Important Role In Diabetic Complications Research Articles

Inquiring about the link between urotensin-II and coronary collateral development in coronary artery patients with and without diabetes

Aims: Coronary collateral circulation consists of vascular channels activated to maintain perfusion in major epicardial coronary arteries in severe stenosis or occlusion. Yet, coronary collateral development (CCD) in diabetic patients was previously proven to be poor. Urotesin-II (U-II) is famous for being the most potent vasoconstrictor agent, and plasma levels are known to elevate in diabetic patients and play an important role in diabetic complications. In this study, we inquired about the link between U-II levels and the development of coronary collaterals between diabetic and non-diabetic patients with coronary artery disease (CAD).
 Methods: We recruited 31 diabetic and 30 non-diabetic patients with 95% or more coronary artery stenosis or occlusion and considered Rentrop’s classification for grading collaterals. In this sense, while Rentrop grades 0-1 are regarded as poor CCD, Rentrop grades 2-3 correspond to well-developed collaterals. Moreover, we compared the patients’ serum levels of U-II by the degree of CCD.
 Results: The findings revealed that demographic characteristics did not significantly differ between the groups (p >0.05). Although CCD seemed worse in diabetic patients than those without diabetes (DM), the finding was not statistically significant. However, the diabetic patients had significantly higher U-II levels than non-diabetic patients (388.1±314.2 vs. 229.8±216.9, p=0.026). Despite not being significant, U-II levels were higher in patients with poor CCD than those with well-developed collaterals in the non-diabetic group (370.6±298; 178.6±158.3, p=0.2). In the diabetic group, on the other hand, U-II levels were significantly higher in patients with poor CCD and significantly lower in patients with good CCD (582.7±316.4 and 180.4±121.6, respectively; p

Peroxisome proliferator-activated receptor-α (PPARα) regulates wound healing and mitochondrial metabolism in the cornea

Diabetes can result in impaired corneal wound healing. Mitochondrial dysfunction plays an important role in diabetic complications. However, the regulation of mitochondria function in the diabetic cornea and its impacts on wound healing remain elusive. The present study aimed to explore the molecular basis for the disturbed mitochondrial metabolism and subsequent wound healing impairment in the diabetic cornea. Seahorse analysis showed that mitochondrial oxidative phosphorylation is a major source of ATP production in human corneal epithelial cells. Live corneal biopsy punches from type 1 and type 2 diabetic mouse models showed impaired mitochondrial functions, correlating with impaired corneal wound healing, compared to nondiabetic controls. To approach the molecular basis for the impaired mitochondrial function, we found that Peroxisome Proliferator-Activated Receptor-α (PPARα) expression was downregulated in diabetic human corneas. Even without diabetes, global PPARα knockout mice and corneal epithelium-specific PPARα conditional knockout mice showed disturbed mitochondrial function and delayed wound healing in the cornea, similar to that in diabetic corneas. In contrast, fenofibrate, a PPARα agonist, ameliorated mitochondrial dysfunction and enhanced wound healing in the corneas of diabetic mice. Similarly, corneal epithelium-specific PPARα transgenic overexpression improved mitochondrial function and enhanced wound healing in the cornea. Furthermore, PPARα agonist ameliorated the mitochondrial dysfunction in primary human corneal epithelial cells exposed to diabetic stressors, which was impeded by siRNA knockdown of PPARα, suggesting a PPARα-dependent mechanism. These findings suggest that downregulation of PPARα plays an important role in the impaired mitochondrial function in the corneal epithelium and delayed corneal wound healing in diabetes.

Rab31, a receptor of advanced glycation end products (RAGE) interacting protein, inhibits AGE induced pancreatic β-cell apoptosis through the pAKT/BCL2 pathway.

