What is fructosamine• Fructosamine is one of the blood tests that canbe carried out to measure the blood glucoselevelsofpeople whohavediabetes.• Many people with this disease check theirblood glucose levels daily with a home bloodsugarmeter.• Glucose levels can fluctuate throughout the day,however, and doctors frequently wish to knowtheoverall levels ofthis sugarintheblood.
• Usually, glucose control is monitored by thehemoglobin A1c test, which determines theblood sugar levels overthepastthreemonths.• The fructosamine test is an alternate test thatdetermines glucose levels over the previous 2-3weeks.• The common symptom of different types ofdiabetes mellitus is excessive levels of the sugarglucose inthe blood.• Over time, high levels of sugar can severelydamage the kidneys, eyes, feet, andcardiovascular system.
• Therefore, diabetes is treated aggressively,frequently with medication.• To determine how well the treatmentschedule is working, patients generally checktheir blood sugar levels at least once a daywithablood sugar meter.• It may appear that the levels of glucose areat their ideal levels, but levels may changewildlyoverthe course oftheday.
• To get a more accurate measurement of theglucose levels over time, doctors frequentlyperform blood tests to assess the average levelofglucose overaperiod oftime.• There are two lab tests commonly performed tocheckblood glucose levels:1. Thehemoglobin A1Ctest2. Thefructosamine test.•Bothmeasure theamount ofglucose that hasbound to proteins in the blood, known aglycated proteins.
The formation of Fructosamine• Fructosaminecanbeformedby asfollows:-• FormationofAmadoriproduct:-Itisanintermediateintheproductionofanadvancedglycationend-product(AGE)asaresultofglycation,theformationofanAGEinvolvesthefollowingsteps:1. Advancedglycationendproducts(AGEs)2. Advancedglycationendproducts(AGEs)aremodificationsofproteinsorlipidsthatbecomenonenzymaticallyglycatedandoxidizedaftercontactwithaldosesugars.
• In other words, they are the result of a chain ofchemical reactions which follow an initialglycation reaction.• The intermediate products are known as Schiffbase, Amadori, and Maillard products, after theresearcherswho firstdescribed them.• Initially, glycation involves covalent reactionsbetween free amino groups of amino acids,such as lysine, arginine, or protein terminalamino acids and sugars (glucose, fructose,ribose, etc), tocreatethefollowingreactions
Figure 2. Formation of glycated hemoglobin A1c (HbA1c). HbA1c is anAmadori product and is formed through the intermediate Schiff basestep.
• AGE formation from fructoselysine involves thenonoxidative dissociation of fructoselysine to formnew reactive intermediates that again modify proteinsto form AGEs of various different chemical structures(Figure3).• Alternatively, fructoselysine decays and releases itscarbohydrate moiety either as glucose or as the morereactive hexoses, such as 3-deoxyglucosone, whichthemselvesmaymodifyproteins.• In addition, it has recently been found that glucosecan auto-oxidize to form reactive carbonyl compounds(glyoxal and methylglyoxal) which can react withproteinstoformglycoxidationproducts.
• In addition to this, products of oxidative stress, such asperoxynitrite, can also induce the formation ofcarboxymethyl lysine by oxidative cleavage of Amadoriproducts and/or the generation of reactive dicarbonylcompoundsfromglucose(Figure2and3).• Thus, AGEs can arise from glucose and lipids throughseveral,partiallyinterminglingreactions.• Once formed, they may damage cellular structures viaa number of mechanisms, including the formation ofcross-links between key molecules in the basementmembrane of the extracellular matrix (ECM) and theinteraction of AGEs with RAGEs on cell surfaces, thusalteringcellularfunctions.
Fig (3)Schematic representation of the formation ofsome common advanced glycation end products(AGEs).
• Accumulation of AGEs in the ECM occurs onproteins with a slow turnover rate, with theformation of cross-links that can trap otherlocalmacromolecules.• In this way, AGEs alter the properties of thelarge matrix proteins collagen, vitronectin, andlaminin. AGE cross-linking on type I collagenand elastin causes an increase in the area ofECM, resulting in increased stiffness of thevasculature.
• Glycation results in increased synthesis oftype III collagen, type V collagen, type VIcollagen, laminin, and fibronectin in the ECM,most likely via upregulation of transforminggrowth factor-â pathways. Formation of AGEson laminin results in reduced binding to typeIV collagen, reduced polymer elongation, andlower binding of heparan sulfateproteoglycan.
• AGE-induced alterations of vitronectin andlaminin may explain the reduction in binding ofheparan sulfate proteoglycan, a stimulant ofother matrix molecules in the vessel wall, to thediabetic basement membrane.• As for the role of lipids, glycated low-densitylipoprotein (LDL) reduces nitric oxide (NO)production and suppresses uptake andclearance of LDL through its receptor onendothelial cells.
• The amount of these proteins is muchhigher in people that have poor controlof their diabetes.• Many factors affect the amount of freeglucose in the blood, but changes in thelevels of glycated proteins happen muchmore slowly and give much morereproducible readings.
• The measurement of fructosamine detectsthe reaction product of glucose that hasbound to the accessible amino group on aprotein such as albumin, for example, givingglycated albumin.• Albumin has a circulating half life ofapproximately 17 days, compared to 120 daysforHbA1c.• Fructosamine is considered to be anintermediate indicator of diabetic controlbecause it is not as immediate as bloodglucose, butnot aslongstanding asHbA1c.
