Insulin is a endocrine which regulates glucose metamorphosis ( Nicholson, Perkins and Korber, 2006 ) ( Kaaks and Lukanova, 2001 ) ( McKern et al, 2006 ) ( Cohen, 2006 ) by originating glucose uptake into cells ( Marshall and Bangert, 2008 ) which will in return, diminish the blood glucose concentration.
Diabetess Mellitus ( DM ) is a metabolic upset, characterized by a high blood glucose concentration ( Gernstein et al, 2007 ) due to the defect in insulin secernment by pancreatic beta cells, insulin action or both ( Farrar et al, 2008 ) . The glucose can non come in the cells and will stay in the blood stream, ensuing in an increased value of blood glucose concentration. DM Type 1 and Type 2 are the most common types of DM.
DM Type 1 ( Insulin Dependent DM ) ( Farrar et al, 2008 ) is caused by the harm of beta cells in the Isles of Langerhans ( Gotto and Toth, 2007 ) . When the beta cells of the Islets of Langerhans are damaged, really small or no insulin is produced. Glucose uptake into the cells does non happen and the concentration of blood glucose will be elevated.
Type 1 DM can be categorized into DM Type 1A ( immune mediated ) and DM Type 1B ( non immune mediated ) harmonizing to the American Diabetes Association ( Gotto and Toth, 2007 ) . DM Type 1A is caused by factors such as autoimmune diseases whereas DM Type 1B is caused by factors such as chronic viral infections. Due to the insufficient or absent insulin production, these patients are dependent on insulin therapy for endurance ( Farrar et al, 2008 ) .
DM Type 2 is due to insulin opposition. Insulin opposition is a status where although, insulin is secreted in big sums, glucose consumption into the cells does non happen. The absence of glucose supply into the cells, causes the beta cells in the Isles of Langerhans to release more insulin to originate glucose consumption into the cells ( Alwan, Tuffnell and West, 2009 ) ( Carr and Gabbe, 1998 ) to cut down the blood glucose concentration in DM Type 2 patients. Therefore due to insulin opposition, the blood glucose concentration remains high even though big sums of insulin were secreted. These patients usually do non necessitate insulin therapy and can be treated and managed by equal exercising and a healthy diet.
internal construction of pancreas
Figure 1: Isles of Langerhans, which is situated in the pancreas ( taken from www.tutorvista.com )
Treatment of DM is aimed to enable glucose uptake by cells and to diminish the injury caused by hyperglycemia in diabetes patients ( Fowler, 2008 ) . Hyperglycaemia causes hardening of blood vass, which amendss their map. Failure in the intervention and direction of diabetes AIDSs in the development of macrovascular ( big blood vass ) and microvascular ( little blood vass ) complications ( Pickup et Al, 2005 ) . Macrovascular complications cause shot ( Fowler, 2008 ) and microvascular complications can take to diabetic kidney disease ( Fowler, 2008 ) . In order to forestall these complications, glucose monitoring in diabetes patients should be done often ( Pickup et Al, 2005 ) .
Glucose Monitoring in Diabetes Mellitus Patients
2.1 Glucose Monitoring
Glucose monitoring in DM patients can fundamentally be described as a procedure of detecting the glucose degree in diabetes patients in order to accomplish an optimal glycaemic control ( Marshall and Bangert, 2008 ) . Glycaemic control is the control of blood glucose concentration in a diabetes patient. DM patients with first-class glycaemic control will show a blood glucose value, about similar to a non diabetic person. DM patients with ill controlled glycaemic control on the other manus, will show blood glucose values higher or lower than the normal scope ( Figure 3 ) .
