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Background: Glycated hemoglobin (HbA1c) is widely used for the monitoring of glycemic balance in diabetic patients and has also been proposed as a tool for the diagnostic of diabetes mellitus. Accordingly, HbA1c quantification must be performed using robust, reliable and efficient methods. Here are reported the results of the evaluation of a new high performance liquid chromatography (HPLC) system for HbA1c quantification, the D-100™ system from Bio-Rad Laboratories. Methods: The analytical performances of the method as well as the influence of the most frequent interferences regarding HbA1c assays (e.g., labile HbA1c, carbamylated hemoglobin, high HbF) have been tested. Results: Intra- and between-assay CVs were respectively lower than 0.93% and 1.46% (HbA1c results expressed in NGSP units) and lower than 1.67% and 2.27% (HbA1c results expressed in IFCC units). The linearity proved to be excellent from 15 mmol/mol (3.5%) to 184 mmol/mol (19.0%) (r = 0.999). The results were well correlated with those obtained by another HPLC method (VARIANT™ II Hemoglobin A1c Program reorder pack 270-2101NU-Bio-Rad): HbA1c [VARIANT™ II, mmol/mol] = 1.013 x HbA1c [D-100™, mmol/mol]+0.637 (r = 0.993, n = 2000). The D-100™ system provided results consistent with IFCC-assigned external quality control samples and the presence of labile HbA1c, carbamylated hemoglobin and HbF did not interfere with HbA1c measurement. Conclusions: The D-100™ system proved to be a robust and reliable method for HbA1c measurement suitable for routine practice in clinical chemistry laboratories. [ABSTRACT FROM AUTHOR]

In living organisms, proteins are regularly exposed to 'molecular ageing', which corresponds to a set of non-enzymatic modifications that progressively cause irreversible damage to proteins. This phenomenon is greatly amplified under pathological conditions, such as diabetes mellitus. For their survival and optimal functioning, cells have to maintain protein homeostasis, also called 'proteostasis'. This process acts to maintain a high proportion of functional and undamaged proteins. Different mechanisms are involved in proteostasis, among them degradation systems (the main intracellular proteolytic systems being proteasome and lysosomes), folding systems (including molecular chaperones), and enzymatic mechanisms of protein repair. There is growing evidence that the disruption of proteostasis may constitute a determining event in pathophysiology. The aim of this review is to demonstrate how such a dysregulation may be involved in the pathogenesis of diabetes mellitus and in the onset of its long-term complications. [ABSTRACT FROM AUTHOR]

In living organisms, proteins are progressively modified by spontaneous non-enzymatic reactions generating many post-translational modification derived products (PTMDPs) which exert deleterious effects and may be considered endogenous toxins in diabetes mellitus and chronic renal failure. Non-enzymatic glycation, which refers to the spontaneous binding of reducing sugars to free amino groups, is increased in diabetes mellitus because of hyperglycemia and is amplified by oxidative processes ('glycoxidation'). Glycoxidation leads to the formation of 'advanced glycation end products' (AGEs), together with products of other oxidative pathways. AGEs alter tissue organization and cell-protein interactions, mainly in the case of long-lived extracellular matrix proteins, and interact with membrane receptors, among which RAGE (receptor of AGEs), a multiligand receptor which triggers intracellular signaling pathways stimulating inflammatory functions. Another major protein modification, carbamylation, is increased in chronic renal failure, which may occur during the course of diabetes mellitus. Carbamylation is due to the binding of isocyanic acid on the α-NH2 extremity of proteins or amino acids, or on ε-NH2 lysine groups, generating homocitrulline, a potential biomarker in atherosclerosis. Isocyanic acid is formed in vivo either by spontaneous dissociation of urea or by myeloperoxidase action on thiocyanate. Carbamylated proteins exhibit altered properties. For example, carbamylated collagen is unable to stimulate oxidative functions of polymorphonuclear neutrophils but increases matrix metalloproteinase-9 production by monocytes. Lipoprotein functions are altered by carbamylation and may contribute to atherogenesis. Thus, the numerous PTMDPs may be considered both hallmarks of protein damage in chronic diseases and endogenous toxins acting at the molecular and cellular levels. [ABSTRACT FROM AUTHOR]