Receptor of advanced glycation end products (RAGE) mediates diverse signal transduction following ligand stimulation and plays an important role in diabetes complications and aging associated disease. We have previously verified that advanced glycation end products (AGE) bind to RAGE to cause pancreatic β-cell apoptosis through the mitochondrial pathway. However, the direct interacting protein(s) of RAGE in β cells has never been appreciated. In the present study, we utilized GST pull-down assay combined with mass spectrometry to identify the interacting proteins of the RAGE intracellular domain (C-terminal 43 amino acid of RAGE). Overall four RAGE interacting proteins, including Rab31, were identified with scores over 160. Rab31 was detected in three β-cell lines and confirmed to have interacted with RAGE via co-immunoprecipitation and immunostaining assays. This interaction was further enhanced by glycation-serum (GS) stimulation due to membrane distribution of Rab31 following treatment with GS. We further confirmed that Rab31 promoted RAGE endocytosis and inhibited GS-induced β-cell apoptosis through the pAKT/BCL2 pathway. These findings reveal a new RAGE interaction protein Rab31 that prevents AGE/RAGE-induced pancreatic β-cell apoptosis. Rab31 is therefore a promising therapeutic target for preserving functional β cells under diabetes conditions.

Hydrogen Sulfide in Diabetic Complications: Focus on Molecular Mechanisms.

A growing number of studies have indicated that hydrogen sulfide (H2S) affects the development of diabetes and its complications, but the specific mechanism is not completely clear. To summarize the effects and recent molecular mechanisms of H2S in various diabetic complications. Articles regarding the role of H2S channels in diabetic complications and relevant mechanisms were selected. Relevant articles published from 2006 to present were selected from PubMed. The search terms were "hydrogen sulfide" and "diabetes". Important references from selected articles were also retrieved. The reduction of endogenous H2S contribute to diabetic injury and the supply of exogenous H2S protect tissues from diabetic injury through anti-apoptosis, anti-fibrosis, inhibited oxidative stress and inflammation in different complications, including cardiomyopathy, vascular injury, retinopathy, nephropathy, and encephalopathy. H2S may play an important role in diabetic complications and may be a potential target for therapeutic intervention of diabetic related diseases.

Adipocytokines, inflammatory, epigenetic instability & angiogenesis biomarkers in type 2 diabetic Egyptian women with breast cancer

Obesity is the main determinant of type 2 diabetes. Some adipocytokines play important roles in diabetic complications. Lipid transport is an important aspect of lipid metabolism in cancer.Present study aimed to evaluate the effect of some adipocytokines, inflammatory, epigenetic instability & angiogenesis biomarkers in type 2 diabetic Egyptian women with breast cancer.Study Design was performed on eighty females divided into 20 healthy subjects (Group I), 20 patients with type 2 diabetes (Group II), 20 patients with breast cancer (Group III) & 20 patients with diabetes and breast cancer (Group IV). Demographic data & body mass index have been collected. Biochemical analysis included fasting & postprandial blood glucose, lipid profile, fatty acid-binding proteins-4 (FABP-4), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), 8-hydroxy-2′-deoxyguanosine (8-OHdG) & thioredoxin reductase (TrxR) activity.Results revealed significant increase in FABP-4, TNF-α, VEGF, 8-OHdG and significant decreased TrxR activity in diabetic patients with breast cancer in comparison with other groups. These changes were evident in breast cancer subjects than diabetic and healthy cases and in diabetic than healthy cases.Conclusion: This study confirmed the role of FABP-4 in pathogenesis of type 2 diabetes & breast cancer via enhancing angiogenesis, inflammatory and epigenetic instability biomarkers.

OZONE THERAPY IN DIABETES AND ITS COMPLICATIONS

OZONE THERAPY IN DIABETES AND ITS COMPLICATIONS

Effects of Apelin Peptides on Diabetic Complications.

