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1.  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.
doi:10.1186/1475-2840-12-165
PMCID: PMC4225762  PMID: 24209601
Glycated albumin; Coronary collateralization; Diabetes
2.  Increased blood glycohemoglobin A1c levels lead to overestimation of arterial oxygen saturation by pulse oximetry in patients with type 2 diabetes 
Background
Non-enzymatic glycation increases hemoglobin-oxygen affinity and reduces oxygen delivery to tissues by altering the structure and function of hemoglobin.
Objectives
We investigated whether an elevated blood concentration of glycosylated hemoglobin (HbA1c) could induce falsely high pulse oximeter oxygen saturation (SpO2) in type 2 diabetic patients during mechanical ventilation or oxygen therapy.
Methods
Arterial oxygen saturation (SaO2) and partial pressure of oxygen (PO2) were determined with simultaneous monitoring of SpO2 in 261 type 2 diabetic patients during ventilation or oxygen inhalation.
Results
Blood concentration of HbA1c was >7% in 114 patients and ≤ 7% in 147 patients. Both SaO2 (96.2 ± 2.9%, 95% confidence interval [CI] 95.7-96.7% vs. 95.1 ± 2.8%, 95% CI 94.7-95.6%) and SpO2 (98.0 ± 2.6%, 95% CI 97.6-98.5% vs. 95.3 ± 2.8%, 95% CI 94.9-95.8%) were significantly higher in patients with HbA1c >7% than in those with HbA1c ≤ 7% (Data are mean ± SD, all p < 0.01), but PO2 did not significantly differ between the two groups. Bland-Altman analysis demonstrated a significant bias between SpO2 and SaO2 (1.83 ±0.55%, 95% CI 1.73% -1.94%) and limits of agreement (0.76% and 2.92%) in patients with HbA1c >7%. The differences between SpO2 and SaO2 correlated closely with blood HbA1c levels (Pearson’s r = 0.307, p < 0.01).
Conclusions
Elevated blood HbA1c levels lead to an overestimation of SaO2 by SpO2, suggesting that arterial blood gas analysis may be needed for type 2 diabetic patients with poor glycemic control during the treatment of hypoxemia.
doi:10.1186/1475-2840-11-110
PMCID: PMC3489581  PMID: 22985301
Glycohemoglobin A1c; Diabetes mellitus; Arterial blood gas analysis; Pulse oxygen saturation
3.  Plasma concentrations of osteopontin, but not thrombin-cleaved osteopontin, are associated with the presence and severity of nephropathy and coronary artery disease in patients with type 2 diabetes mellitus 
Background
The aim of the present cross-sectional study was to assess possible associations between osteopontin (OPN), and thrombin-cleaved (N-half) OPN, and nephropathy and coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).
Methods
Plasma levels of OPN, N-half OPN, and high-sensitivity C-reactive protein (hsCRP) were determined in 301 diabetic patients with (n = 226) or without (n = 75) angiographically documented CAD (luminal diameter narrowing >50%), as well as in 75 non-diabetic controls with normal angiography. The estimated glomerular filtration rate (eGFR) was calculated in all patients.
Results
Plasma levels of OPN and hsCRP were significantly higher in patients with T2DM compared with controls. In addition, there was a higher occurrence of moderate renal insufficiency and lower eGFR in patients with T2DM (all P < 0.01). T2DM patients in whom OPN levels were greater than the median value had higher serum creatinine levels, a greater prevalence of mild or moderate renal insufficiency, a higher incidence of CAD, and lower eGFR (all P < 0.05) than T2DM patients in whom OPN levels were the same as or lower than the median value. However, there were no differences in these parameters when patients were stratified according to plasma N-half OPN levels. Furthermore, there was a significant correlation between OPN, but not N-half OPN, and the severity of nephropathy and CAD in diabetes. After adjustment for potential confounders and treatments, multiple linear regression analysis demonstrated an independent association between OPN, but not N-half OPN, and eGFR. Multivariate logistic regression revealed that higher OPN levels conferred a fourfold greater risk of renal insufficiency and CAD in patients with T2DM.
Conclusions
The results of the present study demonstrate that there is an independent association between plasma levels of OPN, but not N-half OPN, and the presence and severity of nephropathy and CAD in diabetes.
doi:10.1186/1475-2840-9-70
PMCID: PMC2988001  PMID: 21034455
4.  Chromosome 9p21.3 polymorphism in a Chinese Han population is associated with angiographic coronary plaque progression in non-diabetic but not in type 2 diabetic patients 
Background
We sought to explore the association of variant rs1333049 on chromosome 9p21.3 with coronary artery disease (CAD) and angiographic plaque progression in non-diabetic and type 2 diabetic patients.
