Yancheng Xu

Glycemic control among patients in China with type 2 diabetes mellitus receiving oral drugs or injectables

BackgroundThe prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly among Chinese adults, and limited data are available on T2DM management and the status of glycemic control in China. We assessed the efficacy of oral antidiabetes drugs (OADs), glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin for treatment of T2DM across multiple regions in China.MethodsThis was a multicenter, cross-sectional survey of outpatients conducted in 606 hospitals across China. Data from all the patients were collected between April and June, 2011.ResultsA total of 238,639 patients were included in the survey. Eligible patients were treated with either OADs alone (n=157,212 [65.88%]), OADs plus insulin (n=80,973 [33.93%]), or OADs plus GLP-1 receptor agonists (n=454 [0.19%]). The OAD monotherapy, OAD + insulin, and OAD + GLP-1 receptor agonist groups had mean glycosylated hemoglobin (HbA1c) levels (±SD) of 7.67% (±1.58%), 8.21% (±1.91%), and 7.80% (±1.76%), respectively. Among those three groups, 34.63%, 26.21%, and 36.12% met the goal of HbA1c <7.0%, respectively. Mean HbA1c and achievement of A1c <7.0% was related to the duration of T2DM.ConclusionsLess than one third of the patients had achieved the goal of HbA1c <7.0%. Glycemic control decreased and insulin use increased with the duration of diabetes.

Intermittent high glucose enhances proliferation of vascular smooth muscle cells by upregulating osteopontin

OBJECTIVE Hyperglycemia induces vascular smooth muscle cells (VSMCs) proliferation and may thus contribute to the formation of atherosclerotic lesions. Glucose fluctuations are strong predictor of diabetic vascular complications. We investigate the effects of exposure to constant and intermittent high glucose concentrations on the proliferation and matrix metalloproteinase (MMP)-2 activity of rat aortic VSMCs in culture, as well as the expression of osteopontin (OPN). METHODS Rat aortic VSMCs were grown to confluence and then exposed to 5 mmol/L glucose, 25 mmol/L glucose, or 5 mmol/L alternating with 25 mmol/L glucose in the absence or presence of neutralizing antibodies to OPN, beta3 integrin receptor and beta5 integrin receptor. The cell proliferation, MMP-2 activity and the expression of OPN were assessed. RESULTS In cultured VSMCs, treatment with constant or intermittent high glucose significantly increased [(3)H]thymidine incorporation in a time-dependent manner. A modest increase was observed at 12h, and further deteriorated afterwards, and reached the maximum expression at 48h. However, [(3)H]thymidine incorporation was more pronounced in intermittent high glucose than in constant high glucose. Treatment with constant high glucose for 48 h significantly increase cell number, MMP-2 activation, OPN protein and mRNA expression compared with VSMCs treated with the cells normal glucose, and these effects were further enhanced when VSMCs were treated with intermittent high glucose. In addition, neutralizing antibodies to either OPN or its receptor beta3 integrin but not neutralizing antibodies to beta5 integrin significantly suppressed increase in [(3)H]thymidine incorporation and MMP-2 activity induced by constant or intermittent high glucose. CONCLUSIONS In cultured VSMCs, constant high glucose concentrations enhanced MMP-2 activity, cell proliferation and OPN expression. These effects are enhanced following intermittent exposure to high glucose, indicating that short lived excursions in glycaemic control have important pathological effects on the development of diabetic atherosclerosis, which is mediated by the stimulation of OPN expression and synthesis.

Polymorphism of human leptin receptor gene is associated with type 2 diabetic patients complicated with non-alcoholic fatty liver disease in China.

Background and Aim:  To investigate the relationship between human leptin receptor (LEPR) gene G3057A polymorphism and type 2 diabetes mellitus (T2DM) patients complicated with or without non‐alcoholic fatty liver disease (NAFLD).

Methylenetetrahydrofolate reductase polymorphism associated with susceptibility to coronary heart disease in Chinese type 2 diabetic patients

OBJECTIVE Epidemiological studies have identified hyperhomocyst(e)inemia as an independent risk factor for atherosclerosis. The C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, might play a role in the development of coronary heart disease (CHD). In this study, we examined the distribution of the MTHFR genotypes in the Chinese population and the association between the C677T variant and CHD in Chinese type 2 diabetic patients. METHODS Two hundred and twenty-eight unrelated patients with type 2 diabetes mellitus (126 with coronary heart disease) and 114 healthy control subjects were recruited. The MTHFR genotype was analyzed by PCR followed by HinfI digestion. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. RESULTS In 114 healthy control subjects, the frequency of the mutant T allele was 38.0%, comparable to that of a Hong Kong (Chinese) population. The genotype distribution did not differ between control subjects and type 2 diabetic patients (chi(2) = 3.67, P > 0.05). Genotypic analysis revealed that type 2 diabetic patients with CHD displayed a greater prevalence of T allele (45.2%) than type 2 diabetic patients without CHD (30.4%) (chi(2) = 8.72, P < 0.005). The odds ratio for CHD in type 2 diabetic patients in presence of T allele was 1.89 (CI 95%, 1.24-2.88). The MTHFR genotype were different between diabetic patients with and without CHD (chi(2) = 11.98, P < 0.005). Moreover, plasma homocysteine levels were markedly higher in individuals with TT genotype than those with CC or CT genotype or CC plus CT genotype. CONCLUSIONS The C677T mutation of MTHFR gene is common in the Chinese population. MTHFR C677T gene polymorphism associated with a predisposition to increased plasma homocysteine levels could constitute a useful predictive marker for CHD in Chinese type 2 diabetic patients.

