Glycated proteins: Clinical utility and analytical approaches

The progressive complications of unmanaged diabetes include heart disease, blindness, kidney failure, amputation of extremities due to circulation problems, and nerve disorders, as well as other chronic conditions. Decades of research have established that prolonged exposure to excess glucose is the cause of diabetes complications, and that long-term control of blood glucose levels is required to avoid or lessen the damage caused by excess glucose. The process of protein glycation is now understood to be both a marker for the progress of diabetes complications and an underlying cause of many of the most serious complications. Diabetes monitoring for protein glycation, an essential element for the long-term control of the complications of diabetes mellitus, is currently managed by a combination of daily self-monitoring of blood glucose (SMBG) measurements and physician-assessed hemoglobin A1c (A1C) levels every 3–6 months. Short term methods like self-monitoring of blood glucose and long term methods like measurement of HbA1c have limitations. Various researchers have identified glycated albumin (GA) as the ideal marker for an intermediate index to measure glycation.

Clinical Biochemistry, 2005

Non-enzymatic glycation products are a complex and heterogeneous group of compounds which accumulate in plasma and tissues in diabetes and renal failure. There is emerging evidence that these compounds may play a role in the pathogenesis of chronic complications associated with diabetes and renal failure. So measurement of the products of non-enzymatic glycation has a twofold meaning: on one hand, measurement of early glycation products can estimate the extent of exposure to glucose and the subject's previous metabolic control; on the other hand, measurement of intermediate and late products of the glycation reaction is a precious instrument in verifying the relationship between glycation products and tissue modifications. This review summarizes current knowledge about the diagnostic utility of measuring non-enzymatic glycation products.

Clinical Biochemistry, 2007

Objective: The measurement of plasma glycated albumin is particularly useful in the short-middle term monitoring of glycometabolic control in diabetics. The aim of this work is to evaluate a new enzymatic method for the measurement of glycated albumin in plasma, with particular attention to some selected cases and comparison with other relevant tests (fasting plasma glucose, after glucose load, fructosamine, glycated hemoglobin).

Glycation is a general spontaneous process in proteins which has significant impact on their physical and functional properties. These changes in protein properties could be related to several pathological consequences such as cataract, arteriosclerosis and Alzheimer's disease. Among the proteins, glycation of Human serum albumin (HSA) is of special interest. Human serum albumin is the most abundant protein in the plasma and because of its high sensitivity for glycation, undergoes structural and functional changes due to binding of reducing sugars in vitro. The glycation process occurs by plasma glucose in vivo which has great impacts on the three dimensional structure of protein. These changes are efficient and stable enough which makes the protein to be considered as a new special disease marker instead of HbA1C for diabetes. In some cases, glycated albumin was used as an alternative marker for glycemic control. Glycated albumin reacts with glucose ten times more rapidly than HbA1C and has shorter half-life which makes it more reliable for indicating glycemic states. In this review, glycation of Human Serum Albumin has been overviewed, starting from overall concepts of glycation, followed by some Examples of pathological consequences of protein glycation. The BSA aggregation was reviewed in terms of structural and biological impacts of glycation on the protein followed by reporting documents which indicate possibility of glycated albumin to be used as specific marker for diabetes. Finally, some of the studies related to the models of glycated albumin have been briefly described, with an emphasis on In vitro studies. It is interesting to note the relationship found between in vitro glycation experiments and the propensity of proteins to form amyloid structures, a point that could be further explored as to its significance in hyperglycemic states.

Hossam, B. Bahnasy

Diabetes mellitus (DM) is a chronic metabolic disease that represents a high global incidence rate. Glycated hemoglobin (HbA1C) is the long - term glucose reference test it appears to be associated with chronic diabetes complications,(Hb A1C) is not recommended for use in clinical situations that may interfere with metabolism of hemoglobin, as in hemolytic anemia, secondary or iron deficiency, hemoglobinopathies, pregnancy, and uremia. Glycated albumin (GA)is ashort term blood sugar test that is not affected by cases that incorrectly change A1c leveles.GA is the top part of glucose of fructosamine .it is meashured by the standard enzyme methodology , easy and fast performance. These Laboratory properties have ensured the spotlight on GA in studies from the past decade,as asign of monitoring and screening for diabetes as well as predicting long –term outcomes of the disease . The aim of this review was to discuss the physiological and biochemistry characteristics of the GA, as well as its clinical utility in DM. Key words: Diabetes mellitus; glycated albumin; glycated proteins

Clinica Chimica Acta, 2013

Glycation involves the non-enzymatic addition of reducing sugars and/or their reactive degradation products to amine groups on proteins. This process is promoted by the presence of elevated blood glucose concentrations in diabetes and occurs with various proteins that include human serum albumin (HSA). This review examines work that has been conducted in the study and analysis of glycated HSA. The general structure and properties of HSA are discussed, along with the reactions that can lead to modification of this protein during glycation. The use of glycated HSA as a short-to-intermediate term marker for glycemic control in diabetes is examined, and approaches that have been utilized for measuring glycated HSA are summarized. Structural studies of glycated HSA are reviewed, as acquired for both in vivo and in vitro glycated HSA, along with data that have been obtained on the rate and thermodynamics of HSA glycation. In addition, this review considers various studies that have investigated the effects of glycation on the binding of HSA with drugs, fatty acids and other solutes and the potential clinical significance of these effects.