Diabetes is a metabolic disorder with multiple complications, including cardiomyopathy, retinopathy, nephropathy and neuropathy. Diabetic complications are the major cause of disability and death in diabetic patients. Apelin, a recently identified adipokine peptide, has been found to play important roles in diabetic complications. Here we summarize the current knowledge on the role of apelin in the pathogenesis of different diabetic complications. We also propose that similar to insulin resistance or leptin resistance, diabetics may also show apelin resistance. Potential clinical application of apelin and its analogue peptides in treating diabetic complications is discussed.

Association Between the Polymorphism of Glu298Asp in Exon 7 of the eNOS Gene With Foot Ulcer and Oxidative Stress in Adult Patients With Type 2 Diabetes.

Diabetic foot ulcer (DFU) is a common and major manifestation in patients with diabetes. Oxidative stress (OS) plays an important role in diabetic complications, such as DFU. Nitric oxide deficiency contributes to the impairment of diabetic wound healing. The aim of this study was to examine the association between the eNOS Glu298Asp polymorphism and DFU and oxidative stress in patients with type 2 diabetes mellitus in an Iranian population. In this case-control study, 123 patients with type 2 diabetes and DFU and 134 patients without DFU were recruited. The genotypes of eNOS Glu298Asp polymorphism in exon 7 were determined by the polymerase chain reaction-restriction fragment length polymorphism analysis. We measured the levels of thiobarbituric reactive substances and ferric-reducing ability of plasma as the potential markers of OS. There were significant differences in genotype frequencies of eNOS Glu298Asp polymorphism between case and control groups (GG+TG vs. TT; p=0.002; OR=0.22, 95% CI 0.83 to 0.62). Also, the frequency of the T allele in cases was less common than in controls (p=0.004). There was no significant difference in levels of OS parameters and various genotypes (p>0.05). These results imply that the T allele might be protective against DFU.

Elevated cardiac 3-deoxyglucosone, a highly reactive intermediate in glycation reaction, in doxorubicin-induced cardiotoxicity in rats

3-Deoxyglucosone (3-DG) is a highly reactive carbonyl intermediate in glycation reaction (also known as Maillard reaction) and plays an important role in diabetic complications. We investigated the potential involvement of 3-DG in doxorubicin (DXR)-induced cardiotoxicity. Male Crl:CD(SD) rats received intravenous injections of DXR at 2mg/kg, once weekly, for 6 weeks, with/without daily intraperitoneal treatment with 3-DG scavenging agents, i.e., aminoguanidine (AG, 25mg/kg/day) and pyridoxamine (PM, 60mg/kg/day). Cardiac levels of 3-DG, thiobarbituric acid reactive substances (TBARS), fructosamine, and pentosidine, plasma glucose levels and cardiac troponin I (cTnI), echocardiography, and histopathology were assessed at 4 and 6 weeks after treatment. Cardiac 3-DG levels were significantly increased by DXR treatment at 4 and 6 weeks. Cardiac fructosamine levels and plasma glucose were not altered by DXR; however, TBARS levels in the heart were significantly increased at 4 and 6 weeks, suggesting that the enhanced generation of 3-DG is not attributed to any abnormal glycemic status, but may be related to oxidative stress by DXR. An advanced glycation end-product, pentosidine, was significantly increased by DXR treatment at 6 weeks. Intervention by AG and PM ameliorated the DXR-induced echocardiographic abnormalities, increased cTnI in plasma, and histopathological lesion as well as normalizing the elevation of 3-DG and pentosidine levels. These results suggest that 3-DG is generated by DXR and involved, at least in part, in the pathogenesis of DXR-cardiotoxicity through glycation reaction.

Genetic variants in the receptor for advanced glycation end products (RAGE) gene were associated with circulating soluble RAGE level but not with renal function among Asians with type 2 diabetes: a genome-wide association study.

