Barbara Góralczyk

Triglycerides as an early pathophysiological marker of endothelial dysfunction in nondiabetic women with a previous history of gestational diabetes.

Abstract  Objective. To investigate whether baseline triglyceride levels are associated with early glucose dysregulation and/or cardiovascular risk in women with a previous history of gestational diabetes. Design. Prospective postpregnancy cohort study. Setting. Polish university hospitals. Sample. Participants included 125 women with previous gestational diabetes and 40 women with normal glucose regulation during pregnancy. Methods. All women were studied 2–24months (mean 12±10months) after the index pregnancy. Women with previous gestational diabetes were divided into tertiles in accordance with baseline triglyceride levels. Main Outcome Measures. We assessed glucose regulation (oral glucose tolerance test), insulin resistance (homeostasis model assessment), markers of endothelial dysfunction (soluble: intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, E‐selectin, tissue plasminogen activator antigen, von Willebrand factor antigen), fibrinolysis (plasminogen activator inhibitor antigen), inflammation (high‐sensitivity C‐reactive protein) and lipid levels. Results. Women with previous gestational diabetes (78% normal glucose regulation, 22% impaired glucose tolerance) had a high cardiometabolic risk profile compared with control women (100% normal glucose regulation). Baseline triglycerides >0.83mmol/l were associated with a higher prevalence of impaired glucose tolerance, higher high‐sensitivity C‐reactive protein and triglyceride/high‐density lipoprotein‐cholesterol ratio. Triglycerides >1.22mmol/l were associated with higher body fat indexes, higher insulin resistance, higher levels of endothelial dysfunction biomarkers, higher plasminogen activator inhibitor antigen and dyslipidemia. Only E‐selectin was independently associated with triglyceride levels. Conclusions. Baseline triglyceride levels are a cardiovascular risk marker as well as a pathophysiological parameter independently associated with endothelial dysfunction in nondiabetic women with previous gestational diabetes at 2–24months after an index pregnancy. Normalization of triglycerides should be included in preventive therapy after a pregnancy complicated by gestational diabetes.

A preliminary evaluation of VEGF-A, VEGFR1 and VEGFR2 in patients with well-controlled type 2 diabetes mellitus

Objective: Decompensated chronic hyperglycemia often leads to late microvascular complications such as retinopathy, diabetic foot syndrome, and diabetic kidney disease. The aim of this study was to determine the concentration of vascular endothelial growth factor A (VEGF-A) and its receptors in patients with well-controlled diabetes. Methods: The study was conducted on 31 patients with well-controlled type 2 diabetes without micro-or macroangiopathy. Thirty healthy volunteers were enrolled in a control group. Serum concentrations of VEGF-A, VEGF receptors 1 and 2 (VEGFR1 and VEGFR2), fasting glucose, and lipid profiles were measured, and the plasma concentration of glycated hemoglobin (HbA1c) was determined. Results: No significant differences were observed between the concentration of VEGF-A, VEGFR1 or VEGFR2 in the subject group and that in the control group. Positive correlations were noted between the levels of VEGF-A, VEGFR2, and triglyceride, and there was a negative correlation between the levels of VEGFR2 and high-density lipoprotein (HDL)-cholesterol in the study group. Conclusions: The concentrations of VEGF-A and its receptors 1 and 2 in patients with well-controlled diabetes are comparable to those of healthy individuals, which may indicate that appropriate control of glucose levels delays the occurrence of vascular complications. A negative correlation between VEGFR2 and HDL-cholesterol levels, and positive correlations between VEGF-A, VEGFR2, and triglyceride levels, suggest that lipid abnormalities occurring in diabetes may be involved in the modulation of angiogenesis.

