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Hba1 c
Be serious Doctor
1. I am making India the capital of the
world shortly !
2. Already I have a big… family of 200
millions on the globe.
3. I am happily troubling 12% urban and
8.2% of rural Indians.
4. In my name I am sweet but my effects
are very hot !
5. I am not easily controlled (< 45%)
Dr.E.P.Joslin
“The greatest burden on doctors will be
not the management of diabetes, but
the associated macro and micro-
vascular complications of it.” ..1926
“The goal of therapy in diabetes should
be to make serious efforts to keep the
blood sugar levels as close normal as
possible.” ….. 1929
HbA1c: the blood test with a
memory
What is HbA1c?
Hemoglobin is a protein that makes
your red blood cells red-colored.
When hemoglobin picks up glucose
from your bloodstream, the hemoglobin
becomes glycosylated.
Glycosylated hemoglobin is HbA1c.
The HbA1c test measures the
percentage of HbA1c in your blood—
a number that corresponds to your
average blood glucose for the previous
3 months.
HbA1c in your bloodstream.
Different types of Glycation products
are formed from the HbA0depending on
the carbohydrate moiety – namely
 HbA1a1 - Fr 1,6 diphos –N-term. valine
 HbA1a2 - Gl 6 phos –N-terminal valine
 HbA1b - Other CHO – N-term. valine
 HbA1c - Glucose –N-terminal valine
Normally less than 6% of Hb is HbA1c
Glycated Hb - GHb
(Previously called glycosylated Hb.)
Haemoglobin
Structure of Hb
Formation of Glycated
Haemoglobin
HC=O HC=N-βA HC=N+H2-βA
  
HCOH HCOH HCOH
  
HOCH HOCH HOCH
β-NH2 +   
HCOH HCOH HCOH
  
HCOH HCOH HCOH
  
CH2OH CH2OH CH2OH
Glucose Schiff Base Amadori Product
(Aldimine) (Ketoamine)
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
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
Hba1 c
Reference values of HbA1c
1. Less than 6% - Normal
2. 6 to 7% - Good control of DM
3. 7 to 9% - Unsatisfactory control
4. More than 9% - Very poor control
Values depend on the method of estimation
They vary from lab to lab.
Estimation of HbA1c
 There are many methods of estimation
 HPLC (High Performance Liquid
Chromatography) – Gold standard.
 Immuno-turbimetric meth. – HbA1cAb
 Affinity chromatography
 Electrophoretic methods
 Method based on chemical reactions.
Lowering Hb A1c reduces risk of complications
How well it measures ?
Dr.Sarma@works
UKPDS:
Risk of Macro and Microvascular
Complications
UKPDS Group. BMJ 2000;321:405-412
DCCT:
Risk of Microvascular
Complications
DCCT Group. N Engl J Med. 1993; 329: 977-86
Correlation of MPG - HbA1c
Mean Plasma Glucose =
(33.3 x HbA1C%) - 86
(Nathan et. al. NEJM, vol. 310, No 6, Feb 9, 1994)
HbA1C %
5
7
9
11
Mean BG mg %
80.5
147.1
213.7
280.3
Dr.Sarma@works
Dr.Sarma@works
Advantages of HbA1c
• Index of long-term control over 120
days and not a snap shot like PG
• Can be done at any time of day
• Not influenced by diet, exercise,
emotional disturbances on test day
• Useful index in clinical trials
• Useful if missed drugs / default diet
• Useful in DD of stress hyperglycemia
Limitations of HbA1c
• Cannot be an emergency room test to
titrate Insulin or OHA dosage
• Cannot register hypoglycemia
• More sensitive to sin than repentance –
if it is elevated it confirms poor control,
if it is boarder line, it cannot assure
good control in the recent past.
• Not sensitive enough for use in GDM
∀↓ Anaemia, Uraemia, Pregnancy
Hba1 c

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Hba1 c

  • 2. Be serious Doctor 1. I am making India the capital of the world shortly ! 2. Already I have a big… family of 200 millions on the globe. 3. I am happily troubling 12% urban and 8.2% of rural Indians. 4. In my name I am sweet but my effects are very hot ! 5. I am not easily controlled (< 45%)
  • 3. Dr.E.P.Joslin “The greatest burden on doctors will be not the management of diabetes, but the associated macro and micro- vascular complications of it.” ..1926 “The goal of therapy in diabetes should be to make serious efforts to keep the blood sugar levels as close normal as possible.” ….. 1929
  • 4. HbA1c: the blood test with a memory What is HbA1c? Hemoglobin is a protein that makes your red blood cells red-colored. When hemoglobin picks up glucose from your bloodstream, the hemoglobin becomes glycosylated. Glycosylated hemoglobin is HbA1c. The HbA1c test measures the percentage of HbA1c in your blood— a number that corresponds to your average blood glucose for the previous 3 months. HbA1c in your bloodstream.
  • 5. Different types of Glycation products are formed from the HbA0depending on the carbohydrate moiety – namely  HbA1a1 - Fr 1,6 diphos –N-term. valine  HbA1a2 - Gl 6 phos –N-terminal valine  HbA1b - Other CHO – N-term. valine  HbA1c - Glucose –N-terminal valine Normally less than 6% of Hb is HbA1c Glycated Hb - GHb (Previously called glycosylated Hb.)
  • 7. Formation of Glycated Haemoglobin HC=O HC=N-βA HC=N+H2-βA    HCOH HCOH HCOH    HOCH HOCH HOCH β-NH2 +    HCOH HCOH HCOH    HCOH HCOH HCOH    CH2OH CH2OH CH2OH Glucose Schiff Base Amadori Product (Aldimine) (Ketoamine)
  • 8. 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
  • 9. 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
  • 11. Reference values of HbA1c 1. Less than 6% - Normal 2. 6 to 7% - Good control of DM 3. 7 to 9% - Unsatisfactory control 4. More than 9% - Very poor control Values depend on the method of estimation They vary from lab to lab.
  • 12. Estimation of HbA1c  There are many methods of estimation  HPLC (High Performance Liquid Chromatography) – Gold standard.  Immuno-turbimetric meth. – HbA1cAb  Affinity chromatography  Electrophoretic methods  Method based on chemical reactions.
  • 13. Lowering Hb A1c reduces risk of complications How well it measures ?
  • 15. UKPDS: Risk of Macro and Microvascular Complications UKPDS Group. BMJ 2000;321:405-412
  • 16. DCCT: Risk of Microvascular Complications DCCT Group. N Engl J Med. 1993; 329: 977-86
  • 17. Correlation of MPG - HbA1c Mean Plasma Glucose = (33.3 x HbA1C%) - 86 (Nathan et. al. NEJM, vol. 310, No 6, Feb 9, 1994) HbA1C % 5 7 9 11 Mean BG mg % 80.5 147.1 213.7 280.3
  • 20. Advantages of HbA1c • Index of long-term control over 120 days and not a snap shot like PG • Can be done at any time of day • Not influenced by diet, exercise, emotional disturbances on test day • Useful index in clinical trials • Useful if missed drugs / default diet • Useful in DD of stress hyperglycemia
  • 21. Limitations of HbA1c • Cannot be an emergency room test to titrate Insulin or OHA dosage • Cannot register hypoglycemia • More sensitive to sin than repentance – if it is elevated it confirms poor control, if it is boarder line, it cannot assure good control in the recent past. • Not sensitive enough for use in GDM ∀↓ Anaemia, Uraemia, Pregnancy