Non-altered incretin secretion in women with impaired fasting plasma glucose in the early stage of pregnancy: a case control study.

BACKGROUNDS: Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) may be involved in pathogenesis of gestational diabetes mellitus (GDM). The aim was to compare GLP-1 and GIP production in fasting state and during 3 h mixed meal tolerance test (MMTT) measured by mean area under the curve (AUC) between pregnant women with normal and impaired fasting glucose in an early phase of pregnancy, and healthy non-pregnant controls. METHODS: This study was undertaken as a case-control study. Repeated measurement of fasting plasma glucose ≥ 5.1 mmol/L and < 7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes according to IADSPG criteria was used to find women with impaired fasting glucose (n = 22). Age-matched controls consisted of healthy pregnant (n = 25) and non-pregnant (n = 24) women. In addition to incretins, anthropometric parameters and markers of insulin resistance and beta-cell function were assessed. Variables were summarized as median (interquartile range). RESULTS: Fasting GLP-1 and GIP concentration or their AUC during MMTT did not significantly differ between pregnant women with impaired fasting plasma glucose [GLP-1AUC 19.0 (53.1) and GIPAUC 302 (100) pg/mL/min] and healthy pregnant women [GLP-1AUC 16.7 (22.3) and GIPAUC 297 (142) pg/mL/min] or non-pregnant controls [GLP-1AUC 16.8 (9.8) and for GIPAUC 313 (98) pg/mL/min]. Although women with impaired fasting glucose were more obese and showed decreased beta-cell function, there were not significant correlations between incretin production and parameters of insulin secretion, insulin resistance, or obesity. CONCLUSIONS: Women with impaired fasting plasma glucose did not show altered incretin production in the first trimester of pregnancy. In contrast to type 2 diabetes, impaired incretin secretion does not seem to play a major role in the early development of GDM.

[Pharmacokinetics and therapeutic monitoring of piperacillin/tazobactam].

Given their wide therapeutic index, beta-lactam antibiotics are commonly used to treat critically ill patients. It is in these patients that significant heterogeneity in pharmacokinetics was noted, compared to the population average, especially in the volume of distribution, drug clearance and biological half-life, with values increasing as much as two-fold or, in the case of biological half-life, as much as four-fold. Significant pharmacokinetic changes also occur in cases of morbid obesity or renal insufficiency and when complex surgical techniques such as extracorporeal circulation are used. Therapeutic monitoring of piperacillin/tazobactam is a way to personalize and optimize therapy for these groups of patients. Preclinical data show a correlation between the probability of therapeutic success and concentrations of the unbound fraction of an antibiotic exceeding the minimum inhibitory concentration (MIC) for 40-50 % of the dosing interval. This time appears to be the preferred pharmacodynamic target for beta-lactam antibiotics. In critically ill patients, however, an even higher target may be required, ideally 100 % fT > 4xMIC. A better pharmacodynamic profile can be obtained using prolonged or continuous infusion. The biggest obstacle to routine TDM in ß-lactams is the speed of quality sample determination. Currently, the most widely used method of measuring plasma concentrations is liquid chromatography coupled with UV or MS detection.

Association of serum adipocyte fatty acid-binding protein and apolipoprotein B /apolipoprotein A1 ratio with intima media thickness of common carotid artery in dyslipidemic patients.

BACKGROUND: Diseases caused by atherosclerosis play the most important role in mortality and morbidity worldwide. Serum adipocyte fatty acid binding protein (A-FABP) seems to be a new promising marker to determine the risk of atherosclerosis. OBJECTIVE: The aim of this study was to evaluate relationships between serum A-FABP levels in studied individuals and to assess the possibility of modeling the intima media thickness of the common carotid artery (C-IMT) using A-FABP levels and other observed characteristics. METHODS: Seventy two Caucasian individuals were enrolled and divided into 3 groups: dyslipidemic patients with or without metabolic syndrome (MetS+, n=17; MetS-, n= 34) and controls (n=21). RESULTS: There was confirmed the well-established risk profile of individuals with MetS (unfavorable lipid and lipoprotein profile, as well as increased parameters of insulin resistence and C-IMT). A-FABP concentrations in this group were significantly higher in comparison with both MetS- and controls. CONCLUSION: Using multiple linear regression models of C-IMT values for all individual data, healthy controls and dyslipidemic patients without metabolic syndrome (MetS-) A-FABP levels were not revealed as an important predictor of C-IMT in our model. In contrast, age, gender, waist circumference, nonHDL cholesterol levels and ApoB/ApoA1 ratio were important repressors of C- IMT in study individuals. This finding may be attributed to the overwhelming effect of other more robust risk factors for atherosclerosis in these individuals.

