The Correlation Between Circulating Betatrophin and Insulin Resistance in General Population: A Meta-Analysis.

Many inconsistent findings are reported on the correlation between circulating betatrophin and insulin resistance in the different population. The aim of this analysis was to explore the correlation between the level of betatrophin and insulin resistance in the general population. The databases of PubMed, EMBASE, and the Cochrane Library (inception to October 26, 2016) were searched without language restrictions for publications that reported studies on associations between betatrophin and insulin resistance in adults. Subgroup analyses were performed to investigate potential sources of heterogeneity. The pooled effect size was calculated using a random-effects model. Twenty-five studies were included in this meta-analysis. Meta-analysis showed that betatrophin was positively and significantly correlated with insulin resistance (r=0.16, 95% CI: 0.08-0.25). When all participants were divided into DM, GDM, and Non-DM groups, this association was also significant in T2DM, GDM, and Non-DM participants (T2DM: r=0.09, 95% CI: 0.01-0.17; I 2=45.1%; GDM: r=0.39, 95% CI: 0.24-0.55; I 2=0.0%; non-DM: r=0.15, 95% CI: 0.04-0.26; I 2=89.3%), and it was obvious that heterogeneity existed in Non-DM group (I 2=89.3%, p<0.001). Subgroup analysis revealed that gender, serum sample and ELISA kits for full-length betatrophin had significant influence on the association between betatrophin and insulin resistance. In conclusion, the level of circulating betatrophin is positively associated with insulin resistance in the general population, especially in T2DM and GDM patients. Gender, serum sample, and ELISA kits for full-length betatrophin may affect this association. More large-scale studies are needed to determine whether improving insulin resistance concomitantly declines betatrophin levels in different diseases.

[Regulatory effect of liraglutide on the expression of eNOS in the corpus cavernosum of diabetic rats].

UNLABELLED: OCTOBER: To explore the effects of the glucagon-like peptide 1 (GLP-1) liraglutide on the penile erectile function of rats with diabetic erectile dysfunction (DED) by observing the impact of liraglutide on the expression of eNOS in the corpus cavernosum of diabetic rats. METHODS: We randomly divided 30 six-week-old male SD rats into a normal control (n = 10) and an experimental group (n = 20) , established models of diabetes mellitus (DM) in the experimental rats, and subdivided them into a DM (n = 8) and a GLP-1 group (n = 8) to receive intramuscular injection of normal saline and liraglutide at 5 mg per kg of the body weight per day, respectively. After 12 weeks of intervention, we obtained the levels of FPG, FINS, TG, TC, HDL-C, LDL-C, testosterone, and IL-6 and the indexes of Homa-IR and Homa-ß, detected the expressions of Akt/p-Akt and eNOS/p-eNOS in the corpus cavernosum by Western blot, and compared the erectile function between different groups. RESULTS: The frequency and rate of penile erection were significantly lower in the DM group than in the GLP-1 and normal control groups (P < 0.05) and also lower in the GLP-1 group than in the normal controls (P < 0.05). Immunofluorescence staining showed the expression of eNOS mainly in the cytoplasm of the cavernosal vessels and sinusoidal endothelial cells, markedly lower in the DM and GLP-1 groups than in the normal rats (P < 0.05), but higher in the GLP-1 than in the DM group (P < 0.05). The level of eNOS/p-eNOS in the penile tissue was significantly decreased in the DM and GLP-1 groups in comparison with the normal controls (P < 0.01 or P < 0.05), while that of p-eNOS was markedly increased in the GLP-1 group as compared with the DM group (P < 0.05). No statistically significant differences were observed in the Akt level among the three groups of animals (P > 0.05). The expression of p-Akt was remarkably reduced in the DM and GLP-1 groups in comparison with the control rats (P < 0.01 or P < 0.05), but higher in the GLP-1 than in the DM group (P < 0.05). CONCLUSION: GLP-1 can protect the function of endothelial cells in the corpus cavernosum and improve the erectile function of DED rats by regulating the Akt/ eNOS signaling pathway, which indicates that GLP-1 could be an important option for the treatment and prevention of DED.

