LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers.

A diabetic foot ulcer (DFU) is one of the most devastating complications of diabetes. It has been reported that lncRNA GAS5 plays a vital role in wound healing in DFUs. However, the specific mechanism remains unclear. In this research, we aimed to investigate the role of GAS5 in wound healing in DFUs as well as the underlying mechanism. qPCR or western blotting was performed to measure the expression levels of GAS5, HIF1A, VEGF and TAF15. CCK-8 or EdU assays, flow cytometry, wound healing assays and tube formation assays were carried out to assess the proliferation, apoptosis, wound healing and in vitro angiogenesis of HUVECs, respectively. RNA pull-down and RIP assays were performed to verify the interaction between GAS5 and TAF15. ChIP and luciferase assays were conducted to verify the binding of TAF15 to the HIF1A promoter. In the DFU mouse model, H&E and Masson staining were used to determine epidermal and dermal thickness and collagen formation. GAS5 and HIF1A were downregulated in the skin tissues of DFU patients, and GAS5 overexpression promoted cell proliferation, wound healing and tubule formation in HG-treated HUVECs. In addition, GAS5 facilitated HIF1A expression by interacting with TAF15. Rescue assays demonstrated that the suppression of HIF1A/VEGF pathway activation partially reversed the functional roles of GAS5 in HUVECs. Furthermore, GAS5 accelerated wound healing by activating the HIF1A/VEGF pathway in mice with DFUs. GAS5 activates the HIF1A/VEGF pathway by binding to TAF15, resulting in accelerated wound healing in DFUs. Our findings may provide a theoretical basis for the clinical treatment of DFUs.

Plasma asprosin, CCDC80 and ANGPTL4 levels are associated with metabolic and cardiovascular risk in patients with inflammatory bowel disease.

Asprosin, coiled-coil domain-containing 80(CCDC80) and angiopoietin-like4(ANGPTL4) are newly discovered adipocytokine that affects glucose tolerance, insulin resistance and cardiovascular diseases. The goal of this study was to investigate if a relationship exists among asprosin, CCDC80 and ANGPTL4 and inflammatory bowel disease (IBD). Fifty subjects with newly diagnosed IBD and fifty healthy individuals were enrolled. Patients were treated with standard therapies for 3 months. Plasma asprosin, CCDC80 and ANGPTL4 levels were measured with enzyme-linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate.Compare with healthy individuals, plasma CCDC80,erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and homeostasis modelassessment of insulin resistance (HOMA-IR) were significantly higher (p < 0.05, respectively), whereas plasma asprosin,ANGPTL4 levels and FMD were significantly lower inboth UC and CD patients(p <0.05). Plasma CCDC80 levels were significantly higher in patients with CD (p<0.05), while plasma asprosin and ANGPTL4 levels were lower (p<0.05) as compared with those in patients with UC. Standard therapies increased plasma asprosin, ANGPTL4 levels and FMD in both UC and CD (p<0.05),UC and CD patientswhile decreased plasma CCDC80, ESR, CRP levels and HOMA-IR (p<0.05). The changes in HOMA-IR and FMD were correlated with the changes in plasma asprosin, CCDC80 and ANGPTL4 levels over the study period (p<0.05). Plasma asprosin, CCDC80 and ANGPTL4 levels may be applied as a significant marker for early stage of insulin resistance and atherosclerosis in IBD, especially of CD.

Serum HMGB1 levels and its association with endothelial dysfunction in patients with polycystic ovary syndrome.

