Glycation In Diabetes Research Articles

Glycation injury effects on aging and possible ways of prevention

Glycation is both a physiological and pathological process that mainly affects proteins, nucleic acids, and lipids. Advanced glycation end product (AGE) formation begins with the non-enzymatic glycation of free amino groups by sugars and aldehydes which leads to a succession of rearrangements of intermediate compounds and ultimately to irreversibly bound products known as AGEs. Recent studies have revealed the contributing roles of AGEs in the development of various aging-related conditions, such as diabetes, heart disease, and cancer. Controlling the blood sugar level is a natural method to inhibit glycation in diabetes. It is also seen from animal studies that exercise reduces the concentration of AGEs and highly reactive intermediates of AGE.

Myofilament glycation in diabetes reduces contractility by inhibiting tropomyosin movement, is rescued by cMyBPC domains

Diabetes doubles the risk of developing heart failure (HF). As the prevalence of diabetes grows, so will HF unless the mechanisms connecting these diseases can be identified. Methylglyoxal (MG) is a glycolysis by-product that forms irreversible modifications on lysine and arginine, called glycation. We previously found that myofilament MG glycation causes sarcomere contractile dysfunction and is increased in patients with diabetes and HF. The aim of this study was to discover the molecular mechanisms by which MG glycation of myofilament proteins cause sarcomere dysfunction and to identify therapeutic avenues to compensate. In humans with type 2 diabetes without HF, we found increased glycation of sarcomeric actin compared to non-diabetics and it correlated with decreased calcium sensitivity. Depressed calcium sensitivity is pathogenic for HF, therefore myofilament glycation represents a promising therapeutic target to inhibit the development of HF in diabetics. To identify possible therapeutic targets, we further defined the molecular actions of myofilament glycation. Skinned myocytes exposed to 100 μM MG exhibited decreased calcium sensitivity, maximal calcium-activated force, and crossbridge kinetics. Replicating MG's functional affects using a computer simulation of sarcomere function predicted simultaneous decreases in tropomyosin's blocked-to-closed rate transition and crossbridge duty cycle were consistent with all experimental findings. Stopped-flow experiments and ATPase activity confirmed MG decreased the blocked-to-closed transition rate. Currently, no therapeutics target tropomyosin, so as proof-of-principal, we used a n-terminal peptide of myosin-binding protein C, previously shown to alter tropomyosin's position on actin. C0C2 completely rescued MG-induced calcium desensitization, suggesting a possible treatment for diabetic HF.

Influence of Human Serum Albumin Glycation on the Binding Affinities for Natural Flavonoids

AbstractIncreasing the degree of glycation in diabetes could affect the ability of plasma proteins in binding to small molecules and active compounds. In this study, the influence of glycation of Human serum albumin (HSA) on the binding affinities for six dietary flavonoids was investigated by fluorescence spectra. Glycated HSA was prepared through incubation with glucose and characterized by several methods to confirm the glycation. It was found that the level of glycation increased with the increasing incubation time. The glycation of HSA increased the binding affinities for flavonoids by 1.40 to 48.42 times, which indicates that modifications caused by the glycation may have different influences on the interactions of flavonoids with HSA at separate binding sites on this protein. These results are valuable for understanding the influence of diabetes on the metabolism of flavonoids and other bioactive small molecules in human body.

Role of Human Serum Albumin and Oxidative Stress in Diabetes

Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Albumin, a major protein in the blood circulation, can undergo increased glycation in diabetes. From recent studies, it has become evident that glycation has important implications for albumin actions and impact on cell functioning. Human serum albumin (HSA) is the most abundant serum protein whose redox modifications modulate its physiological function, as well as serves as bio-marker for oxidative stress. Previous experimental and clinical studies report that oxidative stress plays a major role in the pathogenesis and development of complications of both types of DM. Hypoalbuminemia is the strongest clinical indicator of progression of many human diseases including cancer, diabetes, rheumatic diseases, liver and other diseases. Also, there is currently great interest in the potential contribution of increased oxidative stress to the development of complications in diabetes mellitus. This mini review highlights the association of human serum albumin and oxidative stress in diabetes.

