A Review: Assessment of Hba1c as A Diagnostic Tool in Diabetes Mellitus
Abstract
Background: Hemoglobin A1C (HbA1c) measures the average plasma glucose level over the two to three months before by expressing the ratio of total to glycated hemoglobin. It has emerged as the most significant indicator of long-term hyperglycemia and is highly associated with late complications from diabetes. Now that the analysis has been standardized, it may be linked to international reference sources and reference techniques. The major method for identifying diabetes was made possible by the standardization of HbA1c analyses. The addition of HbA1c as a diagnostic tool will simplify the diagnosis of diabetes compared to the glucose criteria, and should increase the avoidance of late consequences of diabetes, despite some limitations in which HbA1c is not reflective of average glucose concentration.
References
1. Vinik A, Flemmer M. Diabetes and macrovascular disease. Journal of Diabetes and its Complications 2001; 16(3): 235–245. doi: 10.1016/S1056-8727(01)00212-4
2. Sultanpur CM, Deepa K, Kumar SV. Comprehensive review on HbA1c in diagnosis of diabetes mellitus. International Journal of Pharmaceutical Sciences Review and Research 2010; 3(2): 119–122.
3. Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. New England Journal of Medicine 2003; 348(5): 383–393. doi: 10.1056/NEJMoa021778
4. Larsen ML, Hørder M, Mogensen EF. Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus. New England Journal of Medicine 1990; 323(15): 1021–1025. doi: 10.1056/NEJM199010113231503
5. Diabetic 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. New England Journal of Medicine 1993; 329(14): 977–986. doi: 10.1056/NEJM199309303291401
6. Koenig RJ, Peterson CM, Jones RL, et al. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. New England Journal of Medicine 1976; 295(8): 417–420. doi: 10.1056/NEJM197608192950804
7. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). The Lancet 1998; 352(9731): 837–853. doi: 10.1016/S0140-6736(98)07019-6
8. American Diabetes Association. Standards of medical care in diabetes—2006. Diabetes Care 2006; 29(S1): S4–S42. doi.org/10.2337/diacare.29. s1.06. s4
9. Longo-Mbenza B, Muaka MM, Mbenza G, et al. Risk factors of poor control of HBA1c and diabetic retinopathy: Paradox with insulin therapy and high values of HDL in African diabetic patients. International Journal of Diabetes & Metabolism 2008; 16(2): 69–78. doi.org/10.1159/000497655
10. Woerle HJ, Neumann C, Zschau S, et al. Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes: Importance of postprandial glycemia to achieve target HbA1c levels. Diabetes Research and Clinical Practice 2007; 77(2): 280–285. doi.org/10.1016/j.diabres.2006.11.011
11. Gough A, Sitch A, Ferris E, Marshall T. Within-subject variation of HbA1c: A systematic review and meta-analysis. Plos one. 2023 Aug 2; 18(8):e0289085.
12. Kumar PJ, Clark ML. Kumar & Clark’s Clinical Medicine, 8th ed. Saunders/Elsevier, Edinburgh; 2012.
13. American Diabetes Association. Standards of medical care in diabetes—2009. Diabetes Care 2009; 32(S1): S6–S12. doi: 10.2337/dc09-S006
14. Beach KW. A theoretical model to predict the behavior of glycosylated hemoglobin levels. Journal of Theoretical Biology 1979; 81(3): 547–561. doi: 10.1016/0022-5193(79)90052-3
15. Nathan DM, Kuenen J, Borg R, et al. Translating the A1C assay into estimated average glucose values. Diabetes Care 2008; 31(8): 1473–1478. doi: 10.2337/dc08-0545
16. Shimazaki T, Kadowaki T, Ohyama Y, et al. Hemoglobin A1c (HbA1c) predicts future drug treatment for diabetes mellitus: A follow-up study using routine clinical data in a Japanese university hospital. Translational Research 2007; 149(4): 196–204. doi: 10.1016/j.trsl.2006.09.008
