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1.
Background
To investigate the ameliorating effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood glucose control in patients with type 2 diabetes mellitus who were previously untreated with or who have a poor responsive to existing antidiabetic drugs.Methods
Sitagliptin (50 mg/day) was added on to the pre-existing therapy for type 2 diabetes and changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline and performed exploratory analysis.Results
HbA1c levels were significantly decreased after 1 month of treatment compared to baseline, with a mean change in HbA1c level from baseline of ?0.73% (range, ?0.80 to ?0.67) in the entire study population at 3 months. Patients who received a medium dose of glimepiride showed the least improvement in HbA1c levels. The percentage of patients who achieved an HbA1c level of <7.0% significantly increased after 1 month of treatment, reaching 53.1% at 3 months. The percentage of patients who achieved a fasting blood glucose level of <130 mg/dL significantly increased after 1 month of treatment, reaching 50.9% at 3 months.Conclusions
Sitagliptin improved the HbA1c level and rate of achieving the target control levels in patients with type 2 diabetes mellitus who were previously untreated with, or poorly responsive to, existing antidiabetic drugs. Thus, sitagliptin is expected to be useful in this patient group. However, the additional administration of sitagliptin in patients treated with medium-dose glimepiride only slightly improved blood glucose control when corrected for baseline HbA1c level.2.
Min?Liu Zhiguang?Zhou Jinhua?Yan Pin?Li Wenhui?Song Junfen?Fu Xiaobo?Chen Weigang?Zhao Li?Xi Xiaoping?Luo Liang?Sha Xueyuan?Deng Chunxiu?Gong
Background
We aimed to describe the safety and efficacy of insulin glargine in Chinese paediatric patients with type 1 diabetes mellitus (T1DM). Neutral protamine Hagedorn (NPH) insulin was the reference therapy.Methods
This open-label, randomised, Phase III study was conducted at 10 sites in China. Children aged ≥6 to <18 years with T1DM were randomised (2:1) to insulin glargine or NPH insulin asbasal insulinfor a 24-week treatment period. For all patients, insulin aspart was given as bolus insulin. The primary endpoint was absolute change in glycated haemoglobin(HbA1c) from baseline to Week 24. Secondary endpoints included the percentage of patients reaching HbA1c <7.5% (<58.5 mmol/mol), and safety. The study was registered at clinicaltrials.gov (NCT01223131).Results
In total,196 patients were screened, and 162 were randomised (107 and 55 patients were randomised to insulin glargine and NPH insulin, respectively). The mean?±?SD of absolute change in HbA1c was–0.25?±?1.68% (–2.69?±?18.32 mmol/mol) in the insulin glargine group and –0.54?±?1.67% (–5.55?±?20.32 mmol/mol) in the NPH insulin group. At Week 24, 18.7 and 21.6% of patients in the insulin glargine and NPH insulin groups achieved HbA1c <7.5% (<58.5 mmol/mol). Both treatments were generally well tolerated. A numerically lower rate of symptomatic hypoglycaemia per patient year was observed for insulin glargine versus NPH insulin (24.3?±?45.8 versus32.3?±?43.2); severe hypoglycaemia was rare (<2%).Conclusions
Initiation of insulin glargine can aid Chinese paediatric patients with T1DM to safely reduce their HbA1c levels.3.
Background
The purpose of this study was to determing which psychological traits of Japanese type 2 diabetes patients would provide reliability and validity to the Japanese version of the Acceptance and Action Diabetes Questionnaire (AADQ-J).Methods
Various questionnaires were administered to type 2 diabetes patients who were registered on the database of the research service provider; data from a total of 600 patients (mean?±?SD age was 57.50?±?9.87 years, female 21.83%) were analyzed.Results
Three items were excluded because of psychometric concerns related to the original 11-item AADQ. Confirmation factor analyses revealed that the eight-item version demonstrated the best indicators of a goodness of fit. The questionnaire showed adequate internal consistency. The questionnaire demonstrated high measurement accuracy in broad trait values by the test information function of Item Response Theory. The questionnaire showed stronger positive correlations with self-care activities and HbA1c than with diabetes distress and depressive mood.Conclusions
The eight-item Japanese version of AADQ has reliability and validity for type 2 diabetes patients.4.
