A rationally designed Fe-tetrapyridophenazine complex: a promising precursor to a single-atom Fe catalyst for an efficient oxygen reduction reaction in high-power Zn-air cells.

The development of low-cost and highly efficient single-atom oxygen reduction catalysts to replace platinum for fuel cells and metal-air cells is highly desirable but remains challenging. Herein, we report the fabrication of isolated single-atom Fe anchored on porous nitrogen-doped carbon from the pyrolysis of a well-designed solely Fe-tetrapyridophenazine coordination complex. The N-rich bridging ligand, tetrapyridophenazine (tpphz) is first employed as a spatial isolation agent of Fe that suppresses its aggregation during high temperature pyrolysis, resulting in highly reactive and stable single-atom Fe ORR catalysts. The catalyst shows remarkable ORR activity with a half-wave potential of 0.863 V versus the reversible hydrogen electrode (RHE) (21 mV more positive than that of commercial 20 wt% Pt/C) and excellent durability in 0.1 M KOH. Whereas in acidic media, the Fe single atoms also demonstrate ORR activity comparable to and stability much higher than those of Pt/C. Notably, Zn-air cells made using the as-prepared catalyst as the cathode provide a high open circuit voltage (1.53 V) and gravimetric energy density (947 W h kg-1), which are higher than commercial Pt/C based Zn-air cells (1.50 V and 828 W h kg-1). This work will open a new avenue to design single-atom catalysts for clean renewable energy storage and conversion devices.

One-Step In Situ Growth of Iron-Nickel Sulfide Nanosheets on FeNi Alloy Foils: High-Performance and Self-Supported Electrodes for Water Oxidation.

Efficient and durable oxygen evolution reaction (OER) catalysts are highly required for the cost-effective generation of clean energy from water splitting. For the first time, an integrated OER electrode based on one-step direct growth of metallic iron-nickel sulfide nanosheets on FeNi alloy foils (denoted as FeNi3 S2 /FeNi) is reported, and the origin of the enhanced OER activity is uncovered in combination with theoretical and experimental studies. The obtained FeNi3 S2 /FeNi electrode exhibits highly catalytic activity and long-term stability toward OER in strong alkaline solution, with a low overpotential of 282 mV at 10 mA cm-2 and a small Tafel slope of 54 mV dec-1 . The excellent activity and satisfactory stability suggest that the as-made electrode provides an attractive alternative to noble metal-based catalysts. Combined with density functional theory calculations, exceptional OER performance of FeNi3 S2 /FeNi results from a combination of efficient electron transfer properties, more active sites, the suitable O2 evolution kinetics and energetics benefited from Fe doping. This work not only simply constructs an excellent electrode for water oxidation, but also provides a deep understanding of the underlying nature of the enhanced OER performance, which may serve as a guide to develop highly effective and integrated OER electrodes for water splitting.

2D Nanoporous Fe-N/C Nanosheets as Highly Efficient Non-Platinum Electrocatalysts for Oxygen Reduction Reaction in Zn-Air Battery.

It is an ongoing challenge to fabricate nonprecious oxygen reduction reaction (ORR) catalysts that can be comparable to or exceed the efficiency of platinum. A highly active non-platinum self-supporting Fe-N/C catalyst has been developed through the pyrolysis of a new type of precursor of iron coordination complex, in which 1,4-bis(1H-1,3,7,8-tetraazacyclopenta(1)phenanthren-2-yl)benzene (btcpb) functions as a ligand complexing Fe(II) ions. The optimal catalyst pyrolyzed at 700 °C (Fe-N/C-700) shows the best ORR activity with a half-wave potential (E1/2 ) of 840 mV versus reversible hydrogen electrode (RHE) in 0.1 m KOH, which is more positive than that of commercial Pt/C (E1/2 : 835 mV vs RHE). Additionally, the Fe-N/C-700 catalyst also exhibits high ORR activity in 0.1 m HClO4 with the onset potential and E1/2 comparable to those of the Pt/C catalyst. Notably, the Fe-N/C-700 catalyst displays superior durability (9.8 mV loss in 0.1 m KOH and 23.6 mV loss in 0.1 m HClO4 for E1/2 after 8000 cycles) and better tolerance to methanol than Pt/C. Furthermore, the Fe-N/C-700 catalyst can be used for fabricating the air electrode in Zn-air battery with a specific capacity of 727 mA hg-1 at 5 mA cm-2 and a negligible voltage loss after continuous operation for 110 h.

