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HbA1c for screening and diagnosis of diabetes mellitus

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Abstract

HbA1c has become the gold standard for monitoring glycemic control in patients with diabetes mellitus. The use of this test has been expanded to diagnose and screen for diabetes mellitus with the endorsement of influential diabetes societies and the World Health Organization. The literature on the use of HbA1c for the diagnosis and screening of diabetes mellitus was critically examined. There is substantial recent literature on this topic with strong advocates for the use of HbA1c to diagnose and screen for diabetes and equally strong detractors for its use. Advocates of the use of HbA1c cite challenges in respect of patient compliance and the analysis of glucose and inconsistency of diagnosis with glucose-based diabetes diagnosis with the elimination or reduction in these challenges in HbA1c-based diagnosis. Detractors of its use cite increased cost, concerns about the availability of HbA1c testing, and the influence of demographic and clinical factors on HbA1c results that make the use of a single-threshold values questionable for different ethnic and age groups. Despite the recommendation of many international diabetes societies that HbA1c be used for screening and diagnosis of diabetes mellitus, there is a wide divergence of opinion on this use

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References

  1. S.W. Wild, G. Roglic, A.G. Green, R. Sicree, H. King, Global prevalence of diabetes. Diabetes Care 27, 1047–1053 (2004)

    Article  PubMed  Google Scholar 

  2. International Diabetes Foundation, Diabetes Atlas, 3rd ed. (IDF, Brussels, 2008)

  3. P. Onkamo, S. Vaänänen, M. Karvonen, J. Tuomilento, Worldwide increase in incidence of type 1 diabetes—the analysis of the data on published incidence trends. Diabetologia 42, 1395–1403 (1999)

    Article  PubMed  CAS  Google Scholar 

  4. M.C. Thomas, S.L. Hardoon, A.O. Papacosta, R.W. Morris, S.G. Wannamethee, A. Sloggett, P.H. Whincup, Evidence of an accelerating increase in prevalence of diagnosed type 2 diabetes in British men, 1978–2005. Diabet. Med. 26, 756–772 (2009)

    Article  Google Scholar 

  5. A. Ohinmaa, J. Jacobs, S. Simpson, J.A. Johnson, The projection of prevalence and cost of diabetes in Canada: 2000 to 2016. Can. J. Diabetes 28, 116–123 (2004)

    Google Scholar 

  6. C.C. Cowie, K.F. Rust, E.S. Ford, M.S. Eberhardt, D.D. Byrd-Holt, C. Li et al., Full accounting of diabetes and pre-diabetes in U.S. populations in 1988–1994 and 2005–2006. Diabetes Care 32, 287–294 (2009)

    Article  PubMed  Google Scholar 

  7. W. Yang, K.H. Yoon, F.B. Hu, Diabetes in Asia. N. Engl. J. Med. 36, 1090–1101 (2010)

    Article  Google Scholar 

  8. J.C. Chan, V. Malik, W. Jia, T. Kadowaki, C.S. Yaijnik, K.H. Yoon, F.B. Hu, Diabetes in Asia: epidemiology, risk factors and pathophysiology. JAMA 301, 2129–2140 (2009)

    Article  PubMed  CAS  Google Scholar 

  9. W.M. Wannazaimoon, M. Suraiami, Prevalence of diabetes, impaired fasting glucose and metabolic syndrome among female Orang Asli community in Penninsular Malaysia. Int. J. Diabetes Dev. Ctries. 30, 118–122 (2010)

    Article  Google Scholar 

  10. G. Roglic, N. Unwin, P.H. Bennett, C. Mathers, J. Tuomilhrto, S. Nag et al., The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care 28, 2130–2135 (2005)

    Article  PubMed  Google Scholar 

  11. ADA, Economic costs of diabetes in the US in 2007. Diabetes Care 32, 1090–1091 (2008)

    Google Scholar 

  12. K. Santos-Rey, P. Fernandez-Riejos, J. Mateo, V. Sanchez-Margalet, R. Gaberna, Glycated hemoglobin vs. the oral glucose tolerance test for the exclusion on impaired glucose tolerance in high-risk individuals. Clin. Chem. Lab. Med. 48, 1719–1722 (2010)

    Article  PubMed  CAS  Google Scholar 

  13. G.T. Ko, J.C. Chan, J. Woo, E. Lau, V.T. Yeung, C.C. Chow et al., The reproducibility and usefulness of the oral glucose tolerance test in screening for diabetes and other cardiovascular risk factors. Clin. Biochem. 35, 62–67 (1998)

