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Dr.Sarma@works
Dr.R.V.S.N. Sarma, M.D., M.Sc.,
Paradigmshift inDiabeticcare
How true ?
Dr.Sarma@works
Once there was a tiger which boasted
that it can run faster than any one.
One day he chased a rabbit and failed to
catch it.
“All right” said the tiger; “of course I
failed on my boast.
But, remember the rabbit was running
for its life and I, for my dinner.”
Now, decide who is the rabbit and who
is the tiger - among we and our patient !
Dr.E.P.Joslin
Dr.Sarma@works
“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
Be serious Doctor
Dr.Sarma@works
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%)
Haemoglobin
Structure of Hb
Dr.Sarma@works
Different Hbs
Dr.Sarma@works
1. Fetal Hemoglobin – Hb F
2. Adult Hemoglobin – Hb A
3. Sickle cell disease – Hb S
4. Hemoglobinopathies – Hb C, Hb E
Glucose in the blood reacts with the
Hemoglobin A to form Glycated Hb.
Dr.Sarma@works
Different types of Glycation products
are formed from the HbA0 depending
on the carbohydrate moiety – namely
– HbA1a1 - Fr 1,6 diphos –N-term. valine
– HbA1a2 - Gl 6 phos –N-terminal valine
– HbA1b
– HbA1c
- Other CHO – N-term. valine
- Glucose –N-terminal valine
Glycated Hb - GHb
Nor(m
Pra
elv
li
y
ou
le
sls
y
scta
h
la
le
n
d6
g%
lyco
os
fyH
lat
b
ed
isH
H
b.b
)A1c
Reference values of HbA1c
Dr.Sarma@works
• Less than 6% - Normal
• 6 to 7.5% - Good control of DM
• 7.6 to 9% - Unsatisfactory control
• More than 9% - Very poor control
Values depend on the method of estimation
They vary from lab to lab.
Note if all GHb is measured instead of HbA1c
Factors affecting HbA1c
Dr.Sarma@works
• Acute hyperglycemia
• Severe aneamia
• Gestational diabetes
• Life span of the RBC
• Abnormal Hb like S-Hb, Hb C
• Serum opalescence -↑TG
• On the method of estimation
Estimation of HbA1c
Dr.Sarma@works
• 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.
HbA1c is ‘weighted’
Dr.Sarma@works
Lowering Hb A1c reduces risk of complications
Dr.Sarma@works
How well it measures ?
Advantages of HbA1c
Dr.Sarma@works
• 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
Dr.Sarma@works
• 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
Correlation of MPG - HbA1c
Mean Plasma Glucose =
(33.3 x HbA1C%) - 86
(Nathan et. al. NEJM, vol. 310, No 6, Feb 9, 1994)
HbA1C % Mean BG mg %
5
7
9
11
80.5
147.1
213.7
280.3
Dr.Sarma@works
Glycosylation of hair
Dr.Sarma@works
•
•
•
•
•
•
•
Hair glycosylation using thiobarbituric acid TBA
Glycosylation of hair is  in diabetes mellitus
Both insulin dependent , non-insulin dependent
Glycosylation of hair is proportionate to HbA1c
Due to the presence of hexosyl lysome in hair
Long hair sample provides a long term record.
May have forensic application & in population
studies.
BMJ, 1996, vol. 288 pp. 669-670
Blood Glucose Monitoring
Type Frequency Sample
Type 2 DM Monthly FPG / PPG
Type 1 DM 4-6 times
initially
6th hourly
to 4th hourly
Stabilized Twice a week. 3 samples
Pregnancy Once a week. FPG / PPG
Peri-operative 4-6 times
a day
6th hourly
to 4th hourly
Dr.Sarma@works
“Blood Glucose 80 min. after
breakfast correlates with MAGE
( Mean Amplitude of Glycaemic
Excursions ) throughout the day”
Dr.Sarma@works
Molnar et. al.
MAGE
SMBG
Dr.Sarma@works
• On intensive insulin therapy
• Diabetes in pregnancy
• IDDM who lack warning symptoms
of hypoglycaemia
• Insulin - requiring diabetics
• Diabetics with unusually high/low
RTMG.
• Insulin - resistant diabetics on large
insulin doses
• Motivated diabetics for tight control.