The soluble receptor for advanced glycation end products (sRAGE) has been shown to play an important role in diabetic complications. We conducted genome-wide association study (GWAS) of sRAGE in Asian type 2 diabetes mellitus (T2DM) patient and validated the association in an independent cohort of T2DM. GWAS for sRAGE was performed in 2058 T2DM patients. Associations between single-nucleotide polymorphisms (SNPs) and plasma sRAGE level were analyzed in an additive model using a linear mixed model. To validate the associations, we performed de novo genotyping in an independent cohort (n = 1984). We selected the top SNP for assessment with diabetic kidney disease (DKD). The strongest SNP, rs2070600C>T (P = 1.21 × 10-52), was a genotyped, missense SNP located on chromosome 6, corresponding to the RAGE (AGER) gene locus, the gene encoding RAGE. Conditioning analysis on rs2070600 revealed that rs2071288C>T was the top genotyped independent SNP (P = 8.36 × 10-10). Both SNPs were strongly and dose-dependently correlated with sRAGE level (TT = 399.6 pg/mL, CT = 737.0 pg/mL and CC = 967.0 pg/mL, P < 0.001 for rs2070600; TT = 687.9 pg/mL, CT = 737.6 pg/mL and CC = 904.7 pg/mL, P < 0.001 for rs2072188). Both SNPs were robustly replicated in the independent cohort, especially among Chinese patients (P = 9.02 × 10-72 for rs2070600; P = 1.13 × 10-9 for rs2071288). Log-transformed sRAGE was associated with DKD after adjustment for age, gender and ethnicity in pooled cohorts [odds ratio 2.536 (95% confidence interval 1.864-3.450), P < 0.001]. However, we did not observe any significant association between rs2070600 and DKD. Common variants in RAGE are strongly associated with plasma sRAGE level, which is associated with DKD. However, we did not find a causal link between sRAGE and renal function by Mendelian randomization.

Aldose Reductase Inhibitory Activity of Butea monosperma for the Management of Diabetic Complications

Background: Aldose Reductase (AR) enzyme and advanced glycation end products (AGEs) play an important role in diabetic complications. The AR and AGEs inhibitors are beneficial in prevention of diabetic complications. Objective: Aim of present study was to evaluate the in vitro and in vivo AR and AGEs inhibitory activity of an antidiabetic plant Butea monosperma. Methods: The methanolic extract, standardized extract of flower and the major constituent butein were studied for their inhibitory activity against Rat Lens AR (RLAR), rat kidney AR and generation of AGEs. In addition, in vivo inhibition of lens galactitol accumulation in galactose-fed rat model was studied. Results: The plant extracts and butein were shown to possess AR inhibitory activity in both in vitro and in vivo assays with equal potency to that of standard quercetin. In case of inhibited AGEs formation, the plant extracts showed insignificant activity where as butein was found to be potent. Conclusion: The results obtained in this study provide a new dimension to the hitherto unknown activity of the plant as possible protective agent against long-term diabetic complications.

Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice

Oxidative stress and inflammation play important roles in diabetic complications, including diabetic nephropathy. Metallothionein (MT) is induced in proximal tubular epithelial cells as an antioxidant in the diabetic kidney; however, the role of MT in renal function remains unclear. We therefore investigated whether MT deficiency accelerates diabetic nephropathy through oxidative stress and inflammation. Diabetes was induced by streptozotocin injection in MT-deficient (MT(-/-)) and MT(+/+) mice. Urinary albumin excretion, histological changes, markers for reactive oxygen species (ROS), and kidney inflammation were measured. Murine proximal tubular epithelial (mProx24) cells were used to further elucidate the role of MT under high-glucose conditions. Parameters of diabetic nephropathy and markers of ROS and inflammation were accelerated in diabetic MT(-/-) mice compared with diabetic MT(+/+) mice, despite equivalent levels of hyperglycemia. MT deficiency accelerated interstitial fibrosis and macrophage infiltration into the interstitium in the diabetic kidney. Electron microscopy revealed abnormal mitochondrial morphology in proximal tubular epithelial cells in diabetic MT(-/-) mice. In vitro studies demonstrated that knockdown of MT by small interfering RNA enhanced mitochondrial ROS generation and inflammation-related gene expression in mProx24 cells cultured under high-glucose conditions. The results of this study suggest that MT may play a key role in protecting the kidney against high glucose-induced ROS and subsequent inflammation in diabetic nephropathy.