    Google Scholar 

  14. A.W. Lyon, E.T. Larsen, A.L. Edwards, The impact of new guidelines for glucose tolerance testing on clinical practice and laboratory services. CMAJ 171(9), 1067–1069 (2004)

    PubMed  Google Scholar 

  15. C.D. Saudek, W.H. Herman, D.B. Sacks, R.M. Bergenstal, D. Edelman, M.B. Davison, A new look at screening and diagnosing diabetes mellitus. J. Clin. Endocrinol. Metab. 93, 447–453 (2008)

    Article  Google Scholar 

  16. International Expert Committee, International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 32, 1327–1334 (2009)

    Google Scholar 

  17. WHO Consultation, Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. WHO website. http://www.who.int/entity/diabetes/publications/report-hba1c_2011.pdf. Accessed 2 Mar 2012

  18. American Association of Endocrinologists, Board of Directors, American College of Endocrinologists Board of Trustees, American Association of Clinical Endocrinologists/American College of Endocrinology statement on the use of Hemoglobin A1c for the diagnosis of diabetes. Endocr. Pract. 16, 1555–1556 (2010)

    Google Scholar 

  19. R.M. Goldberg, A.Y. Cheung, Z. Punthakee, Use of glycated hemoglobin (A1c) in the diagnosis of type 2 diabetes mellitus in adults. Can. J. Diabetes 7, 247–248 (2011)

    Google Scholar 

  20. M.S. Kirkmans, D.M. Kendall, Hemoglobin A1c to diagnosis diabetes; why the controversy over adding a new tool? Clin. Chem. 57, 255–257 (2009)

    Article  Google Scholar 

  21. Z.T. Bloomgarden, D. Einhorn, Hemoglobin A1c in diabetes diagnosis: time for caution. Endocr. Pract. 16, 5–6 (2010)

    PubMed  Google Scholar 

  22. M.J.L. Hare, I.E. Shaw, P.Z. Zimmet, Current controversies in the use of hemoglobin A1c. J. Int. Med. 271, 227–236 (2012)

    Article  CAS  Google Scholar 

  23. S. Malkani, J.P. Mordes, Implications of using hemoglobin A1c for diagnosing diabetes mellitus. Am. J. Med. 124, 395–401 (2010)

    Article  Google Scholar 

  24. E.S. Kilpatrick, Z.T. Bloomgarden, P.Z. Zimmer, Is haemoglobin A1c a step forward for diagnosing diabetes? BMJ 339, 1288–1290 (2009)

    CAS  Google Scholar 

  25. T.N. Higgins, D. Tran, G.S. Cembrowski, C. Shalapay, P. Steele, C. Wiley, Is HbA1c a good screening test for diabetes? Clin. Biochem. 44, 1469–1472 (2011)

    Article  PubMed  CAS  Google Scholar 

  26. D.E. Olson, M.K. Rhee, K. Herrick, D.C. Zemer, J.G. Tvombly, L.S. Phillips, Screening for diabetes and pre-diabetes with proposed A1C-based diagnostic criteria. Diabetes Care 33, 2184–2189 (2010)

    Article  PubMed  Google Scholar 

  27. E. Van ‘t Rift, M.A. Assema, J.M. Rijleliijkhuizen, P.J. Kostense, G. Nijela, J.M. Dekker, Relationship between A1c and glucose levels in the general Dutch population. The new Hoorn Study. Diabetes Care 33, 61–66 (2010)

    Google Scholar 

  28. E.S. Kilpatrick, Z.T. Bloomgarden, P.Z. Zimmer, International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 32, c59 (2009)

  29. D.M. Nathan, International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 12, c160 (2009)

    Article  Google Scholar 

  30. J.B. Buse, Screening for diabetes and prediabetes with the proposed A1C-based diagnostic criteria. Diabetes Care 33, c174 (2010)

  31. D.B. Sacks, The diagnosis of diabetes is changing: how implementation of hemoglobin A1c will impact clinical laboratories. Clin. Chem. 55, 1612–1614 (2009)

    Article  PubMed  CAS  Google Scholar 

  32. D.M. Nathan, International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 12, c160 (2010)

  33. E.S. Kilpatrick, P.W. Maylor, B.G. Keevil, Biological variation of glycated hemoglobin. Implications for diabetes and monitoring. Diabetes Care 21, 261–264 (1998)

    Google Scholar 

  34. T. Higgins, G. Cembrowski, D. Tran, E. Lim, J. Chan, Influence of variables on HbA1c values and the nonheterogeneity of HbA1c reference ranges. J. Diabetes Sci. Technol. 3, 644–648 (2009)