Relationship between plasma glycation with membrane modification, oxidative stress and expression of glucose trasporter-1 in type 2 diabetes patients with vascular complications

Background of studyEnhanced protein glycation in diabetes causes irreversible cellular damage through membrane modifications. Erythrocytes are persistently exposed to plasma glycated proteins; however, little are known about its consequences on membrane. Aim of this study was to examine the relationship between plasma protein glycation with erythrocyte membrane modifications in type 2 diabetes patients with and without vascular complications. MethodWe recruited 60 healthy controls, 85 type 2 diabetic mellitus (DM) and 75 type 2 diabetic patients with complications (DMC). Levels of plasma glycation adduct with antioxidants (fructosamine, protein carbonyl, β-amyloids, thiol groups, total antioxidant status), erythrocyte membrane modifications (protein carbonyls, β-amyloids, free amino groups, erythrocyte fragility), antioxidant profile (GSH, catalase, lipid peroxidation) and Glut-1 expression were quantified. ResultCompared with controls, DM and DMC patients had significantly higher level of glycation adducts, erythrocyte fragility, lipid peroxidation and Glut-1 expression whereas declined levels of plasma and cellular antioxidants. Correlation studies revealed positive association of membrane modifications with erythrocyte sedimentation rate, fragility, peroxidation whereas negative association with free amino groups, glutathione and catalase. ConclusionOur data suggest that plasma glycation is associated with oxidative stress, Glut-1 expression and erythrocyte fragility in DM patients. This may further contribute to progression of vascular complications.

Glycation in human fingernail clippings using ATR-FTIR spectrometry, a new marker for the diagnosis and monitoring of diabetes mellitus

Although HbA1c is a good diagnostic tool for diabetes, the precarity of the health system and the costs limit the use of this biomarker in developing countries. Fingernail clippings contain ±85% of keratins, which are prone to glycation. Nail keratin glycation may reflect the average glycemia over the last months. We explored if attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) can be used as a non-invasive tool for assessing glycation in diabetes. Using ATR-FTIR spectroscopy, glycation and deglycation experiments with fructosamine 3-kinase allowed to identify the spectrum that corresponds with keratin glycation in fingernail clippings. Clippings of 105 healthy subjects and 127 diabetics were subjected to the standardized ATR-FTIR spectroscopy method. In vitro glycation resulted in an increased absorption at 1047cm-1. Following enzymatic deglycation, this peak diminished significantly, proving that the AUC between 970 and 1140cm-1 corresponded with glycated proteins. Within-run CV of the assay was 3%. Storage of nail clippings at 37°C for 2weeks did not significantly change results. In diabetics, glycated nail protein concentrations (median: 1.51μmol/g protein, IQR: 1.37-1.85μmol/g protein) were significantly higher than in the controls (median: 1.19μmol/g protein, IQR: 1.09-1.26μmol/g protein) (p<0.0001). ROC analysis yielded an AUC of 0.92 at a cut-off point of 1.28μmol/g nail (specificity: 82%; sensitivity: 90%). No correlation was observed between the glycated nail protein concentrations and HbA1c. Protein glycation analysis in fingernails with ATR-FTIR spectroscopy could be an alternative affordable technique for diagnosing and monitoring diabetes. As the test does not consume reagents, and the preanalytical phase is extremely robust, the test could be particularly useful in developing countries.

Advanced glycation in diabetes, aging and age-related diseases: editorial and dedication.

Advanced glycation in diabetes, aging and age-related diseases: editorial and dedication.

Development of Diagnostic Fragment Ion Library for Glycated Peptides of Human Serum Albumin: Targeted Quantification in Prediabetic, Diabetic, and Microalbuminuria Plasma by Parallel Reaction Monitoring, SWATH, and MSE

Human serum albumin is one of the most abundant plasma proteins that readily undergoes glycation, thus glycated albumin has been suggested as an additional marker for monitoring glycemic status. Hitherto, only Amadori-modified peptides of albumin were quantified. In this study, we report the construction of fragment ion library for Amadori-modified lysine (AML), N(ε)-(carboxymethyl)lysine (CML)-, and N(ε)-(carboxyethyl)lysine (CEL)-modified peptides of the corresponding synthetically modified albumin using high resolution accurate mass spectrometry (HR/AM). The glycated peptides were manually inspected and validated for their modification. Further, the fragment ion library was used for quantification of glycated peptides of albumin in the context of diabetes. Targeted Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH) analysis in pooled plasma samples of control, prediabetes, diabetes, and microalbuminuria, has led to identification and quantification of 13 glycated peptides comprised of four AML, seven CML, and two CEL modifications, representing nine lysine sites of albumin. Five lysine sites namely K549, K438, K490, K88, and K375, were observed to be highly sensitive for glycation modification as their respective m/z showed maximum fold change and had both AML and CML modifications. Thus, peptides involving these lysine sites could be potential novel markers to assess the degree of glycation in diabetes.

