Send Orders for Reprints to reprints@benthamscience.ae 14 Current Diabetes Reviews, 2016, 12, 14-19 HbA1c, Fructosamine, and Glycated Albumin in the Detection of Dysgly- caemic Conditions Rogério Tavares Ribeiro 1,2 , Maria Paula Macedo 1,2 and João Filipe Raposo 1,2,3,* 1 Education and Research Center (APDP-ERC), APDP – Diabetes Portugal; 2 CEDOC Chronic Diseases FCM Nova; 3 Public Health Department, - NOVA Medical School /Universidade Nova de Lisboa, Portugal Abstract: Glycated haemoglobin (HbA1c) is currently the gold standard for glucose monitoring in pa- tients with diabetes, and has been increasingly adopted as a criteria for diabetes diagnosis. However, conditions that determine alterations in haemoglobin metabolism can interfere with the reliability of HbA1c measurements. Glycated albumin and fructosamine (total glycated serum proteins) are alternative markers of glycae- mia, which have been recognised to provide additional information to HbA1c or to provide a reliable measure when HbA1c is observed not to be dependable. Additionally, while HbA1c monitors the exposure to circulating glycaemia in the previous 3 months, glycated albumin and fructosamine represent exposure for a shorter period, which may be benefi- cial to monitor rapid metabolic alterations or changes in diabetes treatment. The present review further discusses the relative value of HbA1c, glycated albumin, and fructosamine, in prediabetes and diabetes diagnosis, evaluation of glucose variability, and complications risk prediction. Also, a novel molecular role for albumin is presented by which glycated albumin contributes to glucose intolerance development and thus to progression to diabetes, besides the role of glycated albumin as a pro-atherogenic factor. Keywords: HbA1c, fructosamine, glycated albumin, diabetes, diagnosis, glucose variability, glucose monitoring. GLYCATED HAEMOGLOBIN (HbA1c) It is recognized that there is a continuum in the progres- sion of dysglycaemic states starting from the known normal regulation of glucose metabolism to prediabetes [character- ised as impaired fasting glycaemia (IFG) and/or impaired glucose tolerance (IGT)], which eventually leads to diabetes [1]. Historically, the diagnosis of prediabetes and diabetes were based solely on glycaemic criteria, being either fasting or after oral glucose tolerance tests (OGTT). These criteria were criticized due to their low reproducibility in individual and population studies and also because they represent just a point of observation in a rather long-term pathophysiological process. Nonetheless, the importance of diagnosing these condi- tions results from the associated risks of long-term complica- tions, namely micro- and macrovascular complications [2]. Non-enzymatic glycation of proteins is a process known to occur in normal physiology having been described to have two components: an initial, reversible chemical reaction and a second that is irreversible. Most organisms have developed mechanisms of recognizing and disposing of the latter, known as AGE’s – advanced glycation end-products [3]. Apart from the potentially deleterious consequences of *Address correspondence to this author at the APDP – Diabetes Portugal, Rua Rodrigo da Fonseca, 1, 1250-189 Lisboa, Portugal; Tel: (351)213816107; Fax: (351)213859371; E-mail: filipe.raposo@apdp.pt AGEs, especially if the capacity of neutralising its effects is overwhelmed, it was soon recognized that they could repre- sent a potential indicator of the exposure of cells, tissues or organs to a hyperglycaemic environment. Amongst the glycated proteins known to be of interest in diabetes, glycated haemoglobin (HbA1c) was identified in those with diabetes more than 40 years ago [4], and found to represent exposure to the glucose environment of 2-3 months, due to the half-life of erythrocytes [5]. Several studies assessed possible correlations between HbA1c values and average glucose blood concentrations, with the ADAG study finally proposing a direct correlation between different values of HbA1c and estimated average glucose levels in different populations settings [6]. Recognizing also other advantages related to the absence of preparation (no need to subject the individual to fasting or the time needed to perform an OGTT), soon HbA1c was introduced and easily adapted in clinical practice as an indi- cator of the metabolic control of people with diabetes and most of the guidelines on diabetes propose HbA1c goals as a surrogate for glycaemic control. The negative points were mainly correlated to the associated costs, the absence of a widely accepted process of standardisation and the possible interferences with its reliability, namely haemoglobi- nopathies, genetic defects and concomitant presence of other illnesses [7]. The discussion of diagnostic value of HbA1c for diabetes only recently achieved consensus [8]. Earlier studies had 1875-6417/16 $58.00+.00 © 2016 Bentham Science Publishers