SYNOPSIS
For the study of thesis entitled ‘’ ESTIMATION OF GLYCOSYLATED HEMOGLOBIN AND ITS VALUE IN THE ESTIMATION OF THE CONTROL OF PATIENTS OF DIABETES MELLITUS OF JAMSHEDPUR , JHARKHAND’’
Submitted for the degree of
DOCTOR OF PHILOSOPHY
IN
BIOCHEMISTRY
SUBMITTED BY:-
DR MATIN AHMAD KHAN
UNDER THE GUIDANCE OF:-
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SUPERVISOR CERTIFICATE
This is to certify that DR MATIN AHMAD KHAN has completed the Ph.D. synopsis titled ESTIMATION OF GLYCOSYLATED HEMOGLOBIN AND ITS VALUE IN THE ESTIMATION OF THE CONTROL OF PATIENTS OF DIABETES MELLITUS OF JAMSHEDPUR , JHARKHAND’’under my Supervision. He has met all the requirements of the Ph.D. ordinance of this university for the submission of Synopsis.
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DECLARATION
“I hereby declare that this submission is my own work and that, to the best of my knowledge and belief, it contains no material previously published or written by another person nor material which has been accepted for the award of any other degree or diploma of the university or other institute of higher learning, except where due acknowledgment has been made in the text.
Place: Signature
Date
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CONTENT PAGE NO.
1. INTRODUCTION……………………………… 04
2. IMPORTANCE OF THE STUDY…………… 10
3. SCOPE OF THE STUDY…………………… 12
4. OBJECTIVES OF THE STUDY…………… 13
5. STATEMENT OF THE PROBLEM……… 15
6. RESEARCH METHODOLOGY…………… 15
6.1. COLLECTION OF DATA………………………… 15
6.2. SELECTION OF SAMPLE………………………. 15
6.3. CONTENT OF SCHEDULE…………………….. 16
6.4. DATA ANALYSIS……………………………… 17
6.5. LIMITATION…………………………………… 17
6.6. DELIMITATION………………………………. 17
7. REVIEW OF RELATED LITERATURE. 18
8. REFERENCES…………………………….. 23
Abstract
Diabetes is a global endemic with rapidly increasing prevalence in both developing and developed countries. The American Diabetes Association has recommended glycated hemoglobin (HbA1c) as a possible substitute to fasting blood glucose for diagnosis of diabetes. HbA1c is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. HbA1c not only provides a reliable measure of chronic hyperglycemia but also correlates well with the risk of long-term diabetes complications. Elevated HbA1c has also been regarded as an independent risk factor for coronary heart disease and stroke in subjects with or without diabetes. The valuable information provided by a single HbA1c test has rendered it as a reliable biomarker for the diagnosis and prognosis of diabetes. This review highlights the role of HbA1c in diagnosis and prognosis of diabetes patients.
KEYWORDS: diabetes, HbA1c, diagnosis, prognosis, blood test
1.INTRODUCTION
Both science and the practice of medicine change rapidly. In recent year, new developments have taken place of breath taking speed. The most important of these is the science pertaining to health and disease. One of the new concepts is that careful control of blood glucose helps to prevent or postpone the dread complications of angioplasty and neuropathy in the course of diabetes Mellitus. A deterrent to greater acceptance of this is lack of control of blood sugar. Prospective studies suggest that there is positive relationship between the degree of metabolic control and the frequency and extent of late complications of Diabetes mellitus [1]. Investigation of the structure and biosynthesis of glycosylated Hemoglobin (HbA1c) in the past decade have provided a means to objectively access the average level of glycemia in diabetic patient. The use of Glycosylated hemoglobin level as integrated index of long term blood glucose level, represent a significant tool in our research and therapeutic armamentarium [2]. From the structural and biosynthesis information available it is clear that HbA1c is formed slowly and almost irreversibly by the condensation of glucose and hemoglobin in red blood cell. At any given point of time glycosylated hemoglobin level is better indicator of blood glucose. The process of glycosylation is continuous through whole 120 day life span of red blood cells, so it correlates with glucose levels of previous 6 to 8 weeks [3]. In this study, we have estimatedglycosylated Hemoglobin (HbA1c) in diabetic and non diabetic person and its relationship with fasting and post prandial blood sugar levels. By studying the patients with apparently well controlled diabetes as indicated by their FBS, FUS, PPBS and PPUS levels an attempt has been made to judge the actual control of diabetes using glycosylated Hemoglobin (HbA1c).
The demonstration that the development of microvascular complications in patients with type 1 diabetes can be slowed by treating hyperglycemia has led to increased use of intensive insulin regimens to attain strict glycemic control (figure 1 and figure 2) [1-3]. The efficacy of these regimens requires an accurate method to estimate the degree to which this is achieved. It is helpful to first review some basic concepts before discussing the utility of measurements of glycated hemoglobin (A1C) and serum fructosamine to assess glycemic control.
There are three useful measurements for defining glycemic control:
?The mean blood glucose concentration has often been measured in clinical trials as the mean of values obtained before breakfast, mid-morning, before lunch, mid-afternoon, before dinner, and before sleep each day. Clinically, this can be replaced with or supplemented by the more simple measurement of A1C. In some cases, however, there is a disparity between the A1C values and mean blood glucose values. (See ‘Recommendations in type 1 diabetes’ below.)
?The degree to which blood glucose concentrations fluctuate within the same day can be formally measured as the mean amplitude of glycemic excursions [4].