Excellent Glycaemic Control
Borderline Glycaemic Control
Plasma Glucose Value ( mmol/l )
Fasting ( no glucose consumption )
Non- Fasting ( glucose consumed )
Figure 2: Glucose values in ( mmol/l ) for fasting and non fasting diabetes mellitus patients from plasma sample, with first-class, boundary line and hapless glycaemic control. ( Adapted from, Asian-Pacific Type 2 Diabetes Policy Group, 2002 )
Regular monitoring of glucose in DM ( Deiss et al, 2006 ) ( Pickup et Al, 2005 ) patients are indispensable to accomplish a good metabolic control ( Deiss et al, 2006 ) . This would ensue in a low incidence of unrecognised hyperglycemia and hypoglycemia among diabetes patients ( Pickup et Al, 2005 ) . Based on a survey by Saudek et Al ( 2006 ) , it was proposed that glucose monitoring reduced the frequence of microvascular and macrovascular complications ( Welschen et al, 2005 ) in DM Type 1 and 2 patients. When glucose degrees are monitored, a good glycaemic control is achieved. Hence, diabetes is managed and would non come on and do complications. A good glycaemic control is said to better the quality of life in diabetes patients although in some instances, it had caused hypoglycemia ( low blood glucose concentration ) ( Saudek et al, 2006 ) .
Glucose monitoring in diabetes patients besides helps in the monitoring of intervention dose besides detecting the intervention public presentation ( Marshall and Bangert, 2008 ) ( Logtenberg et al, 2009 ) . If the intervention works expeditiously, a good glycaemic control would be obtained and the intervention dose can be altered based on the glucose degrees, to avoid hypoglycemia.
Glucose supervising done on diabetes patients can be divided into two classs ; the short term glucose monitoring and the long term glucose monitoring. This will be discussed below.
2.2 Glucose monitoring in short term
Glucose monitoring in short term can be described as a manner of supervising glucose degrees in diabetes patients by mensurating the immediate degrees of glucose ( Saudek et al, 2005 ) . In other words, short term glucose monitoring involves the measuring of glucose concentration in one twenty-four hours ( 24 hours ) . The glucose values obtained when the measuring is done are dependent on factors such as diet and intervention dose consumed that twenty-four hours. Due to that fact, it is indispensable to supervise the glucose in diabetes patients often in order to guarantee the glucose concentrations in the blood are under control ( Pickup et Al, 2005 ) .
Self Monitoring Blood Glucose ( SMBG ) instruments has been used ( Skeie et al, 2009 ) by diabetes patients ( Pickup et Al, 2005 ) ( Saudek et al, 2006 ) to mensurate their blood sugar degrees ( Skeie et al, 2009 ) and to measure the intervention public presentations ( Figure 4 and Figure 5 ) ( Logtenberg et al, 2009 ) by themselves, without the fuss of going to the nearest infirmary.
Figure 3: Datas from glucose metre for the past 90 yearss of patient A. SMBG allows the patient to measure their glycaemic control. This patient has a good glycaemic control during the twenty-four hours. The glucose degrees are elevated between 5 to 7 am. This status is known as the morning phenomenon ( hyperglycemia during morning hours ) ( Saudek et al, 2006 ) .
Figure 4: Datas from glucose metre for the past 90 yearss of a patient B. SMBG allows the patient to measure their glycaemic control. This patient has a stable glycaemic control during the twenty-four hours, whereas after tiffin hours, the glucose degrees are elevated. Change in the intervention dose or diet can be done by patient to guarantee the glycaemic control is improved ( Saudek et al, 2006 ) .
SMBG instruments uses glucose strips which has been impregnated with glucose oxidase, glucose dehydrogenase or hexokinase to mensurate blood glucose ( Saudek et al, 2006 ) . SMBG is done by pricking the finger to obtain a little sum of blood sample to mensurate the blood glucose concentration ( Saudek et al, 2006 ) ( Pickup et Al, 2005 ) . When blood is added to the strip, the blood glucose will be converted to gluconic acid and H peroxidase. The concentration of the blood glucose is so quantified by a colorimetric method.
SMBG has been found to be highly utile for DM Type 1 patients compare to Type 2 patients. A stable blood glucose concentration form for DM Type 1 patients ( insulin dependant patients ) are hard to obtain although they are under intervention. These patients have the capableness of going hypoglycemic or hyperglycaemic in an unpredictable mode. Therefore, these patients are required to prove their glucose degrees often at different times ( Pickup et Al, 2005 ) in order to acquire an overall position of their glycaemic control for the twenty-four hours ( Figure 6 ) .