Relationship of Selected Adipokines with Markers of Vascular Damage in Patients with Type 2 Diabetes.

BACKGROUND: In this study we compared levels of selected adipokines between patients with type 2 diabetes (T2D) and healthy individuals and we determined their relationship with early vascular damage markers. METHODS: Seventy-seven subjects: 56 patients with T2D (34 men and 22 women) and 21 healthy controls (8 men and 13 women) were examined in this cross-sectional study. Selected adipokines [adiponectin, adipocyte fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF-21), C1q/TNF-related protein 9 (CTRP-9), and allograft inflammatory factor-1 (AIF-1)] with possible cardiovascular impact were measured in all participants. To identify markers of vascular damage von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and arterial stiffness parameters were examined in all the subjects. RESULTS: When compared with healthy controls, T2D had significantly higher levels of A-FABP [50.0 (38.1-68.6) vs. 28.6 (23.6-32.9) ng/mL, P < 0.0001] and lower levels of adiponectin [5.9 (4.3-9.0) vs. 11.3 (8.7-14.8) µg/mL, P < 0.0001]. Differences in other adipokines were not statistically significant. Adiponectin level correlated negatively with vWF levels (ρ = -0.29, P < 0.05) and PAI-1 (ρ = -0.36, P < 0.05) and A-FABP positively with vWF (ρ = 0.61, P < 0.05) and PAI-1 (ρ = 0.47, P < 0.05) and augmentation index (ρ = 0.26, P < 0.05). Multivariate regression analysis showed independent association between A-FABP and vWF (b = 0.24, P < 0.05). CONCLUSIONS: Patients with T2D have significantly higher levels of A-FABP and lower levels of adiponectin. These adipokines correlate with indicators of vascular damage and could contribute to cardiovascular risk in patients with T2D. A-FABP may participate in direct endothelium damage.

Apolipoprotein B vs non-high-density lipoprotein cholesterol: Association with endothelial hemostatic markers and carotid intima-media thickness.

BACKGROUND: Both apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) are accepted as alternative risk factors or targets for lipid-lowering therapy, which correlate more strongly with cardiovascular events than low-density lipoprotein cholesterol. OBJECTIVE: The aim of this cross-sectional study was to evaluate the differences in plasma levels of plasminogen activator inhibitor-1 (PAI-1) and of von Willebrand factor (vWF) as endothelial hemostatic markers and carotid intima-media thickness (C-IMT) as a morphologic marker for atherosclerotic vascular disease among dyslipidemic individuals with apoB levels higher, estimated or lower based on regression equation of apoB vs non-HDL-C. METHODS: A total of 594 dyslipidemic subjects without atherosclerotic manifestation were divided into 3 groups (according to tertiles of apoB levels above, within, and below the line of identity): H-apoB (n = 200), E-apoB (n = 194), and L-apoB (n = 200). PAI-1, vWF, C-IMT and lipids, anthropometric parameters, markers of insulin resistance, and inflammation were measured. Differences in variables between groups were analyzed using analysis of variance. RESULTS: There was a strong association between apoB and non-HDL-C. The correlations of apoB and of non-HDL-C with markers of endothelial damage and C-IMT were very similar. Despite these facts, individuals with higher apoB levels had significantly higher levels of PAI-1 compared with individuals with estimated (P < .05) or lower apoB (P < .001). There were no significant differences in vWF, C-IMT, markers of insulin resistance, obesity, and inflammation. CONCLUSION: Individuals with apoB higher than predicted by non-HDL-C had significantly higher levels of PAI-1, which may contribute to the increased risk of future atherothrombotic events.

Troponin T in acute ischemic stroke.