EFFECT OF GLYCATED SERUM ALBUMIN ON FUNCTIONAL MARKERS IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS IN THE PRESENCE OF SHEAR STRESS

Regions of the vasculature subjected to low wall shear stress and disturbed flow patterns are prone to atherosclerotic plaque formation. Pro-inflammatory conditions induced by products of protein glycation in diabetes substantially enhance this risk. One of the contributory factors is the enhanced production of ROS by advanced glycation end products (AGE) of proteins and lipids formed in chronic diabetes. In this study, we examine the interaction of oscillatory wall shear stress and glycated serum albumin (AGE-HSA) in modulating NOsynthase activity and expression of pro-inflammatory molecules such as RAGE, s-ICAM-1 and matrix metalloproteinase (MMP-9) in cultured HUVEC. Our findings indicate that orbital shear stress (OSS) up-regulates RAGE expression at low (LSS 4.5 dyn/cm2) more than at high shear stress (HSS 12 dyn/cm2) at 4 h. This effect is promoted in the AGE-HSA (2 mg/mL) in a dose-dependent manner. Augmentation of NOsynthase activity was lower at LSS and further inhibited in the presence of AGE-HSA. Expression of s-ICAM-1 was found to be shear stress modulated with additive up-regulation in combination with AGE-HSA while MMP-9 was not affected by shear stress or AGE-HSA individually but in combination caused significant up-regulation. These changes in endothelial function correlate with mechanisms that initiate atherogenic process in diabetic macrovascular pathology.

Glycated serum albumin stimulates expression of endothelial cell specific molecule-1 in human umbilical vein endothelial cells: Implication in diabetes mediated endothelial dysfunction.

Pro-inflammatory conditions induced by products of protein glycation in diabetes substantially enhance the risk of endothelial dysfunction and related vascular complications. Endothelial cell specific molecule-1 (ESM-1) or endocan has been demonstrated as a potential biomarker in cancer and sepsis. Its role in diabetes-induced pathologies remains unknown. The expression of ESM-1 gene is under cytokine regulation, indicating its role in endothelium-dependent pathological disorders. In this study, we investigated the effect of advanced glycated human serum albumin (AGE-HSA) on the production of ESM-1. We show that AGE-HSA exerts a modulating role on the expression of ESM-1 in human umbilical vein endothelial cells. It up-regulates expression of ESM-1 protein in a dose-dependent manner which correlates with its messenger RNA (mRNA) transcription. RAGE and galectin-3, both AGE receptors, show antagonistic action on its expression. While gene silencing of RAGE has down-regulatory effect, that of galectin-3 has up-regulatory effect on AGE-induced expression of ESM-1. Inhibition of MAPKKK and JNK pathways did not alter the expression. In contrast, phosphatidylinositol 3 kinase (PI3K) inhibition significantly up-regulated ESM-1 expression. In conclusion, these results suggest that AGE-induced activation of human umbilical vein endothelial cells promotes formation of endocan which is an endothelial dysfunction marker and may be related to vascular disease in diabetes.

Histone Protein Glycation and Diabetes

Glycation and oxidation are two mechanisms that have been widely attributed with the generation of advanced glycation end products upon proteins in various pathological conditions. Histones being lysine and arginine rich are prone to these reactions and hence they are susceptible to glycoxidation reactions. Post translational modifications in the highly conserved basic core histone proteins are known to induce changes in their structural integrity. Various researchers have documented the structural alterations in histone proteins upon glyoxidation reactions and correlated the same with various disorders. This review aims at presenting the background research in the field of histone glycation and its role in diabetic complications. It tracks the histone modifications under hyperglycaemic conditions and proposes the future avenues of research in the field. This review clearly indicates the lack of research on histone glycation in diabetes. It may be instrumental for future researches on opening new vistas in the field.