A Systematic Review of Oxidative Stress and Safety of Antioxidants in Diabetes: Focus on Islets and Their Defense

A growing body of evidence suggests that hyperglycemia-induced oxidative stress plays an important role in diabetic complications, especially β-cell dysfunction and failure. Under physiological conditions, reactive oxygen species serve as second messengers that facilitate signal transduction and gene expression in pancreatic β-cells. However, under pathological conditions, an imbalance in redox homeostasis leads to aberrant tissue damage and β-cell death due to a lack of antioxidant defense systems. Taking into account the vulnerability of islets to oxidative damage, induction of endogenous antioxidant enzymes or exogenous antioxidant administration has been proposed as a way to protect β-cells against diabetic insults. Here, we consider recent insights into how the redox response becomes deregulated under diabetic conditions, as well as the therapeutic benefits of antioxidants, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with β-cell failure.

SmD3 Regulates Intronic Noncoding RNA Biogenesis

Accumulation of excess lipid in nonadipose tissues is associated with oxidative stress and organ dysfunction and plays an important role in diabetic complications. To elucidate molecular events critical for lipotoxicity, we used retroviral promoter trap mutagenesis to generate mutant Chinese hamster ovary cell lines resistant to lipotoxic and oxidative stress. A previous report of a mutant from this screen demonstrated that under lipotoxic conditions, small nucleolar RNAs (snoRNAs) in the rpL13a gene accumulate in the cytosol and serve as critical mediators of lipotoxic cell death. We now report a novel, independent mutant in which a single provirus disrupted one allele of the gene encoding the spliceosomal protein SmD3, creating a model of haploinsufficiency. We show that snoRNA expression and the abundance of snoRNA-containing intron lariats are decreased in SmD3 mutant cells, even though haploinsufficiency of SmD3 supports pre-mRNA splicing. The mechanism through which SmD3 regulates the expression of intronic snoRNAs likely involves effects of SmD3 on the levels of small nuclear RNAs (snRNAs) U4 and U5. Our data implicate SmD3 as a critical determinant in the processing of intronic noncoding RNAs in general and as an upstream mediator of metabolic stress response pathways through the regulation of snoRNA expression.

Catalase Deficiency Accelerates Diabetic Renal Injury Through Peroxisomal Dysfunction

Mitochondrial reactive oxygen species (ROS) play an important role in diabetes complications, including diabetic nephropathy (DN). Plasma free fatty acids (FFAs) as well as glucose are increased in diabetes, and peroxisomes and mitochondria participate in FFA oxidation in an interconnected fashion. Therefore, we investigated whether deficiency of catalase, a major peroxisomal antioxidant, accelerates DN through peroxisomal dysfunction and abnormal renal FFA metabolism. Diabetes was induced by multiple injections of low-dose streptozotocin into catalase knock-out (CKO) and wild-type (WT) C57BL/6 mice. Murine mesangial cells (MMCs) transfected with catalase small interfering RNA followed by catalase overexpression were used to further elucidate the role of endogenous catalase. Despite equivalent hyperglycemia, parameters of DN, along with markers of oxidative stress, were more accelerated in diabetic CKO mice than in diabetic WT mice up to 10 weeks of diabetes. CKO mice and MMCs showed impaired peroxisomal/mitochondrial biogenesis and FFA oxidation. Catalase deficiency increased mitochondrial ROS and fibronectin expression in response to FFAs, which were effectively restored by catalase overexpression or N-acetylcysteine. These data provide unprecedented evidence that FFA-induced peroxisomal dysfunction exacerbates DN and that endogenous catalase plays an important role in protecting the kidney from diabetic stress through maintaining peroxisomal and mitochondrial fitness.