Metallic MoO2 cocatalyst significantly enhances visible-light photocatalytic hydrogen production over Mo2/Zn0.5Cd0.5S heterojunction.

As semiconductor-based nanoheterostructures play a decisive role in current electronics and optoelectronics, the introduction of active heterojunctions can afford new and improved capabilities that will enhance the conversion of solar energy into chemical energy. In this work, a novel metal/semiconductor MoO2/Zn0.5Cd0.5S heterojunction has been designed and prepared to significantly enhance photocatalytic H2 production efficiency. The photocatalytic activity of the as-prepared MoO2/Zn0.5Cd0.5S for H2 generation from water under visible-light irradiation (λ ≥ 420 nm) is measured. MoO2/Zn0.5Cd0.5S hybrid nanoparticles have a higher photocatalytic activity than Zn0.5Cd0.5S even without the noble metal cocatalyst. The results show that the rate of H2 evolution over annealed MoO2/Zn0.5Cd0.5S is about 13 times higher than that of Zn0.5Cd0.5S alone, and 10 times higher than that of simply mixed MoO2/Zn0.5Cd0.5S. Implying that the strong coupling at the interface of MoO2 and Zn0.5Cd0.5S facilitates electron transfer from the conduction band of Zn0.5Cd0.5S to metallic MoO2, thus promoting the separation of photogenerated electrons and holes. MoO2 (2 wt%)/Zn0.5Cd0.5S heterostructured photocatalyst calcined at 673 K achieves the optimal overall activity for H2 evolution. The introduction of metallic MoO2 cocatalyst leads to a remarkable improvement in the photo current and photocatalytic H2 production activity of Zn0.5Cd0.5S, and the content of MoO2 in this catalyst has an important influence on the photocatalytic activity. It is shown that 2 wt% metallic MoO2 loaded on Zn0.5Cd0.5S sample produces a maximum photocatalytic H2 production rate of 252.4 µmol h(-1). The junctions formed between metallic MoO2 and semiconductor Zn0.5Cd0.5S by calcination play a key role in high photocatalytic water splitting to produce H2. Our study demonstrates that metallic MoO2 is an excellent H2 evolution cocatalyst, and could be used as a cocatalyst for other semiconductors to improve performances.

Self-assembled metastable γ-Ga2O3 nanoflowers with hexagonal nanopetals for solar-blind photodetection.

Metastable γ-Ga2O3 nanoflowers assembled from hexagonal nanopetals are successfully constructed by the oxidation of metallic Ga in acetone solution. The nanoflowers with a hollow interior structure exhibit a short response time and a large light-current-dark-current ratio under a relatively low bias voltage, suggesting an especially important potential application in solar-blind photodetection.

Increased serum level of soluble vascular endothelial growth factor receptor-1 is associated with poor coronary collateralization in patients with stable coronary artery disease.

BACKGROUND: The present study investigated whether serum levels of soluble vascular endothelial growth factor receptor (sVEGFR)-1, -2 and -3 are related to poor coronary collateralization in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Serum levels of sVEGFR-1, -2, -3, VEGF, and placental growth factor (PLGF) were determined in 403 consecutive patients with angiographic total or subtotal occlusion of at least 1 major coronary artery. The degree of collateralization was graded according to the Rentrop scoring system. Low (Rentrop score of 0 or 1) and high (Rentrop score of 2 or 3) coronary collateralization occurred in 161 and 242 patients, respectively. Serum levels of sVEGFR-1 and -2 were significantly elevated, in contrast, VEGF and PLGF levels were remarkably decreased in patients with low collateralization than in those with high collateralization (all P<0.05). Significant differences in sVEGFR-1, VEGF and PLGF levels was consistently detected between the low and high collateralization subgroups for patients with and without type 2 diabetes mellitus (DM) (for all comparisons, P<0.01). Multivariable regression analysis revealed that DM, dyslipidemia, elevated sVEGFR-1, and reduced VEGF and PLGF in serum were independently associated with a low degree of coronary collateralization. CONCLUSIONS: Increased serum sVEGFR-1 level is associated with poor coronary collateralization in patients with stable CAD. Type 2 DM is a predominant factor affecting collateral growth in these patients.