17. Alphabetical hemoglobin variant list. Hemoglobin 1996; 20(3): 313–335.
18. Schnedl WJ, Korninger RE, Liebminger A, et al. Hemoglobin variants and determination of glycated hemoglobin (HbA1c). Diabetes Metabolism Research and Reviews 2001; 17(2): 94–98. doi: 10.1002/dmrr.186
19. Camargo JL, Gross JL. Conditions associated with very low values of glycohaemoglobin measured by an HPLC method. Journal of Clinical Pathology 2004; 57(4): 346–349. doi: 10.1136/jcp.2002.007088
20. Lahousen T, Roller RE, Lipp RW, Schnedl WJ. Silent haemoglobin variants and determination of HbA1c with the HPLC Bio-Rad Variant II. Journal of Clinical Pathology 2002; 55(9): 699–703. doi: 10.1136/jcp.55.9.699
21. Schnedl WJ, Krause R, Halwachs-Baumann G, et al. Evaluation of HbA1c determination methods in patients with hemoglobinopathies. Diabetes Care 2000; 23(3): 339–344. doi: 10.2337/diacare.23.3.339
22. Nakanishi T, Miyazaki A, Iguchi K, Shimizu A. Effect of hemoglobin variants on routine glycohemo-globin measurements assessed by a mass spectrometric method. Clinical Chemistry 2000; 46(10): 1689–1692. doi: 10.1093/CLINCHEM/46.10.1689
23. Blincko S, Anzetse J, Edwards R. Measurement of glycated haemoglobin in whole blood by a novel fluorescence quenching assay. Annals of Clinical Biochemistry 2000; 37: 492–497. doi: 10.1177/000456320003700410
24. Goldstein DE, Walker B, Rawlings SS, Hess RL, England JD, Peth SB, Hewett JE. Hemoglobin A1C levels in children and adolescents with diabetes mellitus. Diabetes Care. 1980 Jul 1; 3(4):503-7.
25. Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivates on assays for glycohemoglobin. Clinical Chemistry 2001; 47(2): 153–163. doi: 10.1093/clinchem/47.2.153
26. Edo AE, Akhuemokhan K. Relationships between hemoglobin A1C and spot glucose measurements in Nigerians with type 2 diabetes mellitus. Nigerian journal of clinical practice 2012; 15(1): 23–26. doi: 10.4103/1119-3077.94091
27. Matheka DM, Kilonzo JM, Munguti CM, Mwangi PW. Pattern, knowledge and practices of HbA1C testing among diabetic patients in a Kenyan tertiary referral hospital. Global Health 2013; 5(9): 55. doi: 10.1186/1744-8603-9-55
28. Kilpatrick ES, Atkin SL. Using haemoglobin A (1c) to diagnose type 2 diabetes or to identify people at high risk of diabetes. The BMJ 2014; 348: g2867. doi: 10.1136/bmj. g2867
29. Cohen DB, Allain TJ, Glover S, et al. A survey of the management, control, and complications of diabetes mellitus in patients attending a diabetes clinic in Blantyre, Malawi, an area of high HIV prevalence. The American Journal of Tropical Medicine and Hygiene 2010; 83(3): 575–581. doi: 10.4269/ajtmh.2010.10-0104
30. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33(S1): S62–S69. doi: 10.2337/dc10-S062
31. The International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009; 32(7): 1327–1334. doi: 10.2337/dc09-9033
32. Bower JK, Brancati FL, Selvin E. No ethnic differences in the association of glycated hemoglobin with retinopathy: The national health and nutrition examination survey 2005–2008. Diabetes Care 2013; 36(3): 569–573. doi: 10.2337/dc12-0404
33. Colagiuri S, Lee CM, Wong TY, et al. Glycemic thresholds for diabetes-specific retinopathy: Implications for diagnostic criteria for diabetes. Diabetes Care 2011; 34(1): 145–150.
