(1):51–7. doi:10.1016/j.diabres.2009.01.002.

    Article  CAS  PubMed  Google Scholar 

  78. Suh S, Joung JY, Jin SM, et al. Strong correlation between glycaemic variability and total glucose exposure in type 2 diabetes is limited to subjects with satisfactory glycaemic control. Diabetes Metab. 2014. doi:10.1016/j.diabet.2014.01.006.

    PubMed  Google Scholar 

  79. Sun J, Dou J-T, Wang X-L, et al. Correlation between 1,5-anhydroglucitol and glycemic excursions in type 2 diabetic patients. Chin Med J (Engl). 2011;124(22):3641–5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22340217. Accessed 4 May 2014.

    CAS  Google Scholar 

  80. Furusyo N, Koga T, Ai M, et al. Utility of glycated albumin for the diagnosis of diabetes mellitus in a Japanese population study: results from the Kyushu and Okinawa Population Study (KOPS). Diabetologia. 2011;54(12):3028–36. doi:10.1007/s00125-011-2310-6.

    Article  CAS  PubMed  Google Scholar 

  81. Zhang T, He H, Yang H-L, et al. Study of glycated albumin cut-off point in diabetes mellitus and impaired glucose regulation. Sichuan Da Xue Xue Bao Yi Xue Ban. 2014;45(2):274–7. 298. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24749356. Accessed 4 May 2014.

    PubMed  Google Scholar 

  82. Li Q, Pan J, Ma X, et al. Combined utility of hemoglobin A1c and glycated albumin in diabetic screening. Zhonghua Yi Xue Za Zhi. 2011;91(26):1813–6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22093780. Accessed 4 May 2014.

    CAS  PubMed  Google Scholar 

  83. Ma X-J, Pan J-M, Bao Y-Q, et al. Combined assessment of glycated albumin and fasting plasma glucose improves the detection of diabetes in Chinese subjects. Clin Exp Pharmacol Physiol. 2010;37(10):974–9. doi:10.1111/j.1440-1681.2010.05417.x.

    Article  CAS  PubMed  Google Scholar 

  84. Garber AJ, Handelsman Y, Einhorn D, et al. Diagnosis and management of prediabetes in the continuum of hyperglycemia: when do the risks of diabetes begin? A consensus statement from the American College of Endocrinology and the American Association of Clinical Endocrinologists. Endocr Pract. 2008;14(7):933–46. doi:10.4158/EP.14.7.933.

    Article  PubMed  Google Scholar 

  85. Juraschek SP, Steffes MW, Miller ER, Selvin E. Alternative markers of hyperglycemia and risk of diabetes. Diabetes Care. 2012;35(11):2265–70. doi:10.2337/dc12-0787.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Shipman KE, Jawad M, Sullivan KM, Ford C, Gama R. HbA1c is a reliable test for type 2 diabetes in primary care irrespective of chronic kidney disease. BMJ. 2014;348:g3780. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24942952. Accessed 25 Jul 2014.

    Article  PubMed  Google Scholar 

  87. Peacock TP, Shihabi ZK, Bleyer AJ, et al. Comparison of glycated albumin and hemoglobin A(1c) levels in diabetic subjects on hemodialysis. Kidney Int. 2008;73(9):1062–8. doi:10.1038/ki.2008.25.

    Article  CAS  PubMed  Google Scholar 

  88. Little RR, Rohlfing CL, Tennill AL, et al. Measurement of Hba(1C) in patients with chronic renal failure. Clin Chim Acta. 2013;418:73–6. doi:10.1016/j.cca.2012.12.022.

    Article  CAS  PubMed  Google Scholar 

  89. Sany D, Elshahawy Y, Anwar W. Glycated albumin versus glycated hemoglobin as glycemic indicator in hemodialysis patients with diabetes mellitus: variables that influence. Saudi J Kidney Dis Transpl. 2013;24(2):260–73. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23538348. Accessed 29 Mar 2014.

  90. Chen F-K, Sun X-F, Zhang D, et al. Glycated albumin may be a choice, but not an alternative marker of glycated hemoglobin for glycemic control assessment in diabetic patients undergoing maintenance hemodialysis. Chin Med J (Engl). 2013;126(17):3295–300. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24033952. Accessed 29 Mar 2014.

    CAS  Google Scholar 

  91. Meyer L, Chantrel F, Imhoff O, et al. Glycated albumin and continuous glucose monitoring to replace glycated haemoglobin in patients with diabetes treated with haemodialysis. Diabet Med. 2013;30(11):1388–9. doi:10.1111/dme.12294.

