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HbA1c as a compass- pointing you to the right diagnosis?

HbA1c as a compass- pointing you to the right diagnosis?. Eric S. Kilpatrick Department of Clinical Biochemistry Hull Royal Infirmary/Hull York Medical School. HbA 1c : Historical Aspects. 1962: Huisman and Dozy

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HbA1c as a compass- pointing you to the right diagnosis?

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  1. HbA1c as a compass-pointing you to the right diagnosis? Eric S. KilpatrickDepartment of Clinical Biochemistry Hull Royal Infirmary/Hull York Medical School

  2. HbA1c: Historical Aspects 1962: Huisman and Dozy Increases in minor fractions of haemoglobin in four diabetic patients treated with tolbutamide. 1968: Rahbar ‘Diabetic haemoglobin component’ found in 49 Iranian diabetic patients. 1968: Rahbar Component the same structure as the previously described HbA1c

  3. Formation of Glycated Haemoglobin

  4. HbA1c: Historical Aspects HbA1c correlated with: • Plasma ‘glucose brackets’ Koenig RJ et al. N Engl J Med 1976; 295: 417-420 • Daily mean plasma glucose Gonen B et al. Lancet 1977; ii; 734-737 • 24 hour urinary glucose excretions Gabbay KH et al. J Clin Endocrinol Metab 1977; 44: 859-864 • Glucose control over past 6-8 weeks Goldstein D et al. Clin Chem 1986; 32(Suppl): B64-70

  5. DCCT: Risk of Microvascular Complications DCCT Group. N Engl J Med. 1993; 329: 977-86

  6. Retinopathy Risk Reduction • Absolute risk reduction in falling from: HbA1c= 86 mmol/mol (10%)to HbA1c= 83mmol/mol (9.7%) is the same asHbA1c= 53mmol/mol (7%)to HbA1c= 36mmol/mol (5.4%)

  7. UKPDS:Risk of Macro and Microvascular Complications UKPDS Group. BMJ 2000;321:405-412

  8. HbA1c: Historical Aspects HbA1c correlated with: • Plasma ‘glucose brackets’ Koenig RJ et al. N Engl J Med 1976; 295: 417-420 • Daily mean plasma glucose Gonen B et al. Lancet 1977; ii; 734-737 • 24 hour urinary glucose excretions Gabbay KH et al. J Clin Endocrinol Metab 1977; 44: 859-864 • Glucose control over past 6-8 weeks Goldstein D et al. Clin Chem 1986; 32(Suppl): B64-70

  9. Model of Glycated Haemoglobin Formation

  10. Model of Glycated Haemoglobin Formation y= 2x -x2

  11. What about using HbA1c to diagnose diabetes? Why did it take so long?

  12. Advantages in using HbA1c • Does not require a fasting sample • Assesses glycaemia over previous weeks/months • Lower biological variability than FPG or 2hr • Fewer pre-analytical concerns • Already used to guide management

  13. HbA1c to diagnose diabetes • Lack of standardisation in measurement • Unsure whether it was as good as glucose in diagnosing diabetes

  14. DCCT HbA1c (%) 6 7 8 9 10 IFCC (SI) HbA1c(%) 4.2 5.3 6.4 7.5 8.6 DCCT vs. IFCC HbA1c

  15. DCCT HbA1c (%) 6 7 8 9 10 IFCC (SI) HbA1c(mmol/mol) 4.2 5.3 6.4 7.5 8.6 DCCT vs. IFCC HbA1c

  16. DCCT HbA1c (%) 6 7 8 9 10 IFCC (SI) HbA1c(mmol/mol) 42 53 64 75 86 DCCT vs. IFCC HbA1c Clin Chem Lab Med 2007;45:1081-1082

  17. HbA1c to diagnose diabetes • Lack of standardisation in measurement • Unsure whether it was as good as glucose in diagnosing diabetes

  18. What is diabetes defined as being?  • Someone at increased risk of heartdisease • Someone at increased risk of diabeticretinopathy X • Someone at increased risk of diabeticnephropathy X

  19. DETECT-2 study n=44,623 ROC 0.87(95% CI 0.85-0.89) ROC 0.89 (0.87-0.91) ROC 0.90 (0.88-0.92) Diabetes Care doi: 10.2337/dc10-1206

  20. HbA1c and CV risk ARIC (n=11,092) • HbA1c was as predictive of future diabetes as FPG • HbA1c was at least as predictive as FPG for CV disease • No mention of 2hr glucose N Engl J Med 2010;362:800-11.

  21. HbA1c vs. glucose for detecting vascular complications

  22. But Doctor, WHO

  23. WHO, January 2011 www.who.int/cardiovascular_diseases/report-hba1c_2011_edited.pdf

  24. Executive Summary www.who.int/cardiovascular_diseases/report-hba1c_2011_edited.pdf

  25. UK Guidance John et al Practical Diabetes 2012; 29: 12-13

  26. UK Guidance Diabet. Med. 29, 1350–1357 (2012)

  27. Some case studies

  28. 56 yr old male • BMI 34kg/m2 • Father developed type 2 diabetes aged 60 years • Asymptomatic • Glucose or HbA1c? • HbA1c 45mmol/mol

  29. What would you do next? X • Check a fasting blood glucoseimmediately • Check a fasting glucose now and repeatHbA1c in a year  • Check HbA1c in a year X

  30. 56 yr old male • BMI 34kg/m2 • Father developed type 2 diabetes aged 60 years • Asymptomatic • Fasting glucose 6.5mmol/L

  31. What would you do next?  • Check the fasting glucose • Do a GTT X • Check HbA1c X

  32. 16 year old boy • BMI 38kg/m2 • Lethargic for last year • Glucose + in urine • Glucose or HbA1c?

  33. 68 year old female • BMI 32kg/m2 • Thirst and polyuria for the last 2 weeks

  34. What would you do next? X • A fasting glucose X • An HbA1c  • A fasting or a non-fasting glucose

  35. DO NOT use HbA1c in these circumstances • All children and young people. • Pregnancy—current or recent (< 2 months). • Suspected type 1 diabetes, no matter what age • Short duration of diabetes symptoms. • Patients at high risk of diabetes who are acutely ill

  36. DO NOT use HbA1c in these circumstances • Patients taking medication that may cause rapid glucose rise; for example, corticosteroids, antipsychotic drugs (2 months or less). • Acute pancreatic damage or pancreatic surgery. • Renal failure. • Human immunodeficiency virus (HIV) infection.

  37. BE CAREFUL using HbA1c in these circumstances • Abnormal haemoglobins • Anaemia • Altered red cell lifespan • Ethnicity

  38. HbA1c vs. glucose for detecting vascular complications

  39. Predicting risk using glucose and HbA1c Glucose HbA1c

  40. Summary • HbA1c can now be used for type 2 diabetes diagnosis • POCT HbA1c measurement is not currently recommended • Be mindful of the exclusions to using the test • Do not ‘mix and match’ HbA1c and glucose

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