Background: Glycated Albumin (GA) has been proposed as an important index in assessing chronic glycaemic control in diabetic patients other than glycated hemoglobin (HbA1c), besides it reflects shorter periods of glycaemia.
Aim: This  study sought  to  validate  the  use  of  Glycated  Albumin  and  Glycated Hemoglobin, as biomarkers of glycaemic control among Ghanaian diabetes patients.
Research  design  and  methods:  Venous  blood  samples  were  taken  from  200 participants of whom 150 were type 2 diabetic patients and 50 healthy individuals without diabetes. The blood samples were analyzed for fasting glucose, lipid profile, renal function (BUN, CRT and eGFR), serum total protein and albumin on fully automated analyzer, Roche COBAS Integra 400 Plus System. The A1 fast fraction – cation exchange method was used to estimate the level of glycated hemoglobin whilst the sandwich enzyme-linked immunosorbent one-step process assay (ELISA) was used for the assay of the Human Glycosylated Albumin (GA) level in the samples.
Results: Blood glucose, Glycated hemoglobin, Glycated albumin, GA/HbA1c and serum albumin were significantly (P < 0.05) increased in the patients with diabetes compared to the non-diabetics. Renal assessment indicated significant differences (< 0.05) in levels of serum urea, creatinine and sodium with increased levels in the diabetic patients.  The  estimated  glomerular  filtration  rate  (eGFR)  was  also  significantly (P <0.0001) reduced in the diabetics (eGFR value) compared to the non-diabetes (eGFR value). The proportion of excellent control of blood glucose assessed using GA, 11.3%, was lower than that assessed by HbA1c (16.7%). Also, glycemic control assessed by GA showed a greater proportion of poor control (35.3%) than when assessed by HbA1c (28.7%). Across the various age groups, diabetic nephropathy (29.3%) was more prevalent in the diabetic patients aged between 70-79 years and retinopathy (43.3%) more prevalent in the patients aged 60-69 years. Correlation between the levels of HbA1c  and  Glycated  albumin  among  patients  with  diabetes  a  showed  a  highly significant relationship (P < 0.001). Poor glycaemic control determined by HbA1c and GA were highly associated with Obesity and reduced kidney function.

Conclusion: Glycated albumin reflects glucose excursions more strongly than HbA1c; hence GA might be a more sensitive index for some diabetic complications than HbA1c.

1.1 General Introduction
Diabetes mellitus is a cluster of metabolic disorders whose main characteristic is persistent hyperglycaemia. Type 1 diabetes mellitus (T1DM) is largely due to cellular mediated autoimmune destruction of the β-cells of islets of langerhans and results in decreased insulin production. Type 2 diabetes (T2DM) is characterized by insulin resistance or abnormal insulin secretion (Kumar et al., 2005).

An estimated 2.8% of the world’s population has diabetes and this is expected to increase to about 4.4% by the year 2030. T2DM however makes up about 90% of the cases (Hedley et al., 2004; Wild et al., 2004). In Ghana, type 2 diabetes mellitus is at a crude prevalence rate of 6.3% and an age-adjusted prevalence of 6.4% (Amoah et al., 2002).

With the rapidly increasing prevalence and projections on diabetes mellitus, there is an urgent need to develop affordable and effective preventive strategies and identify high-risk populations in whom such strategies can be implemented (King et al., 1998).

Various laboratory tests are available for screening and monitoring or managing diabetic cases. These include: fasting or random blood glucose (FBG/RBG), oral glucose tolerance test (OGTT), two (2) hour post prandial test and glycated haemoglobin (HbA1c). HbA1c, the most widely used assay, measures the percentage of circulating haemoglobin that has chemically reacted with glucose and reflects blood glucose concentrations over the prior 120 days, with the most profound effect in the preceding 30 days (Calisti & Tognetti, 2005). It therefore reflects the ability of metabolic control within the desired range and also enables the estimation of the risk of chronic diabetic complications (Takahashi et al., 2007).

This has however come with its own problems and limitations. HbA1c values are influenced significantly in all conditions or haemoglobinopathies characterized by either shortening of the life span of erythrocytes or the changing proportion of young to old erythrocytes (Goldstein et al., 2004). Some of these include, haemoglobin variants (HbS, HbC, HbD), drugs, anaemia, uremia, alcoholism and dialysis. Limitations resulting from most inherent assay methods also compromise the clinical utility of the HbA1c maker (Calisti et al., 2005).