    Article  CAS  PubMed  Google Scholar 

  92. Freedman BI, Shenoy RN, Planer JA, et al. Comparison of glycated albumin and hemoglobin A1c concentrations in diabetic subjects on peritoneal and hemodialysis. Perit Dial Int. 2010;30(1):72–9. doi:10.3747/pdi.2008.00243.

    Article  CAS  PubMed  Google Scholar 

  93. Nagayama H, Inaba M, Okabe R, et al. Glycated albumin as an improved indicator of glycemic control in hemodialysis patients with type 2 diabetes based on fasting plasma glucose and oral glucose tolerance test. Biomed Pharmacother. 2009;63(3):236–40. doi:10.1016/j.biopha.2008.04.002.

    Article  CAS  PubMed  Google Scholar 

  94. Park H-I, Kim YS, Lee J, Kim Y, Shin SJ. Performance characteristics of glycated albumin and its clinical usefulness in diabetic patients on hemodialysis. Korean J Lab Med. 2009;29(5):406–14. doi:10.3343/kjlm.2009.29.5.406.

    Article  CAS  PubMed  Google Scholar 

  95. Yamada S, Inaba M, Shidara K, et al. Association of glycated albumin, but not glycated hemoglobin, with peripheral vascular calcification in hemodialysis patients with type 2 diabetes. Life Sci. 2008;83(13–14):516–9. doi:10.1016/j.lfs.2008.08.001.

    Article  CAS  PubMed  Google Scholar 

  96. Kumeda Y, Inaba M, Shoji S, et al. Significant correlation of glycated albumin, but not glycated haemoglobin, with arterial stiffening in haemodialysis patients with type 2 diabetes. Clin Endocrinol (Oxf). 2008;69(4):556–61. doi:10.1111/j.1365-2265.2008.03202.x.

    Article  CAS  Google Scholar 

  97. Mittman N, Desiraju B, Fazil I, et al. Serum fructosamine versus glycosylated hemoglobin as an index of glycemic control, hospitalization, and infection in diabetic hemodialysis patients. Kidney Int Suppl. 2010;117:S41–5. doi:10.1038/ki.2010.193.

    Article  CAS  PubMed  Google Scholar 

  98. Murea M, Moran T, Russell GB, et al. Glycated albumin, not hemoglobin A1c, predicts cardiovascular hospitalization and length of stay in diabetic patients on dialysis. Am J Nephrol. 2012;36(5):488–96. doi:10.1159/000343920.

    Article  CAS  PubMed  Google Scholar 

  99. Ding FH, Lu L, Zhang RY, et al. Impact of elevated serum glycated albumin levels on contrast-induced acute kidney injury in diabetic patients with moderate to severe renal insufficiency undergoing coronary angiography. Int J Cardiol. 2013;167(2):369–73. doi:10.1016/j.ijcard.2011.12.101.

    Article  PubMed  Google Scholar 

  100. Fukuoka K, Nakao K, Morimoto H, et al. Glycated albumin levels predict long-term survival in diabetic patients undergoing haemodialysis. Nephrology (Carlton). 2008;13(4):278–83. doi:10.1111/j.1440-1797.2007.00864.x.

    Article  CAS  Google Scholar 

  101. Freedman BI, Andries L, Shihabi ZK, et al. Glycated albumin and risk of death and hospitalizations in diabetic dialysis patients. Clin J Am Soc Nephrol. 2011;6(7):1635–43. doi:10.2215/CJN.11491210. This was one of the first prospective studies to assess associations of glycated albumin with clinical outcomes in a population of persons with diabetes and ESRD. It included 444 participants with diabetes and included follow-up just over 2 years.

    Article  CAS  PubMed  Google Scholar 

  102. Isshiki K, Nishio T, Isono M, et al. Glycated albumin predicts the risk of mortality in type 2 diabetic patients on hemodialysis: evaluation of a target level for improving survival. Ther Apher Dial. 2013. doi:10.1111/1744-9987.12123.

    PubMed  Google Scholar 

  103. Ma W-Y, Wu C-C, Pei D, et al. Glycated albumin is independently associated with estimated glomerular filtration rate in nondiabetic patients with chronic kidney disease. Clin Chim Acta. 2011;412(7–8):583–6. doi:10.1016/j.cca.2010.12.013.

    Article  CAS  PubMed  Google Scholar 

  104. Okada T, Nakao T, Matsumoto H, et al. Influence of proteinuria on glycated albumin values in diabetic patients with chronic kidney disease. Intern Med. 2011;50(1):23–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21212569. Accessed 24 May 2014.