Circulating level of TRAIL concentration is positively associated with endothelial function and increased by diabetic therapy in the newly diagnosed type 2 diabetic patients.

OBJECTIVE: Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is associated with atherosclerosis. This study was to investigate the changes of circulating TRAIL and its association with flow-mediated endothelium-dependent arterial dilation (FMD) before and after diabetic treatment in newly diagnosed type 2 diabetes. MATERIALS AND METHODS: The study subjects included 55 newly diagnosed type 2 diabetes and 52 healthy subjects. Circulating TRAIL concentration was measured by an ELISA, and high-resolution ultrasound was used to measure FMD of brachial artery. RESULTS: The circulating TRAIL in patients before treatment was 64·46 pg/ml, which was significantly lower than that in control (80·70 pg/ml, P < 0·001). After 6 months of diabetic treatment, TRAIL level increased markedly (75·11 pg/ml), which was still lower than that in control (P < 0·001). FMD was reduced compared with controls at baseline and increased after diabetic therapy (P < 0·001). In multivariate analysis, circulating TRAIL was significantly associated with FMD, fasting blood glucose (FBG), 2-h blood glucose (2-h BG), haemoglobinA1c (HbA1c) and C-reactive protein (CRP) at baseline (P < 0·01). The absolute change in TRAIL was correlated with the changes in FMD, FBG, 2-h BG, HbA1c and CRP (P < 0·01) before and after diabetic treatment. CONCLUSION: Circulating TRAIL level decreased in newly diagnosed type 2 diabetes and increased after 6 months of diabetic treatment significantly. The circulating TRAIL level is positively associated with endothelial function. Our data showed that circulating TRAIL level may be a protective maker of endothelial function in type 2 diabetes.

Autoantibodies against ß1 receptor and AT1 receptor in type 2 diabetes patients with left ventricular dilatation.

OBJECTIVES: To explore the relationship between the autoantibodies against the ß1 and AT1 receptors and left ventricular dilatation in patients with type 2 diabetes (T2DM). METHODS: The autoantibodies against the ß1 and angiotensin II type 1 (AT1) receptors of T2DM patients with and without hypertension were screened by ELISA. Multiple logistic regression was used to analyze the risk factors for left ventricular dilatation. The reversing effect of left ventricular dilatation was evaluated after receptor blocker treatment. RESULTS: The positive rates of autoantibodies against the ß1 and AT1 receptors (43.0 and 44.1%, respectively) in T2DM patients with hypertension were significantly higher than those in normotensive patients (16.0 and 10.4%, respectively; all p < 0.01). Furthermore, among T2DM patients with hypertension, the positive rates (61.4 and 64.9%, respectively) in patients with left ventricular dilatation were remarkably higher than those with normal left ventricular dimensions (34.4 and 36.1%, respectively; all p < 0.01). The presence of ß1 receptor antibody and AT1 receptor antibody were risk factors for left ventricular dilatation (p < 0.05). The curative effect of metoprolol tartrate and valsartan in reversing left ventricular hypertrophy in the group positive for autoantibodies was much better than in the negative group. CONCLUSION: The findings show that autoantibodies against the ß1 and AT1 receptors may play a role in predicting left ventricular dilatation in T2DM patients in combination with hypertension. Metoprolol tartrate and valsartan are effective and safe in the treatment of these patients.

Method for real-time prediction of cutter wear during shield tunnelling: A new wear rate index and MCNN-GRU.

Cutter wear is one of the key factors influencing construction efficiency during shield tunnelling. Prediction of cutter wear can improve construction efficiency by reducing the times of cutter inspections in engineering practice. Evaluation of cutter life is vital for cutter wear prediction, however, existing cutter life indices can only estimate the health condition of all cutters on cutterhead on a holistic basis. A new index was proposed to evaluate cutter wear located at a specific installation position on cutterhead. A deep learning model integrating the index was developed for the estimation of accumulated cutter wear during real time shield tunnelling. The new index can be obtained by monitored field parameters and can predict cutter wear with historical wear patterns. The input and output data samples were reshaped for multi-step prediction. A shield tunnelling section in Guangzhou weathered granite was used for validation. The proposed method can help reduce the cost of cutter replacement by reducing the times of machine interventions. The method article is a companion paper to the original article [1].•Proposed index for prediction of cutter wear rate.•Deep learning model of 1D-CNN and GRU.•Multi-step cutter wear prediction.