Figure 5: The overall form of glycaemic control in Type 1 DM patients can be observed with frequent testing of blood glucose. Patients who tested their blood glucose 3 to 4 times per twenty-four hours, missed 2 hypoglycemic episodes ( bluish circle ) whereas, patients who tested their blood glucose 4 to 5 times a twenty-four hours observed their hypoglycemic episodes ( Pickup et Al, 2005 ) .
In research labs, Fasting Blood Glucose ( FBG ) trial is done ( Menaka et al, 2007 ) . FBG is done to supervise the concentration of blood glucose during fasting period. Fasting period is a period when no nutrient is consumed. The blood glucose concentration will be somewhat low during fasting period in patients with a good glycaemic control ( Figure 3 ) . Patients are required to fast for 8-10 hours prior to FBG trial. Blood is drawn from the patient and is analyzed. FBG tests the public presentations of intervention based on the betterment in the efficiency of insulin map in diabetes patients ( Grant et Al, 2009 ) . If a patient is found to be hyperglycaemic, changes can be done by increasing the intervention dose of patient ( common in Type 1 DM ) or diet form ( Type 2 DM ) in order to obtain a good glycaemic control.
2.3 Glucose Monitoring in Long term
Glucose monitoring in long term can be described as a manner of supervising glucose degrees in diabetes patients by mensurating the long term glycaemic degrees ( Saudek et al, 2005 ) . In other words, long term glucose monitoring allows the measuring of the overall glucose degrees over the past hebdomads or months, depending on the technique applied.
Continuous Glucose Monitoring ( CGM ) is a non invasive method, used in the monitoring of glucose concentration in diabetes patients to accomplish a good glycaemic control ( Klonoff, 2005 ) . A detector with bantam filament strands is attached onto the arm, to mensurate the glucose concentration in the interstitial fluid of hypodermic tissue ( Saudek et al, 2006 ) . Interstitial fluids are the fluid which flows between cells. The sender will be attached to the detector in order to direct the glucose measuring consequences in the signifier of wireless moving ridges to the receiving system. The demonstrates the consequences and is able to hive away the consequences up to 2 months, to let monitoring of glucose degrees.
Figure 6: A CGM device allows patients to supervise glucose values by detecting the uninterrupted glycaemic form. This enables patients to supervise and better their glycaemic control by altering their intervention dose or diet ( Maran et al, 2005 ) .
CGM was shown to cut down the frequence of unrecognised hypoglycemia and hyperglycemia in diabetes patients ( Klonoff, 2005 ) . CGM instruments are provided with an dismay system to alarm the patient if they are hypoglycemic or hyperglycaemic ( Deiss et al, 2006 ) ( Saudek et al, 2006 ) . There are still correlativities whether is CGM categorized as a short term or long term glucose monitoring method.
C-peptide, a signifier of peptide made during the synthesis of insulin in the organic structure ( Couri et al, 2009 ) ( Hans et al, 2010 ) , is besides used in the monitoring of glucose in diabetes patients besides being used as a diagnosing method to distinguish between DM Type 1 and 2 ( Hans et al, 2010 ) . When insulin is non produced or deficient, the sum of C- peptide will be decreased ( Couri et al, 2009 ) .
Blood is drawn from the patient and the C- peptide is measured by utilizing Enzyme- Linked Immunosorbant Assay ( ELISA ) . The normal scope of C -peptide are 0.5 -2.0 ng/ml ( 0.17 -0.66 nmol//l ) ( Tietz, 1995 ) .
In type 1 patients, C- peptide is used to detect the sum of insulin which can be produced by beta cells ( Hans et al, 2010 ) , in order to supervise the dose of insulin therapy needed by diabetes patients ( Couri et al, 2009 ) . Type 2 DM intervention is aimed to better the consumption of glucose into cells so hence an elevated C- peptide degree with a high blood glucose concentration value indicates that the insulin is still immune. Therefore, intervention public presentations can be monitored and indicant for an insulin therapy can be observed.
Haemoglobin A, a normal grownup hemoglobin ( Smaldone, 2008 ) , when exposed to glucose in the blood stream, an irreversible, non enzymatic glycosylation procedure takes topographic point. This glycated hemoglobin is known as Haemoglobin A1c ( HbA1c ) ( Schnedl et al, 2000 ) . The lifetime of an red blood cell is about 120days. Therefore since the red blood cells contain haemoglobin A, the hemoglobin remains glycated until the red blood cells are destroyed. In other words, the norm of glucose concentration the ruddy cells have been exposed to in its life rhythm, reflects the sugar degree of a diabetes patient.