    Article  CAS  PubMed  Google Scholar 

  105. Chen H-S, Wu T-E, Lin H-D, et al. Hemoglobin A(1c) and fructosamine for assessing glycemic control in diabetic patients with CKD stages 3 and 4. Am J Kidney Dis. 2010;55(5):867–74. doi:10.1053/j.ajkd.2009.10.064.

    Article  CAS  PubMed  Google Scholar 

  106. Kim WJ, Park C-Y, Lee K-B, et al. Serum 1,5-anhydroglucitol concentrations are a reliable index of glycemic control in type 2 diabetes with mild or moderate renal dysfunction. Diabetes Care. 2012;35(2):281–6. doi:10.2337/dc11-1462.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  107. Kim S, Min W-K, Chun S, Lee W, Park H-I. Glycated albumin may be a possible alternative to hemoglobin A1c in diabetic patients with anemia. Clin Chem Lab Med. 2011;49(10):1743–7. doi:10.1515/CCLM.2011.646.

    Article  CAS  PubMed  Google Scholar 

  108. Koga M, Hashimoto K, Murai J, et al. Usefulness of glycated albumin as an indicator of glycemic control status in patients with hemolytic anemia. Clin Chim Acta. 2011;412(3–4):253–7. doi:10.1016/j.cca.2010.10.014.

    Article  CAS  PubMed  Google Scholar 

  109. Sugimoto T, Hashimoto M, Hayakawa I, et al. Alterations in HbA1c resulting from the donation of autologous blood for elective surgery in patients with diabetes mellitus. Blood Transfus. 2014;12 Suppl 1:s209–13. doi:10.2450/2013.0271-12.

    PubMed Central  PubMed  Google Scholar 

  110. Kim PS, Woods C, Georgoff P, et al. A1C underestimates glycemia in HIV infection. Diabetes Care. 2009;32(9):1591–3. doi:10.2337/dc09-0177.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  111. Koga M, Kasayama S, Kanehara H, Bando Y. CLD (chronic liver diseases)-HbA1C as a suitable indicator for estimation of mean plasma glucose in patients with chronic liver diseases. Diabetes Res Clin Pract. 2008;81(2):258–62. doi:10.1016/j.diabres.2008.04.012.

    Article  CAS  PubMed  Google Scholar 

  112. Bando Y, Kanehara H, Toya D, Tanaka N, Kasayama S, Koga M. Association of serum glycated albumin to haemoglobin A1C ratio with hepatic function tests in patients with chronic liver disease. Ann Clin Biochem. 2009;46(Pt 5):368–72. doi:10.1258/acb.2009.008231.

    Article  CAS  PubMed  Google Scholar 

  113. Koga M, Murai J, Saito H, et al. 1,5-Anhydroglucitol levels are low irrespective of plasma glucose levels in patients with chronic liver disease. Ann Clin Biochem. 2011;48(Pt 2):121–5. doi:10.1258/acb.2010.010053.

    Article  CAS  PubMed  Google Scholar 

  114. Hashimoto K, Noguchi S, Morimoto Y, et al. A1C but not serum glycated albumin is elevated in late pregnancy owing to iron deficiency. Diabetes Care. 2008;31(10):1945–8. doi:10.2337/dc08-0352.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  115. Hashimoto K, Osugi T, Noguchi S, et al. A1C but not serum glycated albumin is elevated because of iron deficiency in late pregnancy in diabetic women. Diabetes Care. 2010;33(3):509–11. doi:10.2337/dc09-1954.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  116. Metzger BE, Lowe LP, Dyer AR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991–2002. doi:10.1056/NEJMoa0707943.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

C.M. Parrinello is supported by NIH/NHLBI Cardiovascular Epidemiology training grant T32HL007024. E. Selvin is supported by NIH/NIDDK grant R01DK089174. The authors thank Dr. David B. Sacks (Department of Laboratory Medicine, National Institutes of Health) for his thoughtful review of a draft of this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. With regard to the authors’ research cited in this paper, all procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.

Author information

Authors and Affiliations

  1. Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St., Suite 2-600, Baltimore, MD, 21287, USA

    Christina M. Parrinello & Elizabeth Selvin

  2. Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Elizabeth Selvin

Authors
  1. Christina M. Parrinello
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth Selvin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizabeth Selvin.

Additional information

This article is part of the Topical Collection on Diabetes Epidemiology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Parrinello, C.M., Selvin, E. Beyond HbA1c and Glucose: the Role of Nontraditional Glycemic Markers in Diabetes Diagnosis, Prognosis, and Management. Curr Diab Rep 14, 548 (2014). https://doi.org/10.1007/s11892-014-0548-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11892-014-0548-3

Keywords

Search

Navigation