Evaluation of environmental impact of red tide around Pearl River Estuary, Guangdong, China.

This paper presents a case study of red tide hazards around the Pearl River Estuary (PRE). Red tide hazards, meteorological data, and seawater monitoring data were collected from 1996 to 2020 at different locations around the PRE to investigate the internal and external factors influencing the occurrence of red tides. The enhancement of the assessment of estuarine trophic status (ASSETS) method enables us to evaluate the effects of meteorological factors and seawater eutrophication status on the red tide risk level. Using ASSETS, we established a framework for red tide risk assessment of the Pearl River Estuary. We analysed the external and internal factors causing the red tide based on meteorological data and seawater monitoring data in the PRE. The results show that the temperature was higher than the annual monthly average temperature of 1.265 °C, and east and north winds at velocities of 3-4 m/s could result in the formation of red tides. However, precipitation inhibits the formation of the red tide in PRE.

1,5-Diamino-tetra-zolium chloride.

The title compound, CH(5)N(6) (+)·Cl(-), crystallized with two indepedent 1,5-diamino-tetra-zolium cations and two independent chloride anions in the asymmetric unit. In the crystal, there are a number of N-H⋯Cl hydrogen-bonding inter-actions, which generate a three-dimensional network.

[Positive rate of autoantibodies against adrenergic receptors beta1 and angiotensin II type 1 receptors in the type 2 diabetes mellitus with or without hypertension].

OBJECTIVE: To observe the positive rates of autoantibodies against beta1 adrenergic receptors (beta1-receptor) and angiotensin II type 1 receptors (AT(1)-receptor) in type 2 diabetes patients with or without hypertension. METHODS: The epitopes of the second extracellular loop of beta1-receptor (197 - 222) and AT(1) receptor (165 - 191) were synthesized and serum autoantibodies were determined in type 2 diabetes patients with hypertension (n = 171) or without hypertension (n = 106). Left ventricular dimension was determined by echocardiography. The 24-hour urinary protein was measured by ELISA. The risk factors for enlarged left ventricle were analyzed by multiple logistic regressions. RESULTS: The positive rates of the autoantibodies against beta1-receptors (45.0%) and AT(1)-receptor (46.2%) in patients with type 2 diabetes with hypertension were significantly higher than those in patients with type 2 diabetes without hypertension (16.0% and 10.4%, respectively, all P < 0.01). In type 2 diabetes patients with hypertension and enlarged left ventricle, the positive rates of the autoantibodies against beta1-receptor 61.4% (35/57) and against AT(1)-receptor 64.9% (37/57)were significantly higher than those in type 2 diabetes patients with normal left ventricular dimension (36.8%, 42/114 and 36.8%, 42/114, respectively, all P < 0.01). Regression analysis demonstrated that course of disease, systolic pressure, serum autoantibodies against beta1 adrenergic receptor and angiotensin II type 1 receptors sera autoantibodies were independent risk factors for left ventricular enlargement (all P < 0.05). CONCLUSION: The serum beta1 and AT(1)-receptor autoantibodies are related to enlarged left ventricle in type 2 diabetes patients with hypertension and suggest that autoantibodies against beta1 and AT(1)-receptor might play important roles in the pathogenesis of type 2 diabetes patients with hypertension and enlarged left ventricle.

The antioxidant alpha-lipoic acid improves endothelial dysfunction induced by acute hyperglycaemia during OGTT in impaired glucose tolerance.