Two Fluorescent Wavelengths, 440ex/520emnm and 370ex/440emnm, Reflect Advanced Glycation and Oxidation End Products in Human Skin Without Diabetes

Advanced glycation end products (AGEs) and oxidation products (OPs) play an important role in diabetes complications, aging, and damage from sun exposure. Measurement of skin autofluorescence (SAF) has been promoted as a noninvasive technique to measure skin AGEs, but the actual products quantified are uncertain. We have compared specific SAF measurements with analytically determined AGEs and oxidative biomarkers in skin collagen and determined if these measurements can be correlated with chronological aging and actinic exposure. SAF at four excitation (ex)/emission (em) intensities was measured on the upper inner arm ("sun protected") and dorsal forearm ("sun exposed") in 40 subjects without diabetes 20-60 years old. Skin collagen from the same sites was analyzed by liquid chromatography-tandem mass spectrometry for three AGEs-pentosidine, carboxymethyllysine (CML), and carboxyethyllysine (CEL)-and the OP methionine sulfoxide (MetSO). There was poor correlation of AGE-associated fluorescence spectra with AGEs and OP in collagen, with only pentosidine correlating with fluorescence at 370(ex)/440(em) nm. A little-studied SAF (440(ex)/520(em) nm), possibly reflecting elastin cross-links, correlated with all AGEs and OPs. Levels of CML, pentosidine, and MetSO, but not SAF, were significantly higher in sun-exposed skin. These AGEs and OPs, as well as SAF at 370(ex)/440(em) nm and 440(ex)/520(em) nm, increased with chronological aging. SAF measurements at 370(ex)/440(em) nm and 335(ex)/385(em) nm, except for pentosidine, which correlated with fluorescence at 370(ex)/440(em), correlate poorly with glycated and oxidatively modified protein in human skin and do not reflect actinic modification. A new fluorescence measurement (440(ex)/520(em) nm) appears to reflect AGEs and OPs in skin.

Induced fit binding of aldose reductase inhibitors to AKR1B10

AKR1B10 is a recently identified NADP+ dependent aldo–keto reductase. It is strongly over expressed in lung and hepatic carcinomas as well as in colorectal and uterine cancers. AKR1B10 has 71% sequence identity with aldose reductase, the latter plays an important role in diabetic complications. The enzyme also exhibits substrate-specificity and inhibitor-sensitivity similar to aldose reductase. Various aldose reductase inhibitors show induced fit phenomenon in aldose reductase. It is reported that the selective ALR2 inhibitor, zopolrestat, also inhibits wild type AKR1B10. In this study, we have performed the induced fit docking of a few aldose reductase inhibitors in crystal structure of AKR1B10 (i.e., 1ZUA). This study elucidates the binding mode of various aldose reductase inhibitors in AKR1B10 and provides insights for the design of more selective and specific inhibitors.

Impairment of human keratinocyte mobility and proliferation by advanced glycation end products-modified BSA

The migration and proliferation of keratinocytes is critical to wound re-epithelialization and defects in this function are associated with the clinical phenomenon of chronic non-healing wounds. Advanced glycation end products (AGEs) occur through non-enzymatic glycation of long-lived proteins in diabetes and play important roles in diabetic complications. However, specific roles for AGEs in keratinocyte migration and proliferation, and the underlying molecular mechanisms, have not been fully established. The aim of the current study was to elucidate the interaction between AGE-modified bovine serum albumin (AGE-BSA) and keratinocytes. As a result, we found that AGE-BSA had no effect on the viability of keratinocytes for up to 48h of incubation with 50μg/ml of AGE-BSA. AGE-BSA (but not non-glycated BSA) exerted a concentration-dependent suppression of keratinocyte migration at a range of concentrations. The expression of matrix metalloproteinase-9 (MMP-9) was significantly up-regulated in keratinocytes incubated with increasing AGE-BSA, but tissue inhibitor of metalloproteinases-1 (TIMP-1) expression was down-regulated. AGE-BSA also profoundly depressed phospho-focal adhesion kinase-Tyr397 (p-FAK) and α2β1 integrin expression, while total-FAK expression levels remained constant, in keratinocytes. The proliferative capacity of keratinocytes was diminished after 72h AGE-BSA incubation. Taken together, these findings suggested that in the presence of AGE-BSA, keratinocytes lose their migratory and proliferation abilities. These data also indicated that, in the context of the chronic hyperglycemia in diabetes, the effects of AGE-BSA on keratinocyte migration might be mediated through MMP-9/TIMP-1, p-FAK and α2β1 integrin.