Elif Erdem Ibrahim Inan Harbiyeli Hazal Boral Macit Ilkit Meltem Yagmur Reha Ersoz 《Mycopathologia》2018,183(3):521-527
Purpose
To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.Design
Retrospective case series in a tertiary university hospital.Participants
CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.Methods
The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.Main Outcome Measures
Grade of the corneal infection.Results
Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).Conclusions
The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.5.
Background
Subcutaneous peginterferon beta-1a provided clinical benefits at Year 1 (placebo-controlled period) of the 2-Year Phase 3 ADVANCE study in relapsing-remitting multiple sclerosis (RRMS). Here we report the effect of peginterferon beta-1a on brain magnetic resonance imaging (MRI) lesions, and no evidence of disease activity (NEDA; absence of clinical [relapses and 12-week confirmed disability progression] and MRI [gadolinium-enhancing, and new or newly-enlarging T2 hyperintense lesions] disease activity) during Year 1.Methods
RRMS patients (18–65 years; Expanded Disability Status Scale score ≤5) were randomized to double-blind placebo or peginterferon beta-1a 125 μg every 2 or 4 weeks. Sensitivity analyses of last observation carried forward and composite disease activity (using minimal MRI allowance definitions) were conducted.Results
1512 patients were randomized and dosed (placebo n?=?500; peginterferon beta-1a every 2 [n?=?512] or 4 [n?=?500] weeks). Every 2 week dosing significantly reduced, versus placebo and every 4 week dosing, the number of new or newly-enlarging T2 hyperintense lesions at Weeks 24 (by 61% and 51%, respectively) and 48 (secondary endpoint; by 67% and 54%, respectively); all p?<?0.0001. Every 2 week dosing also provided significant reductions versus placebo and every 4 week dosing in the number of new T1 hypointense, gadolinium-enhancing, and new active (gadolinium-enhancing plus non-enhancing new T2) lesions (all p?<?0.0001), as well as the volume of T2 and T1 lesions (p?<?0.05) at Weeks 24 and 48. Significantly more patients dosed every 2 weeks had NEDA versus placebo and every 4 weeks (all p?<?0.01) from baseline to Week 48 (33.9% versus 15.1% and 21.5%, respectively [odds ratios, ORs: 2.89 and 1.87]), from baseline to Week 24 (41.0% versus 21.9% and 30.7%, [ORs: 2.47 and 1.57]) and from Week 24 to Week 48 (60.2% versus 28.9% and 36.6%, [ORs: 3.71 and 2.62]). Consistent results were seen when allowing for minimal MRI activity.Conclusion
During Year 1 of ADVANCE, significantly more RRMS patients receiving peginterferon beta-1a every 2 weeks had NEDA, and early and sustained improvements in all MRI endpoints, versus placebo and every 4 week dosing. NEDA sensitivity analyses align with switch strategies in clinical practice settings and provide insight into future responders/non-responders.Trial registration
ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT009063996.