A newer indicator of glycaemic control, the Glycated Albumin (GA) has been proposed and is rapidly becoming a significant index in assessing glycaemic control. Early stage reaction product of albumin or serum protein is called Glycated Albumin or Fructosamine (Ahmad, 2005). It has been suggested that GA provides a significantly better glycaemic control in patients with conditions that may cause decreased red cell lifespan, especially haemodialysis. Assessment of HbA1C in such patients is likely to cause an underestimation mostly due to increasing proportions of young erythrocytes (Inaba et al., 2007).

Moreover, serum albumin has a shorter lifespan (15-20days) than that of red blood cells (120 days) and with a higher turnover than haemoglobin. This also makes GA better in assessing short-term changes (2 weeks) in diabetic control. There have also been suggestions on the need for a mid-range test that could be performed monthly as a means of helping people with diabetes manage their glucose levels more effectively (Takahashi et al., 2007).

In the light of these benefits, GA may also be affected by other factors like BMI, treatment modalities and endogenous insulin secretion. There is therefore the need to also evaluate other factors which may affect the interpretation and use of this marker.

Moreover the characteristics and applicability of this marker in the Ghanaian population remains to be determined. The current study therefore seeks to evaluate the use of Glycated Albumin compared to HbA1C as biomarkers of glycaemic control and other factors which may be associated with its use.

1.2 Study Hypothesis
Plasma GA is a more accurate marker of glycaemic control than HbA1c which could help in the determination of short term glucose control, hence better management of diabetic patients.

1.3 Problem Statement
Glycated hemoglobin has over the years been a very useful tool in the monitoring of glycaemic control in diabetics. This has however come with several challenges. The test is relatively expensive and is affected by several conditions, which may decrease red blood cell survival, a pre-requisite for adequate chemical bonding of glucose. This therefore is an indication of the non-applicability of the test in all populations, hence the need to identify a better marker of glycaemic control for every population. Glycated Albumin has therefore been suggested. There are reports that, Glycated Albumin is also affected by endogenous insulin secretion in diabetics(Koenig et al., 1976), thus necessitating the evaluation of the marker, especially among type 2 diabetes patients.

1.4 Justification
Internationally, at least one person dies every 10 seconds whereas four limbs are surgically remove every 30 seconds as a result of diabetic complications. Prevalence and projections on Diabetes Mellitus is alarming and there is an urgent need to develop affordable and effective preventive strategies (King et al., 1998). The numerous complications that present with diabetes will also be prevented or reduced drastically upon effective strategies to diagnose, predict and manage the condition.

The HbA1c test is designed to measure the average blood glucose levels over previous 2-3 months, giving an indicator of longer-term blood glucose control(Calisti et al., 2005). Aside the high cost of performing the test, which is largely borne by patients, the test comes with various limitations, which make it unreliable and inappropriate for monitoring glycaemic control(Goldstein et al., 2004). Some of these include, haemoglobin variants (HbS, HbC,HbD), drugs, anemia, uremia, alcoholism and dialysis.Limitations resulting from most inherent assay methods also compromise the clinical utility of the HbA1c maker(Calisti et al., 2005). The characteristics of GA and HbA1c in a cross-section of diabetic patients have not been compared in Ghana. Hence we have no justification yet, to include or adopt this as a marker of glycaemic control in Ghana.

There is therefore the need to conduct such a study in Ghana, which will add to existing database on diabetes by providing baseline information. The study will assess the ability of Glycated Albumin to better demonstrate glycaemic control and management. It will also determine which factors may be associated with these levels in the Ghanaian population.

1.5 Expected Benefits
Success in proving our hypothesis will help reduce cost incurred by patients on HbA1c analysis, better detect changes in glycaemic control and thus early prevention of the onset of complications. It will also identify factors, which may affect the levels of Glycated Albumin among the Ghanaian population, hence, the better interpretation in the use of the marker in management.

1.6 Aim
The aim of the study was to validate the use of Glycated Hemoglobin and Glycated Albumin, as biomarkers of glycaemic control among Ghanaian diabetic patients.

1.6.1 Specific objectives
To compare Glycated Hemoglobin and Glycated Albumin as biomarkers of glycaemic control.

To determine the effects of anthropometric variables on Glycated Albumin levels

To determine the relationship between Glycated Albumin and dyslipidemia in diabetics.

To determine the relationship between glycaemic control and complications associated with Diabetes Mellitus

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Item Type: Ghanaian Postgraduate Material  |  Attribute: 102 pages  |  Chapters: 1-5
Format: MS Word  |  Price: GH50  |  Delivery: Within 30Mins.


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