Hemoglobin A1c (HbA1c) has been accepted as an index of glycemic control since the mid-1970s and is the best marker for diabetic microvascular complications. Clinically, it is now used to assess glycemic control in people with diabetes. Assays are most reliable when certified by the National Hemoglobin Standardization Program but are subject to confounders and effect modifiers, particularly in the setting of hematologic abnormalities. Other measures of chronic glycemic control—fructosamine and 1,5-anhydroglucitol—are far less widely used. The relationship of HbA1c to average blood glucose was intensively studied recently, and it has been proposed that this conversion can be used to report an “estimated average glucose, eAG” in milligrams/deciliter or millimolar units rather than as per cent glycated hemoglobin. Finally, HbA1c has been proposed as a useful method of screening for and diagnosing diabetes.
KunkelHGWalleniusG. New hemoglobin in normal adult blood. Science.1955;122 (3163): 288.
2.
HuismanTHDozyAM. Studies on the heterogeneity of hemoglobin. V. Binding of hemoglobin with oxidized glutathione. J Lab Clin Med.1962;60: 302–19.
3.
KilpatrickES. Haemoglobin A1c in the diagnosis and monitoring of diabetes mellitus. J Clin Pathol.2008;61 (9): 977–82.
4.
RahbarSBlumenfeldORanneyHM. Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem Biophys Res Commun.1969: 36 (5): 838–43.
5.
BunnHFHaneyDNKaminSGabbayKHGallopPM. The biosynthesis of human hemoglobin A1c: Slow glycosylation of hemoglobin in vivo. J Clin Invest.1976;57 (6): 16529.
6.
KoenigRJBlobsteinSHCeramiA. Structure of carbohydrate of hemoglobanA1c. J. Biol. Chem.1977: 252 (9): 2992–2997.
7.
KoenigRJPetersonCMJonesRLSaudekCLehrmanMCeramiA. Correlation of glucose regulation and hemoglobin A1c in diabetes mellitus. N Engl J Med.1976;295 (8): 417–20.
8.
The Diabetes 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. N Engl J Med.1993;329 (14): 977–86.
9.
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet.1998;352 (9131): 854–65.
10.
SaudekCDDerrRLKalyaniRR. Assessing glycemia in diabetes using self-monitoring blood glucose and hemoglobin A1c. JAMA.2006;295 (14): 1688–97.
CaglieroELevinaEVNathanDM. Immediate feedback of HbA1c levels improves glycemic control in type 1 and insulin-treated type 2 diabetic patients. Diabetes Care.1999;22 (11): 1785–9.
13.
MillerCDBarnesCSPhillipsLSZiemerDCGallinaDLCookCBMarymanSDEl-KebbiIM. Rapid A1c availability improves clinical decision-making in an urban primary care clinic. Diabetes Care.2003;26 (4): 1158–1163.
14.
American Diabetes Association. Standards of medical care in diabetes–2009. Diabetes Care.2009;32 (Suppl 1): S13–61.
15.
RodbardHWBlondeLBraithwaiteSSBrettEMCobinRHHandelsmanYHellmanRJellingerPSJovanovicLGLevyPMechanickJIZangenehF, AACE Diabetes Mellitus Clinical Practice Guidelines Task Force, American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract.2007;13 (Suppl 1): 1–68.
16.
HuangESZhangQGandraNChinMHMeltzerDO. The effect of comorbid illness and functional status on the expected benefits of intensive glucose control in older patients with type 2 diabetes: A decision analysis. Ann Intern Med.2008;149 (1): 11–9.
17.
SaudekCDKalyaniRR. Does comorbidity affect the benefit of intensive glycemic control in older patients with type 2 diabetes mellitus?Nat Clin Pract Endocrinol Metab.2009;5 (2): 78–9.
18.
PaniLNKorendaLMeigsJBDriverCChamanySFoxCSSullivanLD'AgostinoRBNathanDM. 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): 1991–6.
19.
SaaddineJBFagot-CampagnaARolkaDNarayanKMGeissLEberhardtMFlegalKM. Distribution of HbA(1c) levels for children and young adults in the U.S.: Third National Health and Nutrition Examination Survey. Diabetes Care.2002;25 (8): 1326–30.
20.
HermanWHMaYUwaifoGHaffnerSKahnSEHortonESLachinJMMontezMGBrennemanTBarrett-ConnorE, Diabetes Prevention Program Research Group, Differences in A1C by ace and ethnicity among patients with impaired glucose tolerance in the Diabetes Prevention Program. Diabetes Care.2007;30 (10): 2453–7.
21.
HempeJMGomezRMcCarterRJJr.ChalewSA. High and low hemoglobin glycation phenotypes in type 1 diabetes: A challenge for interpretation of glycemic control. J Diabetes Complications.2002;16 (5): 313–20.
