Hb A1c by Dr Sarma RVSN

[email protected]. Sarma, M.D., M.Sc.,

Paradigm shift in Diabetic care

Dr.Sarma@works

How true ? 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.Sarma@works

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

Dr.Sarma@works

Be serious Doctor1. 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.Sarma@works

Haemoglobin

Structure of Hb

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Different Hbs

1. Fetal Hemoglobin – Hb F2. Adult Hemoglobin – Hb A3. Sickle cell disease – Hb S4. Hemoglobinopathies – Hb C, Hb E

Glucose in the blood reacts with theHemoglobin 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 - 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.)

Dr.Sarma@works

Reference values of HbA1c1. Less than 6% - Normal2. 6 to 7.5% - Good control of DM3. 7.6 to 9% - Unsatisfactory control4. 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

Dr.Sarma@works

Factors affecting HbA1c• 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

Dr.Sarma@works

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.

Dr.Sarma@works

HbA1c is ‘weighted’

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Lowering Hb A1c reduces risk of complications

How well it measures ?

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

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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

Dr.Sarma@works

Correlation of MPG - HbA1cMean Plasma Glucose =

(33.3 x HbA1C%) - 86

(Nathan et. al. NEJM, vol. 310, No 6, Feb 9, 1994)

HbA1C %

579

11

Mean BG mg %

80.5147.1213.7280.3

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Glycosylation of hair

• 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

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Blood Glucose MonitoringType 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

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“Blood Glucose 80 min. after breakfast correlates with MAGE

( Mean Amplitude of Glycaemic Excursions ) throughout the day”

Molnar et. al.

MAGE

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SMBG • 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.

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New era in monitoring control