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Paradigm shift in Diabetic care Dr.R.V.S.N. Sarma, M.D., M.Sc., 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 microvascular 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 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.Sarma@works Haemoglobin Structure of Hb Dr.Sarma@works Different Hbs 1. 2. 3. 4. Fetal Hemoglobin – Hb F Adult Hemoglobin – Hb A Sickle cell disease – Hb S Hemoglobinopathies – Hb C, Hb E Glucose in the blood reacts with the Hemoglobin A to form Glycated Hb. Dr.Sarma@works Glycated Hb - GHb Different types of Glycation products are formed from the HbA0 depending on the carbohydrate moiety – namely – – – – Dr.Sarma@works 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 (Previously called glycosylated Hb.) Reference values of HbA1c 1. 2. 3. 4. 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 Dr.Sarma@works 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 • 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’ Dr.Sarma@works How well it measures ? Lowering Hb A1c reduces risk of complications 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 Dr.Sarma@works 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 - HbA1c Mean Plasma Glucose = (33.3 x HbA1C%) - 86 (Nathan et. al. NEJM, vol. 310, No 6, Feb 9, 1994) Dr.Sarma@works HbA1C % Mean BG mg % 5 7 9 11 80.5 147.1 213.7 280.3 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 Dr.Sarma@works Blood Glucose Monitoring Dr.Sarma@works Type Frequency Sample Type 2 DM Monthly FPG / PPG Type 1 DM Stabilized 4-6 times initially Twice a week. 6th hourly to 4th hourly 3 samples Pregnancy Once a week. FPG / PPG Peri-operative 4-6 times a day 6th hourly to 4th hourly MAGE “Blood Glucose 80 min. after breakfast correlates with MAGE ( Mean Amplitude of Glycaemic Excursions ) throughout the day” Molnar et. al. Dr.Sarma@works 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. New era in monitoring control Dr.Sarma@works