Fructosamine and hg a1c
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The document discusses fructosamine and hemoglobin A1C (HbA1C) blood tests used to measure blood glucose levels in people with diabetes. Fructosamine measures glucose levels over the previous 2-3 weeks by detecting glucose bound to proteins like albumin. HbA1C measures levels over the past 3 months by detecting glucose bound to hemoglobin. Both tests are alternatives to daily blood glucose monitoring and provide a longer-term view of diabetes control. The document also explains what glycated proteins are and how they are formed through glycation reactions between glucose and amino groups on proteins.
Fructosamine and hg a1c
- 1. Fructosamine and Hemoglobin A1C (bHA1C) Dr. Yousef Elshrek
- 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
- 8. • first,theSchiffbaseandthenAmadoriproducts,of whichthebestknownareHbA1c(Figure1)and fructosamine(fructoselysine). • Additionalreactionsoccursuccessively • Fig.1:TheinitialstepoftheMaillardreactionbetweenglucoseandan aminoacid(RNH2),inwhichRistheaminoacidsidegroup
- 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.
- 13. Fig (3)Schematic representation of the formation of some common advanced glycation end products (AGEs).
- 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.
- 16. • Glycation oflaminin andtypeIandtypeIV collagens, keymolecules inthebasement membrane, causes inhibited adhesion to endothelial cellsforboth matrixglycoproteins. • Inaddition, ithasbeensuggested thatAGE formation leadstoareduction inthebinding of collagen andheparan totheadhesive matrix molecule vitronectin.
- 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.
- 34. (%) (mmol/ mol) 6.0 42 6.5 48 7.0 53 7.5 58 8.0 64 9.0 75 Table (1) Conversion of Hg A1c to mmol/ mol