Harmonizing to the American Diabetes Association, HbA1c is considered as a first-class long term method in the monitoring of glucose for diabetes patients ( Kilpatrick, 2008 ) ( Schnedl et al, 2000 ) ( Smaldone, 2008 ) ( Gerstl et al, 2008 ) . Blood is drawn from the patient and is tested for HbA1c utilizing methods such as High Performance Liquid Chromatography ( HPLC ) , Cation -Exchange Chromatography ( Schnedl et al, 2000 ) and Immunoassay techniques ( Smaldone, 2008 ) .
HbA1c is present in little sums ( 1 to 4 % ) in a non diabetic patient ( Kilpatrick, 2008 ) whereas in ill controlled diabetes patients, HbA1c is present in high sums due to the exposure of the hemoglobin to high blood glucose concentration ( Smaldone, 2008 ) . The HbA1c value is straight relative to the blood glucose concentration in a diabetes patient for the past 6 -8 hebdomads ( Kilpatrick, 2008 ) ( Hans et al, 2007 ) .
American Diabetes Association ( ADA ) has proposed that HbA1c value of more than 7.0 % ( Hans et al, 2007 ) shows a hapless glycaemic control in patients.
Haemoglobin A1c ( % )
Estimated Glucose Average
( mmol/l )
Figure 7: HbA1c ( % ) values in mmol/l and mg/dl. These values are used to supervise the blood glucose degrees of a diabetic patient ( taken from Wikipedia ) .
In DM Type 1 patients, a high HbA1c value indicates the demand for an addition of insulin dose of the patient to keep a good glycaemic control. In type 2 patients, HbA1c is used to supervise their intervention and direction ( Gerstl et al, 2008 ) . HbA1c is besides used to bespeak the happenings of macrovascular and microvascular complications ( Kilpatrick, 2008 ) ( Smaldone, 2008 ) ( Schnedl et al, 2000 ) .
Haemoglobin A1c measuring in Diabetes Mellitus patients with hemoglobinopathies.
Hemoglobinopathies is the familial upset of a protein which carries O in red blood cells known as hemoglobin. Haemoglobin S, Haemoglobin C, and Haemoglobin D are signifiers of unnatural hemoglobins. As discussed above, the normal Haemoglobin A, HbA0 glycates and signifiers HbA1c when exposed to glucose. Abnormal hemoglobins such as Hb S in diabetes patients are assumed to organize HbS1c and so on alternatively of HbA1c when exposed to glucose. As a consequence, the HbA1c values of these diabetes patients with hemoglobinopathies are non accurate and can non be used to supervise glucose in diabetes patients.
A survey by Schnedl et Al ( 2000 ) showed that diabetes patients who had an unrecognised familial unnatural hemoglobin E, HbE resulted in highly low values of HbA1c when tested for HbA1c. The HbA1c values obtained in these patients were lower than the normal scope of a non diabetic patient.
The unnatural values of HbA1c in diabetes patients with unnatural hemoglobins are believed to be caused by 3 chief factors ; due to the change in the glycosylation procedure of the unnatural hemoglobin, shortened lifetime of red blood cells and the technique used to mensurate HbA1c ( Smaldone, 2008 ) . This will farther be discussed below.
Haemoglobin E disease is one of the most common types of hemoglobinopathy caused by the permutation of glutamine with lysine in the 26th place of the beta concatenation of the hemoglobin. Haemoglobin E causes a difference in the glycosylation rate. The normal Haemoglobin A undergoes glycosylation on one or both NH2 terminus valines of the beta concatenation. Due to the permutation of aminic acids in Haemoglobin E, when this unnatural hemoglobin is exposed to glucose, the glycation rates for this unnatural hemoglobin is believed to be significantly different from the normal Haemoglobin A. This can do the values of HbA1c to be highly high or low ( Small et Al, 2008 ) .