Influence of vitamin E supplementation on endothelial complications in type 2 diabetes mellitus patients who underwent coronary artery bypass graft

Background Diabetes mellitus (DM) is associated with increased risk for complications following coronary artery bypass graft (CABG) surgery, in which tissue damage involves leukocyte–endothelial interactions mediated by endothelin-1 (ET-1) and adhesion molecules (AMs). Aim This study compared lipids and their peroxidation product, malondialdehyde (MDA), high-sensitivity C-reactive protein (hsCRP), ET-1, platelet-selectin (P-selectin), intercellular AM-1 (ICAM-1), and vascular cell AM-1 (VCAM-1) between healthy controls and type 2 DM subjects who did not receive CABG surgery as well as those who did. Vitamin E as an adjunctive therapy in subjects who underwent CABG was evaluated. Methods ELISA was used to measure hsCRP, ET-1, and AMs. For all subjects, glycosylated hemoglobin (HbA 1c) and lipid profile were estimated. Results Percentage of HbA 1c, lipids, MDA, hsCRP, ET-1, P-selectin, ICAM-1, and VCAM-1 levels were significantly higher in the diabetic groups than in healthy controls. Vitamin E supplementation for 3 successive months significantly lowered MDA, hsCRP, ET-1, ICAM-1, and VCAM-1 levels by 64%, 47%, 12%, 74%, and 25%, respectively. However, high-density lipoprotein cholesterol (HDL-C) and vitamin E serum levels were increased by 65% and 90.55%, respectively ( P≤.05). Vitamin E cosupplementations correlated restored ET-1, P-selectin, and ICAM-1 levels, which have been functionally damaged by decreased HDL-C, hypercholesterolemia, and hypertriacylglycerolemia, respectively. Conclusion This study indicates that increased levels of the proinflammatory markers and AMs occur in type 2 DM. Vitamin E administration appears beneficial in lowering proinflammatory markers and their downstream effectors that played an important role in diabetic complications following CABG.

Serum selenium and glutathione peroxidase concentrations in type 2 diabetes mellitus patients

Antioxidant selenium (Se) properties and, its protective role against oxidative damage play an important role in diabetic complications. Our objective was to gain further insight on a link between selenium status and diabetic nephropathy. We assessed glutathione peroxidase (GPx) and Se in type 2 diabetes mellitus patients with microalbuminuria (MA) (group 1), without microalbuminuria (group 2), and in control subjects (group 3). Glucose, urea, creatinine and glycated hemoglobin tests were tested in sera. A complete clinical record was elaborated. For diabetic patients both, the time from diagnosis and plasma glucose concentration were higher in group 1 as compared to group 2. Control group showed higher serum Se concentrations as compared to the diabetic groups. The two groups of diabetic patients showed similar serum Se levels. Serum concentration of GPx was significantly lower in group 1 as compared to groups 2 and 3. Microalbuminuria (MA) test showed a positive correlation with glucose, and a negative relationship with serum Se and GPx. Multiple regression revealed an inverse relationship between selenium or GPx in serum and the results of the MA test. Our results suggest that lower Se and GPx levels in diabetic patients may be implicated in the diabetic nephropathy.