Association of increased serum glycated albumin levels with low coronary collateralization in type 2 diabetic patients with stable angina and chronic total occlusion.

BACKGROUND: We investigated whether serum glycated albumin (GA) levels are related to coronary collateralization in type 2 diabetic patients with chronic total occlusion. METHODS: Blood levels of GA and glycosylated hemoglobin (HbA1c) were determined in 317 diabetic and 117 non-diabetic patients with stable angina and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as low (Rentrop score of 0 or 1) or high collateralization (Rentrop score of 2 or 3). RESULTS: For diabetic patients, GA (21.2 ± 6.5% vs. 18.7 ± 5.6%, P < 0.001) but not HbA1c levels (7.0 ± 1.1% vs. 6.8 ± 1.3%, P = 0.27) was significantly elevated in low collateralization than in high collateralization group, and correlated inversely with Rentrop score (Spearmen's r = -0.28, P < 0.001; Spearmen's r = -0.10, P = 0.09, respectively). There was a trend towards a larger area under the curve of GA compared with that of HbA1c for detecting the presence of low collateralization (0.64 vs. 0.58, P = 0.15). In non-diabetic patients, both GA and HbA1c levels did not significantly differ regardless the status of coronary collateralization. In multivariable analysis, female gender, age > 65 years, smoke, non-hypertension, duration of diabetes > 10 years, metabolic syndrome, eGFR < 90 ml/min/1.73 m2, and GA > 18.3% were independently determinants for low collateralization in diabetic patients. CONCLUSIONS: Increased GA levels in serum are associated with impaired collateral growth in type 2 diabetic patients with stable angina and chronic total occlusion.

Clinical and angiographic features associated with coronary collateralization in stable angina patients with chronic total occlusion.

OBJECTIVE: Coronary collateral circulation is an alternative source of blood supply to myocardium in the presence of advanced coronary artery disease. We sought to determine which clinical and angiographic variables are associated with collateral development in patients with stable angina and chronic total coronary occlusion. METHODS: Demographic variables, biochemical measurements, and angiographic findings were collected from 478 patients with stable angina and chronic total coronary occlusion. The presence and extent of collaterals supplying the distal aspect of a total coronary occlusion from the contra-lateral vessel were graded from 0 to 3 according to the Rentrop scoring system. RESULTS: Low (Rentrop score of 0 or 1) and high (Rentrop score of 2 or 3) coronary collateralizations were detected in 186 and 292 patients, respectively. Despite similar age, cigarette smoking, and medical treatment, patients with low collateralization were female in a higher proportion and less hypertensive, and had higher rates of type 2 diabetes and dyslipidemia than those with high collateralization (for all comparisons, P<0.05). In addition, patients with low collateralization exhibited more single-vessel disease, less right coronary artery occlusion, more impaired renal function, and higher serum levels of high-sensitivity C-reactive protein (hsCRP) compared with those with high collateralization. Multivariate analysis revealed that age of ≥65 years, female gender, diabetes, no history of hypertension, dyslipidemia, moderate to severe renal dysfunction, single-vessel disease, and elevated hsCRP levels were independently associated with low coronary collateralization. CONCLUSIONS: Coronary collateralization was reduced in almost 40% of stable angina patients with chronic total occlusion, which was related to clinical and angiographic factors. The impact of coronary collateralization on outcomes after revascularization needs further investigation.

Glycation of apoprotein A-I is associated with coronary artery plaque progression in type 2 diabetic patients.

OBJECTIVE: To investigate whether glycation level of apoprotein (apo)A-I is associated with coronary artery disease (CAD) and plaque progression in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Among 375 consecutive type 2 diabetic patients undergoing quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), 82 patients with nonsignificant stenosis (luminal diameter narrowing <30% [group I]) and 190 patients with significant CAD (luminal diameter stenosis ≥70% [group II]) were included for analysis of apoA-I glycation level and serum activity of lecithin: cholesterol acyltransferase (LCAT). The control group had 136 healthy subjects. At the 1-year follow-up, angiography and IVUS were repeated mainly in group II patients for plaque progression assessment. RESULTS: Relative intensity of apoA-I glycation by densitometry was increased, and serum LCAT activity was decreased stepwise across groups control, I, and II. These two measurements were associated with the number of diseased coronary arteries and extent index in group II. During 1-year follow-up, QCA detected 45 patients with plaque progression in 159 subjects, and IVUS found 38 patients with plaque progression in 127 subjects. Baseline relative intensity of apoA-I glycation was significantly increased in patients with plaque progression compared with those without, with values associated with changes in QCA and IVUS measurements. Multivariable regression analysis revealed that baseline relative intensity of apoA-I glycation was an independent determinant of CAD and plaque progression in type 2 diabetic patients. CONCLUSIONS: ApoA-I glycation level is associated with the severity of CAD and coronary artery plaque progression in type 2 diabetic patients.