Intermittent high glucose exacerbates the aberrant production of adiponectin and resistin through mitochondrial superoxide overproduction in adipocytes

Hypoadiponectinemia and hyperresistinemia may be important in mediating signals from adipocytes to insulin-sensitive tissue and vasculature. However, the mechanism that mediates the aberrant production of adipokines remains poorly understood. In this study, we have investigated the effect of intermittent high glucose on the expression of adiponectin and resistin, and the production of 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine in the adipocytes, either in the presence or in the absence of Mn(III) tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) or thenoyltrifluoroacetone (TTFA). 3T3-L1 adipocytes were incubated for 72 h in media containing different glucose concentrations: 5 mmol/l, 20 mmol/l, 5 mmol/l alternating with 20 mmol/l glucose, with or without MnTBAP and TTFA. We measured the expression of resistin and adiponectin. The production of nitrotyrosine and 8-OHdG as oxidative stress parameter was measured. Both constant and intermittent high glucose significantly suppressed the expression and secretion of adiponectin, and increased expression and secretion of resistin in mature adipocytes compared to normal glucose conditions. However, these effects were significantly greater under intermittent high glucose conditions compared to constant high glucose. The levels of nitrotyrosine and 8-OHdG were significantly elevated under both intermittent and constant high glucose conditions, the effect being greater under intermittent high glucose. In addition, the antioxidants MnTBAP or TTFA reversed the aberrant production of adiponectin and resistin, as well as overproduction of nitrotyrosine and 8-OHdG in adipocytes induced by constant or intermittent high glucose. Intermittent high glucose exacerbates the aberrant production of adiponectin and resistin through reactive oxygen species overproduction at the mitochondrial transport chain level in adipocytes, indicating that glycemic variability has important pathological effects on the secretion of adipokines.

Expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats

AbstractAim:To study the expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats.Methods:pCMV.Ins, an expression plasmid of the human insulin gene, was constructed. In total, 100 μg pCMV.Ins wrapped with chitosan nanoparticles (chitosan–pCMV.Ins) was transfected to NIH3T3 cells and diabetes rats through lav age and coloclysis, respectively. The transfected cells were grown in Dulbeccos modified Eagles medium, containing G418, for 72 h after transfection. The clones were selected and continued to grow in G418 medium for 24 d. The expression of human insulin was detected by immunohistochemistry. Human insulin in the culture medium of transfected cells was measured. Fasting blood glucose and plasma human insulin of diabetic rats were measured for 5 d after transfection. RT–PCR and Western blotting were performed to confirm the expression of the human insulin gene in diabetic rats.Results:Approximately 10% of NIH3T3 cells transfected by chitosan–pCMV.Ins expressed human insulin. Human insulin in the culture medium of NIH3T3 cells transfected by chitosan–pCMV.Ins significantly increased compared with that of the control group (P<0.01). Fasting blood glucose levels of the lavage group and the coloclysis group decreased significantly in 5 d (P<0.01) in comparison, while plasma insulin levels were much higher (P<0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and the coloclysis groups.Conclusion:The human insulin gene can be transfected and expressed successfully by chitosan–pCMV.Ins in NIH3T3 cells and diabetes rats, which indicates that chitosan is a promising, non-viral vector for gene expression.

Polymorphism of the methylenetetrahydrofolate reductase gene association with homocysteine and ischemic stroke in type 2 diabetes

BACKGROUND Ischemic stroke is a frequent heterogeneous multifactorial disease. A number of genetic mutations and environmental factors have been implicated. A polymorphism in the gene for methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with hyperhomocysteinemia a risk for atherosclerotic vascular diseases. AIM A cross-sectional study was performed to determine the relationship between the gene polymorphism for MTHFR and ischemic stroke in type 2 diabetes mellitus. MATERIALS AND METHODS Of the 215 unrelated patients with type 2 diabetes mellitus recruited, 119 patients had ischemic stroke, Control group included 142 healthy subjects. The genotype of the subjects for the C677T polymorphism of MTHFR was analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by HinfI digestion. Plasma total homocysteine (Hcy) levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. RESULTS The genotype distribution did not differ between the control subjects and type 2 diabetic patients (P > 0.05). Plasma homocysteine levels were markedly higher in diabetic patients with TT genotype than those with CC or CT genotype (P > 0.05). Ischemic stroke was more frequently observed in type 2 diabetic patients with the TT genotype than in those with the CT and CC genotype (odds ratio = 4.04, 95% CI = 1.95-8.34, P = 0.0036). Logistic regression analysis revealed that the C677T mutation of MTHFR gene was independently associated with ischemic stroke in type 2 diabetes. CONCLUSION MTHFR C677T gene polymorphism associated with a predisposition to hyperhomocysteinemia could constitute a useful predictive marker for ischemic stroke in type 2 diabetic Chinese patients.

