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1.
INTRODUCTION: The aim of this study was to analyze the influence of DHEA therapy on fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations in men with decreased serum DHEA-S levels and angiographically verified coronary heart disease (CHD). MATERIAL AND METHODS: The study included thirty men aged 41-60 years (mean age 52 +/- 0.90 yr) with serum DHEA-S concentration < 2000 mg/l, who were randomized into a double-blind, placebo-controlled, cross-over trial. Subjects completed the 80 days study of 40 days of 150 mg oral DHEA daily or placebo, and next groups were changed after 30 days of wash-out. Fasting early morning blood samples were obtained at baseline and after each treatment to determine serum hormones levels (testosterone, DHEA-S, LH, FSH and estradiol) and also fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations. RESULTS: Administration of DHEA was associated with 4.5-fold increase in DHEA-S levels. Estrogen levels significantly increased after DHEA from 22.1 +/- 0.7 pg/ml to 26.4 +/- 1.6 pg/l (mean +/- SEM; p < 0.05), while testosterone levels did not changed. Fibrinogen concentrations significantly decreased in DHEA group from 4.5 +/- 0.3 g/l to 3.83 +/- 0.2 g/l (p < 0.05 vs. placebo). Changes of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were not statistical significant (respectively: 8.37 +/- 0.4 ng/ml vs. 8.93 +/- 0.5 ng/ml and 82.3 +/- 6.3 ng/ml vs. 92.7 +/- 9.1 ng/ml (mean +/- SEM; NS vs. placebo). Tolerance of the treatment was good and no adverse effects were observed. CONCLUSIONS: DHEA therapy in dose of 150 mg daily during 40 days in men with DHEAS levels < 2000 mg/l and angiographically verified coronary heart disease (CHD) was connected with significant decreasing of fibrinogen concentration and increasing of estradiol levels, and did not influence on plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations.  相似文献   

2.
Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.  相似文献   

3.
Plasma fibrinogen level represents a strong cardiovascular risk factor and is regulated by an interplay of genetic and environmental factors. Hyperfibrinogenemia frequently occurs in cluster with dyslipidemia within the frame of insulin resistance syndrome (IRS) and type 2 diabetes mellitus. Genetic variants with a pleiotropic effect have been proposed to cause IRS features including hyperfibrinogenemia. We studied the influence of polymorphisms in lipoprotein lipase (LPL) gene, beta-fibrinogen gene (FIBB) and environmental factors on plasma fibrinogen levels in type 2 diabetes patients. 131 type 2 diabetes patients (mean age 62+/-10 years, 33% male) were genotyped for polymorphisms in LPL gene (intron 6 PvuII, intron 8 HindIII) and FIBB gene (-148C/T, -455G/A) by PCR-RFLP method. Fibrinogen was measured by thrombin coagulation method, albuminuria by immunoturbidimetric assay. Polymorphism LPL PvuII showed a gene-dose effect on fibrinogen levels, with the highest fibrinogen in P-P- homozygotes (p = 0.05, analysis of variance). P-carriers (P-P- and P+P- combined) had significantly higher fibrinogen levels compared with P+P+ homozygotes (3.74+/-1.40 g/l vs 3.06+/-1.20 g/l, p=0.03). Other studied polymorphisms were not significantly related to fibrinogen levels. Age- and sex-adjusted fibrinogenemia correlated significantly with albuminuria (r = 0.48, p=0.001), serum uric acid (r = 0.42, p=0.006) and serum creatinine (r = 0.32, p=0.04). Multiple stepwise linear regression identified interaction term of LPL PvuII and albuminuria as an independent predictor of fibrinogen level, explaining 18% of fibrinogen variance. Albuminuria thus appears to be the best predictor of fibrinogen plasma levels in type 2 diabetic patients. Relationship between albuminuria and fibrinogenemia may be modified by the genotype LPL PvuII, which also shows a weak association with plasma fibrinogen level in type 2 diabetes patients.  相似文献   