OBJECTIVE: Impaired glucose tolerance (IGT) is considered a transitional phase in the development of type 2 diabetes, and is also independently associated with the occurrence of cardiovascular disease. Endothelial dysfunction (ED) represents a very early step in the development of atherosclerosis. The aim of the present study was to examine ED in the fasting state and after a glucose challenge as well as after administration of an antioxidant agent. PATIENTS AND METHODS: The study subjects included 42 IGT patients and 26 healthy individuals (control group). The IGT patients were randomly divided into two groups, 21 in each group (the alpha-lipoic acid group and the placebo group). In the alpha-lipoic acid group, 300 mg of alpha-lipoic acid was administrated before an oral glucose tolerance test (OGTT); in the placebo group, 250 ml of 0.9% sodium chloride was administrated before the OGTT. In addition, 250 ml of 0.9% sodium chloride was also administrated to the control subjects before the OGTT (control group), and then vascular function was examined in the fasting state and repeated 1 and 2 h after the glucose load. High-resolution ultrasound was used to measure flow-mediated endothelium-dependent arterial dilation (FMD) and glyceryltrinitrate (GTN)-induced endothelium-independent arterial dilation. RESULTS: In the fasting state, and at 60 and 120 min, FMD in both the placebo and alpha-lipoic acid groups was significantly lower than in the controls (P < 0.01). In the control group, FMD tended to decrease at 60 min after glucose loading and returned to the baseline levels at 120 min (P > 0.05). In the placebo group, FMD decreased significantly at 60 min after glucose loading (P < 0.01) and increased markedly from 60 to 120 min (P < 0.01). The alpha-lipoic acid-treated patients showed FMD values intermediate between the control subjects and the IGT patients treated with placebo, at both 60 and 120 min, and the differences were significant (P < 0.01). In multiple regression analysis, FMD was significantly correlated to fasting blood glucose (FBG), low density lipoprotein cholesterol (LDL-C), lipoprotein (a) [Lp(a)], C-reactive protein (CRP), thiobarbituric acid reactive substances (TBARS) and age in IGT patients at baseline (P < 0.01). Spearman's analysis showed a significant negative correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients (placebo group) (P < 0.01). There was also a significant correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients treated with alpha-lipoic acid (P < 0.05), although the power of association decreased. CONCLUSION: In subjects with IGT, FMD was impaired both in the fasting state and after a glucose challenge, probably through increased production of oxygen-derived free radicals. The ED observed after a glucose challenge is related to the extent of hyperglycaemia and TBARS, and an antioxidant agent can improve the impairment of endothelial function induced by acute hyperglycaemia.

[The relation between positive rate of autoantibodies against beta1 and M2-adrenergic receptors and urinary albumin excretion rate in the type 2 diabetes mellitus with refractory hypertension].

OBJECTIVE: To explore the relation between the positive rates of autoantibodies against beta(1) adrenergic receptor (beta1-receptor)and (M2-receptor) with urinary albumin excretion rate (UAER) in type 2 diabetes patients with refractory hypertension. METHODS: Autoantibodies against beta(1)- and M(2)-receptor as well as autoantibodies were determined in type 2 diabetes patients with (n = 136) or without (n = 111) refractory hypertension, hypertensive patients without renal failure (n = 60) and healthy control subjects (n = 40, control) by ELISA. RESULTS: The positive rates of the autoantibodies against beta1-receptors (44.9%) and M(2)-receptor (37.5%) in patients with type 2 diabetes with refractory hypertension were significantly higher than those in patients with type 2 diabetes without refractory hypertension (27.9% and 24.3%, respectively, all P < 0.05), in patients with hypertension without renal failure (11.7% and 15.0%, all P < 0.01) and in healthy controls (8.3% and 7.5%, all P < 0.01). In type 2 diabetes patients with refractory hypertension and renal failure (UAER > or = 200 microg/min), the positive rates of the autoantibodies against beta(1)-receptor (87.1%, 27/31) and against M(2)-receptor (67.7%, 21/31) were significantly higher than those in type 2 diabetes patients with refractory hypertension but without renal failure (UAER 20 - 199 microg /min, 46.7%, 28/60 and 41.7%, 25/60, respectively, all P < 0.05). CONCLUSION: The serum beta(1)- and M (2)-receptor autoantibodies are positively associated with the UAER level and suggest that these autoantibodies against beta(1) and M(2)-receptor may play important roles in the pathogenesis of the type 2 diabetes with refractory hypertension.