Markus Rotter Stefan Brandmaier Cornelia Prehn Jonathan Adam Sylvia Rabstein Katarzyna Gawrych Thomas Brüning Thomas Illig Heiko Lickert Jerzy Adamski Rui Wang-Sattler 《Metabolomics : Official journal of the Metabolomic Society》2017,13(1):4
Introduction
Few studies have investigated the influence of storage conditions on urine samples and none of them used targeted mass spectrometry (MS).Objectives
We investigated the stability of metabolite profiles in urine samples under different storage conditions using targeted metabolomics.Methods
Pooled, fasting urine samples were collected and stored at ?80 °C (biobank standard), ?20 °C (freezer), 4 °C (fridge), ~9 °C (cool pack), and ~20 °C (room temperature) for 0, 2, 8 and 24 h. Metabolite concentrations were quantified with MS using the AbsoluteIDQ? p150 assay. We used the Welch-Satterthwaite-test to compare the concentrations of each metabolite. Mixed effects linear regression was used to assess the influence of the interaction of storage time and temperature.Results
The concentrations of 63 investigated metabolites were stable at ?20 and 4 °C for up to 24 h when compared to samples immediately stored at ?80 °C. When stored at ~9 °C for 24 h, few amino acids (Arg, Val and Leu/Ile) significantly decreased by 40% in concentration (P < 7.9E?04); for an additional three metabolites (Ser, Met, Hexose H1) when stored at ~20 °C reduced up to 60% in concentrations. The concentrations of four more metabolites (Glu, Phe, Pro, and Thr) were found to be significantly influenced when considering the interaction between exposure time and temperature.Conclusion
Our findings indicate that 78% of quantified metabolites were stable for all examined storage conditions. Particularly, some amino acid concentrations were sensitive to changes after prolonged storage at room temperature. Shipping or storing urine samples on cool packs or at room temperature for more than 8 h and multiple numbers of freeze and thaw cycles should be avoided.7.
Shohei Ouchi Kazunori Shimada Tetsuro Miyazaki Shuhei Takahashi Yurina Sugita Megumi Shimizu Azusa Murata Tomoyasu Kadoguchi Takao Kato Tatsuro Aikawa Shoko Suda Eiryu Sai Masaru Hiki Hiroshi Iwata Takatoshi Kasai Katsumi Miyauchi Hiroyuki Daida 《Cardiovascular diabetology》2017,16(1):151
Background
Diabetes mellitus is considered an important risk factor for cardiovascular diseases. High hemoglobin A1c (HbA1c) levels, which indicate poor glycemic control, have been associated with occurrence of cardiovascular diseases. There are few parameters which can predict cardiovascular risk in patients with well-controlled diabetes. Low 1,5-anhydroglucitol (1,5-AG) levels are considered a clinical marker of postprandial hyperglycemia. We hypothesized that low 1,5-AG levels could predict long-term mortality in acute coronary syndrome (ACS) patients with relatively low HbA1c levels.Methods
The present study followed a retrospective observational study design. We enrolled 388 consecutive patients with ACS admitted to the cardiac intensive care unit at the Juntendo University Hospital from January 2011 to December 2013. Levels of 1,5-AG were measured immediately before emergency coronary angiography. Patients with early stent thrombosis, no significant coronary artery stenosis, malignancy, liver cirrhosis, a history of gastrectomy, current steroid treatment, moderately to severely reduced kidney function (estimated glomerular filtration rate < 45 ml/min/1.73 m2; chronic kidney disease stage 3B, 4, and 5), HbA1c levels ≥ 7.0%, and those who received sodium glucose co-transporter 2 inhibitor therapy were excluded.Results
During the 46.9-month mean follow-up period, nine patients (4.5%) died of cardiovascular disease. The 1,5-AG level was significantly lower in the cardiac death group compared with that in the survivor group (12.3 ± 5.3 vs. 19.2 ± 7.7 µg/ml, p < 0.01). Kaplan–Meier survival analysis showed that low 1,5-AG levels were associated with cardiac mortality (p = 0.02). Multivariable Cox regression analysis showed that 1,5-AG levels were an independent predictor of cardiac mortality (hazard ratio 0.76; 95% confidence interval 0.41–0.98; p = 0.03).Conclusion
Low 1,5-AG levels, which indicate postprandial hyperglycemia, predict long-term cardiac mortality even in ACS patients with HbA1c levels < 7.0%.8.