Methylglyoxal in diabetes: link to treatment, glycaemic control and biomarkers of complications

Diabetic complications are major health problems worldwide, with the cost of caring for diabetes rising to US$245 billion in 2012 in the U.S.A. alone. It is widely recognized that non-enzymatic glycation in diabetes is a major cause of damage and dysfunction of key vascular cells. MG (methylglyoxal) is directly toxic to tissues, and is a major precursor of AGEs (advanced glycation end-products). Various propensities to diabetic complications are seen among individuals with diabetes, with accelerated rates occurring in some individuals with modest hyperglycaemia, while others never progress in spite of poor glycaemic control over many years. Since production and detoxification of MG is ultimately controlled by enzymatic mechanisms, both genetic and environmental factors could regulate tissue glycation and potentially account for these variable complication rates. Activation of pathways that determine MG levels occurs in susceptible patients, indicting an important role in pathogenesis. MG leads to formation of specific AGEs, which are likely to predict propensity to diabetic complications. We have shown recently that three specific plasma AGE biomarkers [MG-H1 (MG-derived hydroimidazolones), CEL (Nε-carboxyethyl-lysine) and CML (Nε-carboxymethyl-lysine)] predict biopsy-documented fast DN (diabetic nephropathy) progression. Since two of the predictive biomarkers are MG end-products, these outcomes support a role for MG in the development of DN. Our studies on MG and its end-products have also shown anti-complication effects of the drug metformin, which binds and inactivates MG, thus reducing MG-related AGEs. We have also shown that reducing post-meal glucose decreases MG levels, as well as levels of MG-related AGEs. Our clinical outcome studies have been based on the novel concept that the unique glycation products that we can measure reflect the activity of specific chemical pathways that are selectively activated by hyperglycaemia in patients that are inherently more susceptible to diabetic complications, and can be used to solve other diabetes-related medical questions.

Critical concentration of Glucose changes human serum albumin conformation: Circular Dichroism (CD)and UV Spectroscopyapproaches

HSA plays an important role in transporting metabolites and drugs throughout the vascular system. In as much as its performance is very vital in the presents of different kinds of ligands at the specific body temperatures, its examination is crucial. This molecule can undergo increased glycation in diabetes. Therefore, glucose as the one of the most fundamental ligands dealing with albumin in human body is examined in this study at 100 mg/dl concentration in correspond to normal condition on human body, 175 mg/dl as a kidney glucose tolerance point and also 400 mg/dl as the critical point at the two most important temperatures in diabetic patients. Thermal conformational changes of (HSA) are important. These conformational alterations are accompanied by a mild alteration of secondary structures. For this reason, possible secondarystructural changes of HSA in presence of glucose has beeninvestigated by circular dichroism (CD) using Hepes bufferat the normal temperature 37˚C and 42˚C as a high fever condition.UV spectroscopystudies confirmed CD findings and indicate that critical concentration of glucoselead to generation of new structural feature of albumin similar to 42 o C. However, as the temperature increases from 37˚C to 42˚C this process is no more capable of responding to glucose concentration changes.These results indicate that the native form of HSA is changed in the severe diabetic condition; likewise, same consequences can be achieved as the temperature arises from 37˚C to 42˚C.

Protein glycation in diabetes as determined by mass spectrometry.

Diabetes is a common endocrine disorder characterized by hyperglycemia leading to nonenzymatic glycation of proteins, responsible for chronic complications. The development of mass spectrometric techniques able to give highly specific and reliable results in proteome field is of wide interest for physicians, giving them new tools to monitor the disease progression and the possible complications related to diabetes, as well as the effectiveness of therapeutic treatments. This paper reports and discusses some of the data pertaining protein glycation in diabetic subjects obtained by matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS). The preliminary studies carried out by in vitro protein glycation experiments show clear differences in molecular weight of glycated and unglycated proteins. Then, the attention was focused on plasma proteins human serum albumin (HSA) and immunoglobulin G (IgG). Enzymatic degradation products of in vitro glycated HSA were studied in order to simulate the in vivo enzymatic digestion of glycated species by the immunological system leading to the highly reactive advanced glycation end-products (AGEs) peptides. Further studies led to the evaluation of glycated Apo A-I and glycated haemoglobin levels. A different MALDI approach was employed for the identification of markers of disease in urine samples of healthy, diabetic, nephropathic, and diabetic-nephropathic subjects.