The relationship between plasma osteoprotegerin and endothelium-dependent arterial dilation in type 2 diabetes.

Osteoprotegerin is a recently identified inhibitor of bone resorption. Recent studies indicate that osteoprotegerin also acts as an important regulatory molecule in the vasculature. The purpose of this study was to investigate the relationship between plasma osteoprotegerin levels and endothelium-dependent arterial dilation in type 2 diabetic patients. The study subjects included 40 newly diagnosed type 2 diabetic patients and 46 healthy subjects. All patients were given insulin therapy for 6 months. Plasma osteoprotegerin concentration was measured in duplicate by a sandwich enzyme-linked immunosorbent assay method, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual glyceryltrinitrate. The plasma osteoprotegerin level in patients before treatment was 3.36 +/- 0.32 ng/l, which was significantly higher than that in control subjects (2.38 +/- 0.25 ng/l, P < 0.001). After 6 months of treatment, osteoprotegerin levels decreased markedly (2.83 +/- 0.34 ng/l, P < 0.001). Flow-mediated endothelium-dependent arterial dilation in patients before treatment was 3.21 +/- 0.52%, which was significantly lower than that in control subjects (4.46 +/- 0.56%, P < 0.01), and it improved markedly after 6 months of treatment (4.03 +/- 0.49%, P < 0.01). In multivariate analysis, osteoprotegerin was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), HbA(1c) (A1C), and ultrasensitive C-reactive protein (CRP) at baseline (P < 0.01). The absolute changes in osteoprotegerin showed significant correlation with changes in endothelium-dependent arterial dilation, FBG, A1C, and CRP in diabetic patients during the course of treatment (P < 0.01). This study shows that plasma osteoprotegerin levels are elevated in newly diagnosed diabetic patients and are significantly associated with endothelial function.

Changes of osteoprotegerin before and after insulin therapy in type 1 diabetic patients.

OBJECTIVE: Osteoprotegerin (OPG) regulates osteoclast and immune functions and appears to represent a protective factor for vascular system. However, the role of OPG in endothelial dysfunction of type 1 diabetic patients has not been evaluated. The purpose of this study was to investigate the relationship between plasma OPG levels and endothelium-dependent arterial dilation in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: This study subjects included 22 newly diagnosed type 1 diabetic patients and 28 healthy subjects. All patients were then given insulin therapy for 6 months. Plasma OPG concentration was measured in duplicate by a sandwich ELISA method, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia and after sublingual glyceryltrinitrate (GTN). RESULTS: Plasma OPG level in patients before treatment was 3.09+/-0.70 ng/L, which was significantly higher than that in control (2.07+/-0.75 ng/L) (p<0.001). After 6 months treatment, OPG levels decreased markedly (2.58+/-0.59 ng/L) (p<0.001). The flow-mediated endothelium-dependent arterial dilation in patients before treatment was 3.35+/-0.67%, which was significantly lower than that in control (5.17+/-0.83%) (p<0.001), and improved markedly after 6 months treatment (4.27+/-0.63%) (p<0.001). In multivariate analysis, OPG was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and ultra sensitive C-reactive protein (CRP) at baseline (p<0.01). The absolute changes in OPG showed significant correlation with the changes in endothelium-dependent arterial dilation, FBG, HbA1c, and CRP in diabetic patients during the course of treatment (p<0.01). CONCLUSION: This study shows that plasma OPG levels are elevated in newly diagnosed type 1 diabetic patients, and that plasma OPG levels are significantly associated with endothelial function.

[Changes in plasma concentrations of osteoprotegerin before and after levothyroxine replacement therapy in hypothyroid patients].