4.
5.
INTRODUCTION: It has been reported that hyperthyroidism is associated with an altered endothelial function and increased risk of arterial thromboembolism. The aim of our study was to estimate chosen markers of endothelial dysfunction in iodine-induced thyrotoxicosis (IIT). MATERIALS AND METHODS: The groups studied consisted of 41 hyperthyroid subjects, who had been treated with amiodarone (n = 6) or vitamin preparations supplemented with iodine (n = 35) and 40 persons with normal thyroid function. The following parameters were measured: thyroglobulin antibodies (TG Ab), thyroid peroxidase antibodies (TPO Ab), THS receptor antibodies (TR Ab), soluble adhesion molecules: sVCAM-1 and sICAM-1, von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), fibrinogen and urine iodine concentration. RESULTS: Patients with IIT had significantly higher levels of sVCAM-1 (p < 0.01), IL-6 (p < 0.005), fibrinogen (p < 0.005) and CRP (p < 0.05) in comparison to healthy subjects, whereas sICAM-1, PAI-1 and vWF concentrations did not differ between the groups studied. The highest sVCAM-1 levels were observed in patients with amiodarone induced thyrotoxicosis, and fibrinogen and CRP--in subjects receiving vitamin preparations. There were significant correlations between sVCAM-1 concentration and the levels of sICAM-1 (r = 0.341; p = 0.029) and PAI-1 (r = 0.347; p = 0.026), as well as with urine iodine concentration (r = 0.448; p = 0.004). IL-6 concentration correlated with vWF (r = 0.456; p = 0.003), TPO Ab (r = 0.328; p = 0.036) and PAI-1 level (r = 0.319; p = 0.042). CONCLUSION: Iodine induced thyrotoxicosis is associated with an increase of sVCAM-1 and IL-6 levels, possibly reflecting inflammatory and destructive processes in the thyroid gland. However, increased procoagulant activity was not found in patients with IIT.  相似文献   

6.
C-reactive protein (CRP) has been suggested to exert direct adverse effects on the vasculature in experimental setups, including endothelial dysfunction and proinflammatory changes. Here, we assessed the consequences of 1.25 mg/kg highly purified recombinant human CRP, administered as an intravenous bolus, in six patients with familial hypercholesterolemia (FH) and six normocholesterolemic subjects. Endothelium-dependent and -independent vasoreactivity to serotonin and nitroprusside, respectively, were assessed using venous occlusion plethysmography before and after CRP infusion. For biochemical analyses, blood was drawn at different time points. At baseline, FH patients showed blunted endothelium-dependent vasodilation (maximum, 89.2 +/- 30.0% vs. 117.7 +/- 13.1% in normolipidemic subjects; P = 0.037). Procoagulant activity was also higher in FH patients, illustrated by increased prothrombin fragment 1+2 (F(1+2)) levels (P = 0.030) and plasminogen activator inhibitor type-1 (PAI-1) activity (P = 0.016). Upon CRP challenge, endothelium-dependent vasodilator capacity further deteriorated in FH patients (P = 0.029), whereas no change in vascular reactivity was observed in normolipidemic subjects. Additionally, coagulation activation was augmented in FH patients compared with normolipidemic subjects (P = 0.009 for F(1+2) levels; P = 0.018 and P = 0.003 for PAI-1 antigen and activity, respectively). No difference in inflammatory responses was observed between groups. In hypercholesterolemic patients, CRP aggravates endothelial dysfunction and also evokes augmented procoagulant responses. These findings suggest that particularly in hypercholesterolemia, CRP-lowering strategies should be considered in addition to LDL reduction.  相似文献   

7.
In patients with excessive venous thrombosis, genetic defects predisposing to thrombosis can be found in 60-80%. Increased plasma levels of coagulation proteins such as fibrinogen and plasminogen activator inhibitor-1 (PAI-1) are associated with an increased risk of myocardial infarction. However, despite the presence of polymorphisms that regulate plasma levels of factor VIII, PAI-1, and fibrinogen the association between common polymorphisms of these coagulation protein and ischemic cardiac disease remains ambiguous. Up to 10% of the population have defects that predispose them to excessive venous thrombosis. In spite of the essential role of thrombosis in coronary ischemic syndrome, no convincing evidence has implicated the two most common venous hypercoagulable states in ischemic heart disease. Pathogenic polymorphisms in the platelet fibrinogen and collagen receptors remains an area of intense research interest. Finally, it has been shown that lipoproteins can act as mediators of coagulation processes.  相似文献   