M. Abawi F. Nijhoff P.R. Stella M. Voskuil D. Benedetto P.A. Doevendans P. Agostoni 《Netherlands heart journal》2016,24(9):544-551
Objective
The coronary sinus Reducer is a recently introduced device to treat patients with severe angina symptoms refractory to optimal medical therapy and not amenable for conventional revascularisation. We aimed to assess the safety and efficacy of the Reducer in a real-world cohort of patients with refractory angina.Methods
This is a single-centre retrospective registry. Patients with severe angina symptoms, objective evidence of myocardial ischaemia using any adequate non-invasive modality and without options for conventional revascularisation were regarded eligible for Reducer implantation.Results
Twenty-three patients (74?% male, mean age 70?±?8 years, 91.3?% previous bypass surgery, 82.6?% previous percutaneous intervention, 47.8?% previous myocardial infarction, 52.2?% diabetes mellitus) underwent Reducer implantation. The safety endpoint (successful implantation of the first device without device-related adverse events) was met in all patients. After a median follow-up of 9 (8–14) months the efficacy (any reduction in Canadian Cardiovascular Society (CCS) class and revascularisation-free survival) was reached in 17 patients (74?%): 8 patients (34.8?%) improved by 1 CCS class, 7 (30.4?%) by 2 CCS classes and 2 (8.7?%) by 3 CCS classes. One patient died 4 months after implantation because of progressive heart failure (not associated with Reducer implantation).Conclusion
In this single-centre real-world experience, Reducer implantation was safe and demonstrated excellent clinical efficacy in the treatment of refractory angina at mid-term follow-up.9.
Ylva Gårdinger Anna Dieden Joanna Hlebowicz Ola Björgell Magnus Dencker 《Cardiovascular ultrasound》2017,15(1):10
Background
Myocardial performance index (MPI) has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether myocardial performance index is affected by food intake in healthy subjects.Methods
Twenty-three healthy subjects aged 25.6?±?4.5 years were investigated. MPI was measured before, 30 min after, and 110 min after a standardized meal.Results
MPI decreased significantly (P?<?0.05) from fasting values 30 min after the meal, and had almost returned to baseline after 110 min. MPI decreased from 0.28?±?0.06 (fasting) to 0.20?±?0.07 30 min after eating. At 110 min after eating the index value was almost back to the baseline value 0.26?±?0.06. (P?=?0.15).Conclusions
This study shows that myocardial performance index is affected by food intake in healthy subjects.10.
11.
N. W. E. van den Berg J. Neefs W. R. Berger S. W. E. Baalman E. Meulendijks M. Kawasaki E. M. Kemper F. R. Piersma M. W. Veldkamp R. Wesselink S. P. J. Krul J. R. de Groot 《Netherlands heart journal》2017,25(12):664-668
Background
Monosodium glutamate (MSG), also referred to as Vetsin or E621, is a flavour enhancer frequently used in Asian cuisine and abundantly present in the famous Chinese dish Peking duck. MSG is notorious for triggering the onset of the so-called ‘Chinese restaurant syndrome’ (CRS), a complex of unpleasant symptoms, which might include flushing, sweating and the onset of atrial fibrillation (AF). This study aims to determine the effects of MSG on the occurrence of AF.Methods
We conducted a placebo self-controlled single-arm study in the Academic Medical Centre in Amsterdam. We included paroxysmal AF patients who reported a consistent onset of AF upon MSG intake. During three admissions, participants were subsequently administered: placebo, 1.5?g and 3?g MSG. If AF was recorded after the dose of 1.5?g MSG, patients were given another placebo instead of 3?g MSG. The primary outcome was the onset of AF registered by 24-hour Holter monitoring. The secondary outcomes were any other arrhythmia and the onset of CRS defined as two or more symptoms of CRS after MSG intake.Results
Six men participated in the study. Both 1.5?g and 3?g MSG were unrelated to CRS, arrhythmias or AF occurrence.Conclusion
Peking duck can be put on the Christmas menu without risking guests to be admitted to the emergency department with new episodes of AF.12.