Elevation of sE-Selectin Levels 2–24 Months following Gestational Diabetes Is Associated with Early Cardiometabolic Risk in Nondiabetic Women

Objective. We hypothesised that the endothelial dysfunction is associated with early glucose dysregulation and/or atherosclerosis risk factors in nondiabetic women with a previous history of gestational diabetes (pGDM). Material/Methods. Anthropometric parameters, glucose regulation (OGTT), insulin resistance (HOMA), lipids, biomarkers of endothelial dysfunction, and inflammation were evaluated in 85 women with pGDM and in 40 controls 2–24 months postpartum. Results. The pGDM group consisted of 67% normoglycemic women (pGDM-N) and 33% with prediabetic state (pGDM-P). The BMI, waist circumference, fasting and 2 h glucose (OGTT), soluble adhesion molecules, tissue plasminogen activator antigen, high sensitivity C-reactive protein, total-, LDL-cholesterol, and triglycerides/HDL-cholesterol ratio were higher in the pGDM women compared with the controls. After adjustment for BMI and fasting glucose, only higher triglycerides, higher TG/HDL and lower HDL-cholesterol were associated with pGDM. The pGDM-P differed from pGDM-N for only higher triglycerides and TG/HDL. The plasma level of sE-selectin was not independently associated with glucose concentration in pGDM group. sE-selectin level correlated with triglycerides, TG/HDL, plasminogen activator inhibitor-1 antigen, and sICAM-1. Conclusions. sE-selectin level correlated with components of metabolic syndrome, but only the atherogenic lipid profile was independently associated with a previous history of GDM in nondiabetic women 2–24 months postpartum.

Risk of venous thromboembolic disease in postmenopausal women taking oral or transdermal hormone replacement therapy.

ObjectiveThe influence of hormone replacement therapy (HRT) on hemostasis processes depends on the type of hormone, the combination of doses, the time of taking HRT, and the route of administration (oral, transdermal, implanted). The aim of the current study was to assess some parameters of coagulation, especially tissue factor pathway inhibitor (TFPI) and tissue factor (TF) in postmenopausal women using oral or transdermal HRT.MethodsThe study was conducted on 76 healthy women, including 46 women aged 44–58 years who were taking oral (26) or transdermal (20) HRT, and 30 women aged 44–54 years who did not take HRT as the control group. Plasma concentrations of TF, TFPI, thrombin-antithrombin complex (TAT), and D-dimer were performed by enzyme-linked immunosorbent assay (ELISA). Moreover, the concentration of fibrinogen and activity of protein C were measured by chromogenic and chronometric methods.ResultsWe observed a significantly higher concentration of TF and a significantly lower concentration of TFPI in women taking oral and transdermal HRT in comparison with the control group. We also found a significantly lower concentration of fibrinogen in women taking oral HRT vs. the control group. Moreover, no statistically significant changes in concentrations of TAT and D-dimer, or activity of protein C were noted.ConclusionsIn this study, the occurrence of an increased TF concentration simultaneously with a decreased concentration of TFPI in women taking HRT indicates hypercoagulability. No significant modification of TAT or D-dimer occurred, and thus there may not be increased risk of thrombosis.

Orexin in Patients with Alcohol Dependence Treated for Relapse Prevention: A Pilot Study

AIM The aim of the study was to assess the blood concentration of orexin and its association with other clinical factors in patients with alcohol dependence. METHODS Thirty-two males hospitalized on an addiction treatment ward due to alcohol dependence and 23 healthy men as a control group were enrolled in the study. The measurement of orexin in the blood was made at the beginning of the treatment (after withdrawal symptoms had stopped) and again after 4 weeks of observation. RESULTS At the beginning of the observation, the alcohol-dependent patients had significantly greater orexin blood concentration than the control group. After 4 weeks of treatment for relapse prevention, the blood orexin level decreased significantly to a value similar to that in the control group. At the beginning of the study, more severely alcohol-dependent patients (Short Alcohol Dependence Data [SADD] score range: 20-45) had significantly greater orexin blood concentration than individuals with moderate addiction severity (SADD score range: 10-19). However, after 4 weeks of abstinence, the peptide blood concentration was similar in both groups of alcoholic patients. CONCLUSIONS Orexin or its receptor is a potential target for relapse prevention treatment, but further study with long-term observation is needed to verify the usefulness of blood orexin determination as a marker of alcohol relapse risk.

Effect of uncontrolled hyperglycemia on levels of adhesion molecules in patients with diabetes mellitus type 2.