8.
Increased concentrations of plasma fibrinogen, an independent risk factor for cardiovascular disease (CVD), in obese children have been reported. The underlying mechanism for this, however, remains to be defined. In the current study, we measured the fractional synthesis rates (FSR) of plasma fibrinogen in six healthy postpubertal obese girls [body mass index (BMI) 36.6 +/- 1.8 kg/m(2); age 16.6 +/- 0.5 yr] and six age-matched lean normal control girls (BMI 20.8 +/- 0.7 kg/m(2); age 16.4 +/- 0.4 yr) during a primed, continuous infusion of L-[1-(13)C]leucine in the postabsorptive state. The method involved purification of plasma fibrinogen by use of immunoaffinity chromatography followed by measurement of [(13)C]leucine enrichment using gas chromatography-combustion-isotope ratio mass spectrometry. The FSR of fibrinogen in obese girls (35.06 +/- 2.61%/day) was almost double that in lean girls (17.02 +/- 1.43%/day), and this increase was associated with a relative increase in plasma concentration of fibrinogen as well as BMI in the subjects studied. Obese subjects had high fasting insulin levels (138 +/- 47 pmol/l) compared with lean subjects (54 +/- 11 pmol/l), whereas their glucose concentrations were similar (4.5 +/- 0.3 mmol/l in obese and 4.4 +/- 0.4 mmol/l in lean subjects), suggesting insulin resistance. The doubling of the FSR of fibrinogen provides novel insight into the mechanism of elevated levels of plasma fibrinogen and suggests a primary role for increased synthesis in producing the hyperfibrinogenemia associated with obesity. This finding may have important implications in the design of therapies for modulating plasma fibrinogen levels in obesity and/or CVD in childhood.  相似文献   

9.
BACKGROUND: Inflammatory processes have importance in atherosclerosis. We evaluated if subjects below 55 years of age with occlusive carotid artery disease have higher serum levels of antibodies against oxidized LDL and endothelial cells and the chemokines MCP-1 and RANTES than age matched subjects without atherosclerosis. METHODS AND RESULTS: Sixty patients with occlusive carotid artery disease (stenosis or occlusion) and 30 age-matched controls participated in the study. We measured the degree of carotid artery stenosis and intima-media thickness (IMT) by duplex ultrasound. White blood cell count (WBC), C-reactive protein (CRP), and fibrinogen levels were significantly higher in patients (means+/-SD: 7.5+/-1.8 vs. 6.1+/-1.1 G/L, p<0.001; 7.7+/-20.7 vs. 2.5+/-1.9 mg/L, p=0.015; and 3.7+/-0.9 vs. 3.1+/-0.5 g/L, p<0.001, respectively). Antibody levels against oxidized LDL and endothelial cells (21.1+/-22.9 and 19.9+/-15.3 EU/mL, p=0.6; and 19+/-15 vs. 20+/-9 U/mL, p=0.07) and RANTES and MCP-1 levels (72.4+/-32.3 vs. 73.8+/-27.3 ng/mL, p=0.7; and 468+/-1041 vs. 318+/-131 pg/mL, p=0.7) did not differ significantly between patients and controls and did not correlate with IMT. CONCLUSIONS: Higher levels of WBC, CRP, and fibrinogen suggest an ongoing inflammation in early-onset carotid atherosclerosis, but increased IMT is not associated by the elevation of serum levels of chemokines and antibodies evaluated in this study.  相似文献   

10.
The alveolar fibrinolytic system is altered in acute lung injury (ALI). Levels of the fibrinolytic protease inhibitor, plasminogen activator inhibitor-1 (PAI-1), are too low in bronchoalveolar lavage to address its prognostic significance. This study was performed to assess whether PAI-1 antigen in undiluted pulmonary edema fluid levels can identify patients with ALI and predict their outcome. PAI-1 antigen levels in both plasma and edema fluid were higher in ALI compared with hydrostatic edema, and edema fluid PAI-1 values identified those with ALI with high sensitivity and specificity. Both the high plasma and edema fluid PAI-1 antigen values were associated with a higher mortality rate and fewer days of unassisted ventilation in patients with ALI. Differences in PAI-1 activity were concordant with levels of PAI-1 antigen. Although the fibrin-derived alveolar D-dimer levels were strikingly similar in both groups, ALI patients had a higher relative proportion of D-monomer. In conclusion, PAI-1 levels in edema fluid and plasma identify those with ALI that have a poor prognosis. The data indicate that fibrin turnover in early ALI is a consequence of a rapid fibrinogen influx and fractional fibrinolytic inhibition.  相似文献   

