¿Aún no está registrado?

Cree su cuenta. Regístrese en Elsevier y obtendrá: información relevante, máxima actualización y promociones exclusivas.

Registrarme ahora
Ayuda - - Regístrese - Teléfono 902 888 740
Buscar en

doi: 10.1016/S0140-6736(11)60789-7

HbA 1c and blood glucose for the diagnosis of diabetes

Anoop Misra a, , Satish Garg b

a Fortis C-DOC Centre of Excellence for Diabetes, Obesity, Metabolic Diseases and Endocrinology, Fortis Hospital, New Delhi 110016, India
b Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO

Artículo Relacionado

HbA 1c 5·7–6·4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study

Yoriko Heianza, Shigeko Hara, Yasuji Arase, Kazumi Saito, Kazuya Fujiwara, Hiroshi Tsuji, Satoru Kodama, Shiun Dong Hsieh, Yasumichi Mori, Hitoshi Shimano, Nobuhiro Yamada, Kinori Kosaka, Hirohito Sone
Lancet. 2011;378:147-55.


Traditionally, blood glucose values (fasting, 2-h postprandial, or after a 75 g oral glucose load) have been used to diagnose diabetes, but the cutoff for diagnosis has been revised several times in the past few decades. For about a decade, it has been debated whether measures of glycated haemoglobin (HbA1c), a standard monitoring test for the control of diabetes, could also be used as diagnostic criteria.1, 2 Those who support this idea argue that a convenient laboratory test (eg, non-fasting), which reflects long-term hyperglycaemia over the preceding 2–3 months and is a proven measure of diabetes-related complications, should diagnose the disease more successfully than a single measurement of blood glucose.2 An international expert committee, after considering data on association of HbA1c and retinopathy, recommended that diabetes be diagnosed when HbA1c is more than 48 mmol/mol (>6·5%), provided this assay is done in a standardised laboratory.3 Further, HbA1c of 39–46 mmol/mol (5·7–6·4%) was stated for the identification of prediabetes (an increased risk for diabetes).4 The recommendation made sense in many other aspects: measures of HbA1c might indicate prevalence of retinopathy better than fasting plasma glucose, and HbA1c has low pre-analytic instability and is relatively unaffected by acute situations. In particular, day-to-day and within-person variability of HbA1c was less than 2% compared with 12–15% for fasting plasma glucose.5, 6

In The Lancet, data from a longitudinal study in a Japanese cohort (TOPICS 3) by Yoriko Heianza and colleagues7 highlight that impaired fasting glucose and HbA1c identify people with different cardiovascular risk profiles. More importantly, when both tests were used simultaneously, more high-risk individuals were identified, which suggests unique roles in the prediction of diabetes for both tests.

This work fuels further debate on HbA1c as a diagnostic and predictive test for diabetes.8 Importantly, in this context, impaired fasting glucose (mostly due to hepatic insulin resistance), impaired glucose tolerance (because of muscle insulin resistance) and HbA1c (chronic exposure to basal and postprandial hyperglycaemia) represent different facets of glucose metabolism,9 and could be a result of different risk phenotypes. Many believe that introduction of HbA1c as a diagnostic criterion for diabetes is premature in view of problems in its interpretation in clinical settings such as haemolysis, haemoglobinopathies, blood transfusions, iron and erythropoietin therapy, and in situations when hyperglycaemia is acute.10, 11 Compared with glucose-based diagnostic tests, HbA1c seems to have lower sensitivity but is fairly specific.12 Further, diagnostic values of HbA1c in different ethnic groups continue to be debated.13, 14, 15 Some data suggest that a single determination of fasting plasma glucose and 2-h plasma glucose is a more precise correlate of insulin resistance and secretion than is HbA1c in non-Hispanic whites.12 The use of HbA1c for diagnosis of diabetes and prediabetes might be premature in children and adolescents as well;16 measures of HbA1c and mean blood glucose used together to make therapeutic decisions for children with diabetes have also been recommended.16, 17 Additionally, substantial discordance between fasting plasma glucose and HbA1c values has been reported in older individuals.18 With the widespread presence of anaemia, the cost involved, and the ethnic variability of HbA1c, its use for diagnosis has been questioned in resource-constrained developing countries.

