SUMMARY GUIDELINES FEBRUARY 2013 Diagnosing Diabetes using HbA1c Key messages Aim of the guideline To test for diabetes, use HbA1c instead of fasting plasma glucose or glucose tolerance testing EXCEPT in pregnancy, presence of acute symptoms and in some other circumstances. This guidance aims to support the use of HbA1c as a diagnostic test for diabetes to replace the use of blood glucose in most circumstances. Diabetes is confirmed with HbA1c 48mmol/mol (6.5%), on two occasions in an asymptomatic individual. If symptomatic, a single HbA1c test will suffice if 48mmol/mol or above. Diabetes can be diagnosed using glycated haemoglobin (HbA1c) or glucose tests. ISBN 978-0-9551179-9-2
Contents 1. Reason for the change 3 2. Diagnosis of diabetes 3 3. Raised HbA1c without diabetes 3 4. Issues when using HbA1c 4 5. Diagnostic criteria and IFCC values 5 6. Diagnostic pathway for diabetes 6 References 7 Error A mistake on p3 has been corrected: code for pre-diabetes should be C11y5 This document was authored by Dr T Chowdhury, Consultant physician, Barts Health NHS Trust and John Robson GP, Reader, Queen Mary University of London and Phil Bennett-Richards GP, Diabetes lead, Tower Hamlets CCG. Any queries regarding this document should be addressed to CEG at ihse-ceg-admin@qmul.ac.uk 58 Turner St London E1 2AB Tel: 0207 882 2553
DIAGNOSING DIABETES USING HBA1c 3 1. Reason for the change Diagnosis of diabetes has been dependent on glucose tests for a number of years, and case finding relied on fasting glucose values, augmented by oral glucose tolerance testing (OGTT) if fasting glucose levels were abnormal. A World Health Organisation (WHO) consultation has concluded that glycated haemoglobin (haemoglobin A1c or HbA1c) can be used to diagnose diabetes. 1 The rationale for this is the observation that the cut point of 48 mmol/mol (6.5%) correlates with a significant increase in risk for the development of diabetic retinopathy, and the correlation is stronger than that for fasting plasma glucose. 2 It is now recommended to use HbA1c rather than fasting or random glucose testing, or OGTT to diagnose diabetes in patients whom you suspect of having the condition. Random glucose testing is rarely helpful unless the patient is symptomatic, and should be discouraged. (Diabet Med 2012;29:1350 1357) 2. Diagnosis of diabetes HbA1c 48mmol/mol (6.5%), on two occasions in an asymptomatic individual, diagnoses diabetes. If symptomatic, a single test will suffice. Diagnostic criteria are outlined in Table 1. HbA1c should not be used in the following circumstances: Abnormal haemoglobins (haemoglobinopathies/traits) However, most haemoglobulin traits do not affect the level of HbA glycation or its analytical quantitation. In particular, Sickle Cell trait and HbA/HbC, HbA/HbD, HbA/HbE heterozygotes do not interfere with HbA1c analysis and the result is valid. Thalassaemia α and β do not interfere with HbA1c analysis and the result is valid. Rarer haemoglobinopathies including homozygous sickle cell and complex thalassaemia/ haemoglobinopathy hetereozygotes may interfere and blood glucose/ogtt are advised. 3. Raised HbA1c without diabetes Elevated HbA1c of 42 47 mmol/mol (6.0 6.4%) should be coded as Pre-diabetes and undergo yearly HbA1c testing. Where testing is in asymptomatic individuals, diagnosis of diabetes should depend on two readings both of which should be 48mmol/mol. If one is above and one below this level then calssify as 'Pre-diabetes'. This group should receive vigorous lifestyle advice, weight reduction support where appropriate, smoking cessation, increasing physical activity and control of other cardiovascular risk factors. The Read code for pre-diabetes is C11y5 which is scheduled to be avialable from April 2013. In the meantime EMIS havea temporary code, EMISNQPR215. Children and young adults <18 years Pregnancy Symptoms suggesting Type 1 diabetes (any age) Anaemia HbA1c should not be used if haemoglobin under 10 g/dl Short or acute onset of diabetes symptoms Patients in whom you suspect diabetes who are acutely ill Patients taking medications that may elevate glucose acutely (steroids) Acute pancreatic disease / surgery
4 DIAGNOSING DIABETES USING HBA1c 4. Issues when using HbA1c There are some potential problems with using HbA1c to diagnose diabetes. HbA1c reflects prevailing glycaemia over the preceding two or three months, so may not be elevated if glucose levels have risen acutely, or where there is abnormal haemoglobin metabolism. Clinicians need to be aware of certain clinical situations where HbA1c may not be suitable for diagnostic use in diabetes, and where glucose tests must be undertaken (above). Tuomilehto has clearly set out the pros and cons of HbA1c testing. 9 IFCC are the new units for HbA1c and a converter is available at http://www.diabetes.co.uk/hba1c-unitsconverter.html. Table 2 tabulates some common HbA1c values. 