11.
The effects of recombinant tissue-type plasminogen activator (rt-PA) and of an inactive mutant of rt-PA, obtained by mutagenesis of the active site Ser478 to Ala (rt-PA-Ala478), on the synthesis and secretion of plasminogen activator inhibitor-1 (PAI-1) by human umbilical vein endothelial cells (HUVEC) in culture were studied. Under base-line conditions, PAI-1 antigen secretion was 4.3 +/- 1.0 micrograms (mean +/- S.D., n = 8) per 10(6) cells in 24 h. This PAI-1 had a low specific activity (6,000 +/- 1,600 units/mg) and Mr of 50,000, which was not altered by addition of rt-PA. In HUVEC cultured with 2 micrograms/ml rt-PA-Ala478, PAI-1 antigen secretion was 2.1 +/- 0.8 micrograms (n = 5) per 10(6) cells in 24 h with a specific activity of 120,000 +/- 42,000 units/mg and Mr of 50,000. Addition of rt-PA to this conditioned medium resulted in generation of three main components: 16% migrated as an Mr 106,000 rt-PA.PAI-1 complex, 16% as an Mr 81,000 degraded rt-PA.PAI-1 complex and the remainder as an Mr 45,000 degradation product of PAI-1. HUVEC cultured with 2 micrograms/ml rt-PA secreted 3.9 +/- 0.6 micrograms (n = 8) PAI-1 antigen per 10(6) cells within 24 h, of which 20-50% occurred as intact or degraded complexes with t-PA (Mr 106,000 and 81,000) and the rest as an inactive Mr 45,000 degradation product of PAI-1. PAI-1 mRNA levels, determined by Northern blot analysis and expressed relative to beta-actin mRNA levels, were very similar for HUVEC cultured in the absence or the presence of rt-PA or rt-PA-Ala478. It is concluded that PAI-1 is secreted by HUVEC in culture in fully active form which spontaneously inactivates. PAI-1 can be stabilized by addition of rt-PA-Ala478 to the culture medium, resulting in a 20-fold increase in specific activity. Interaction of rt-PA with active PAI-1 produces both t-PA.PAI-1 complex and an inactive degradation product of PAI-1.  相似文献   

12.
A path model and associated statistical method for the analysis of data on twin families are introduced and applied to high density lipoprotein cholesterol (HDL-c) observations in the Swedish Twin Family Study. The proposed path model incorporates both genetic and environmental sources of familial resemblance, maternal environmental effects, intergenerational differences in heritabilities, marital resemblance due to either primary or secondary phenotypic homogamy, and twin residual environmental correlations. Application of the model to HDL-c levels resulted in parameter estimates consistent with those reported in earlier reviews and in the analysis of nuclear family and twin data. Genetic heritability was estimated as h2 = .363 +/- .243, cultural heritability as c2 = .187 +/- .082, and the proportion of phenotypic variance due to residual environmental effects as r2 = .450 +/- .207. Although the parameter estimates were comparable, the statistical tests of hypotheses were, relative to other designs, of low statistical power. It appears that environmental indices are necessary for powerful tests of hypotheses.  相似文献   

13.
High plasma levels of fibrinogen and plasminogen activator inhibitor (PAI-1) are reported to be correlated with coronary heart disease. Therefore the level of fibrinogen concentration in plasma was examined and verified for the possible correlation with the previously explored PAI-1 antigen and PAI-1 activity in the pathogenesis of premature atherosclerosis (Grzywacz et al., 1998, Blood Coagul Fibrinol. 9, 245-249). Examination included only men, aged 33-46 years, who were in a stable condition for at least six months after the acute event. They were divided into two subgroups: group A (n = 14) with and group B (n = 15) without ischaemic changes in 24 h Holter electrocardiogram. The number of involved vessels visible on the coronarography picture was similar in both groups. In the patients of group A the mean level of fibrinogen (3.92 vs 3.23 g/l, P < 0.05) was higher than in the controls (n = 15). No statistically differences were found between group B and control healthy subjects in any of the parameters measured. There were no correlation between fibrinogen concentration and PAI-1 antigen and activity levels, which were elevated in both groups of patients according to our previous study. Our results indicate that elevated levels of plasma fibrinogen and PAI-1 appeared in the group of patients with more severe disease, as revealed by silent myocardial ischaemia.  相似文献   