Multiple interactions are considered to occur among the various forms of cardiovascular and cerebrovascular diseases. The aim of this study was to assess the serum level profile of cardiac troponin T (cTnT) in patients with acute ischemic stroke (AIS) to evaluate factors associated with increased serum levels of cTnT. Patients with AIS enrolled in this prospective observational study were admitted to the hospital <12 hours after stroke onset. At admission, and 4 hours later, all patients were subjected to neurologic examinations and brain computed tomography or magnetic resonance imaging; standard laboratory tests, including cTnT and other cardiac markers; and repeated electrocardiography. Correlations between cTnT and several baseline parameters were tested, and multivariate regression analysis was used to assess the predictors of cTnT elevation. In total, 107 consecutive patients with AIS (65 men, mean age 67.2 ± 14.2 years) were enrolled. Thirty-nine patients (36.4%) presented with elevated cTnT above the upper limit of normal. The cTnT levels were correlated significantly with age (r = 0.448) and the levels of N-terminal pro-brain natriuretic peptide (r = 0.528), cystatin C (r = 0.457), creatine kinase-MB mass (r = 0.253), urea (r = 0.281), and albumin (r = -0.219). Multiple logistic regression analysis found creatinine >90 µmol/L (odds ratio 3.45, 95% confidence interval 1.09 to 10.85), N-terminal pro-brain natriuretic peptide (odds ratio 100 µg/L increase 1.09, 95% confidence interval 1.03 to 1.16), and creatine kinase-MB mass (odds ratio per 1 µg/L increase 1.45, 95% confidence interval 1.04 to 2.04) were associated with cTnT elevation in patients with AIS. In conclusion, elevated cTnT can be frequently detected in patients with AIS. To reliably identify patients with current acute myocardial impairment, more in-depth clinical investigation is needed.

Assessment of relationship between acute ischemic stroke and heart disease--protocol of a prospective observational trial.

BACKGROUND: Stroke and acute myocardial infarction are the leading causes of death and disability in industrialized countries. Multiple interactions exist between the various forms of cardiovascular and cerebrovascular diseases, and risk factors for development of stroke and major cardiovascular events are similar. There is currently no clear link between acute coronary syndrome and stroke, although it has been repeatedly described. In addition, there are currently no clear recommendations for how to proceed in the case of signs of myocardial damage in patients with acute stroke and how to manage the next follow-up. METHODS-DESIGN: In this prospective observational trial, 500 consecutive ischemic stroke patients admitted at the Comprehensive Stroke Center will be enrolled within 12 h from stroke onset. The set of examinations will consist of: 1) Acute brain computed tomography or magnetic resonance imaging 2) Laboratory tests: A) within 12 h from stroke onset: NT pro B-type of natriuretic peptide, pro-atrial natriuretic peptide, creatinekinase MB, troponin T (cTnT), interleukin 6, procalcitonin, high sensitive C-reactive protein and D-dimers. B) control level of cTnT after 4 h from admission C) non-acute laboratory samples within 60 h from stroke onset: glycated haemoglobine, serum lipids; 3) Electrocardiogram (ECG) on admission and 4 h from stroke onset; 4) Transesophageal or transthoracal echocardiography and 24-h ECG-Holter within 15 days from stroke onset; 5) Neurosonological examination within 60 h from stroke onset; 6) Thirty patients with a positive finding of acute myocardial ischemia (ECG, cTnT) will be examined by coronary angiography (CAG); 7) Epidemiological data will be acquired. STATISTICS: The epidemiological characteristics of the whole sample of patients; correlation between differences between group of cardioembolic ischemic stroke patients and group of patients with ischemic stroke of another etiology; correlation of infarction volume on DWI-MRI with the level of cTnT; correlation of the ECG findings with the level of cTnT and clinical signs; correlation of the CAG findings with level of cTnT and ECG findings will be statistically evaluated at the 5% level of statistical significance. CONCLUSION: The main goal of the project is to improve identification of patients with acute coronary syndrome and with concurrent acute ischemic stroke as these patients require specific treatment and secondary prevention of ischemic events. TRIAL REGISTRATION: Clinicaltrials.gov NCT01541163.