34. Gallagher EJ, Le Roith D, Bloomgarden Z. Review of hemoglobin A (1c) in the management of diabetes. Journal of Diabetes 2009; 1(1): 9–17. doi: 10.1111/j.1753-0407.2009. 00009.x
35. Kilpatrick ES, Bloomgarden ZT, Zimmet PZ. Is haemoglobin A1C a step forward for diagnosing diabetes? The BMJ 2009; 339: b4432. doi: 10.1136/bmj. b4432
36. Zhou XH, Ji LN, Luo YY, et al. Performance of HbA(1c) for detecting newly diagnosed diabetes and pre-diabetes in Chinese communities living in Beijing. Diabetes Medicine 2009; 26(12): 1262–1268. doi: 10.1111/j.1464-5491.2009. 02831.x
37. Pani LN, Korenda L, Meigs JB, et al. Effect of aging on A1C levels in individuals without diabetes: Evidence from the framingham offspring study and the national health and nutrition examination survey 2001–2004. Diabetes Care 2008; 31(10): 1991–1996. doi: 10.2337/dc08-0577
38. Herman WH, Ma Y, Uwaifo G, et al. Differences in A1C by race and ethnicity among patients with impaired glucose tolerance in the diabetes prevention program. Diabetes Care 2007; 30(10): 2453–2457. doi: 10.2337/dc06-2003
39. Herman WH. Do race and ethnicity impact hemoglobin A1C independent of glycemia? Journal of Diabetes Science and Technology 2009; 3(4): 656–660. doi: 10.1177/19322968090030040
40. Grimsby JL, Porneala BC, Vassy JL, et al. Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: The third national health and nutrition examination survey (NHANES III). BMC Medical Genetics 2012; 13(1): 30. doi: 10.1186/1471-2350-13-30
41. Mostafa SA, Davies MJ, Webb D, et al. The potential impact of using glycated haemoglobin as the preferred diagnostic tool for detecting type 2 diabetes mellitus. Diabetes Medicine 2010; 27(7): 762–769. doi: 10.1111/j.1464-5491.2010. 03015.x
42. Carson AP, Reynolds K, Fonseca VA, Muntner P. Comparison of A1C and fasting glucose criteria to diagnose diabetes among U.S. adults. Diabetes Care 2010; 33(1): 95–97. doi: 10.2337/dc09-1227
43. Kumar PR, Bhansali A, Ravikiran M, et al. Utility of glycated hemoglobin in diagnosing type 2 diabetes mellitus: a community-based study. The Journal of Clinical Endocrinology & Metabolism 2010; 95(6): 2832–2835. doi: 10.1210/jc.2009-2433
44. Rohlfing CL, Little RR, Wiedmeyer HM, et al. Use of GHb (HbA1c) in screening for undiagnosed diabetes in the U.S. population. Diabetes Care 2000; 23(2): 187–191. doi: 10.2337/diacare.23.2.187
45. Bao Y, Ma X, Li H, et al. Glycated haemoglobin A1C for diagnosing diabetes in Chinese population: Cross sectional epidemiological survey. The BMJ 2010; 340: c2249. doi: 10.1136/bmj.c2249
46. Cohen RM, Franco RS, Khera PK, et al. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood 2008; 112(10): 428–491. doi: 10.1182/blood-2008-04-154112
47. Slama L, Palella FJJ, Abraham AG, et al. Inaccuracy of haemoglobin A1C among HIV-infected men: Effects of CD4 cell count, antiretroviral therapies and haematological parameters. Journal of Antimicrobial Chemotherapy 2014; 69(12): 3360–3367. doi: 10.1093/jac/dku295
48. Assayed AA, Muula AS, Nyirenda MJ. The quality of care of diabetic patients in rural Malawi: A case of Mangochi district. Malawi Medical Journal 2014; 26(4): 109–114.