Phosphatidylethanolamines Glycation, Oxidation, and Glycoxidation: Effects on Monocyte and Dendritic Cell Stimulation

Lipid glycation is a non-enzymatic reaction between glucose and the free amino group of aminophospholipids, particularly in chronic hyperglycemia. Glycated phosphatidylethanolamine have been found in plasma and atherosclerotic plaques of diabetic patients and was correlated with increased oxidative and inflammatory stress in diabetes. However, the biological roles of glycated lipids are not fully understood. In this study, we evaluated the effect of palmitoyl-oleoyl-phosphatidylethanolamine (POPE) oxidation, glycation, and glycoxidation products on monocyte and myeloid dendritic cell stimulation. Flow cytometry analysis was used to evaluate the capability of each modified PE to induce the expression of different cytokines (IL-1β, IL-6, IL-8, MIP-1β, and TNF-α) in monocytes or myeloid dendritic cells (mDC). Our results showed that PE modifications induced different effect on the stimulation of cells producing cytokines. All PE modifications induced higher frequencies of cytokine-producing cells than basal state. Higher stimulation levels were obtained with glycated POPE, followed by glycoxidized POPE. In contrast, oxidized POPE negatively regulated the frequency of monocytes and mDC producing cytokines, when compared with non-modified POPE. In conclusion, we verified that PE glycation, compared with oxidation and glycation plus oxidation, had higher ability to stimulate monocytes and mDC. Thus detection of increased levels of PE glycation in diabetes could be considered a predictor of a inflammatory state.

Impaired drug-binding capacities of in vitro and in vivo glycated albumin

Albumin, the major circulating protein in blood, can undergo increased glycation in diabetes. One of the main properties of this plasma protein is its strong affinity to bind many therapeutic drugs, including warfarin and ketoprofen. In this study, we investigated whether or not there were any significant changes related to invitro or invivo glycation in the structural properties and the binding of human albumin to both therapeutic drugs. Structural parameters, including redox state and ketoamine contents of invitro and invivo glycated purified albumins, were investigated in parallel with their affinity for warfarin and ketoprofen. High-performance liquid chromatography was used to determine the free drug concentrations and dissociation constants according to the Scatchard method. An alternative method based on fluorescence spectroscopy was also used to assess drug-binding properties. Oxidation and glycation levels were found to be enhanced in albumin purified from diabetic patients or glycated with glucose or methylglyoxal, after determination of their ketoamine, free thiol, amino group and carbonyl contents. In parallel, significant impairments in the binding affinity of invitro and invivo glycated albumin, as indicated by the higher dissociation constant values and confirmed by higher free drug fractions, were observed. To a lesser extent, this alteration also significantly affected diabetic albumin affinity, indicated by a lower static quenching in fluorescence spectroscopy. This work provides useful information supporting invivo diabetic albumin could be the best model of glycation for monitoring diabetic physiopathology and should be valuable to know if glycation of albumin could contribute to variability in drugs response during diabetes.

Quercertin as a Possible Inhibitor of Glycation in Diabetes

Previous work has indicated Quercertin inhibits the glycation of proteins in an in vitro system designed to closely simulate interactions between proteins and sugars in diabetic patients. The addition of sugars to proteins and other biological molecules is a major contributor to the development of the complications of diabetesThis experiment compared the effects of the addition of concentrations of 150 μg/ml, 200 μg/ml, and 3000 μg/ml of Quercetin to mixtures of 400μg/ml of albumin and 0.5M glucose Testing was done using spectrophotometry to measure glycoproteins at 530 nm. The hypothesis is that there would be lower absorption levels of the solutions containing Quercetin than those of the albumin/glucose solution. Our results show that high levels of Quercetin, such as the 300 μg/ml concentration does not show inhibition; while the 150 μg/ml, and 200 μg/ml concentrations are variable; indicating that under certain conditions the Quercetin may have some inhibition properties, but the inconsistencie suggest the need for further investigation.This Project is supported by the Smith Glynn Callaway Medical Foundation.