Vascular endothelial growth factor gene polymorphisms and renal cell carcinoma: A systematic review and meta-analysis

Renal cell carcinoma (RCC) accounts for 3% of all cancer-related mortalities in adults. The risk factors for the development of RCC remain under investigation. Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis and is crucial for the development and metastasis of tumors, including RCC. VEGF gene polymorphisms may alter VEGF protein concentrations, affect the process of angiogenesis and may be involved in inter-individual variation in carcinogenesis. In the present study, a systematic review and meta-analysis were performed based on published case-control studies in order to estimate the association between VEGF gene polymorphisms and the susceptibility to RCC. A total of five studies that involved eight polymorphisms and were published between January 2000 and December 2012 were identified from PubMed. The results of this systematic review and meta-analysis indicate that the VEGF 936C/T, 1612G/A, −1154G/A, −2549I/D, −460T/C and 405G/C gene polymorphisms are not associated with the risk of RCC. There was no polymorphism in 702C/T and RCC and the −2578C/A gene polymorphism may be associated with an increased risk of RCC. However, due to the limitations of the present study, further high quality case-control studies are warranted to confirm these findings.

RIP140 is Associated with Subclinical Inflammation in Type 2 Diabetic Patients

AIMS To evaluate the expression level of RIP140 (receptor interaction protein 140) and its correlation with inflammatory cytokine production and free fatty acids (FFAs) in type 2 diabetes. METHODS Plasma and peripheral blood mononuclear cells (PBMCs) were collected from 24 diabetic and 30 healthy individuals. The levels of FFAs, TC, TG, HDL-C, LDL-C, FIN, and FBG were measured. The insulin resistance index was calculated using the homeostasis model assessment (HOMA). Additionally, PBMCs from control group were cultured alone or with 500 μmol/L palmitic acid (PA). Levels of RIP140 TNF-α, and IL-6 in PBMCs were analyzed using real-time RT-PCR, Western blots and ELISA. The relationship between RIP140 and other variables was performed using SPSS 11.5 software. RESULTS TG, LDL-C, FIN, FBG, HOMA, and HDL-C were significantly different between diabetic patients and the control group. Levels of RIP140, TNF-α, and IL-6 were higher in the diabetic group compared to control. RIP140 expression was positively correlated with FFAs, HDL-c, TNF-α, IL-6, FIN, FBG, and HOMA. Finally, 500 μmol/L PA treatment increased RIP140 expression and the secretion of inflammatory cytokines in cultured control PBMCs. CONCLUSIONS Increased RIP140 level may be closely associated with inflammation and disorder of lipid and glucose metabolism in diabetic patients.

Glycemic Control Rate of T2DM Outpatients in China: A Multi-Center Survey

Background Type 2 diabetes mellitus (T2DM)-associated mortality and morbidity are strongly dependent on glycemic control. With T2DM prevalence increasing in China, we aimed to assess glycemic control rates in Chinese T2DM outpatients. Material/Methods A total of 9065 adult T2DM outpatients (5035 men) were assessed in 26 Chinese medical centers between August 2010 and April 2012. Patients were stratified according to BMI (kg/m2): <24, 24–28, and >28. Successful glycemic control was defined as glycated hemoglobin A1c (HbA1c) ≤7% or fasting plasma glucose (FPG) <7.0 mmol/L. Results Among the participants included in this study, 2939 had BMI <24, 3361 had BMI of 24–28, and 2764 had BMI >28. The glycemic control rate was only 32.6%, and the triple control rate for glycemia, blood pressure, and lipidemia was only 11.2%. Glycemic control rates by BMI group were 33.7% (<24), 33.8% (24–28), and 30.2% (>28) (p=0.005), and corresponding incidences of cardiovascular diseases (CVD) were 12.2%, 15.7%, and 15.9% (p<0.001). Multivariate logistic regression analysis demonstrated that older age (p<0.001), higher BMI (p=0.026), larger waist circumference (p<0.001), less education (p<0.001), and recent diagnosis (p<0.001) were independent risk factors for poor glycemic control. Conclusions The T2DM glycemic control rate in China is currently low, especially in older obese patients with poor education and recent diagnosis.