    PubMed  Google Scholar 

  35. L.N. Pani, L. Korenda, J.B. Meigs, C. Driver, S. Charmany, C.S. Fox et al., Effect of aging on A1C levels without diabetes: evidence from the Framingham Offspring study and the National Health and Nutrition Examination Survey 2001–2004. Diabetes Care 31, 1991–1996 (2008)

    Article  PubMed  Google Scholar 

  36. B.B. Arentz, A. Kallner, T. Theowell, The influence of aging on haemoglobin A1c (HbA1c). J. Gerentol. 37, 648–650 (1982)

    Article  Google Scholar 

  37. Y. Hashimoto, A. Futamura, M. Ikushima, Effect of ageing on HbA1c in a working male Japanese population. Diabetes Care 18, 1337–1340 (1995)

    Article  PubMed  CAS  Google Scholar 

  38. Y.C. Yang, F.H. Lu, J.S. Wu, C.J. Chang, Age and sex effects on HbA1c: a study in a healthy Chinese population. Diabetes Care 20, 988–991 (1997)

    Article  PubMed  CAS  Google Scholar 

  39. S.V. Polena, V. Lasseree, M. Fonfrede, J. Delattre, A different approach to analyzing age-related HbA1c values in non-diabetic subjects. Clin. Chem. Lab. Med. 42, 423–428 (2004)

    Google Scholar 

  40. L. Hanberger, U. Samuelsson, B. Lindblad, J. Ludvigsson, A1c in children and adolescents with diabetes in relation to certain clinical parameters. The Swedish childhood registry, SWEDIABKIDS. Diabetes Care 31, 927–929 (2008)

    Article  PubMed  Google Scholar 

  41. D. Dilli, I. Bostanci, Y. Dallar, S. Gücük, Glycohemoglobin screening in adolescents attending to the department of paediatrics at a tertiary hospital in Turkey. Diabetes Res. Clin. Res. 79, 305–309 (2008)

    Article  Google Scholar 

  42. A. Parikh, S. Lipsitz, S. Natarajan, Gender differences in the effect of hemoglobin A1c on mortality in adults with diabetes: findings from a national population based follow up. Circulation 118S, 1134 (abstract) (2008)

  43. W.H. Herman, Y. Ma, G. Owaifo, S. Hafner, S.E. Khan, E.S. Horton et al., Differences in A1c by race and ethnicity among patients with impaired glucose tolerance in the Diabetes Prevention Program. Diabetes Care 30, 2453–2457 (2007)

    Article  PubMed  CAS  Google Scholar 

  44. J.K. Kirk, L.V. Passmore, R.A. Bell, K.M. Narayan, R.B. D’Agostino, T.A. Arcury et al., Disparities between Hispanic and non-Hispanic white adults with diabetes: a meta analysis. Diabetes Care 31, 240–246 (2008)

    Article  PubMed  Google Scholar 

  45. N. De Rekeneire, R.N. Rooks, E.M. Simonsick, R.I. Shorr, L.H. Kuller, A.V. Schwartz et al., Health, aging and body composition in glycemic control in a well-functioning older diabetic population; findings from the health, aging and body composition study. Diabetes Care 26, 1986–1992 (2003)

    Article  PubMed  Google Scholar 

  46. A.S. Adams, F. Khang, C. Mah, R.W. Grant, K. Kleinman, J.B. Meiges, D. Ross-Degnan, Race differences in long-term diabetes management in a HMO. Diabetes Care 28, 2844–2849 (2005)

    Article  PubMed  Google Scholar 

  47. A. Parikh, S. Lipsitz, S. Natarajan, Gender differences in the effect of hemoglobin A1c on mortality in adults with diabetes: findings from a national population based follow up. Circulation 118S, 1134 (abstract) (2009)

  48. H. Ishi, H. Suzuki, T. Baba, K. Nakamura, T. Watanabe, Seasonal variation of glycemic control in type 2 diabetic patients. Diabetes Care 24, 1503 (2001)

    Article  Google Scholar 

  49. M. Sohmiya, I. Kanazawa, Y. Kato, Seasonal changes in body composition and blood HbA1c levels without weight change in male patients with type 2 diabetes treated with insulin. Diabetes Care 27, 1238–1239 (2004)

    Article  PubMed  Google Scholar 

  50. J. Asplund, Seasonal variation in HbA1c in adult patients. Diabetes Care 20, 234 (1997)

    PubMed  CAS  Google Scholar 

  51. S. Norfeldt, J. Ludvigsson, Seasonal variation in intensive treatment of children with type 1 diabetes. J. Pediatr. Endrocrinol. Metab. 13, 429–435 (2000)