10 A second HbA1c test would usually be taken 2-4 weeks after the first test Most abnormal haemoglobins will be picked up by standard HbA1c assays, but a frequently encountered important clinical situation in which HbA1c may be raised is in the presence of iron deficiency anaemia (haemoglobin under 10 g/dl). The WHO guideline does not suggest undertaking a full blood count in all patients undergoing HbA1c testing to diagnose diabetes. Other factors influencing HbA1c include carbamylated haemoglobin (seen in end stage renal failure) which increases HbA1c, as does hypertriglyceridaemia and hyperbilirubinaemia. Anti-retroviral therapy, pregnancy and chronic liver disease all modestly lower HbA1c. Glucose tests and HbA1c may detect different populations of people with diabetes, with many studies showing significant discordance between glucose and HbA1c tests. 3 6 Some ethnic groups have modestly higher HbA1c (eg. black African/Caribbeans and South Asians by around 0.4%). Some studies suggest that HbA1c is a more specific, but less sensitive test for diagnosis of diabetes, therefore potentially missing some patients with diabetes diagnosed on glucose tests. Other studies suggest that in some ethnic groups, especially South Asians, HbA1c may increase the diagnosis of diabetes. 7 Proponents for the test, however, suggest that HbA1c of 48 mmol/mol (6.5%) is the level at which risk for complications rises and HbA1c is a better predictor of CVD events than glucose tests. Hence this level is one at which intervention to improve glycaemia might be instituted. HbA1c has been used for population based screening for diabetes in some studies. When compared to the OGTT, the performance of HbA1c 48mmol/mol (6.5%) for T2D diagnosis is variable, and may be influenced by ethnicity. For population based screening of diabetes, a more cost effective and efficient option is to undertake screening using a risk score to identify people at high risk of developing diabetes followed by the use of HbA1c to identify diabetes in people found to be at high risk. 8
DIAGNOSING DIABETES USING HBA1c 5 5. Diagnostic criteria and IFCC values Table 1. Diagnostic criteria for diabetes mellitus and abnormal glucose tolerance Fasting plasma glucose mmol/l 2 hour plasma glucose mmol/l Random plasma glucose mmol/l HbA1c mmol/mol (%) Normal 6.0 < 7.8 < 11.1 < 42 mmol/mol < 6.0% Impaired fasting glucose (IFG) Impaired glucose tolerance (IGT) 6.1 6.9 and < 7.8 - - < 7.0 and 7.8-11.0 - - Pre-diabetes - - - 42 47 mmol/mol 6.0 6.4% Diabetes mellitus 7.0 or 11.1 11.1 48 mmol/mol 6.5% Table 2. HbA1c in DCCT and IFCC units DCCT aligned (%) IFCC HbA1c (mmol/ mol) 6.0 42 6.5 48 7.0 53 7.5 58 8.0 64 9.0 75 10.0 86
6 DIAGNOSING DIABETES USING HBA1c 6. Diagnostic pathway for diabetes not to be used in pregnancy? Diabetes Any of the following? Acute Symptoms (polyuria, polydipsia, weight loss) Possibly Type 1 diabetes YES Use glucose tests: Fasting glucose 7.0mmol/L Random glucose 11.1mmol/L Age under 18 years Check urine for ketones Short duration of symptoms = Diabetes Acutely unwell On steroids Abnormal haemoglobin Anaemia NO Use HbA1c: 48 mmol/mol (6.5%) Confirm on repeat test = Diabetes
DIAGNOSING DIABETES USING HBA1c 7 References 1. World Health Organisation 2011. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. Abbreviated report of a WHO consultation. WHO Geneva. www.who.int/diabetes/publications/report-hba1c_2011.pdf Accessed 16.01.12 2. Colagiuri S, Lee CM, Wong TY, Balkau B, Shaw JE, Borch- Johnsen K; DETECT-2 Collaboration Writing Group. Glycemic thresholds for diabetes-specific retinopathy: implications for diagnostic criteria for diabetes. Diabetes Care 2011;34:145-50. 3. Kumar PR, Bhansali A, Ravikiran M et al. Utility of Glycated Hemoglobin in diagnosing Type 2 diabetes mellitus: A community based study. J Clin Endocrinol Metab 2010;95:2832-5. 4. Davidson MB, Schriger DL, Peters AL et al. Relationship between fasting plasma glucose and glycosylated haemoglobin: potential for false-positive diagnosis of Type 2 diabetes using new diagnostic criteria. JAMA 1999;281:1203-10 5. Carson AP, Reynolds K, Fonseca VA et al. Comparison of A1c and fasting glucose criteria to diagnose diabetes amongst US adults. Diabetes Care 2010:33:95-7. 6. Zhou XH, Ji LN, Luo YY et al. Performance of hba1c for detecting newly diagnosed diabetes and pre-diabetes in Chinese communities living in Beijing. Diabet Med 2009;26:1262-8. 7. 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. Diabet Med 2010;27:762-9. 8. Gray LJ, Davies MJ, Hiles S, Taub NA, Webb DR, Srinivasan BT, Khunti K. Detection of impaired glucose regulation and/or type 2 diabetes mellitus, using primary care electronic data, in a multiethnic UK community setting. Diabetologia 2012;55:959-66. 9. Bonora E, Tuomilehto J. The pros and cons of diagnosing diabetes with HbA1c. Diabetes Care, 34, Supplement 2, May 2011 10. www.diabetes.org.uk/professionals/publications-reports-andresources/tools/changes-to-hba1c-values/ Accessed on 04.06.12
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