Diabetes & metabolic syndrome

Glycation is a non-enzymatic spontaneous process in proteins which has remarkable impact on its physical and functional aspect. This alteration with addition of carbohydrate residue to human serum albumin leads to several pathological events such as diabetic nephropathy, neuropathy, retinopathy and cardiovascular complications. Human serum albumin is the major protein and is most susceptible to non-enzymatic glycation. Structural and biological properties of functional albumin alter due to the addition of reducing carbohydrate to free amino terminal residues vivo. These irreversible changes in functional albumin are stable which makes this modified albumin as new gold standard future diagnostic marker in diabetes associated complications. Glycated albumin can be used to determine the glycemic control due to short half life than erythrocytes which makes it an alternate reliable disease marker in diabetes. In this review, Human serum albumin glycation has been overviewed, stating conc...

Glycated albumin refers to albumin to which glucose has bonded. The amount of glycated albumin decrease or increase as and when plasma glucose changes. Glycated albumin is measured when diabetes therapy is initiated to determinethe medication regimens and doses to assess over all efficacy of therapy. Currently endocrinologists use only HbA1C to monitor diabetic control over the preceding 2-3 months. However HbA1C does not accurately reflect the actual state of glycemic control in patients with anemia, variant hemoglobins and also in chronic kidney diseases. Glycated albumin accurately reflects changes in plasma glucose during a short term of 2-3 weeks and will be useful to monitor changes in glucose level after 2 hours of meal and it correlates well with such changes. Fructosamine measures total concentration of glycated serum proteins including albumin which can fluctuate due to acute or systemic illness or chronic liver disease. Glycated albumin measures the ratio of GA to total albumin and hence minimizes interference due to GA and Non-GA. This article enumerates the research finding during the last decade on the clinical usefulness of GA and recommends its use as a routine glycemic control marker to assess short term changes in plasma glucose. Keywords: GA, HbA1C, HD, T2DM, PG

The Journal of Applied Laboratory Medicine: An AACC Publication

Background: Short to intermediate integrated glycemic control is best determined by glycated albumin (GA). This assay is appropriate when interpretation of glycated hemoglobin (HbA 1c) is critical because of hemoglobinopathies, severe anemias, or other factors that affect red blood lifespan as hemodialysis. We evaluated a new assay based on the enzymatic quantification of GA by ketoamine oxidase and an albumin-specific protease. Methods: Limits of blank, detection, and quantification; precision; linearity; accuracy; interferences; correlation with HbA 1c ; and serum vs plasma study have been evaluated on ILab ® systems. Results: Limit of blank, detection, and quantification for GA (g/L) were, respectively, 0.26, 0.36, and 1.15. Repeatability and within-device precision CVs were lower than 2.11%, 1.61%, and 1.56% for GA (g/L), albumin (g/L), and GA%, respectively. Linearity for GA (g/L) and GA% was 1.2-36.8 and 5.5-92.2, respectively. Highest deviation from linearity was <11% and recovery was higher than 90%. Accuracy against the certified ReCCS Japan Clinical Chemistry Reference Material (JCCRM) 611 was <1%. Classical interfering substances had no significant impact. Correlation of GA% between ILab ® Taurus and ADVIA system was y = 1.02[GA%]+0.25; R 2 = 0.994. No difference was found in the determination of GA% in serum vs plasma. Conclusions: GA enzymatic assay is a reliable, fully automated method allowing accurate and precise determination of GA in a routine laboratory. IMPACT STATEMENT This article will benefit both diabetic patients with hemoglobinopathies or reduced red blood cell lifespan that need an alternative marker for glycemic control and people at risk of developing diabetes. Data show glycated albumin (GA) assay reliability. Moreover, it is easy to use, being a clinical chemistry assay: it can be run on standard clinical chemistry automated systems. This article summarizes almost a full proof of performance report of a GA assay investigating most of the performance aspects as precision, accuracy, linearity, and interference study.

Clinica Chimica Acta, 1987

The level of non-enzymatic glycation of a protein is thought to depend on the number of sites available for reaction, the half-life of the protein and the ambient concentration of glucose. Accordingly, the modification of two blood proteins with a similar number of potential sites but different survival times was examined in non-diabetic patients by periodate oxidation and by reduction with [ 3H]borohydride. The amount of glycation of haemoglobin and its sub-fractions HbA, and HbA,, were determined to be 0.44, 2.42 and 2.24 mol/mol respectively and the corresponding value for albumin was 0.37 mol/mol protein. Amino acid analysis showed that the c amino groups of albumin were more extensively modified than they were in haemoglobin and thus it is concluded that the average rate of reaction of the lysine residues in albumin is markedly faster than in haemoglobin.