Dr.Sarma@works
New era in monitoring
control

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HbA1c.pptx

  • 1. Dr.Sarma@works Dr.R.V.S.N. Sarma, M.D., M.Sc., Paradigmshift inDiabeticcare
  • 2. How true ? Dr.Sarma@works Once there was a tiger which boasted that it can run faster than any one. One day he chased a rabbit and failed to catch it. “All right” said the tiger; “of course I failed on my boast. But, remember the rabbit was running for its life and I, for my dinner.” Now, decide who is the rabbit and who is the tiger - among we and our patient !
  • 3. Dr.E.P.Joslin Dr.Sarma@works “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. Be serious Doctor Dr.Sarma@works 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%)
  • 6. Different Hbs Dr.Sarma@works 1. Fetal Hemoglobin – Hb F 2. Adult Hemoglobin – Hb A 3. Sickle cell disease – Hb S 4. Hemoglobinopathies – Hb C, Hb E Glucose in the blood reacts with the Hemoglobin A to form Glycated Hb.
  • 7. Dr.Sarma@works Different types of Glycation products are formed from the HbA0 depending on the carbohydrate moiety – namely – HbA1a1 - Fr 1,6 diphos –N-term. valine – HbA1a2 - Gl 6 phos –N-terminal valine – HbA1b – HbA1c - Other CHO – N-term. valine - Glucose –N-terminal valine Glycated Hb - GHb Nor(m Pra elv li y ou le sls y scta h la le n d6 g% lyco os fyH lat b ed isH H b.b )A1c
  • 8. Reference values of HbA1c Dr.Sarma@works • Less than 6% - Normal • 6 to 7.5% - Good control of DM • 7.6 to 9% - Unsatisfactory control • More than 9% - Very poor control Values depend on the method of estimation They vary from lab to lab. Note if all GHb is measured instead of HbA1c
  • 9. Factors affecting HbA1c Dr.Sarma@works • Acute hyperglycemia • Severe aneamia • Gestational diabetes • Life span of the RBC • Abnormal Hb like S-Hb, Hb C • Serum opalescence -↑TG • On the method of estimation
  • 10. Estimation of HbA1c Dr.Sarma@works • 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.
  • 12. Lowering Hb A1c reduces risk of complications Dr.Sarma@works How well it measures ?
  • 13. Advantages of HbA1c Dr.Sarma@works • 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
  • 14. Limitations of HbA1c Dr.Sarma@works • 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
  • 15. Correlation of MPG - HbA1c Mean Plasma Glucose = (33.3 x HbA1C%) - 86 (Nathan et. al. NEJM, vol. 310, No 6, Feb 9, 1994) HbA1C % Mean BG mg % 5 7 9 11 80.5 147.1 213.7 280.3 Dr.Sarma@works
  • 16. Glycosylation of hair Dr.Sarma@works • • • • • • • Hair glycosylation using thiobarbituric acid TBA Glycosylation of hair is  in diabetes mellitus Both insulin dependent , non-insulin dependent Glycosylation of hair is proportionate to HbA1c Due to the presence of hexosyl lysome in hair Long hair sample provides a long term record. May have forensic application & in population studies. BMJ, 1996, vol. 288 pp. 669-670
  • 17. Blood Glucose Monitoring Type Frequency Sample Type 2 DM Monthly FPG / PPG Type 1 DM 4-6 times initially 6th hourly to 4th hourly Stabilized Twice a week. 3 samples Pregnancy Once a week. FPG / PPG Peri-operative 4-6 times a day 6th hourly to 4th hourly Dr.Sarma@works
  • 18. “Blood Glucose 80 min. after breakfast correlates with MAGE ( Mean Amplitude of Glycaemic Excursions ) throughout the day” Dr.Sarma@works Molnar et. al. MAGE
  • 19. SMBG Dr.Sarma@works • On intensive insulin therapy • Diabetes in pregnancy • IDDM who lack warning symptoms of hypoglycaemia • Insulin - requiring diabetics • Diabetics with unusually high/low RTMG. • Insulin - resistant diabetics on large insulin doses • Motivated diabetics for tight control.
  • 20. Dr.Sarma@works New era in monitoring control