Structural modifications of human albumin in diabetes

Albumin, a major protein in the blood circulation, can undergo increased glycation in diabetes. From recent studies, it has become evident that glycation has important implications for albumin actions and impact on cell functioning. This study compares the structural and functional properties of albumin glycated by glucose and methylglyoxal (MGO) with those of albumin purified from diabetic patients. Human serum albumin (HSA) was purified from diabetic patients and control subjects using affinity chromatography, and oxidation parameters in various albumin preparations were determined. Tryptophan and 1-anilino-8-naphthalene sulphonic acid (ANSA) probe fluorescence, redox state, antioxidant and copper-binding capacities of the different preparations of albumin were also determined and compared. Occurrence of oxidative modifications was enhanced in albumin whether purified from diabetic patients, or glycated by glucose or MGO, after determination of their fructosamine and free thiol and amino group contents, carbonyl content and antioxidant activities. Whereas more quantitative changes in oxidative and structural parameters were observed in the glucose- and MGO-modified albumins, significant impairment of albumin function (free-radical-scavenging and copper-binding capacities) were demonstrated in the HSA purified from diabetics. These findings reveal different structural and functional features of diabetic HSA compared with in vitro models. This study provides new information supporting albumin as an important biomarker for monitoring diabetic pathophysiology. In addition, it reconfirms the influence of experimental conditions in which advanced glycation end-products (AGEs) are generated in tests designed to mimic the pathological conditions of diabetes.

Amino Acids Glycation Section

It is a great pleasure and honour to present the following reviews on glycation research to kick-off the new Glycation Section of Amino Acids. We start with an introduction to glycation, describing in brief the history of glycation research and its current standing in research across the scientific disciplines (Rabbani and Thornalley 2010a). There are then reviews on current issues of glycation in food science: ‘Physiological relevance of dietary melanoidins’ by Morales et al. (2010), ‘Glycation products in infant formulas—chemical, analytical, and physiological aspects’ by Pischetsrieder and Henle (2010) and ‘Health effects of dietary Maillard reaction products—The results of ICARE and other studies’ by Tessier and BirlouezAragon (2010). New types of glycation of current multidisciplinary interest are reviewed: ‘Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome’ Rabbani and Thornalley (2010b), ‘Enzymatic repair of early glycation’ by Van Schaftingen et al. (2010), and ‘Advanced Glycation Endproducts: From Precursors to the Receptor RAGE’ by Ramasamy et al. (2010). There are then reviews on the current focus of glycation in biomedical research. Four reviews focus on the important impact of glycation in diabetes and related complications: ‘Lipid glycation modifications in diabetes and atherosclerosis’ by Miyazawa et al. (2010), ‘Glycation and biomarkers of vascular complications of diabetes’ by Beisswenger (2010), ‘Glycation in diabetic nephropathy’ by Forbes and Cooper (2010), and ‘Earlyand advanced non-enzymatic glycation in diabetic vascular complications and search for therapeutics’ by Schalkwijk and Miyata (2010). Finally, the compilation concludes with two reviews on the biomedical importance of glycation in ageing-related disorders: ‘The Pathogenic Role of the Maillard Reaction in the Aging Eye’ by Nagaraj et al. (2010), and ‘Advanced glycation endproducts and their pathogenic roles in neurological disorders’ by Munch et al. (2010). We thank all authors for their commitment and contributions to this compilation and we trust that this will be the start of an expanding and long-standing partnership of Amino Acids with glycation research.

Lipid glycation and protein glycation in diabetes and atherosclerosis

Recent instrumental analyses using a hybrid quadrupole/linear ion trap spectrometer in LC-MS/MS have demonstrated that the Maillard reaction progresses not only on proteins but also on amino residues of membrane lipids such as phosphatidylethanolamine (PE), thus forming Amadori-PE (deoxy-D: -fructosyl PE) as the principal products. The plasma Amadori-PE level is 0.08 mol% of the total PE in healthy subjects and 0.15-0.29 mol% in diabetic patients. Pyridoxal 5'-phosphate and pyridoxal are the most effective lipid glycation inhibitors, and the PE-pyridoxal 5'-phosphate adduct is detectable in human red blood cells. These findings are beneficial for developing a potential clinical marker for glycemic control as well as potential compounds to prevent the pathogenesis of diabetic complications and atherosclerosis. Glucose and other aldehydes, such as glyoxal, methylglyoxal, and glycolaldehyde, react with the amino residues of proteins to form Amadori products and Heynes rearrangement products. Because several advanced glycation end-product (AGE) inhibitors such as pyridoxamine and benfotiamine inhibit the development of retinopathy and neuropathy in streptozotocin (STZ)-induced diabetic rats, AGEs may play a role in the development of diabetic complications. In the present review, we describe the recent progress and future applications of the Maillard reaction research regarding lipid and protein modifications in diabetes and atherosclerosis.