?The degree to which blood glucose concentrations fluctuate from day to day can be formally measured as the mean of daily differences [5
2.IMPORTANCE OF THE STUDY
In normal, non-diabetic control group subjects, mean glycosylated haemoglobin concentration is 6.68% and range is 5.02 to 7.93.In present study mean glycosylated haemoglobin concentration is 12.90. Glycosylated haemoglobin correlates significantly with the fasting, post prandial levels. Mean of fasting and post –prandial blood sugar level are 178.68 and 226.28 mg /dl respectively. Glycosylated haemoglobin value found higher in female -13.01 compare to make -12.86 Glycosylated haemoglobin values were higher in Juvenile onset diabetes (IDDM) – 14, 20 than Maturity onset diabetes (NIDDM) 12.26. A Glycosylated haemoglobin value has no relation with the long complication of diabetes mellitus. Glycosylated haemoglobin concentration was found high in Insulin taking 15.26 than patients on oral hypoglycaemic agents 12.25 and on dietary restriction 7.81. Single Haemoglobin A1c measurement reflects the mean blood sugar concentration of the patient for the previous two to three months. Therefore, the glycosylated haemoglobin assay provides information about the degree of long term glucose control that is otherwise obtainable in the usual out patients setting. ION EXCHANGE RESIN method can be used routinely to estimate HbA1c in non-diabetic and diabetic patients. Periodic monitoring of HbA 1c should allow the assessment of chronic diabetic control on an out patients basis in a more objective manner than is now possible and enable one to evaluate various forms of therapy and the relationship between carbohydrate control and the progression of various diabetic sequele.
The ADA has recently recommended HbA1c with a cut-point =6.5% for diagnosing diabetes as an alternative to fasting plasma glucose (FPG =7.0 mmol/L)-based criteria.17 The levels of HbA1c are strongly correlated with FPG (Fig. 3).18 FPG, 2-hour post-glucose load plasma glucose, and oral glucose tolerance tests are recommended for the diagnosis of diabetes only if HbA1c testing is not possible due to unavailability of the assay, patient factors that preclude its interpretation, and during pregnancy.19 HbA1c provides a reliable measure of chronic glycemia and correlates well with the risk of long-term diabetes complications, so that it is currently considered the test of choice for monitoring and chronic management of diabetes. However, the cut-point of HbA1c from the diagnostic point of view is still controversial. Among diabetics, the blood glucose levels increase in the blood and the glucose attaches to the hemoglobin molecule in a concentration-dependent manner. The glucose-bound (glycated) hemoglobin or HbA1c provides the average glucose levels in an individual’s blood as it becomes glycated with the hemoglobin. It is important to note that the HbA1c levels are directly proportional to the blood glucose levels. A simple blood glucose test such as a fasting glucose test (FGT) is a measure of glucose concentration present in an individual’s blood at a given point of time.20 The blood used for the FGT may be obtained through a needlestick of a finger or directly from the arm. A new techno logy, continuous glucose monitoring, has arrived in the market, which allows for non-prick readings.21–23 A small chip is implanted under the skin, which provides continuous glucose monitoring readings to the sensor kept outside, and if the glucose levels are higher or lower, it sends a special signal to the sensor, thus alerting the patient and/or the health-care provider for intervention.22,23The FGT is an excellent test for “in the moment” glucose levels, but it does not provide detailed information about the time course trend of the glucose levels. The HbA1c test, however, is a marker of the average glucose levels spread over a two- to three-month period. Contrary to popular belief, along with the type 2 diabetes, the HbA1c is also used to diagnose, manage, and monitor the type 1 diabetes as well.24 In a series of 12,785 male diabetic patients, Khan et al.11 have shown that the HbA1c cut-point of 6.5% was associated with 3.78% false-negative predictions (Fig. 4), while majority of the false-negative patients had borderline FPG (7.0–8.0 mmol/L) and HbA1c (6.0%–6.5%), and therefore belonged to at-risk category on the basis of HbA1c alone criteria. These findings suggest that the status of individuals with HbA1c between 6.0% and 6.5% should be verified by combined FPG and HbA1c criteria.11 Recently, Khan et al.25 have provided regression equations for interconversions between the levels of FGT and HbA1c for predicting their expected values in diabetic patients.
3.SCOPE OF THE STUDY
Present study will be carried out from the points of view of Physicians treating Diabetes Mellitus , the present study is limited to the analysis from the points of view of the Diabetics of the selected regions of Jamshedpur by taking their FBG PPBS and HbA1c and is observed that In India and in Jamshedpur has been using the these three parameters .extensively
4. OBJECTIVES OF THE STUDY
5. STATEMENT OF THE PROBLEM.
In present our objective is to evaluate the VALUE OF GLYCOSYLATED HEMOGLOBIN IN THE ESTIMATION OF THE CONTROL OF PATIENTS OF DIABETES MELLITUS OF JAMSHEDPUR , JHARKHAND’’
“6. RESEARCH METHODOLOGY
6.1 .COLLECTION OF DATA.
A-Primary data
.\
B-Secondary data-
The relevant secondary data for the study will be collected mainly from various Books, Thesis, Reports, Journals and Periodicals relating to the subject.
6.3. CONTENT OF SCHEDULE
6.4. DATA ANALYSIS
Statistical techniques such as scaling and scoring techniques will be used for the analysis of data.
6.5. LIMITATION
6.6. DELIMITATION
7. REVIEW OF RELATED LITERATURE
8. REFERENCES
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3. Ursula T., et al. Three assays for Glycosylated hemoglobin compared. Clinical chemistry, 1995; 41(2): 191- 195.
4. Sanjiv K Khullar, et al. Diagnostic value of Glycosylated hemoglobin in diabetes mellitus for Indian population. Journal of diabetic association of India, 1984; 24: 41-46.
5. Abraham E.C., T.H.J. Huisman. Determine of Hba1c with a new micro column procedure. Diabetes, 1987; 27: 931-37.
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