22.
McCarterRJHempeJMGomezRChalewSA. Biological variation in HbA1c predicts risk of retinopathy and nephropathy in type 1 diabetes. Diabetes Care.2004;27 (6): 1259–64.
23.
GenuthSLachinJMNathanDM. Biological variation in HbA1c predicts risk of retinopathy and nephropathy in type 1 diabetes: Response to McCarter et al. Diabetes Care.2005;28 (1): 233; author reply 234–5.
24.
RohlfingCWiedmeyerHMLittleRGrotzVLTennillAEnglandJMadsenRGoldsteinD. Biological variation of glycohemoglobin. Clin Chem.2002;48 (7): 1116–8.
25.
BeachKW. A theoretical model to predict the behavior of glycosylated hemoglobin levels. J Theor Biol.1979;81 (3): 547–61.
26.
TaharaYShimaK. Kinetics of HbA1c, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose level. Diabetes Care.1995;18 (4): 440–7.
27.
LindseyCCCarterAWMangumSGreeneDRichardsonABrownSJEssaryJLMcCandlessB. A prospective, randomized, multicentered controlled trial to compare the annual glycemic and quality outcomes of patients with diabetes mellitus monitored with weekly fructosamine testing versus usual care. Diabetes Technol Ther.2004;6 (3): 370–7.
28.
NarbonneHRenaccoEPradelVPortugalHVialettesB. Can fructosamine be a surrogate for HbA(1c) in evaluating the achievement of therapeutic goals in diabetes?Diabetes Metab.2001;27 (5 Pt 1): 598–603.
McGillJBColeTGNowatzkeWHoughtonSAmmiratiEBGautilleTSarnoMJ, U.S. trial of the GlycoMark assay. Circulating 1,5-anhydroglucitol levels in adult patients with diabetes reflect longitudinal changes of glycemia: A U.S. trial of the GlycoMark assay. Diabetes Care.2004;27 (8): 1859–65.
31.
RohlfingCLWiedmeyerHMLittleRREnglandJDTennillAGoldsteinDE. Defining the relationship between plasma glucose and HbA(1c): Analysis of glucose profiles and HbA(1c) in the Diabetes Control and Complications Trial. Diabetes Care.2002;25 (2): 275–8.
32.
NathanDMKuenenJBorgRZhengHSchoenfeldDHeineRJ, A1c-Derived Average Glucose (ADAG) Study Group. Translating the A1C assay into estimated average glucose values. Diabetes Care.2008;31 (8): 1473–8.
33.
JeppssonJOKoboldUBarrJFinkeAHoelzelWHoshinoTMiedemaKMoscaAMauriPParoniRThienpontLUmemotoMWeykampC, International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med.2002;40 (1): 78–89.
34.
HoelzelWWeykampCJeppssonJOMiedemaKBarrJRGoodallIHoshinoTJohnWGKoboldULittleRMoscaAMauriPParoniRSusantoFTakeiIThienpontLUmemotoMWiedmeyerHM, IFCC Working Group on HbA1c Standardization. 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-comparison study. Clin Chem.2004;50 (1): 166–74.
35.
BergAHSacksDB. Haemoglobin A1c analysis in the management of patients with diabetes: From chaos to harmony. J Clin Pathol.2008;61 (9): 983–7.
36.
NathanDMTurgeonHReganS. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia.2007;50 (11): 2239–44.
37.
KahnRFonsecaV. Translating the A1C assay. Diabetes Care.2008;31 (8): 1704–7.
38.
Consensus Committee. Consensus statement on the worldwide standardization of the hemoglobin A1C measurement: The American Diabetes Association, European Association for the Study of Diabetes, International Federation of Clinical Chemistry and Laboratory Medicine, and the International Diabetes Federation. Diabetes Care.2007;30 (9): 2399–400.
39.
CowieCCRustKFFordESEberhardtMSByrd-HoltDDLiCWilliamsDEGreggEWBainbridgeKESaydahSHGeissLS. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006. Diabetes Care.2009;32 (2): 287–94.
40.
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care.1997;20 (7): 1183–97.
41.
TabaeiBPHermanWH. A multivariate logistic regression equation to screen for diabetes: Development and validation. Diabetes Care.2002;25 (11): 1999–2003.
42.
JohnsonSLTabaeiBPHermanWH. The efficacy and cost of alternative strategies for systematic screening for type 2 diabetes in the U.S. population 45–74 years of age. Diabetes Care.205;28(2): 307–11.
43.
SaudekCDHermanWHSacksDBBergenstalRMEdelmanDDavidsonMB. A new look at screening and diagnosing diabetes mellitus. J Clin Endocrinol Metab.2008;93 (7): 2447–53.