OBJECTIVE: To investigate the alteration of plasma osteoprotegerin (OPG) concentration before and after levothyroxine (L-T4) replacement therapy and its association with endothelium-dependent arterial dilation in patients with overt hypothyroidism (oHT) and subclinical hypothyroidism (sHT). METHODS: L-T4 therapy was given to 20 oHT patients and 20 sHT patients, all female, till the free serum triiodothyronine (FT3), free thyroxin (FT4), and thyroid-stimulating hormone (TSH) were near or within the respective normal ranges. Twenty healthy women were used as controls. Sandwich ELISA was used to measure the plasma OPG concentration before and after treatment. RESULTS: The plasma OPG levels before treatment of the oHT and sHT patients were 3.13 ng/L +/- 0.27 ng/L and 2.95 ng/L +/- 0.24 ng/L respectively, both significantly higher than that of the controls (2.42 ng/L +/- 0.26 ng/L, both P = 0.000). Multivariate analysis showed that OPG was significantly associated with TSH (r = 0.306, P < 0.05) and endothelium-dependent arterial dilation (r = -0.675, P < 0.01) at baseline. After the normalization of thyroid function the OPG levels of the oHT and sHT patients decreased markedly to 2.53 ng/L +/- 0.28 ng/L and 2.54 ng/L +/- 0.21 ng/L respectively (both P = 0.000), very close to that in the controls. The absolute changes of OPG was significantly positively correlated with the changes of TSH (P < 0.05), negatively correlated with the changes of endothelium-dependent arterial dilation (P < 0.01), and not significantly correlated with other parameters in the hypothyroid patients during the course of treatment. CONCLUSION: OPG may act as an important regulatory molecule in the vasculature and, particularly, may be involved in the development of vascular dysfunction in hypothyroid patients.

[Changes of osteoprotegerin before and after insulin therapy in type 1 diabetic patients].

OBJECTIVE: To investigate the relationship between the plasma osteoprotegerin (OPG) level and endothelium-dependent arterial dilation in type 1 diabetic patients. METHODS: Sandwich ELISA method was used to detect the plasma OPG levels of 22 newly diagnosed type 1 diabetic patients before and 6 months after treatment and of 28 healthy subjects. All patients were then given insulin therapy for 6 months. High resolution ultrasound was used to measure the brachial artery diameter at rest, after reactive hyperemia and after sublingual administration of glyceryltrinitrate (GTN). RESULTS: The plasma OPG level of the patients before treatment was 3.09 ng/L +/- 0.70 ng/L, significantly higher than that of the healthy controls (2.07 ng/L +/- 0.75 ng/L, P < 0.001). After 6 months treatment, the OPG level of the patients decreased to 2.58 ng/L +/- 0.59 ng/L, significantly lower than that before treatment (P < 0.001). The flow-mediated endothelium-dependent arterial dilation in the patients before treatment was 3.35% +/- 0.67%, significantly lower than that of the healthy controls (5.17% +/- 0.83%, P < 0.001), and was increased to 4.27% +/- 0.63% after 6 months treatment, significantly higher than that before (P < 0.001). Multivariate analysis showed that OPG level was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and ultra-sensitive C-reactive protein (CRP) at baseline (all P < 0.01). The absolute change in OPG level was significantly correlation with the changes in endothelium-dependent arterial dilation, FBG, HbA1c, and CRP in the diabetic patients during the course of treatment (all P < 0.01). CONCLUSION: Plasma OPG level is elevated in newly diagnosed diabetic patients, and the plasma OPG level is significantly associated with endothelial function.

Doxazosin attenuates renal matrix remodeling mediated by anti-α1-adrenergic receptor antibody in a rat model of diabetes mellitus.