ObjectiveUncontrolled diabetes has become a major cause of mortality and morbidity by reason of vascular angiopathy. The aim of this study was to evaluate the concentrations of soluble forms of vascular adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E-selectin, and thrombomodulin in patients with well-controlled and uncontrolled diabetes type 2.MethodsThe study was conducted on 62 patients with diabetes. Group I consisted of 35 patients with well-controlled diabetes. The second group included 27 patients with uncontrolled diabetes with micro-albuminuria. A control group was made up of 25 healthy volunteers. The concentrations of sVCAM-1, sICAM-1, sE-selectin, and soluble thrombomodulin were assayed in plasma. Serum concentration of creatinine was measured and the plasma concentrations of fasting glucose and glycated hemoglobin (HbA1c) determined.ResultsLower concentrations of ICAM-1 were found in the group of uncontrolled diabetes patients compared with those with well-controlled disease. In patients with uncontrolled diabetes, VCAM-1 levels were significantly higher compared with the group with well-controlled diabetes. In patients with uncontrolled diabetes a positive correlation was obtained between glomerular filtration rate and sE-selectin and a negative correlation between the levels of creatinine and ICAM-1, although there was a positive correlation between (HbA1c) and ICAM-1.ConclusionThe study confirmed the participation of the inflammatory process associated with impaired vascular endothelial function in the pathogenesis of type 2 diabetes. The opposite effect of uncontrolled hyperglycemia on adhesion molecules suggests different functions of VCAM-1 and ICAM-1 in complications of diabetes.概要目的评估可溶性血管细胞间黏附分子 (sVCAM-1)、可溶性细胞间黏附分子 (sICAM-1)、可溶性选择素E 和可溶性血栓调节蛋白在血糖控制良好和不受控制的2 型糖尿病患者中的水平。创新点对2 型糖尿病患者的血管内皮炎症标记物进行评估。方法62 例糖尿病患者分成两组: 第一组包括35 个血糖控制良好的糖尿病患者, 第二组包括27 个未控制血糖并伴有微蛋白尿的糖尿病患者。对照组由25 名健康志愿者组成。测定血浆中sVCAM-1、sICAM-1、可溶性选择素E 和可溶性血栓调节蛋白的浓度, 同时测定血清肌酐及血浆中空腹血糖和糖化血红蛋白 (HbA1c) 的浓度。结论与血糖控制良好的糖尿病组相比, 未控制血糖组具有相对低的ICAM-1 水平和更高的VCAM-1 水平。未控制血糖组中患者的糖化血红蛋白和ICAM-1 之间呈正相关, 肾小球滤过率和可溶性选择素E 之间呈正相关, 而肌酐和ICAM-1 之间呈负相关。研究证实2 型糖尿病的发病机理中炎症过程的出现与血管内皮功能受损有关。未受控制的高血糖对粘附分子的反向作用表明, 在糖尿病的并发症中VCAM-1和ICAM-1具有不同功能。

Circulating endothelial progenitor cells and angiogenic factors in diabetes complicated diabetic foot and without foot complications

INTRODUCTION Data about angiogenic factors in diabetic foot syndrome (DFS) are insufficient. Therefore, in the present study we focus on circulating endothelial progenitor cells (EPCs) and two major angiogenic factors: vascular endothelial growth factor (VEGF-A) and fibroblast growth factor (FGF-2) in patients with DFS. MATERIALS AND METHODS We included 75 subjects: 45 patients with type 2 diabetes and 30 controls. The study group was divided into 2 subgroups: 23 patients with diabetic foot and 22 patients without diabetic complications. The concentration of VEGF-A, soluble VEGF receptor 2 (sVEGF-R2) and FGF-2 were measured in plasma samples. The number of circulating EPCs was determined in peripheral venous blood. The number of endothelial progenitor cells was measured with FACSCalibur flow cytometer using monoclonal antibodies directed against antigens specific for EPCs. RESULTS In our study we observed significant higher levels of VEGF-A and FGF-2 and lower sVEGF-R2 concentration in patients with T2DM compared to healthy subjects. The conducted analysis showed decreased levels of VEGF-A and elevated levels of FGF-2 in patients with DM complicated DFS compared to diabetic patients without DFS. Increased circulating EPCs number was reported in patients with DFS, and the difference was almost statistically significant. CONCLUSIONS The high concentration of VEGF-A and FGF-2, and a positive correlation between them indicate their participation in the process of angiogenesis in T2DM. Decreased sVEGF-R2 may result from inactivation of VEGF-A during complexes formation.

CRP, but not TNF-α or IL-6, decreases after weight loss in patients with morbid obesity exposed to intensive weight reduction and balneological treatment.