    Google Scholar 

  52. T.A. Carney, S.P. Guy, C.D. Helliwell, Seasonal variation in HbA1c in patients with type 2 diabetes mellitus. Diabet. Med. 17, 554–555 (2000)

    Article  PubMed  CAS  Google Scholar 

  53. C.L. Tseng, M. Brimacombe, M. Xie, M. Rajan, H. Wang, J. Kolassa et al., Seasonal patterns in monthly A1c values. Am. J. Epidemiol. 161, 565–574 (2005)

    Article  PubMed  Google Scholar 

  54. H. Gaarde, A.M. Hansen, L.T. Skovgaard, J.M. Christensen, Seasonal and biological variation of blood concentrations of total cholesterol, dehydroepiandrosterone silfate, hemoglobin A1c, IgA, prolactin and free testosterone in health women. Clin. Chem. 46, 551–559 (2000)

    Google Scholar 

  55. T. Higgins, S. Saw, K. Sikaris, C.L. Wiley, C.S. Cembrowski, A.W. Lyon et al., Seasonal variation in hemoglobin A1c: is it the same in both hemispheres? J. Diabetes Sci. Technol. 3, 668–671 (2009)

    PubMed  Google Scholar 

  56. H.S. Chen, T.S. Jap, R.L. Chen, H.D. Lin, A prospective study of glycemic control during holiday time in type 2 diabetes patients. Diabetes Care 27, 326–330 (2004)

    Article  PubMed  Google Scholar 

  57. R.C. Hawkins, Circannual variation in glycohemoglobin in Singapore. Clin. Chim. Acta 411, 18–21 (2010)

    Article  PubMed  CAS  Google Scholar 

  58. P.K. Khera, C.H. Joiner, A. Carruthers, C.J. Lindsell, E.P. Smith, R.S. Franco et al., Evidence for interindividual heterogeneity in the glucose gradient across the human red blood cell membrane and its relationship to hemoglobin glycation. Diabetes 57, 2445–2452 (2008)

    Article  PubMed  CAS  Google Scholar 

  59. J.M. Hempe, R. Gomez, R.J. McCarter, S.A. Chalew, High and low hemoglobin phenotype in type 1 diabetes: a challenge for interpretation of glycemic control. J. Diabetes Complicat. 16, 313–320 (2002)

    Article  PubMed  Google Scholar 

  60. E. Coban, M. Ozdogan, A. Timuragaoglu, Effect of iron deficiency of hemoglobin A1c in nondiabetic patients. Acta Haematol. 112, 126–128 (2004)

    Article  PubMed  CAS  Google Scholar 

  61. P.S. Kim, C. Woods, P. Georgoff, D. Crum, A. Rosenberg, M. Smith et al., Hemoglobin A1c underestimates glycemia in HIV infections. Diabetes Care 32, 1591–1593 (2009)

    Article  PubMed  CAS  Google Scholar 

  62. A.M. Syrjälä, P. Yiöstalo, M.C. Niskanen, M.L. Hnuuttila, Role of smoking and HbA1c level in periodontitis among insulin-dependent diabetic patients. J. Clin. Periodontal. 10, 871–875 (2003)

    Article  Google Scholar 

  63. P.M. Nilsson, S. Gudbörnsdottir, B. Elisson, J. Cederholm, Smoking is associated with increased HbA1c values and microalbuminuria in patients with diabetes-data from the National Diabetes Register in Sweden. Diabetes Metab. 30, 261–268 (2004)

    Article  PubMed  CAS  Google Scholar 

  64. P.D. Greenberg, A.S. Rosman, L.S. Eldeiry, Decline in haemoglobin A1c values in diabetic patients receiving interferon alpha and ribavirin for chronic hepatitis C. J. Viral Hepat. 13, 613–617 (2006)

    Article  PubMed  CAS  Google Scholar 

  65. B.N. Gross, L.B. Cross, J.C. Foard, Falsely low hemoglobin A1c levels in a patient receiving ribavirin and peginterferon alfa-2b for hepatitis C. Pharmacotherapy 29, 121–123 (2009)

    Article  PubMed  CAS  Google Scholar 

  66. L.E. Trask, D. Abbott, H.-K. Lee, Low hemoglobin A1c—good diabetic control? Clin. Chem. 58, 648–649 (2012)

    Article  PubMed  CAS  Google Scholar 

  67. R.R. Little, C.L. Rohlfling, S. Hanson, S. Connolly, T.N. Higgins, C.W. Weylamp et al., Effects of hemoglobin (Hb) E and HbD traits on measurements of glycated Hb (HbA1c) by 23 methods. Clin. Chem. 54, 1277–1282 (2008)