Methods
Genotyping and quantitative coronary angiography (QCA) were performed in 2046 Chinese Han patients (1012 diabetic cases) undergoing coronary angiography; 430 of them received repeat angiographic studies at 1-year follow-up.
Results
CC genotype at rs1333049 on chromosome 9p21.3 was associated with CAD (unadjusted OR 1.524, p = 0.001 and adjusted OR 1.859, p = 0.005, respectively). However, CC genotype had no magnified association with CAD in diabetic patients (OR 1.275, p = 0.150) compared with non-diabetic counterparts (OR 1.446, p = 0.020) after adjusting for conventional risk factors. During angiographic follow-up, non-diabetic patients (n = 280) had significant decrease in minimal lumen diameter and increase in percent diameter stenosis among the three genotypes (p = 0.005 and p = 0.038, respectively), demonstrating that CC or GC genotype carriers had a more severe plaque progression than GG genotype carriers. In patients with type 2 diabetes (n = 150), although plaque progression was more severe than that in non-diabetic counterparts, no relations existed between plaque progression and genotypes. Rs1333049 was an independent determinant of plaque progression for non-diabetic (OR 3.468, p = 0.004 and OR 4.339, p = 0.002 for GC and CC genotype, respectively) but not for diabetic patients (OR 0.529, p = 0.077 and 0R 0.878, p = 0.644 for GC and CC genotype, respectively).
Conclusions
This study demonstrates a significant association of homozygous CC genotype of rs1333049 on chromosome 9p21.3 with CAD in Chinese Han population. Rs1333049 polymorphism is an independent determinant for coronary plaque progression in non-diabetic but not in type 2 diabetic patients.
doi:10.1186/1475-2840-9-33
PMCID: PMC2924260  PMID: 20691078
5.  Neointimal hyperplasia persists at six months after sirolimus-eluting stent implantation in diabetic porcine 
Background
Observational clinical studies have shown that patients with diabetes have less favorable results after percutaneous coronary intervention compared with the non-diabetic counterparts, but its mechanism remains unclear. The aim of this study was to examine the changes of neointimal hyperplasia after sirolimus-eluting stent (SES) implantation in a diabetic porcine model, and to evaluate the impact of aortic inflammation on this proliferative process.
Methods
Diabetic porcine model was created with an intravenous administration of a single dose of streptozotocin in 15 Chinese Guizhou minipigs (diabetic group); each of them received 2 SES (Firebird, Microport Co, China) implanted into 2 separated major epicardial coronary arteries. Fifteen non-diabetic minipigs with SES implantation served as controls (control group). At 6 months, the degree of neointimal hyperplasia was determined by repeat coronary angiography, intravascular ultrasound (IVUS) and histological examination. Tumor necrosis factor (TNF)-α protein level in the aortic intima was evaluated by Western blotting, and TNF-α, interleukin (IL)-1β and IL-6 mRNA levels were assayed by reverse transcription and polymerase chain reaction.
Results
The distribution of stented vessels, diameter of reference vessels, and post-procedural minimal lumen diameter were comparable between the two groups. At 6-month follow-up, the degree of in-stent restenosis (40.4 ± 24.0% vs. 20.2 ± 17.7%, p < 0.05), late lumen loss (0.33 ± 0.19 mm vs. 0.10 ± 0.09 mm, p < 0.001) by quantitative angiography, percentage of intimal hyperplasia in the stented area (26.7 ± 19.2% vs. 7.3 ± 6.1%, p < 0.001) by IVUS, and neointimal area (1.59 ± 0.76 mm2 vs. 0.41 ± 0.18 mm2, p < 0.05) by histological examination were significantly exacerbated in the diabetic group than those in the controls. Significant increases in TNF-α protein and TNF-α, IL-1β and IL-6 mRNA levels were observed in aortic intima in the diabetic group.
Conclusion
Neointimal hyperplasia persisted at least up to 6 months after SES implantation in diabetic porcine, which may be partly related to an exaggerated inflammatory response within the blood vessel wall. Our results provide theoretical support for potential direct beneficial effects of anti-diabetic and anti-inflammation medications in reducing the risk of restenosis after stenting.
doi:10.1186/1475-2840-6-16
PMCID: PMC1892541  PMID: 17550588
6.  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 ≥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.
doi:10.1186/1475-2840-5-27
PMCID: PMC1764721  PMID: 17178005

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