High-mobility group box 1 (HMGB1) is newly discovered protein, which play a crucial role in the pathogenesis of systemic inflammation. Recent studies showed that HMGB1 is one of the important pathophysiological mechanisms in the occurrence and development of atherosclerosis. The purpose of the present study was to investigate the relationship between serum HMGB1 levels and endothelial function in patients with polycystic ovary syndrome (PCOS). Eighty newly diagnosed patients with PCOS and eighty normal women of similar age were selected. Metformin treatment (1,500 mg/day) was initiated in all patients for a period of consecutive 3 months. Serum HMGB1 levels were measured by ELISA. High resolution ultrasound was used to measure the brachial artery diameter at rest, after reactive hyperemia (flow-mediated arterial dilation, FMD) and after sublingual glyceryltrinitrate. Serum HMGB1 levels in PCOS were 24.87+/-14.93 ng/ml, which were significantly higher than that in controls (8.82+/-3.55 ng/ml, p<0.01). After 3 months treatment, serum HMGB1 levels decreased significantly (p<0.05). By dividing the distribution of HMGB1 levels into quartiles, serum HMGB1 levels were increased gradually with the increase of testosterone levels (p<0.05), whereas the FMD levels decreased (p<0.05). Multiple stepwise linear regression analysis showed that FMD (estimated coefficient beta=-0.69, p=0.005), testosterone (beta=0.31, p=0.045), TBARS (beta=0.69, p=0.012) and hs-CRP levels (beta=0.68, p=0.001) were significantly associated with HMGB1. The absolute changes in HMGB1 showed a positive correlation with the changes in testosterone (p<0.05) and negative correlation with the changes in FMD (p<0.05) in patients with PCOS during the course of metformin therapy. Serum HMGB1 levels are correlated with endothelial dysfunction in patients with PCOS. Our study suggests that HMGB1 may contribute to the early stage of atherosclerosis in patients with PCOS.

High Human Cytomegalovirus IgG Level is Associated with Increased Incidence of Diabetic Atherosclerosis in Type 2 Diabetes Mellitus Patients.

BACKGROUND At present, whether human cytomegalovirus (HCMV) infection is associated with type 2 diabetes mellitus (T2DM) is debatable. The effect of active HCMV infection on glucose regulation has been poorly studied. Although HCMV infection is correlated with atherosclerosis in cardiovascular disease, the role of HCMV infection in the development of diabetic atherosclerosis in T2DM is unclear and is usually neglected by endocrinologists. The aim of this study was to assess the effects of HCMV infection on glucose regulation and the development of diabetic atherosclerosis in T2DM patients. MATERIAL AND METHODS A total of 222 hospitalized T2DM patients were enrolled. Nested polymerase chain reactions were used to detect HCMV DNA extracted from peripheral blood leukocytes. Quantitative real-time PCR was used to determine viral load. HCMV IgG antibody concentrations were analyzed by chemiluminescence immunoassay. RESULTS HCMV active infection, viral load, and HCMV IgG titers were not correlated with glucose regulation. Binary logistic regression demonstrated that the highest quartile of HCMV IgG concentration (>500 U/ml) was correlated with the incidence of diabetic atherosclerosis (OR: 8.0, 95%CI: 2.3-27.2), and that titer >127 U/ml of HCMV IgG is an independent predictor for the development of diabetic atherosclerosis in T2DM patients (OR: 4.6, 95%CI: 1.9-11.3) after adjustment for all potential confounding factors. CONCLUSIONS Active HCMV infection is unlikely to influence glucose regulation in T2DM. However, HCMV IgG titers are associated with the incidence of diabetic atherosclerosis, and titer >127 U/ml of HCMV IgG might be an independent risk factor for the development of diabetic atherosclerosis in T2DM patients.

Serum gamma-glutamyl transferase is associated with the elevated uric acid levels in normotensive Chinese adults.

BACKGROUND: Although both serum gamma-glutamyltransferase (GGT) and uric acid are correlated with hypertension, studies on the association between serum GGT and uric acid in normotensive individuals are rare. In this study, we tried to reveal this relationship in normotensive Chinese adults. METHODS: Four hundred seven normotensive adults were recruited. The subjects were divided into 3 subgroups according to serum GGT tertiles. Anthropometric parameters as well as systolic blood pressure (SBP), diastolic blood pressure (DBP), uric acid, GGT, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, blood lipids, and fasting insulin were measured. Insulin resistance was assessed using HOMA-IR index. RESULTS: Uric acid was increased in parallel with increasing serum GGT (P<0.001). After correction for age, sex, smoking and alcohol consumption, serum GGT was positively associated with uric acid (r=0.42, P<0.001), SBP (r=0.22, P<0.001), and DBP (r=0.19, P<0.001). When compared with lowest GGT tertile, the odds ratio of the middle tertile for the increased serum uric acid was 3.43 (95% CI, 1.39-8.47) and 7.29 (95% CI, 1.57-33.82) for the highest tertile after adjustment for age, sex, BMI, smoking, alcohol consumption, SBP, DBP, creatinine and HOMA-IR. CONCLUSIONS: Serum GGT is strongly associated with the increased uric acid concentrations in normotensive Chinese adults.