Abstract: Molecular aging of proteins results from the complex association of different reactions that lead to the progressive alteration of their structural and functional properties. These reactions, which include oxidation, glycoxidation, carbonylation and carbamylation, occur during aging and are amplified in various chronic diseases such as diabetes or chronic renal failure. Specific compounds generated throughout this process called post-translational modification derived products (PTMDPs) have been suggested to be promising biomarkers for the management of chronic diseases. During the last decades, the emergence of mass spectrometry and proteomics has largely contributed to the development of sensitive and specific analytical methods devoted to PTMDP quantification in biological fluids. This review aimed at providing evidences for the clinical relevance of PTMDPs as biomarkers in chronic diseases, and at emphasizing on the contribution of mass spectrometric and proteomic methods in this field. Different issues that should be addressed in order to ensure the implementation of these biomarkers in clinical practice have been highlighted. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. [Copyright &y& Elsevier]

An introduction is presented in which the authors discuss various reports within the issue on topics including number of committees (Cs) and working groups (WGs) committed to laboratory medicine, liquid chromatography-mass spectrometry or mass spectrometry of reference measurement procedure (LC-MS/MS RMP) for urinary albumin, and clinical samples for metrological traceability.

Glucose meters have improved considerably since they were first introduced in 1960, but many questions are being asked about their accuracy and reliability in certain clinical situations. These questions have arisen because of the widespread use of these meters into clinical areas they have not been designed for such as critical care. The lack of understanding by some health professionals on factors that affect glucose results, such as sample type, glucose test strip methodologic limitations, calibration to recognized reference methods, and interferences, leads to misleading results that may affect patient care. Much debate continues on the quality specifications for glucose meters. Because there is an extensive use of these meters in different clinical scenarios, the setting of quality specifications will remain a challenge for regulatory and professional organizations. In this article, we have attempted to collect and provide relevant information addressing the limitations above. Pivotal to obtaining the best quality of results is education, particularly for diabetic patients monitoring their glucose. The International Federation of Clinical Chemistry and Laboratory Medicine through its Point-of-Care Testing Task Force and its Working Group on Glucose Point-of-Care Testing is actively working toward improving the quality of glucose results by improving education and working with the industry to improve strip performance and work toward the better standardization of strips. [ABSTRACT FROM AUTHOR]

In clinical practice, glycemic control is generally assessed by measuring and interpreting glycated hemoglobin levels, however, this test should be run under standardized conditions. We focus here on the crucial steps to ensure IFCC standardized HbA1c results, pointing out several residual weak points, mostly relating to the laboratory end-user (calibration, quality control materials, and EQAS). We also review the use of HbA1c for diagnosing diabetes and the various indicators useful for assessing glucose variability because in some cases they seem to represent a patient's glucose profile more accurately than one-off HbA1c assays. Finally, the potential utility of glycated albumin and the glycation gap, the costs involved and the laboratory management issues are briefly discussed. [ABSTRACT FROM AUTHOR]

HbA1c was discovered in the late 1960s and its use as marker of glycemic control has gradually increased over the course of the last four decades. Recognized as the gold standard of diabetic survey, this parameter was successfully implemented in clinical practice in the 1970s and 1980s and internationally standardized in the 1990s and 2000s. The use of standardized and well-controlled methods, with well-defined performance criteria, has recently opened new directions for HbA1c use in patient care, e.g., for diabetes diagnosis. Many reports devoted to HbA1c have been published in Clinical Chemistry and Laboratory Medicine (CCLM) journal. This review reminds the major steps of HbA1c history, with a special emphasis on the contribution of CCLM in this field. [ABSTRACT FROM AUTHOR]