    Article  PubMed  CAS  Google Scholar 

  68. T. Lee, C.W. Weykamp, Y.-W. Lee, J.-W. Kim, C.-S. Ki, Effects of 7 hemoglobin variants on the measurement of glycohemoglobin by 14 analytical methods. Clin. Chem. 53, 2002–2005 (2007)

    Article  Google Scholar 

  69. L. Bry, P.C. Chan, D.B. Sacks, Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin. Chem. 47, 153–163 (2001)

    PubMed  CAS  Google Scholar 

  70. E.L. Frank, L. Moulton, R.R. Little, H.-M. Wiedmeyer, C. Rohlfing, W.L. Roberts, Effects of hemoglobin C and S traits on 7 glycohemoglobin methods. Clin. Chem. 46, 864–867 (2000)

    PubMed  CAS  Google Scholar 

  71. W.L. Roberts, B.K. De, C.M. Hanbury, J.D. Hoyer, W.G. John, T.L. Lambert et al., Effects of hemoglobin C and S traits on eight glycohemoglobin methods. Clin. Chem. 48, 383–385 (2002)

    PubMed  CAS  Google Scholar 

  72. W.L. Roberts, S. Safar-Pour, B.K. De, C.L. Rohlfing, C.W. Weykamp, R.R. Little, Effects of hemoglobin C and S traits on glycohemoglobin measurements by eleven methods. Clin. Chem. 51, 776–778 (2005)

    Article  PubMed  CAS  Google Scholar 

  73. W.L. Roberts, Hemoglobin constant spring can interfere with glycated hemoglobin measurements by boronate affinity chromatography. Clin. Chem. 53, 142–143 (2007)

    Article  PubMed  CAS  Google Scholar 

  74. T.N. Higgins, D. Stewart, E. Boehr, Challenges in HbA1c analysis and reporting: an interesting case illustrating the many pitfalls. Clin. Biochem. 41, 1104–1106 (2008)

    Article  PubMed  CAS  Google Scholar 

  75. C.L. Rohlfing, S.M. Connolly, J.D. England, S.E. Hanson, C.M. Mellering, J.R. Bachelder et al., The effect of elevated fetal hemoglobin on hemoglobin A1c results: five common hemoglobin A1c methods compared with the IFCC reference method. Am. J. Clin. Pathol. 129, 811–814 (2008)

    Article  PubMed  Google Scholar 

  76. R.M. Cohen, A1C: does one size fit all? Diabetes Care 30, 2756–2758 (2007)

    Article  PubMed  Google Scholar 

  77. D.B. Sacks, M. Arnold, D.E. Bakaria, D.E. Bruns, A.R. Horvath, M.S. Kirkman et al., Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin. Chem. 57, e1–e47 (2011)

    Article  PubMed  Google Scholar 

  78. S.E. Wilson, L.L. Lipscombe, L.C. Rosetta, D.G. Manuel, Trends in laboratory testing for diabetes in Ontario, Canada 1995–2005: population-based study. BMC Health. Serv. Res. 9, 41 (2009)

    Article  PubMed  Google Scholar 

  79. S.E. Manley, K.A. Sikaris, Z.X. Lu, P.G. Nightingales, I.M. Stratton, R.A. Round et al., Validation of an algorithm combining haemoglobin A1c and fasting plasma glucose for diagnosis of diabetes mellitus in UK and Australian populations. Diabet. Med. 26, 115–121 (2009)

    Article  PubMed  CAS  Google Scholar 

  80. A.A. Ginde, E. Cagliero, D.M. Nathan, C.A. Camargo, Value of risk stratification to increase the predictive validity of HbA1c in screening for undiagnosed diabetes in the US population. J. Gen. Intern. Med. 23, 346–353 (2009)

    Google Scholar 

  81. S.J. Davie, B.J. Gould, J.S. Yudik, Effects of vitamin C on glycosylation of proteins. Diabetes 41, 167–173 (1991)

    Article  Google Scholar 

  82. J.D. Hoyer, S.H. Kroft, in Color Atlas of Hemoglobin Disorders, (College of American Pathologists, Northfield, (2003)), case 45

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Higgins, T. HbA1c for screening and diagnosis of diabetes mellitus. Endocrine 43, 266–273 (2013). https://doi.org/10.1007/s12020-012-9768-y

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