Screening for significant atherosclerotic renal artery stenosis with a regression model in patients undergoing transradial coronary angiography/intervention.

OBJECTIVE: Early detection of atherosclerotic renal artery stenosis (ARAS) is clinically important with respect to blood pressure control, prevention of renal insufficiency, and even improving survival. We investigated whether the presence of significant ARAS (luminal diameter narrowing ≥70%) could be predicted using a logistic regression model before coronary angiography/intervention. METHODS: Initially, we developed a logistic regression model for detecting significant ARAS based upon clinical and angiographic features and biochemical measurements in a cohort of 1813 patients undergoing transfemoral coronary and renal angiography. This model was then prospectively applied to an additional 495 patients who received transradial renal angiography to ascertain its predictive accuracy for the presence of significant ARAS. RESULTS: Multivariate regression analysis revealed that older age (≥65 years), resistant hypertension, type 2 diabetes, creatinine clearance (Ccr) ≤60 ml/min, and multivessel coronary disease were independent predictors for significant ARAS. A logistic regression model for detecting ARAS by incorporating conventional risk factors and multivessel coronary disease was generated as: P/(1-P)=exp(-2.618+1.112[age≥65 years]+1.891[resistant hypertension]+0.453[type 2 diabetes]+0.587[Ccr≤60 ml/min]+2.254[multivessel coronary disease]). When this regression model was prospectively applied to the additional 495 patients undergoing transradial coronary and renal angiography, significant ARAS could be detected with a sensitivity of 81.2%, specificity of 88.9%, and positive and negative predictive accuracies of 53.8% and 96.7%, respectively. CONCLUSIONS: The logistic regression model generated in this study may be useful for screening for significant ARAS in patients undergoing transradial coronary angiography/intervention.

One-year clinical outcome of interventionalist- versus patient-transfer strategies for primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: results from the REVERSE-STEMI study.

BACKGROUND: Traditional reperfusion options for patients with acute ST-segment elevation myocardial infarction (STEMI) presenting to non-primary percutaneous coronary intervention (PPCI)-capable hospitals generally include onsite fibrinolytics or emergency transfer for PPCI. A third option, involving interventionalist transfer, was examined in the REVERSE-STEMI study. METHODS AND RESULTS: A total of 334 patients with acute STEMI who presented to 5 referral hospitals with angiographic facilities but without interventionalists qualified for PPCI were randomized to receive PPCI with either an interventionalist- (n=165) or a patient-transfer (n=169) strategy. The primary end point of door-to-balloon (D2B) time and secondary end points of left ventricular ejection fraction and major adverse cardiac events (MACE) at 1-year clinical follow-up were compared between the 2 groups. Compared with the patient-transfer strategy, the interventionalist-transfer strategy resulted in a significantly shortened D2B time (median, 92 minutes versus 141 minutes; P<0.0001), with more patients having first balloon angioplasty within 90 minutes (21.2% versus 7.7%, P<0.001). This treatment strategy also was associated with higher left ventricular ejection fraction (0.60±0.07 versus 0.57±0.09, P<0.001) and improved 1-year MACE-free survival (84.8% versus 74.6%, P=0.019). Multivariate Cox proportional hazards modeling revealed that the interventionalist-transfer strategy was an independent factor for reduced risk of composite MACE (hazard ratio, 0.63; 95% CI, 0.45 to 0.88; P=0.003). CONCLUSIONS: The interventionalist-transfer strategy for PPCI may be effective in improving the care of patients with STEMI presenting to a non-PPCI-capable hospital, particularly in a congested cosmopolitan region where patient transfers could be prolonged.

Impact of admission creatinine level on clinical outcomes of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention with drug-eluting stent implantation.