• In general, fructosamine levels reflectglycemic control over the previous 2 to 3weeks• This test measures glucose levels over thelast2-3weeks.• It is an alternative to the more commonhemoglobin a1c test, which can give falsereadings for patients with blood problemssuchashemolytic orsickle cellanemia
• Additional reasons to use this alternatemethod of hematology include the need tomeasurebloodsugarlevelsduringpregnancy.• Because of the mother’s hormonal changes,women with gestational diabetes can haverapidchangesintheirbloodsugar.• Doctors wish to monitor these changes muchmore frequently than with the three monthperiodaffordedbythestandardtest.• With the fructosamine test, they check bloodsugarlevelsforthepast2-3weeks.
• Patientsfrequentlyundergochangesintheirmedication.• Their blood sugar levels may need to be checked frequently todeterminetheeffectofthesechanges.• The fructosamine test is better suited than the glycatedhemoglobin test to measure the rapidly changing glucose levels ofsuchpatients.• It is more important to look at trends when evaluatingfructosaminelevelsthanitistoanalyzetheabsolutepercentage.• Levels that decrease suggest that glucose levels are being broughtunderbettercontrol.• Increasinglevelssuggesttheopposite.• Thistestisnotusefulforscreeningfordiabetes.• At the lower limit of the test, it is not clear whether a patient hasgooddiabeticcontrolorwhethertheyarefreeofthedisease.
• Fructosamine is most useful whenmeasurement of HbA1c is unreliable due to ahemoglobinopathyorhemolysis.• Fructosamine values are not accurate inindividuals with serum albumin levels below 3g/dL or when serum albumin turnover isaccelerated.• Examples include cirrhosis, nephroticsyndrome, thyroid disease andparaproteinemia.• Referencerangeis200–285umol/L.
What is glycated protein• Several authors are improperly using the terms“glucosylated (or glycosylated) hemoglobin”, proteinglucosylation (or glycosylation), etc. to refer to theproducts of nonenzymic reactions between glucose orothersugarsandfreeaminogroupsofproteins.• The compounds so formed are not glycosides,however, but result from the formation of a SchiffsbasefollowedbyanAmadorirearrangement.• For example, the product of the reaction betweenglucose and hemoglobin is not glucosylatedhemoglobin but an amino linked 1-deoxyfructosederivativeofhemoglobin.
• The term glycation for any reaction thatlinks a sugar to a protein, whether it iscatalyzed by an enzyme or not.• The product of glycation is a glycatedprotein, or, in the particular case of thereaction with hemoglobin, glycatedhemoglobin.
• GlycosylatedHemoglobinorHemoglobinA1C(bHA1C)• Reflects average blood sugar levels over the preceding90-dayperiod.• Elevated levels are associated with prediabetes anddiabetes.• Individuals with diabetes have an increased risk of acardiacevent.• A diabetic persons risk for heart attack is the same asanon-diabeticperson, who hasexperienced one heartattack,havingasecondheartattack.• Aggressive global preventive risk reduction efforts,such as lower LDL targets, diet, exercise and bloodpressurecontrol,arerecommended.
• Goal values (per American DiabetesAssociation guidelines):• A range of 5.7-6.4 percent indicates anincreased risk for development of diabetes(i.e., prediabetes), and lifestyle interventionsmaybebeneficial.• A value equal or greater than 6.5 percent isconsidered diabetic.
• This test may be measured any time of the daywithoutfasting.• Glycosylated hemoglobin is blood glucose attachedto hemoglobin (a component of blood). This test isoften called the "diabetic report card." It reflectsthe average blood sugar for the two to threemonthperiodbeforethetest.• To calculate the average blood glucose level fromtheHbA1C:• HbA1C level x (multiplied by) 33.3 – 86 = averagebloodglucoselevelforthepast90days.• HbA1C can be helpful to track diabetic control overtime.
• 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 soyoursissome whereinbetween orapprox. 142-3.• Theformula toconvert A1c to BSis:• =28.7xA1c–46.7.• Thus,anA1cof7%=(28.7x7.0) –(46.7) =154
HbA1c targets• For most people with diabetes, the HbA1c target isbelow 48 mmol /mol , since evidence shows thatthis can reduce the risk of developing diabeticcomplications, such as nerve damage, eye disease,kidney disease and heart disease.• Individuals at risk of severe hypoglycaemia shouldaim for an HbA1c of less than 58 mmol /mol.• However, any reduction in HbA1c levels (andtherefore, any improvement in control), is stillconsidered to have beneficial effects on the onsetand progression of complications
HbA1c results• You will now be getting used to seeing yourHbA1c results reported using the IFCC(International Federation of Clinical Chemistry)reference measurement procedure ofmmol/mol.• A rough guide to the equivalent values can befound inthe following conversion table
• To calculate the average blood glucoselevel from the HbA1C for past 90 days:• HbA1c level x (multiplied by) 33.3 – 86 =average blood glucose level for the past90 days.• HbA1c level = 0.017x Fructosamine +1.61• Fructosamine = HbA1c- 1.61 ) X 58.82• HbA1C and Fructosamine can be helpfulto track diabetic control over time.
(%) (mmol/ mol)6.0 426.5 487.0 537.5 588.0 649.0 75Table (1) Conversion of Hg A1c to mmol/ mol