Any new diagnostic test should be robust, valid, easy, cheap, highly sensitive and specific, and should perform better than existing tests. HbA1c meets some of these requirements, but fails in other areas. Furthermore, application of the HbA1c test for the diagnosis of diabetes will alter the epidemiology of diabetes and prediabetes—eg, it will lead to reclassification of 50 million adults in the USA, previously considered to be healthy, as prediabetic.4 Whether those diagnosed by this test would indeed be correctly classified might be questioned, because lifestyle changes and antihyperglycaemic drugs would be suggested for them. The health and economic implications of such actions would be tremendous; health-care systems would have to invest enormous resources and strengthen existing services to manage increased numbers of individuals now labelled as prediabetic, particularly in developing countries. Unfortunately, no such preparation is discernible.

In those countries that could afford such tests, the use of blood glucose and HbA1c together (especially with the availability of point-of-care standardised testing), as shown by Heianza and co-workers, would identify many more at risk for diabetes and even cardiovascular disease. We believe it is better to cover a larger segment of people with preventive lifestyle advice to prevent future risk for diabetes, but this conclusion requires large-scale longitudinal studies.

We declare that we have no conflicts of interest.


1.Cheng YJ, Gregg EW, Geiss LS, et al. Association of A1C and fasting plasma glucose levels with diabetic retinopathy prevalence in the U.S. population: implications for diabetes diagnostic thresholds. Diabetes Care. 2009; 32:2027-32.
2.International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009; 32:1327-34.
3.Mitka M. Hemoglobin A1c poised to become preferred test for diagnosing diabetes. JAMA. 2009; 301:1528.
4.Mann DM, Carson AP, Shimbo D, Fonseca V, Fox CS, Muntner P. Impact of A1C screening criterion on the diagnosis of pre-diabetes among U.S. adults. Diabetes Care. 2010; 33:2190-5.
5.Ollerton RL, Playle R, Ahmed K, Dunstan FD, Luzio SD, Owens DR. Day-to-day variability of fasting plasma glucose in newly diagnosed type 2 diabetic subjects. Diabetes Care. 1999; 22:394-8.
6.Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrot M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem. 2002; 48:436-72.
7.Heianza Y, Hara S, Arase Y, et al. HbA1c 5·7–6·4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study. Lancet. 2011. published online June 25.
8.Hanas R, John G, on behalf of the International HbAnull Consensus Committee. 2010 consensus statement on the worldwide standardization of the hemoglobin A1c measurement. Clin Chem. 2010; 56:1362-4.
9.Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. 2007; 30:753-9.
10.Ng JM, Cooke M, Bhandari S, Atkin SL, Kilpatrick ES. The effect of iron and erythropoietin treatment on the A1C of patients with diabetes and chronic kidney disease. Diabetes Care. 2010; 33:2310-3.
11.Kim C, Bullard KM, Herman WH, Beckles GL. Association between iron deficiency and A1C levels among adults without diabetes in the National Health and Nutrition Examination Survey, 1999–2006. Diabetes Care. 2010; 33:780-5.
12.Olson DE, Rhee MK, Herrick K, Ziemer DC, Twombly JG, Phillips LS. Screening for diabetes and pre-diabetes with proposed A1C-based diagnostic criteria. Diabetes Care. 2010; 33:2184-9.
13.Getaneh A, Andres R, Brillon DJ, Findley SE. Hemoglobin A1c criterion for diabetes diagnosis among Hispanic and non-Hispanic populations. Endocr Pract. 2011; 17:210-7.
14.Araneta MR, Grandinetti A, Chang HK. A1C and diabetes diagnosis among Filipino Americans, Japanese Americans, and Native Hawaiians. Diabetes Care. 2010; 33:2626-8.
15.Bao Y, Ma X, Li H, et al. Glycated haemoglobin A1c for diagnosing diabetes in Chinese population: cross sectional epidemiological survey. BMJ. 2010; 340:c2249.
16.Agus MS, Alexander JL, Wolfsdorf JI. Utility of immediate hemoglobin A1c in children with type I diabetes mellitus. Pediatr Diabetes. 2010; 11:450-4.
17.Lippi G, Targher G. A laboratory standpoint on the role of hemoglobin A1c for the diagnosis of diabetes in childhood: more doubts than certainties?. Pediatr Diabetes. 2011; 12:183-6.
18.Lipska KJ, De Rekeneire N, Van Ness PH, et al. Identifying dysglycemic states in older adults: implications of the emerging use of hemoglobin A1c. J Clin Endocrinol Metab. 2010; 95:5289-95.