BACKGROUND: Prognosis of patients with acute ST-elevation myocardial infarction (STEMI) and renal dysfunction (RD) who received primary percutaneous coronary intervention (PCI) has not been fully investigated in the drug-eluting stent (DES) era. This study aimed to evaluate the impact of admission serum creatinine level on short-term outcomes in patients with acute STEMI undergoing DES-based primary PCI. METHODS: Primary PCI with DES implantation was attempted in 619 consecutive STEMI patients within 12 hours of symptom onset. Among them, 86 patients had a serum creatinine level > or = 115 micromol/L on admission (RD group), and the remaining 533 patients had normal renal function (non-RD group). The primary endpoint was 30-day major adverse cardiac events (MACE, including death, non-fatal reinfarction, and target vessel revascularization), and the secondary endpoint was subacute stent thrombosis. RESULTS: Patients in the RD group were older than those in the non-RD group. There are more female patients in the RD group and they had a history of hypertension, myocardial infarction and revascularization. The occurrence rates of Killip class > or = 2 (29.1% vs 18.6%, P = 0.02) and multi-vessel (62.8% vs 44.5%, P = 0.001) and triple vessel disease (32.6% vs 18.2%, P = 0.002), in-hospital mortality (9.3% vs 3.8%, P = 0.03), and MACE rate during hospitalization (17.4% vs 7.7%, P = 0.006) were higher in the RD group than those in the non-RD group. At a 30-day clinical follow-up, the MACE-free survival rate was significantly reduced in the RD group (76.7% vs 89.9%, P = 0.0003). Angiographic stent thrombosis occurred in 3 (3.5%) and 7 (1.3%) of patients in the RD group and non-RD group, respectively (P = 0.15). Multivariate analysis revealed that the serum creatinine level > or = 115 micromol/L on admission was an independent predictor for MACE rate at a 30-day follow-up (Hazard ratio (HR) 3.31, 95% CI 1.19 - 9.18, P < 0.001). CONCLUSION: Despite similar prevalence of stent thrombosis at a 30-day clinical follow-up, the short-term prognosis of STEMI patients with elevated serum creatinine on admission undergoing DES-based primary PCI remains unfavorable.

Prospective multicenter randomized trial comparing physician versus patient transfer for primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction.

BACKGROUND: Primary percutaneous coronary intervention (PCI) has been identified as the first therapeutic option for patients with acute ST-segment elevation myocardial infarction (STEMI). The strategy of transferring patient to a PCI center was recently recommended for those with acute STEMI who were present to PCI incapable hospitals, which include lack of facilities or experienced operators. In China, some local hospitals have been equipped with PCI facilities, but they have no interventional physicians qualified for performing primary PCI. This study was conducted to assess the feasibility, safety and efficacy of the strategy of transferring physician to a PCI-equipped hospital to perform primary PCI for patients with acute STEMI. METHODS: Three hundred and thirty-four consecutive STEMI patients with symptom presentation = 12 hours in five local hospitals from November 2005 to November 2007 were randomized to receive primary PCI by either physician transfer (physician transfer group, n=165) or patient transfer (patient transfer group, n=169) strategy. Door-to-balloon time, in-hospital and 30-day major adverse cardiac events (MACE, including death, non-fatal re-infarction, and target vessel revascularization) were compared between the two groups. RESULTS: Baseline characteristics between the two groups were comparable. Thrombolysis in myocardial infarction (TIMI) 3 flow was revealed in more patients in the physician transfer group at initial angiography (17.6% vs 10.1%, P<0.05). The success rate of primary PCI (96.3% vs 95.4%, P>0.05) and length of hospital stay were similar between the two groups ((15+/-4) days vs (14+/-3) days, P>0.05). In the physician transfer group, door-to-balloon time was significantly shortened ((95+/-20) minutes vs (147+/-29) minutes, P<0.0001) and more patients received primary PCI with door-to-balloon time less than 90 minutes (21.2% vs 7.7%, P<0.001). During hospitalization, MACE occurred in 6.7% and 11.2% of patients in the physician and patient transfer groups, respectively (P=0.14). At 30-day clinical follow-up, the occurrence rates of death, non-fatal re-infarction, and target vessel revascularization (TVR) were 3.6% vs 5.9%, 4.2% vs 8.9%, and 1.2% vs 2.4% in the physician and patient transfer groups, respectively (all P>0.05). The cumulative composite of MACE was significantly reduced (8.9% vs 17.2%, P=0.03) and MACE free survival (91.0% vs 82.9%, P<0.05) was significantly improved in the physician transfer group at 30 days. CONCLUSION: The strategy of transferring physician to local hospital to perform primary PCI for patients with acute STEMI is feasible, safe and efficient in reducing the door-to-balloon time and 30-day MACE rate.