Changes of plasma concentration of osteoprotegerin and its association with endothelial dysfunction before and after hypouricemic therapy in patients with hyperuricemia.

OBJECTIVE: Osteoprotegerin (OPG) is a secreted glycoprotein in the regulation of bone turnover. Recently, many studies showed that OPG acts as an important regulatory molecule in the vascular systems. Our objective was to examine the plasma OPG levels alteration and its association with endothelial function before and after hypouricemic therapy in patients with hyperuricemia. METHODS: Thirty patients (28 males and 2 females, serum uric acid > 7.0 mg/dl) with hyperuricemia were selected. Thirty healthy individuals (28 males and 2 females) with normal serum uric acid were also selected as control. Patients were administered with hypouricemic therapy for 6 months. Plasma OPG concentration was measured in duplicate using a sandwich ELISA and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia and after sublingual glyceryltrinitrate. RESULTS: Plasma OPG levels in patients with hyperuricemia before hypouricemic therapy was significantly higher than those in controls (3.39 ± 0.25 vs. 2.05 ± 0.74 ng/L, p < 0.01). After hypouricemic therapy, OPG levels decreased markedly (2.54 ± 0.38 ng/L, p < 0.01). Flow-mediated dilation (FMD) in patients with hyperuricemia was 3.07 ± 1. 23%, which was significantly lower than that in control subjects (4.62 ± 0.69%, p < 0.01), and it improved significantly after hypouricemic therapy (3.91 ± 1.37%, p < 0.01). The absolute changes in OPG showed a significant positive correlation with the changes in serum uric acid (p < 0.05) and negative correlation with the changes in FMD (p < 0.01) in patients with hyperuricemia during the course of hypouricemic therapy. CONCLUSION: The current study demonstrates that plasma OPG levels increased significantly in patients with hyperuricemia and decreased significantly after hypouricemic therapy, and are correlated with FMD. These findings support the growing concept that elevated plasma OPG levels may be involved with the development of endothelial dysfunction in patients with hyperuricemia.

Clinical evaluation of valsartan and metoprolol tartrate in treatment of diabetic nephropathy with positive ß1-adrenergic and anti-angiotensin II type 1 receptor antibody.

BACKGROUND: Studies have confirmed that angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitors (ACEI) in the treatment of diabetic nephropathy (DN) has special advantages. We observed the effects of valsartan and metoprolol tartrate hydrchloride in treatment of DN patients with positive ß1-adrenergic and anti-angiotensin II type 1 (AT1) receptor antibody. METHODS: The epitopes of the second extracellular loop of ß1 receptor (197 - 222) and AT1 receptor (165 - 191), were synthesized and used respectively to screen serum autoantibodies from patients with DN (n = 371, group A), diabetes mellitus (DM) without renal failure (n = 107, group B) and healthy blood donors (n = 47, control, group C) by enzyme-linked immunosorbent assay (ELISA). Metoprolol tartrate 25 - 50 mg, three times per day, valsartan 160 mg, once a day, aspirin 100 mg, once a day, and nitrendipine 10 - 20 mg, three times per day, were given to DN patients with positive or negative autoantibodies. The cystatin C level and 24-hour urinary protein were measured before and after treatment. RESULTS: In DN patients, the positive rate of the autoantibodies against ß1 receptors and AT1 receptor was 47.7% and 51.5%, respectively, which were significantly higher than those in DM patients and healthy controls (all P < 0.01). Patients with anormalous cystatin C had higher positive rates of the autoantibodies than patients with normal cystatin C. Valsartan and metoprolol tartrate reduced proteinuria significantly (P < 0.01) in DN patients with positive autoantibodies. CONCLUSIONS: The findings suggest that these autoantibodies against ß1 and AT1-receptor may play important roles in the pathogenesis of DN. Valsartan and metoprolol tartrate are effective and safe in the treatment of DN.

Postprandial lipaemia suppresses endothelium-dependent arterial dilation in patients with hypothyroidism.