ObjectiveThe aim of this study was to evaluate the concentrations of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the degree of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with morbid obesity exposed to a three-week low-calorie diet and balneotherapy.MethodsThe study included 33 patients (25 females and 8 males; mean age 46 years) with body mass index (BMI) values of >40 kg/m2. Evaluations of CRP, IL-6, TNF-α, lipid profile, HOMA-IR, and fasting glucose were carried out before (baseline data) and three weeks after the treatment. The control group consisted of 20 healthy volunteers (15 females and 5 males) with a mean age of 39 years and BMI values of ≤24.9 kg/m2.ResultsIn the blood of patients with morbid obesity we found significantly elevated levels of CRP, TNF-α, triglycerides, HOMA-IR and fasting glucose, but a decreased level of high density lipoprotein (HDL)-cholesterol, compared with the healthy individuals. The treatment resulted in about a 9.4% reduction in body weight from 122.5 to 111.0 kg and a significant decrease in the concentration of CRP, but no change in TNF-α or IL-6. HOMA-IR was significantly reduced.ConclusionThe decrease in CRP level without changes in TNF-α or IL-6 concentrations after the low-calorie diet and balneological treatment, suggests that an essential amount of adipose tissue must be removed before proper adipocyte function is restored. The decrease in HOMA-IR indicates an improvement in insulin sensitivity, which is beneficial in obese patients.概要目的评估病态肥胖患者在低热量饮食和浸浴治疗前后, C 反应蛋白 (CRP)、肿瘤坏死因子α (TNF-α)、白细胞介素-6 ( IL-6) 以及胰岛素抵抗指数 (HOMA-IR) 的水平变化。创新点研究炎症反应对病态肥胖的影响。方法本研究包括33 个病例和20 个正常对照, 对治疗前后的CRP、IL-6、TNF-α、血脂谱、HOMA-IR以及空腹血糖水平进行评估。结论与对照组相比, 低热量饮食和浸浴治疗后, 病态肥胖患者的CRP水平显著降低, 而TNF-α 和IL-6的水平却没有显著变化, 这表明脂肪细胞的正常功能恢复之前必须先去除一定量的脂肪组织。HOMA-IR 水平的降低说明对胰岛素的敏感性有所提高, 这有利于肥胖患者的治疗。

Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy

ObjectiveIn postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT).MethodsThe study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-1:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA).ResultsWe observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT.ConclusionsThe study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag, which in turn, can lead to a reduction in fibrinolytic activity.

VEGF-A and PDGF-BB--angiogenic factors and the stage of diabetic foot syndrome advancement.

INTRODUCTION In patients with diabetic foot syndrome (DFS), an inadequate angiogenic response is observed. The aim of this study was to evaluate the concentrations of VEGF-A, PDGF-BB, sVEGF-R2 and sVEGF-R1 in patients with diabetes-complicated diabetic foot syndrome and analyse them using selected clinical data. MATERIAL AND METHODS Forty seven diabetic patients, 25 women mean age 63 and 20 men mean age 60.5, with diabetic foot syndrome (DFS) were enrolled in the experimental group. To evaluate angiogenesis factors depending on Wagner grade, the subjects were divided into three subgroups: I - patients with 0 Wagner grade (n = 14); II - patients with 1,2,3 Wagner grades (n = 15); and III - patients with 4,5 Wagner grades (n = 18). The control group consisted of 20 healthy volunteers. The material for research was blood. RESULTS Significantly higher levels of VEGF-A and PDGF-BB in the DFS cases compared to controls were observed (VEGF-A p = 0.000001; PDGF-BB p = 0.000051). Analysis of angiogenic parameters according to the stage of diabetic foot syndrome advancement showed higher VEGF-A level (I: p = 0.000867; II: p = 0.001827; III: p = 0.000024) and PDGF-BB (respectively p = 0.004113, p = 0.004224, p = 0.002480) in all the subgroups. Decreased sVEGF-R2 concentrations were observed in the I (p = 0.054) subgroup and the III (p = 0.03524) subgroup. In this study, a strong positive correlation between VEGF-A and PDGF-BB was observed (R = 0.66; p = 0.000001). CONCLUSIONS Our study revealed that proangiogenic factor levels were increased in DFS. This is associated with lower limb ischaemia and hypoxic conditions. The stage of diabetic foot syndrome advancement influenced VEGF-A and PDGF-BB concentrations.