14.
We investigated whether markers of inflammation, including a cytokine (IL-6), acute-phase reactants [C-reactive protein (CRP) and fibrinogen], and white blood cell (WBC) count are associated with maximal O(2) consumption (Vo(2 max)) in men without coronary heart disease (CHD). In asymptomatic men (n = 172, 51 +/- 9.3 yr old), Vo(2 max) was measured during a symptom-limited graded treadmill exercise test. Physical activity level was assessed by a standardized questionnaire. IL-6 and CRP were measured by immunoassays, fibrinogen by the Clauss method, and WBC count with a Coulter counter. IL-6 and CRP were logarithmically transformed to reduce skewness. Multivariable regression was used to assess whether markers of inflammation were associated with Vo(2 max) after adjustment for age, body mass index, CHD risk factors, and lifestyle variables (physical activity level, percent body fat, and alcohol intake). Vo(2 max) was 34.5 ml.kg(-1).min(-1) (SD 6.1). Log IL-6 (r = -0.38, P < 0.001), log CRP (r = -0.40, P < 0.001), fibrinogen (r = -0.42, P < 0.001), and WBC count (r = -0.22, P = 0.004) were each correlated with Vo(2 max). In separate multivariable linear regression models that adjusted for age, body mass index, CHD risk factors, and lifestyle variables, log IL-6 [beta-coeff = -1.66 +/- 0.63 (SE), P = 0.010], log CRP [beta-coeff = -0.99 +/- 0.33 (SE), P = 0.003], fibrinogen [beta-coeff = -1.51 +/- 0.44 (SE), P = 0.001], and WBC count [beta-coeff = -0.52 +/- 0.30 (SE), P = 0.088] were each inversely associated with Vo(2 max). In conclusion, higher circulating levels of IL-6, CRP, and fibrinogen are independently associated with lower Vo(2 max) in asymptomatic men.  相似文献   

15.
The aim of our study is to determine whether there is a relationship between familial Mediterranean fever (FMF) attacks and serum leptin levels. We enrolled 25 patients (22 males and 3 females) and 25 healthy controls (21 males and 4 females) with a mean age of 24.42 +/- 1.22 (Mean +/- SEM) years and 24.30 +/- 1.19 years (Mean +/- SEM), respectively. We investigated serum levels of leptin, interleukin-6 (IL-6) erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),fibrinogen, and leukocyte counts before the attack and 8-12 hours after the attack started. The same parameters have been investigated in the control subjects. The mean serum leptin levels before the attacks were 6.45 +/- 1.05 (Mean +/- SEM) and during the attacks were 7.59 +/- 1.3 (Mean +/- SEM) in FMF group,respectively. There was a slight increase in serum leptin levels during the attacks but it was not statistically significant (P > .05). The mean serum leptin levels were 16.12 +/- 2.81 in the control group which were not different from the mean serum leptin levels before and during the attack periods in the study group (P > .05). However, there were statistical differences in the serum levels of IL-6, ESR, CRP, fibrinogen, and leukocyte counts before and during the attack periods (P > .05). No correlation was found between serum leptin levels and IL-6, ESR, CRP, fibrinogen, and leukocyte counts (P > .05). Serum leptin levels do not increase during FMF attacks and therefore it is not useful for diagnostic purposes and follow-up during treatment.  相似文献   