G. D’Ancona H. U. Agma S. Kische G. El-Achkar M. Dißmann J. Ortak H. Ince U. Ketterer A. Bärisch A. Öner 《Netherlands heart journal》2017,25(2):106-115
Objectives
We present our single-centre experience with the direct flow medical (DFM) trans-catheter aortic valve implantation (TAVI) prosthesis addressing the impact of learning curve upon outcomes.Background
The DFM has been recently introduced for TAVI. The prosthesis presents original design and implantation features.Methods
Patients were divided into three groups according to the chronological implantation sequence that reflected technical skills acquisition of the entire team.Results
Group I included the first 20 patients (early learning phase), group II the second 20 patients (proctoring to other members of the team), and group III the following 93 patients (technique consolidation). Differences in baseline and procedural variables were analysed. Nonparametric correlation and linear regression were used to identify changes according to institutional cumulative experience. There was a significant correlation between catheterisation time and institutional experience (rho = ?0.4; p < 0.0001) confirmed at linear regression (beta = ?0.2; p = 0.001; CI: ?0.3?–??0.08). Moreover, there was lower rate of valve retrieval in group III (15% vs. 20% vs. 10%; p = 0.5). No intra-procedural mortality was reported and improved early safety (at 30 days) was observed (80% vs. 85% vs. 87.1; p = 0.7). At hospital discharge, valve haemodynamic performance was satisfactory with only mild regurgitation in 10% (I), 20% (II), and 9.7% (III) (p = 0.8).Conclusions
DFM adequate sizing and implantation can be achieved after the early learning phases. A significant reduction in catheterisation time is reported after the first 20 patients. Results remain satisfactory during the proctoring and technical consolidation phase.13.
K. H. A. J. Koolen K. A. Mol B. M. Rahel F. Eerens S. Aydin R. P. T. Troquay L. Janssen W. A. L. Tonino J. G. Meeder 《Netherlands heart journal》2016,24(10):581-588
Objectives
To evaluate the procedural and clinical outcomes of a new primary percutaneous coronary intervention (PPCI) centre without surgical back-up (off-site PCI) and to investigate whether these results are comparable with a high volume on-site PCI centre in the Netherlands.Background
Controversy remains about the safety and efficacy of PPCI in off-site PCI centres.Methods
We retrospectively analysed clinical and procedural data as well as 6?month follow-up of 226 patients diagnosed with ST-elevated myocardial infarction (STEMI) who underwent PPCI at VieCuri Medical Centre Venlo and 115 STEMI patients who underwent PPCI at Catharina Hospital Eindhoven.Results
PPCI patients in VieCuri Medical Centre had similar procedural and clinical outcomes to those in Catharina Hospital. Overall there were no significant differences. The occurrence of procedural complications was low in both groups (8.4?% VieCuri vs. 12.3?% Catharina Hospital). In the VieCuri group there was one procedural-related death. No patients in either group needed emergency surgery. At 30 days, 17 (7.9?%) patients in the VieCuri group and 9 (8.1?%) in the Catharina Hospital group had a major adverse cardiac event.Conclusion
Performing PPCI in an off-site PCI centre is safe and effective. The study results show that the procedural and clinical outcomes of an off-site PPCI centre are comparable with an on-site high-volume PPCI centre.14.
A. F. B. E. Quast V. F. van Dijk A. A. M. Wilde R. E. Knops L. V. A. Boersma 《Netherlands heart journal》2017,25(5):312-317
Introduction
The latest European Society of Cardiology Guidelines recommend consideration of a wearable cardioverter-defibrillator (WCD) for patients with a poor left ventricular ejection fraction (LVEF) who are at risk of sudden arrhythmic death but are not eligible for an implantable defibrillator. For these patients a WCD can be an alternative to long-term hospitalisation.Purpose
To evaluate the use of WCD therapy in these patient groups in two Dutch centres.Methods
All consecutive patients treated with the WCD between 2009 and 2016 were included from two centres in the Netherlands. Data on events and compliance were collected retrospectively through home monitoring systems and adjudicated by the investigators.Results
A total of 79 patients were treated with a WCD. Common indications were newly diagnosed cardiomyopathy without optimal medical treatment in 46 patients (58.2%) and bridge to implantable cardioverter-defibrillator (ICD) implant in 33 patients (41.8%). Bridge to implant indications consisted of contraindications for immediate implantation such as infections (e.?g. previous device-related infections) and radiotherapy. Compliance was over 97% per day (median 23.3?h, 22.6–23.7), during a median of 79 days (50.0–109.8.0). Two patients (2.6%) received an appropriate shock (annual rate 13.6%), there was 1 (1.3%) inappropriate shock (annual rate 6.7%). In 24 patients (52.2%) without optimal medical treatment, the LVEF was sufficiently improved and ICD implant was avoided. Eight (10.1%) patients did not receive an ICD. In 45 patients an ICD was implanted (57.0%).Conclusion
WCD therapy provides a safe and effective treatment in outpatient setting for patients at high risk for sudden cardiac death and reduces the number of ICDs implanted.15.
