2. What is fructosamine
• Fructosamine is one of the blood tests that can
be carried out to measure the blood glucose
levelsofpeople whohavediabetes.
• Many people with this disease check their
blood glucose levels daily with a home blood
sugarmeter.
• Glucose levels can fluctuate throughout the day,
however, and doctors frequently wish to know
theoverall levels ofthis sugarintheblood.
3. • Usually, glucose control is monitored by the
hemoglobin A1c test, which determines the
blood sugar levels overthepastthreemonths.
• The fructosamine test is an alternate test that
determines glucose levels over the previous 2-3
weeks.
• The common symptom of different types of
diabetes mellitus is excessive levels of the sugar
glucose inthe blood.
• Over time, high levels of sugar can severely
damage the kidneys, eyes, feet, and
cardiovascular system.
4. • Therefore, diabetes is treated aggressively,
frequently with medication.
• To determine how well the treatment
schedule is working, patients generally check
their blood sugar levels at least once a day
withablood sugar meter.
• It may appear that the levels of glucose are
at their ideal levels, but levels may change
wildlyoverthe course oftheday.
5. • To get a more accurate measurement of the
glucose levels over time, doctors frequently
perform blood tests to assess the average level
ofglucose overaperiod oftime.
• There are two lab tests commonly performed to
checkblood glucose levels:
1. Thehemoglobin A1Ctest
2. Thefructosamine test.
•Bothmeasure theamount ofglucose that has
bound to proteins in the blood, known a
glycated proteins.
6. The formation of Fructosamine
• Fructosaminecanbeformedby asfollows:-
• FormationofAmadoriproduct:-Itisanintermediatein
theproductionofanadvancedglycationend-product
(AGE)asaresultofglycation,theformationofanAGE
involvesthefollowingsteps:
1. Advancedglycationendproducts(AGEs)
2. Advancedglycationendproducts(AGEs)are
modificationsofproteinsorlipidsthatbecome
nonenzymaticallyglycatedandoxidizedafter
contactwithaldosesugars.
7. • In other words, they are the result of a chain of
chemical reactions which follow an initial
glycation reaction.
• The intermediate products are known as Schiff
base, Amadori, and Maillard products, after the
researcherswho firstdescribed them.
• Initially, glycation involves covalent reactions
between free amino groups of amino acids,
such as lysine, arginine, or protein terminal
amino acids and sugars (glucose, fructose,
ribose, etc), tocreatethefollowingreactions
9. Figure 2. Formation of glycated hemoglobin A1c (HbA1c). HbA1c is an
Amadori product and is formed through the intermediate Schiff base
step.
10. • AGE formation from fructoselysine involves the
nonoxidative dissociation of fructoselysine to form
new reactive intermediates that again modify proteins
to form AGEs of various different chemical structures
(Figure3).
• Alternatively, fructoselysine decays and releases its
carbohydrate moiety either as glucose or as the more
reactive hexoses, such as 3-deoxyglucosone, which
themselvesmaymodifyproteins.
• In addition, it has recently been found that glucose
can auto-oxidize to form reactive carbonyl compounds
(glyoxal and methylglyoxal) which can react with
proteinstoformglycoxidationproducts.
11. • In addition to this, products of oxidative stress, such as
peroxynitrite, can also induce the formation of
carboxymethyl lysine by oxidative cleavage of Amadori
products and/or the generation of reactive dicarbonyl
compoundsfromglucose(Figure2and3).
• Thus, AGEs can arise from glucose and lipids through
several,partiallyinterminglingreactions.
• Once formed, they may damage cellular structures via
a number of mechanisms, including the formation of
cross-links between key molecules in the basement
membrane of the extracellular matrix (ECM) and the
interaction of AGEs with RAGEs on cell surfaces, thus
alteringcellularfunctions.
14. • Accumulation of AGEs in the ECM occurs on
proteins with a slow turnover rate, with the
formation of cross-links that can trap other
localmacromolecules.
• In this way, AGEs alter the properties of the
large matrix proteins collagen, vitronectin, and
laminin. AGE cross-linking on type I collagen
and elastin causes an increase in the area of
ECM, resulting in increased stiffness of the
vasculature.
15. • Glycation results in increased synthesis of
type III collagen, type V collagen, type VI
collagen, laminin, and fibronectin in the ECM,
most likely via upregulation of transforming
growth factor-â pathways. Formation of AGEs
on laminin results in reduced binding to type
IV collagen, reduced polymer elongation, and
lower binding of heparan sulfate
proteoglycan.
17. • AGE-induced alterations of vitronectin and
laminin may explain the reduction in binding of
heparan sulfate proteoglycan, a stimulant of
other matrix molecules in the vessel wall, to the
diabetic basement membrane.
• As for the role of lipids, glycated low-density
lipoprotein (LDL) reduces nitric oxide (NO)
production and suppresses uptake and
clearance of LDL through its receptor on
endothelial cells.
19. • The amount of these proteins is much
higher in people that have poor control
of their diabetes.
• Many factors affect the amount of free
glucose in the blood, but changes in the
levels of glycated proteins happen much
more slowly and give much more
reproducible readings.
20. • The measurement of fructosamine detects
the reaction product of glucose that has
bound to the accessible amino group on a
protein such as albumin, for example, giving
glycated albumin.
• Albumin has a circulating half life of
approximately 17 days, compared to 120 days
forHbA1c.
• Fructosamine is considered to be an
intermediate indicator of diabetic control
because it is not as immediate as blood
glucose, butnot aslongstanding asHbA1c.