Increased serum glycated albumin level is associated with the presence and severity of coronary artery disease in type 2 diabetic patients.

BACKGROUND: Glycated albumin is the predominant circulating Amadori-type glycated protein in vivo and plays a major role in the development of diabetic vascular complications. The aim of this study was to assess the relationship between increased serum glycated albumin level and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: In a total of 320 consecutive patients with T2DM, coronary angiography revealed normal coronary arteries in 83 patients (control group) and significant coronary stenosis (> or = 70% luminal diameter narrowing) in 237, of whom 51 patients had 1-vessel disease (Group I), 80 had 2-vessel disease (Group II), and 106 had 3-vessel disease (Group III). Serum glycated albumin, hemoglobin A(1c) (HbA(1c)) and tumor necrosis factor (TNF)-alpha levels, lipid profile, and renal function were measured. Logistic regression analysis was performed to determine the relative risk of serum glycated albumin level for the presence and severity of CAD. Multivariate stepwise linear regression analysis was done to identify independent determinants of the glycated albumin level. Serum glycated albumin (21.2+/-5.3% vs 19.4+/-4.3%, p=0.005) and TNF-alpha levels (123 +/-115 pg/ml vs 65+/-59 pg/ml, p<0.001) were significantly higher in patients with CAD than in controls, but serum HbAlc level did not significantly differ between them (7.6+/-1.3% vs 7.4+/-1.2%, p=0.19). There was a significant difference in serum glycated albumin level between Groups I and III (19.5+/-3.3% vs 21.8+/-5.7%, p<0.001). The serum glycated albumin level correlated with the number of diseased arteries (Spearman r=0.205, p<0.001), and was closely related to serum levels on admission of glucose (r=0.495, p<0.001), TNF-alpha (r=0.123, p=0.028), blood urea nitrogen (r=0.167, p=0.004), triglycerides (r=0.129, p=0.021), and HbA(1c) (r=0.795, p<0.001). Multivariate analysis indicated that serum levels of glucose (p<0.0001), TNF-alpha (p=0.001), blood urea nitrogen (p=0.004) and triglycerides (p=0.035) were independent determinants for glycated albumin. Logistic regression analysis revealed that glycated albumin > or = 19% (odds ratio (OR) 2.9, p<0.001) was an independent predictor for CAD and glycated albumin > or = 21% (OR 2.3, p=0.032) for 3-vessel disease prediction. The area under the receiver-operating characteristic curve for glycated albumin (0.620, 95% confidence interval (CI) 0.548 to 0.691, p=0.001) was superior to that for HbA(1c) (0.543, 95% CI 0.473 to 0.613, p=0.243). CONCLUSIONS: An increased serum level of glycated albumin is associated with the presence and severity of CAD, and may be useful in screening patients with T2DM.

Association of serum levels of glycated albumin, C-reactive protein and tumor necrosis factor-alpha with the severity of coronary artery disease and renal impairment in patients with type 2 diabetes mellitus.

OBJECTIVES: This study aimed to determine whether elevated serum levels of glycated albumin, high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-alpha were related to an increased risk for coronary artery disease (CAD) and renal insufficiency in patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: Serum levels of glycated albumin, hsCRP, TNF-alpha and blood glycosylated hemoglobin A1c (HbA1c) were measured in 317 consecutive patients with T2DM and 309 normal controls. Patients with T2DM were grouped based upon coronary angiographic findings (Group I: 151 patients with normal coronary arteries; Group II: 166 patients with significant coronary stenosis [>70% luminal diameter narrowing]) and renal functional status evaluated by estimated creatinine clearance (CrCl) (normal renal function group: 187 patients with CrCl >90 mL/min; mild renal insufficiency group: 103 patients with CrCl 60-90 mL/min; moderate renal insufficiency group: 27 patients with CrCl 30-60 mL/min). Multivariate analysis was performed to determine independent risk factors for CAD and renal insufficiency in patients with T2DM. RESULTS: Serum levels of glycated albumin, hsCRP and TNF-alpha were significantly higher in Group II than in controls (P<0.01) and Group I (P<0.01). A significant difference was found in glycated albumin, hsCRP and TNF-alpha levels among diabetic patients with mild, moderate renal insufficiency and normal renal function (P<0.05). These biochemical measurements correlated significantly with number of diseased coronary vessels (P<0.01) and status of renal function (P<0.05). No difference existed in HbA1c levels between Group II and Group I, and among patients with various CrCL stages. Multivariate analysis revealed that male gender, old age and serum levels of glycated albumin, hsCRP, TNF-alpha and lipoprotein (a) were independent risk factors for CAD, and older age, hypertension and glycated albumin were for CrCl <60 mL/min in diabetes. CONCLUSIONS: Increased serum levels of glycated albumin, hsCRP and TNF-alpha are associated with the presence and severity of CAD and renal impairment in patients with T2DM.