Objectives
Renal sympathetic denervation has been studied as a potential therapeutic option for patients with therapy-resistant hypertension; however, a significant proportion of patients do not show a significant reduction in blood pressure and are classified as non-responders. The objective of the present study was to assess whether a redo renal denervation procedure increases response rates.Methods
We present a case series of three consecutive renal denervation non-responders treated with the multi-electrode radiofrequency St. Jude EnligHTN catheter after an average of 22 months. Patients were followed for 6 months.Results
Mean age was 66 years and two patients were male. Patients were previously treated using either ReCor’s Paradise system, the Vessix V2 system or the Covidien OneShot system. Mean office blood pressure one year after the initial procedure was 187/102?mm?Hg with a mean 24?h ambulatory blood pressure of 166/102?mm?Hg. All patients underwent a successful redo procedure using the EnligHTN system because of persistent therapy-resistant hypertension. At 6 months a significant drop in both office and ambulatory blood pressure of ?27/?6?mm?Hg and ?15/?13?mm?Hg, respectively, was observed. No significant renal artery stenosis was observed at 6 months.Conclusions
In patients with therapy-resistant hypertension who do not respond to an initial renal denervation procedure, a redo procedure using the St. Jude EnligHTN system may help to significantly improve blood pressure control.16.
Anjali Gopalan Katherine Kellom Kevin McDonough Marilyn M. Schapira 《BMC endocrine disorders》2018,18(1):79
Background
Poor understanding of diabetes management targets is associated with worse disease outcomes. Patients may use different information than providers to assess their diabetes control. In this study, we identify the information patients use to gauge their current level of diabetes control and explore patient-perceived barriers to understanding the hemoglobin A1c value (HbA1c).Methods
Adults who self-reported a diagnosis of diabetes were recruited from outpatient, academically-affiliated, Internal Medicine clinics. Semi-structured interviews were conducted with participants and collected data were analyzed using thematic analysis.Results
The mean age of the 25 participants was 56.8 years. HbA1c was one of several types of information participants used to assess diabetes control. Other information included perceived self-efficacy and adherence to self-care, the type and amount of medications taken, the presence or absence of symptoms attributed to diabetes, and feedback from self-monitoring of blood glucose. Most participants reported familiarity with the HbA1c (22 of 25), though understanding of the value’s meaning varied significantly. Inadequate diabetes education and challenges with patient-provider communication were cited as common barriers to understanding the HbA1c.Conclusions
In addition to the HbA1c, several categories of information influenced participants’ assessments of their diabetes control. Increased provider awareness of the factors that influence patients’ perceptions of diabetes control can inform effective, patient-centered approaches for communicating vital diabetes-related information, facilitating behavior change towards improved patient outcomes.17.
Josef Marksteiner Imrich Blasko Georg Kemmler Therese Koal Christian Humpel 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):1
Introduction
There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer’s disease (AD) and monitor disease progression. Liquid chromatography–mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity.Objectives
The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique.Methods
Twenty bile acid metabolites were quantitatively measured in plasma of 30 cognitively healthy subjects, 20 patients with mild cognitive impairment (MCI) and 30 patients suffering from AD.Results
Levels of lithocholic acid were significantly enhanced in plasma of AD patients (50?±?6 nM, p?=?0.004) compared to healthy controls (32?±?3 nM). Lithocholic acid plasma levels of MCI patients (41?±?4 nM) were not significantly different from healthy subjects or AD patients. Levels of glycochenodeoxycholic acid, glycodeoxycholic acid and glycolithocholic acid were significantly higher in AD patients compared to MCI patients (p?<?0.05). All other cholic acid metabolites were not significantly different between healthy subjects, MCI patients and AD patients. ROC analysis shows an overall accuracy of about 66%. Discriminant analysis was used to classify patients and we found that 15/23 were correctly diagnosed. We further showed that LCA levels increased by about 3.2 fold when healthy subjects converted to AD patients within a 8–9 year follow up period. Pathway analysis linked these changes to a putative toxic cholesterol pathway.Conclusion
In conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.18.
