ABSTRACT
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 (P < 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.
CHAPTER 1
INTRODUCTION
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.
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.
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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