49. Little RR. Glycated hemoglobin standardization–National Glycohemoglobin Standardization Program (NGSP) perspective. Clinical Chemistry and Laboratory Medicine 2003; 41(9): 1191–1198. doi: 10.1515/CCLM.2003.183
50. Gomez-Perez FJ, Aguilar-Salinas CA, Almeda-Valdes P, et al. HbA1c for the diagnosis of diabetes mellitus in a developing country. A position article. Archives of Medical Research 2010; 41(4): 302–308. doi: 10.1016/j.arcmed.2010.05.007
51. Rahbar S, Blumenfeld O, Ranney HM. Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochemical and Biophysical Research Communications 1969; 36(5): 838–843. doi: 10.1016/0006-291x (69)90685-8
52. Borg R, Kuenen JC, Carstensen B, Zheng H, Nathan DM, Heine RJ, Nerup J, Borch-Johnsen K, Witte DR, ADAG Study Group. Associations between features of glucose exposure and A1C: the A1C-Derived Average Glucose (ADAG) study. Diabetes. 2010 Jul 1; 59(7):1585-90.
53. Massi-Benedetti M. Changing targets in the treatment of type 2 diabetes. Current Medical Research and Opinion 2006; 22(S2): S5–S13. doi: 10.1185/030079906X112714
54. Nathan DM, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia 2007; 50(11): 2239–2244. doi: 10.1007/s00125-007-0803-0
55. Saudek CD, Brick JC. The clinical use of hemoglobin A1C. Journal of diabetes science and technology. 2009 Jul;3(4):629-34.
56. DETECT-2 Collaboration. Is there a glycemic threshold for diabetic retinopathy? Diabetologia 2011; 47: 1411–1415.
57. McCance DR, Hanson RL, Charles MA, et al. Comparison of tests for glycated haemoglobin and fasting and two-hour plasma glucose concentrations as diagnostic methods for diabetes. The BMJ 1994; 308(6940): 1323–1328. doi: 10.1136/bmj.308.6940.1323
58. Ito C, Maeda R, Ishida S, Sasaki H, Harada H. Correlation among fasting plasma glucose, two-hour plasma glucose levels in OGTT and HbA1c. Diabetes research and clinical practice. 2000 Dec 1; 50(3):225-30.
59. Engelgau MM, Thompson TJ, Herman WH, et al. Comparison of fasting and 2-hour glucose and HbA1c levels for diagnosing diabetes. Diagnostic criteria and performance revisited. Diabetes Care 1997; 20(5): 785–791. doi: 10.2337/diacare.20.5.785
60. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20(7): 1183–1197. doi: 10.2337/diacare.20.7.1183
61. Miyazaki M, Kubo M, Kiyohara Y, et al. Comparison of diagnostic methods for diabetes mellitus based on prevalence of retinopathy in a Japanese population: The Hisayama Study. Diabetologia 2004; 47(8): 1411–1415. doi: 10.1007/s00125-004-1466-8
62. Tapp RJ, Tikellis G, Wong TY, et al. Longitudinal association of glucose metabolism with retinopathy: Results from the Australian Diabetes Obesity and Lifestyle (AusDiab) study. Diabetes Care 2008; 31(7): 1349–1354. doi.org/10.2337/dc07-1707
63. Gallagher EJ, Le Roith D, Bloomgarden Z. Review of hemoglobin A1C in the management of diabetes. Journal of Diabetes 2009; 1(1): 9–17. doi: 10.1111/j.1753-0407.2009. 00009.x
64. Roberts WL, De BK, Brown D, et al. Effects of hemoglobin C and S traits on eight glycohemoglobin methods. Clinical Chemistry 2002; 48(2): 383–385. doi: 10.1093/clinchem/48.2.383
65. Little RR, Rohlfing CL, Wiedmeyer HM, et al. The national glycohemoglobin standardization program: A five-year progress report. Clinical Chemistry 2001; 47(11): 1985–1992.
66. Hoelzel W, Weykamp C, Jeppsson JO, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: A method-comparis on study. Clinical Chemistry 2004; 50(1): 166–174. doi: 10.1373/clinchem.2003.024802
67. Goldstein DE, Little RR, Lorenz RA, et al. Tests of glycaemia in diabetes. Diabetes Care 2004; 27(7): 1761–1773. doi: 10.2337/diacare.27.7.1761
68. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33(S1): S62–S69. doi: 10.2337/dc10-S062