Diabetic nephropathy is a major complication of diabetes mellitus (DM). Recent studies suggest that immunological mechanisms have a key role in the pathogenesis of DM, therefore these mechanisms may be important targets for diabetes therapy. The present study evaluated the effects of anti-α1-adrenergic receptor antibody (α1-R Ab) mediation and doxazosin treatment in a rat model of DM. It was observed that levels of 24-h urinary protein, serum creatinine and transforming growth factor-ß1 in DM were significantly increased after α1-R Ab mediation (all P<0.05). In addition, electron microscopy identified severe damage in the renal tissue microstructures of DM rats following α1-R Ab mediation, while only mild abnormalities were observed in that of healthy rats mediated with α1-R Ab and of untreated DM rats. No marked abnormalities were observed in the renal tissue of healthy blank controls. Furthermore, in DM rats treated with α1-R Ab mediation + doxazosin intervention, the expression of TGF-ß1 significantly decreased, and renal functions and renal matrix remodeling were significantly improved, relative to untreated DM controls (P<0.01). These results suggest that α1-R Ab may be involved in renal matrix remodeling during DM, and that kidney protection during DM may be achieved through treatment with corresponding receptor antagonists.

[Autoantibodies against beta1 and M2 receptor in diabetic patients with refractory hypertension].

OBJECTIVE: To explore the role of the autoantibodies against M(2)-muscarinic receptor (M(2)-receptor), beta(1)-adrenergic receptor (beta(1)-receptor) in the development of diabetic with refractory hypertension. METHODS: Serum autoantibodies against M(2) and beta(1) were detected by ELISA using synthesized epitopes of the second extracellular loop of M(2) receptor (169 - 193) and beta(1) receptor (197 - 222) in healthy controls (n = 40), diabetic patients (n = 62), diabetic patients with non-refractory hypertension (n = 55) and diabetic patients with refractory hypertension (n = 81). RESULTS: The positive rates of the autoantibodies against M(2) receptor and beta(1) receptor were similar among healthy controls (15.0% and 17. 5%), diabetes mellitus patients (17.7% and 14.5%) and diabetic patients with non-refractory hypertension (16.4% and 12.7%) but are significantly higher in diabetic patients with refractory hypertension (64.2% and 55.6%, P < 0.01 vs. other 3 groups). CONCLUSION: This finding suggests that autoimmune mechanisms might play a role in the pathogenesis of diabetic patients with refractory hypertension.

[Angiotensin converting enzyme gene and exercise-induced silent myocardial ischemia in type 2 diabetes mellitus].

OBJECTIVE: To investigate the relationship between angiotensin converting enzyme (ACE) gene and exercise-induced silent myocardial ischemia (SI) in patients with type 2 diabetes mellitus. METHODS: One hundred and eight patients suffering from type 2 diabetes mellitus with normal rest electrocardiograph and 50 healthy individuals were selected randomly. SI was diagnosed with treadmill exercise test and ACE genotypes were detected with PCR. RESULTS: (1) The control group and type 2 diabetes mellitus group had similar distribution of ACE genotypes and alleles (P>0.05). Compared with the non-SI group, the SI group had significantly higher ACE D allele prevalence (Chi-square=4.501, P<0.05); however, the two groups had similar prevalence of ACE genotypes (P>0.05). (2) There were no significant differences in clinical characteristics and serum lipoproteins among the three ACE genotypes (II, DD,ID) of type 2 diabetes mellitus (P>0.05). (3) The prevalence of SI in DD group was found to be 68.2%, which was significantly higher than that in II genotype group (39.5%, Chi-square=4.593, P<0.05). CONCLUSION: ACE D allele increases the risk of SI in type 2 diabetes mellitus.

Effect of prazosin on diabetic nephropathy patients with positive α1-adrenergic receptor autoantibodies and refractory hypertension.