Elevation of tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 levels in aortic intima of Chinese Guizhou minipigs with streptozotocin-induced diabetes.

BACKGROUND: Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). METHODS: Twenty-two male Chinese Guizhou minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ-induced diabetic group (n = 12) and control group (n = 10). STZ (125 mg/kg) was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet beta cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-alpha level in tissue conditioned medium by Western blot. TNF-alpha, IL-1beta and IL-6 mRNA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: Significant elevation in serum glucose levels was observed one month and six months after STZ induction (P < 0.001) and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet beta cells, while in pancreas of diabetic minipigs islet beta cells almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Western blot demonstrated dramatically increased TNF-alpha level in aotic intima conditioned medium, and significant elevation of TNF-alpha, IL-1beta and IL-6 mRNA levels was revealed by RT-PCR. CONCLUSIONS: The present study has established Chinese Guizhou minipig models with STZ-induced diabetes. Inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) significantly elevated in aortic intima of diabetic minipigs.

Value of serum glycated albumin and high-sensitivity C-reactive protein levels in the prediction of presence of coronary artery disease in patients with type 2 diabetes.

BACKGROUND: Coronary artery disease (CAD) is a major vascular complication of diabetes mellitus and reveals high mortality. Up to 30% of diabetic patients with myocardial ischemia remain asymptomatic and are associated with worse prognosis compared to non-diabetic counterpart, which warrants routine screening for CAD in diabetic population. The purpose of this study was to evaluate the clinical value of serum glycated albumin and high-sensitivity C-reactive protein (hs-CRP) levels in predicting the presence of CAD in patients with type 2 diabetes. METHODS: Three hundred and twenty-four patients with type 2 diabetes were divided into two groups based on presence (CAD group, n = 241) or absence (control group, n = 83) of angiographically-documented CAD (lumen diameter narrowing > or =70%). Serum levels of glycated albumin and hs-CRP as well as serum concentrations of glucose, lipids, creatinine, blood urea nitrogen and uric acid were measured in both groups. Predictors of CAD were determined using multivariate logistic regression model and receiver-operating characteristic (ROC) curves. RESULTS: Serum glycated albumin and hs-CRP levels were significantly increased in diabetic patients with CAD. Multivariate regression analysis revealed that male gender, age, serum levels of glycated albumin, hs-CRP, creatinine and lipoprotein (a) were independent predictors for CAD. Areas under the curve of glycated albumin and hs-CRP and for regression model were 0.654 (95%CI 0.579-0.730, P < 0.001), 0.721 (95%CI 0.658-0.785, P < 0.001) and 0.824 (95% CI 0.768-0.879, P < 0.001), respectively. The optimal values of cut-off point were 18.7% (sensitivity 67.9%, specificity 60.0%) for glycated albumin and 5.2 mg/l (sensitivity 72.2%, specificity 60.0%) for hs-CRP to predict CAD. Logistic regression model was defined as: P/(1-P) = EXP(-1.5 + 1.265 gender + 0.812 age + 1.24 glycated albumin + 0.953 hs-CRP + 0.902 lipoprotein(a) + 1.918 creatinine). The optimal probability value for predicting CAD in type 2 diabetic patients was 0.648 (sensitivity 82.3%, specificity 68.6%). CONCLUSION: Serum glycated albumin and hs-CRP levels were significantly elevated in patients with type 2 diabetes and CAD. The logistic regression model incorporating with glycated albumin, hs-CRP and other major risk factors of atherosclerosis may be useful for screening CAD in patients with type 2 diabetes.