Dr.R.V.S.N. Sarma, M.D., M.Sc., Paradigm shift in Diabetic care

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.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.” “The goal of therapy in diabetes should be to make serious efforts to keep the blood sugar levels as close normal as possible.” …

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%)

Haemoglobin Structure of Hb

Different Hbs 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.

Different types of Glycation products are formed from the HbA 0 depending on the carbohydrate moiety – namely –HbA 1a1 - Fr 1,6 diphos –N-term. valine –HbA 1a2 - Gl 6 phos –N-terminal valine –HbA 1b - Other CHO – N-term. valine –HbA 1c - Glucose –N-terminal valine Normally less than 6% of Hb is HbA 1c Glycated Hb - GHb (Previously called glycosylated Hb.)

Reference values of HbA 1c 1.Less than 6% - Normal 2.6 to 7.5% - Good control of DM to 9% - Unsatisfactory control 4.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 HbA 1c

Factors affecting HbA 1c 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 HbA 1c There are many methods of estimation HPLC (High Performance Liquid Chromatography) – Gold standard. Immuno-turbimetric meth. – HbA 1c Ab Affinity chromatography Electrophoretic methods Method based on chemical reactions.

HbA 1c is ‘weighted’

Lowering Hb A1c reduces risk of complications How well it measures ?

Advantages of HbA 1c 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 HbA 1c 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 - HbA 1c Mean Plasma Glucose = (33.3 x HbA 1C% ) - 86 (Nathan et. al. NEJM, vol. 310, No 6, Feb 9, 1994) HbA 1C % Mean BG mg %

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

Blood Glucose Monitoring TypeFrequencySample Type 2 DMMonthlyFPG / PPG Type 1 DM4-6 times initially 6 th hourly to 4 th hourly StabilizedTwice a week.3 samples PregnancyOnce a week.FPG / PPG Peri-operative4-6 times a day 6 th hourly to 4 th hourly

“Blood Glucose 80 min. after breakfast correlates with MAGE ( Mean Amplitude of Glycaemic Excursions ) throughout the day” Molnar et. al. MAGE

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.

New era in monitoring control