To investigate the effect of prazosin on patients with diabetic nephropathy (DN), α1-adrenergic receptor (α1-R) autoantibodies and refractory hypertension, a total of 126 patients with DN and hypertension were recruited. The patients were divided into a refractory hypertension group, (n=76) and a non-refractory hypertension group (n=50). The epitope of the second extracellular loop of the α1-R (192-218) was synthesized and an enzyme-linked immunosorbent assay (ELISA) was performed to detect serum autoantibodies. In the group with DN-associated refractory hypertension, the positive rate of autoantibodies against the α1-R was 80.3% (n=61). The 61 patients who were positive for α1-R autoantibodies were randomly divided into a treatment group (n=31) and a control group (n=30). The patients were given drugs at the same dosage and administration, with the exception of prazosin, which was provided only to the patients in the treatment group [1 mg, three times a day (tid)] for a duration of six weeks. Subsequently, prazosin was added (1 mg, tid) to the therapeutic schedule of the patients in the control group and the α1-R autoantibody-negative group for another six weeks. The analysis was carried out on an intention-to-treat basis. The prazosin treatment resulted in significant improvements in hypertension in the treatment group (P<0.05), while there was no marked improvement in the control group. The total effective rate of hypertension improvement was 90.3% in the treatment group, which was higher compared with that of the control group (33.3%). In conclusion, α1-R autoantibodies may play an important role in the pathogenesis of DN with refractory hypertension. Prazosin was demonstrated to be effective and safe in the treatment of DN with refractory hypertension.

Contrast agent suppresses endothelium-dependent arterial dilation after digital subtraction angiography procedure in patients with diabetic foot.

Recent studies showed that contrast agents can induce renal injury. Thus, the present study was designed to assess whether the contrast agents used during digital subtraction angiography (DSA) procedure can damage endothelium. Fow-mediated endothelium-dependent vasodilation (FMD) was measured at baseline, 1, 3, and 7 days after DSA in 198 subjects with diabetic foot. We also measured the levels of thiobarbituric acid-reactive substances (TBARS) and von Willebrand factor (vWF), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP). Compared with baseline (3.60 ± 0.47 %), FMD at 1 day decreased (2.74 ± 0.47 %), and increased significantly from 1 to 3 days (p < 0.01), and returned to baseline level at 7 days after DSA. The plasma TBARS increased at 1 day and decreased from 1 to 3 days (p < 0.01), and returned to baseline level at 7 days after DSA. CRP, IL-6, and TNF-α had similar changes before and after DSA procedure. FMD was significantly correlated to vWF, IL-6, TNF-α, CRP, and TBARS (p < 0.01). A negative correlation between contrast volume and FMD, positive correlation between contrast volume and vWF, TBARS, CRP, IL-6 at 1 or 3 days after DSA exist in diabetic group (p < 0.05). Contrast medium suppresses FMD, probably through an increased production of oxygen-derived free radicals and inflammation although adequate hydration was given in type 2 diabetes. Therefore, an effective prophylaxis should allow to prevent this complication.

Circulating irisin levels are positively associated with endothelium-dependent vasodilation in newly diagnosed type 2 diabetic patients without clinical angiopathy.

OBJECTIVE: Irisin is a newly identified myokine that can promote energy expenditure and alleviate insulin-resistance in animal model. It has been established that insulin resistance is frequently associated with endothelial dysfunction. Therefore, we hypothesize that circulating irisin levels are associated with endothelial dysfunction in type 2 diabetes. METHODS: One hundred and eighty eight patients with newly diagnosed type 2 diabetes and 40 healthy subjects were recruited. Serum irisin concentrations were measured by using enzyme-linked immunosorbent assay, and flow-mediated dilation (FMD) was evaluated by using high-resolution ultrasound. RESULTS: The mean value of circulating irisin levels in newly diagnosed type 2 diabetes was 13.25 ng/ml, which was significantly lower than that in controls (25.98 ng/ml, p < 0.001). By dividing the distribution of FMD levels into quartiles, serum irisin levels were increased gradually with the increase of FMD levels (p < 0.001). Multivariate stepwise regression analysis demonstrated that serum irisin levels were independently associated with FMD (p = 0.009). By logistic regression analysis the odds ratio for lower FMD levels was reduced by 11.8% per 1 ng/ml increase in serum irisin concentration after adjustment for multivariate metabolic factors [OR (95% CI); 0.882 (0.709-0.969)]. CONCLUSION: These results demonstrated that circulating irisin levels were decreased in newly diagnosed Chinese type 2 diabetic patients without clinical angiopathy and positively associated with FMD levels.