Felipe A. de Oliveira Mohamed H. Shahin Yan Gong Caitrin W. McDonough Amber L. Beitelshees John G. Gums Arlene B. Chapman Eric Boerwinkle Stephen T. Turner Reginald F. Frye Oliver Fiehn Rima Kaddurah-Daouk Julie A. Johnson Rhonda M. Cooper-DeHoff 《Metabolomics : Official journal of the Metabolomic Society》2016,12(8):129
Introduction
While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic data acquired from hypertensive individuals treated with atenolol, it may be possible to better understand the pathways that most impact the development of an adverse glycemic state.Objective
To identify biomarkers that can help predict susceptibility to blood glucose excursions during exposure to atenolol.Methods
Plasma samples acquired from 234 Caucasian participants treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses trial were analyzed by gas chromatography Time-Of-Flight Mass Spectroscopy. Metabolomics and genomics data were integrated by first correlating participant’s metabolomic profiles to change in glucose after treatment with atenolol, and then incorporating genotype information from genes involved in metabolite pathways associated with glucose response.Results
Our findings indicate that the baseline level of β-alanine was associated with glucose change after treatment with atenolol (Q = 0.007, β = 2.97 mg/dL). Analysis of genomic data revealed that carriers of the G allele for SNP rs2669429 in gene DPYS, which codes for dihydropyrimidinase, an enzyme involved in β-alanine formation, had significantly higher glucose levels after treatment with atenolol when compared with non-carriers (Q = 0.05, β = 2.76 mg/dL). This finding was replicated in participants who received atenolol as an add-on therapy (P = 0.04, β = 1.86 mg/dL).Conclusion
These results suggest that β-alanine and rs2669429 may be predictors of atenolol-induced hyperglycemia in Caucasian individuals and further investigation is warranted.19.
Background
There are sex differences in the risk of development of cardiovascular disease (CVD). According to the developmental origins of health and disease paradigm (DOHaD), CVD originates in fetal life. This study examines fetal sex differences in cardiovascular development in utero.Methods
In 1028 pregnant women, we assessed fetal circulation using pulsed wave Doppler examinations between 28 and 34 weeks gestation. To test associations between fetal sex and fetal circulation measurements, linear regression models were used adjusting for fetal size, gestational age, and fetal heart rate.Results
A higher pulsatility index in the ductus venosus was observed in male fetuses compared to female fetuses (difference 0.02, 95 % CI 0.01; 0.05) with a lower E/A ratio of the tricuspid (difference ?0.01, 95 % CI ?0.03; ?0.00) and mitral (difference ?0.02, 95 % CI ?0.03; ?0.01) valves. This was mainly determined by differences in the E wave of the tricuspid and mitral valves (differences ?1.02, 95 % CI ?1.81; ?0.24 and ?1.28, 95 % CI ?2.11; ?0.46, respectively). Also in males, a lower peak systolic velocity was seen in the pulmonary artery (difference ?1.33, 95 % CI ?2.63; ?0.03) with a similar lower trend regarding peak systolic velocity in the ascending aorta.Conclusions
Male fetuses exhibit an increased preload and reduced afterload conditions compared to females. While it is difficult to relate these measurements to exact cardiac function, our findings strongly suggest that the known differences in cardiovascular performance between the sexes already start in utero.20.
M. Abawi R. Rozemeijer P. Agostoni R. C. van Jaarsveld C. S. van Dongen M. Voskuil A. O. Kraaijeveld P. A. F. M. Doevendans P. R. Stella 《Netherlands heart journal》2017,25(9):498-509