Endothelial dysfunction represents an early step in the development of atherosclerosis. The purpose of this study was to investigate the relationship between postprandial lipaemia and endothelial dysfunction in patients with overt hypothyroidism (oHT) and subclinical hypothyroidism (sHT). Female subjects with oHT and sHT, as well as female healthy subjects with euthyroid state were enrolled (10 cases in each group). The examination of flow-mediated dilation (FMD) was performed before and after an oral fat-loading by high resolution ultrasound. Endothelial dysfunction after an oral fat challenge was related to the extent of hypertriglyceridemia and free radicals. FMD decreased significantly at 4-h point in 3 groups, (p < 0.05) and then FMD in control and sHT restored to baseline at 8-h point, it was lower than baseline in sHT group at 6-h point (p = 0.042). However, FMD continued to decrease at 6-h point (p < 0.001), and then increased toward to baseline at 8-h point, which was still lower than baseline (p = 0.039) in oHT. Spearman's analysis showed a negative correlation between FMD and triglyceride, a negative correlation between FMD and thiobarbituric acid reactive substances (TBARS), and a positive correlation between triglyceride and TBARS levels during oral lipid-loading test in hypothyroid patients (p < 0.001) and controls (p < 0.05). In hypothyroid subjects including oHT and sHT, even in healthy individuals, FMD was impaired after an oral fat challenge. The endothelial dysfunction observed after an oral fat challenge was related to the extent of hypertriglyceridemia and oxygen-derived free radicals.

Hemoglobin A(1c) proportion, mortality rate, and risk factors for death in diabetic patients with severe hypoglycemia: a multicenter retrospective survey over ten years.

OBJECTIVE: To investigate the HbA(1c) proportion and mortality rate across diabetic patients with severe hypoglycemia and the risk factors for death. METHODS: All the diabetic patients with severe hypoglycemia were divided into HbA(1c)<6.5% group and HbA(1c)≥6.5% group. The proportion of HbA(1c), mortality rate and the risk factors for death were analyzed. Common causes for severe hypoglycemia were also analyzed. RESULTS: The percentages of HbA(1c) in the HbA(1c)<6.5% and HbA(1c)≥6.5% groups were 51.2% and 48.8%, respectively. The mortality rates were not significantly different between the 2 groups (5.3% vs. 5.1%, χ(2)=0.01, p=0.17). Binary logistic regression analysis revealed that in both groups, creatinine, aspartate aminotransferase, and uric acid levels were the risk factors for death. In the HbA(1c)<6.5% and HbA(1c)≥6.5% groups, 65.0% and 64.2% showed common causes of severe hypoglycemia, respectively. CONCLUSIONS: With respect to severe hypoglycemia, equal attention should be paid to patients with an HbA(1c) level of ≥6.5% and those with an HbA(1c) level of <6.5%. The mortality rate is approximately 5% in severe hypoglycemia no matter how the HbA(1c) level is. Creatinine, aspartate aminotransferase, and uric acid are the main risk factors in both groups. Two-thirds of severe hypoglycemia cases could be prevented.

[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.

Regular aerobic exercise training improves endothelium-dependent arterial dilation in patients with subclinical hypothyroidism.

OBJECTIVE: Impairment of flow-mediated endothelium-dependent arterial dilation (FMD) exists in patients with subclinical hypothyroidism (sHT). Several studies showed that exercise training can improve FMD in patients with type 1 and type 2 diabetes. Therefore, we hypothesized that exercise training can also improve FMD in subjects with sHT. The purpose of the study was to test this hypothesis. RESEARCH DESIGN AND METHODS: We selected 30 sedentary women with sHT and 27 sedentary healthy women with euthyroid. All individuals participated in an exercise training of 6 months. Before and after exercise training, high resolution ultrasound was used to measure FMD. RESULTS: At baseline, FMD among subjects with sHT was 3.87%, which was significantly lower than that in controls (5.98%; P<0.001). After 6 months of exercise, there was a remarkable increase in FMD (31.3%) and VO(2) max (36.7%; P<0.01), and significant decreases in total cholesterol (20%), low-density lipoprotein cholesterol (LDL; 29%), triglycerides (TG; 47.6%), and C-reactive protein (CRP; 61.5%; P<0.05) were observed over the exercise in patients with sHT. The absolute changes in FMD showed significant correlation with changes in LDL (r=-0.596), TG (r=-0.532), and CRP (r=-0.511; P<0.01), and multiple regression analysis showed changes of LDL, TG, CRP were significant determinants of changes of FMD in sHT patients during exercise course. CONCLUSION: Regular aerobic exercise improves FMD in sHT patients, and changes of lipids and inflammation during the exercise period may partially contribute to the improvement of endothelial function.

[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 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.

[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.

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.

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.

[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.