16.
C-reactive protein levels are influenced by common IL-1 gene variations   总被引:15,自引:0,他引:15  
Elevated markers of systemic inflammation are associated with the development of acute coronary syndromes, but there is no current explanation for increased inflammation in overtly healthy individuals. The influence of genetic control of the inflammatory response on the observed variability is unknown. We studied the frequency of four polymorphisms in interleukin (IL) 1 genes, known to modulate inflammation, in 454 individuals undergoing coronary angiography and analysed their influence on plasma C-reactive protein (CRP) and fibrinogen levels. Females and smokers had higher levels of CRP than males (Pi = 0.001) and non-smokers (Pi = 0.001). Patients with genotype 2.2 for the IL-1B(+3954) polymorphism had twice the median CRP levels of patients who were genotype 1.1 (4.33 vs 2.01 mg/l; P = 0.001). Patients with genotype 1.2 or 2.2 at the IL-1A(+4845) polymorphism also had higher median CRP (2.92 vs 2.05 mg/l, Pi = 0.023). In multivariate analyses, CRP levels remained significantly associated with IL-1 polymorphisms after adjustment for smoking, gender and age. Fibrinogen levels had similar associations with the IL-1 genotypes. These data indicate that IL-1 gene polymorphisms known to affect the inflammatory response are highly related to plasma levels of CRP and fibrinogen in patients referred for coronary angiography.  相似文献   

17.
ABSTRACT: BACKGROUND: No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. METHODS: Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (+/- standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level [greater than or equal to]180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured. RESULTS: The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 +/- 35.5 vs. 153.2 +/- 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 +/- 33.5 vs. 129.4 +/- 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 +/- 40.2 vs. 223.2 +/- 43.5 mg/dL; p = 0.015), the AUC ([greater than or equal to]180 mg/dL) within 3 hours was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 +/- 41.6 vs. 85.2 +/- 39.9 mug/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. CONCLUSIONS: CGM showed that mean 24-hour blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. Trial registration UMIN000007687 KEYWORDS: Vildagliptin; Sitagliptin; Continuous glucose monitoring (CGM); Brain natriuretic peptide (BNP); plasminogen activator inhibitor-1 (PAI-1).  相似文献   

18.
The aim of this study is to test several biomarkers of inflammation, of endothelial dysfunction, glycated haemoglobin, and their reflection in arterial dilatation, in patients with type 2 diabetes mellitus and in their relatives, in order to demonstrate if relatives present markers as a form of precocious indicators of diabetes mellitus. Individuals between 30 and 55 years of age and without clinical arterial disease were divided in three groups: type 2 diabetes mellitus patients without complications (12 men and 18 women); first degree relatives of type 2 diabetes mellitus (14 men and 20 women); and control individuals (9 men and 16 women). Body composition was measured with a bioelectrical impedance analyzer and endothelial function with an eco-Doppler device. We determined glucose, insulin, C-peptide, glycated haemoglobin, fibrinogen, E-selectin, P-selectin, soluble intercellular cell adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) in plasma. We also studied endothelium independent dilatation and endothelium dependent dilatation. The results: ICAM-1 and VCAM-1 were significantly higher in the diabetic group (237.5+/-43.4 and 692.5+/-168.6 ng/l) than in controls (197.4+/-51.2 and 573.5+/-121.1 ng/l, p=0.011 and 0.013, respectively), but were not higher in the family group (224.5+/-45.2 and 599.8+/-150.4 ng/l). CRP was higher in the diabetic group (3.35+/-3.27 mg/l) than in the other groups (1.28+/-1.29 and 1.61+/-1.54 mg/l, p=0.002) and correlated with glycated haemoglobin. The non-endothelium mediated dilatation was lesser in the diabetic group than in the family group (17.3+/-6.1 vs. 24+/-8, p=0.029) and controls. In conclusion patients with uncomplicated type 2 diabetes, but not their relatives, have biochemical markers of sub-clinical inflammation in relationship with glycated haemoglobin and dysfunction of the endothelial cells markers. In these patients endothelium independent dilatation is more affected than endothelium dependent dilatation.  相似文献   

19.
20.
Classical quantitative genetic analyses estimate additive and non-additive genetic and environmental components of variance from phenotypes of related individuals without knowing the identities of quantitative trait loci (QTLs). Many studies have found a large proportion of quantitative trait variation can be attributed to the additive genetic variance (VA), providing the basis for claims that non-additive gene actions are unimportant. In this study, we show that arbitrarily defined parameterizations of genetic effects seemingly consistent with non-additive gene actions can also capture the majority of genetic variation. This reveals a logical flaw in using the relative magnitudes of variance components to indicate the relative importance of additive and non-additive gene actions. We discuss the implications and propose that variance component analyses should not be used to infer the genetic architecture of quantitative traits.  相似文献   

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