A research by Aleyassine ( 1979 ) proposed that the value of HbA1c from the Cation -Exchange Chromatography was found to be relative with the per centum or badness of the hemoglobin upset. A more terrible haemoglobinopathy status consequences in more mutated signifiers of hemoglobins. As a consequence, the O transporting capacity of the hemoglobin reduces, and this shortens the life span of an red blood cell. The glycated hemoglobin lifetime is shortened together with the red blood cells, doing the values to be low. This usually occurs in a diabetes patient who has HbS ( Sickle cell ) . In reaping hook cell, due to the sickle form of the red blood cells, the red blood cells are non stiff and is easy haemolysed. When hemolysis occurs in a big graduated table, the glycated hemoglobins are diminished as good ( Schnedl et al, 2000 ) .
The fluctuations of HbA1c value in hemoglobinopathies patients with diabetes depends on the techniques applied to mensurate HbA1c ( Smaldone, 2008 ) . Different methods cause different HbA1c values, and this job leads to the misdirection of diabetes patients with hemoglobinopathies ( Smaldone, 2008 ) .
Figure 7: ( Shaded area- HbA and HbA1c, not shaded area- HbX and HbX1c ) . The possible causes which lead to the fluctuation in HbA1c values when measured with chromatography technique. Diagram ( A ) sample with no variant hemoglobin, ( B ) Haemoglobin discrepancy ( HbX ) and glycated signifier ( HbX1c ) are separated from HbA and HbA1c, therefore the value of HbA1c is non affected, ( C ) HbX migrates with HbA1c and causes the HbA1c value to be increased, ( D ) HbX1c migrates with HbA1c, and HbX is separated from HbA, and this causes the HbA1c value to be mildly increased and ( E ) HbX1c and HbA1c is separated and HbA and HbX migrates together, doing a lessening int he HbA1c value ( Lynn et al, 2001 ) .
Hemoglobinopathies causes a false HbA1c value ( Schnedl et al, 2000 ) . Therefore HbA1c can non be used in the monitoring of glucose for this group of patients. The job arises when diabetes patients have silent ( symptomless and undetected ) hemoglobin discrepancies ( Smaldone, 2008 ) . When this group of patients are monitored with HbA1c, the values obtained are wholly unnatural. These consequences should be diagnosed farther ( Smaldone, 2008 ) to avoid false reading. For case, when a diabetes patient with soundless hemoglobin discrepancy is tested for HbA1c, the per centum of glycated hemoglobin will be unnatural. If the value obtained is abnormally low, and if farther trials are non done, the intervention dose of the patient might be reduced to forestall hypoglycemia. In existent, the patient might hold been hyperglycaemic, and due to the false HbA1c value, the lessening in the dose of intervention may take the patient to be hyperglycaemic
HbA1c values are usually based on diabetes and non diabetes patients without hemoglobinopathies. Therefore, haemoglobinopathies patient ‘s HbA1c consequences can non be considered normal ( Smaldone, 2008 ) ( Schnedl et al, 2000 ) .
As discussed above, glucose monitoring in diabetes patients can be done by the short term and long term monitoring methods. Short term glucose monitoring are known to be convenient, easy, fast and inexpensive. The disadvantages of short term monitoring methods is that the glucose value obtained are influenced based on the 24 hr term. For case, a patient which eats less carbohydrate nutrient and does a short term trials consequences in a lower glucose value comparison to the other repasts type. Short term method need to be done frequwnetly in order to obtain a good glycaemic form to command them. Long term supervising methods such as HbA1c, are non affected by day-to-day factors such as repasts and activities. Long term methods shows an mean true consequences of patient glucose concentration over the past 6 to 8 hebdomads, which is more dependable.
In diabetes patients with unnatural hemoglobins, HbA1c values can non be used. In patients with soundless Haemoglobin discrepancies, when HbA1c trial is done, the value obtained will bve either falsely elevated or decreased, and would non be consistent with their fasting blood glucose consequences. Further probes with trials such as High Performance Liquid Chromatography should be carried out on this samples, in order to avoid false consequences and reading.
Fructosamine values are used to observe the glucose concentration in this patients as a logn term method. Glucose monitoring should be taken into consideration earnestly, in order to pull off diabetes patients to avoid complications or decease in major instances.