21. • In general, fructosamine levels reflect
glycemic control over the previous 2 to 3
weeks
• This test measures glucose levels over the
last2-3weeks.
• It is an alternative to the more common
hemoglobin a1c test, which can give false
readings for patients with blood problems
suchashemolytic orsickle cellanemia
22. • Additional reasons to use this alternate
method of hematology include the need to
measurebloodsugarlevelsduringpregnancy.
• Because of the mother’s hormonal changes,
women with gestational diabetes can have
rapidchangesintheirbloodsugar.
• Doctors wish to monitor these changes much
more frequently than with the three month
periodaffordedbythestandardtest.
• With the fructosamine test, they check blood
sugarlevelsforthepast2-3weeks.
23. • Patientsfrequentlyundergochangesintheirmedication.
• Their blood sugar levels may need to be checked frequently to
determinetheeffectofthesechanges.
• The fructosamine test is better suited than the glycated
hemoglobin test to measure the rapidly changing glucose levels of
suchpatients.
• It is more important to look at trends when evaluating
fructosaminelevelsthanitistoanalyzetheabsolutepercentage.
• Levels that decrease suggest that glucose levels are being brought
underbettercontrol.
• Increasinglevelssuggesttheopposite.
• Thistestisnotusefulforscreeningfordiabetes.
• At the lower limit of the test, it is not clear whether a patient has
gooddiabeticcontrolorwhethertheyarefreeofthedisease.
24. • Fructosamine is most useful when
measurement of HbA1c is unreliable due to a
hemoglobinopathyorhemolysis.
• Fructosamine values are not accurate in
individuals with serum albumin levels below 3
g/dL or when serum albumin turnover is
accelerated.
• Examples include cirrhosis, nephrotic
syndrome, thyroid disease and
paraproteinemia.
• Referencerangeis200–285umol/L.
25. What is glycated protein
• Several authors are improperly using the terms
“glucosylated (or glycosylated) hemoglobin”, 'protein
glucosylation (or glycosylation)', etc. to refer to the
products of nonenzymic reactions between glucose or
othersugarsandfreeaminogroupsofproteins.
• The compounds so formed are not glycosides,
however, but result from the formation of a Schiff's
basefollowedbyanAmadorirearrangement.
• For example, the product of the reaction between
glucose and hemoglobin is not glucosylated
hemoglobin but an amino linked 1-deoxyfructose
derivativeofhemoglobin.
26. • The term 'glycation' for any reaction that
links a sugar to a protein, whether it is
catalyzed by an enzyme or not.
• The product of glycation is a glycated
protein, or, in the particular case of the
reaction with hemoglobin, glycated
hemoglobin.
27. • GlycosylatedHemoglobinorHemoglobinA1C(bHA1C)
• Reflects average blood sugar levels over the preceding
90-dayperiod.
• Elevated levels are associated with prediabetes and
diabetes.
• Individuals with diabetes have an increased risk of a
cardiacevent.
• A diabetic person's risk for heart attack is the same as
anon-diabeticperson, who hasexperienced one heart
attack,havingasecondheartattack.
• Aggressive global preventive risk reduction efforts,
such as lower LDL targets, diet, exercise and blood
pressurecontrol,arerecommended.
28. • Goal values (per American Diabetes
Association guidelines):
• A range of 5.7-6.4 percent indicates an
increased risk for development of diabetes
(i.e., prediabetes), and lifestyle interventions
maybebeneficial.
• A value equal or greater than 6.5 percent is
considered diabetic.
29. • This test may be measured any time of the day
withoutfasting.
• Glycosylated hemoglobin is blood glucose attached
to hemoglobin (a component of blood). This test is
often called the "diabetic report card." It reflects
the average blood sugar for the two to three
monthperiodbeforethetest.
• To calculate the average blood glucose level from
theHbA1C:
• HbA1C level x (multiplied by) 33.3 – 86 = average
bloodglucoselevelforthepast90days.
• HbA1C can be helpful to track diabetic control over
time.
30. • e.g.IfSomeone has HgA1c is6.6?.
• HgA1c is6.6isnot bad
• A6%isanaverage of126.
• If some has HgA1c is 7% is an average of 154 so
yoursissome whereinbetween orapprox. 142-3.
• Theformula toconvert A1c to BSis:
• =28.7xA1c–46.7.
• Thus,anA1cof7%=(28.7x7.0) –(46.7) =154
31. HbA1c targets
• For most people with diabetes, the HbA1c target is
below 48 mmol /mol , since evidence shows that
this can reduce the risk of developing diabetic
complications, such as nerve damage, eye disease,
kidney disease and heart disease.
• Individuals at risk of severe hypoglycaemia should
aim for an HbA1c of less than 58 mmol /mol.
• However, any reduction in HbA1c levels (and
therefore, any improvement in control), is still
considered to have beneficial effects on the onset
and progression of complications
32. HbA1c results
• You will now be getting used to seeing your
HbA1c results reported using the IFCC
(International Federation of Clinical Chemistry)
reference measurement procedure of
mmol/mol.
• A rough guide to the equivalent values can be
found inthe following conversion table
33. • To calculate the average blood glucose
level from the HbA1C for past 90 days:
• HbA1c level x (multiplied by) 33.3 – 86 =
average blood glucose level for the past
90 days.
• HbA1c level = 0.017x Fructosamine +
1.61
• Fructosamine = HbA1c- 1.61 ) X 58.82
• HbA1C and Fructosamine can be helpful
to track diabetic control over time.
