Rosiglitazone decreases postprandial production of acylation stimulating protein in type 2 diabetics

<p>Abstract</p> <p>Background</p> <p>We evaluated plasma ASP and its precursor C3 in type 2 diabetic men with/without rosiglitazone (ROSI) treatment compared to healthy non-obese men. We tested (1) whether plasma ASP or C3 are altered postprandially in subcutaneous adipose tissue or forearm muscle effluent assessed by arteriovenous (A-V) differences in healthy lean men and older obese diabetic men and (2) whether treatment with ROSI changes the arteriovenous gradient of ASP and/or C3.</p> <p>Methods</p> <p>In this ongoing placebo-controlled, crossover, double-blinded study, AV differences following a mixed meal were measured in diabetic men (n = 6) as compared to healthy men (n = 9).</p> <p>Results</p> <p>Postprandial arterial and adipose venous TG and venous NEFA were increased in diabetics vs. controls (p < 0.05–0.0001). ROSI treatment decreased postprandial arterial TG (p < 0.001), adipose venous NEFA (p < 0.005), reduced postprandial glucose (p < 0.0001) and insulin concentrations (p < 0.006). In healthy men, there was no change in postprandial C3, but an increase in adipose venous ASP vs. arterial ASP (p < 0.02), suggesting ASP production, with no change in forearm muscle. In older, obese diabetic subjects, arterial C3 was greater than in controls (p < 0.001). Arterial C3 was greater than venous C3 (p < 0.05), an effect that was lost with ROSI treatment. In diabetics, postprandial venous ASP was greater than arterial (p < 0.05), indicating ASP production, an effect that was lost with ROSI treatment (p < 0.01).</p> <p>Conclusion</p> <p>Increased postprandial venous production of ASP is specific for adipose tissue (absent in forearm muscle). Increased postprandial C3 and ASP in diabetic subjects is consistent with an ASP resistant state, this state is partially normalized by treatment with ROSI.</p

Liraglutide Reduces Carotid Intima-Media Thickness by Reducing Small Dense Low-Density Lipoproteins in a Real-World Setting of Patients with Type 2 Diabetes: A Novel Anti-Atherogenic Effect

Introduction: Liraglutide has several non-glycemic effects, including those on plasma lipids and lipoproteins, contributing to its cardiovascular benefit; however, the exact underlying mechanisms remain unclear. We investigated a novel anti-atherogenic effect of liraglutide in a real-world prospective study on patients with type 2 diabetes (T2DM). Methods: Sixty-two patients with T2DM (31 men, 31 women; mean age ± standard deviation 61 ± 9&nbsp;years) naïve to incretin-based therapies were treated with liraglutide (1.2&nbsp;mg/day) as add-on therapy to metformin (1500–3000&nbsp;mg/day) for 4&nbsp;months. Laboratory analyses included the assessment of lipoprotein subclass profile by gel electrophoresis (Lipoprint; Quantimetrix Corp., Redondo Beach, CA, USA). Carotid intima-media thickness (cIMT) was assessed by Doppler ultrasonography. Statistical analyses included the paired t test, Spearman correlation and multiple regression analysis. Results: The addition of liraglutide to metformin monotherapy resulted in significant reductions in fasting glycemia, hemoglobin A1c, body mass index, waist circumference, total cholesterol, triglycerides and low-density lipoprotein (LDL)-cholesterol, as well as in cIMT. There was an increase in the large LDL-1 subfraction, with a concomitant reduction in atherogenic small dense LDL-3 and LDL-4 subfractions. Correlation analysis revealed a significant association between changes in cIMT and changes in small dense LDL-3 subfraction (r = 0.501; p &lt; 0.0001). Multivariate analysis, including all of the measured anthropometric and laboratory parameters, revealed that only changes in the small dense LDL-3 subfraction were independent predictors of changes in cIMT (p &lt; 0.0001). Conclusion: Our findings are the first to show that the vascular benefit of liraglutide in patients with T2DM is associated with reductions in atherogenic small dense LDL. This effect is independent of glycemic control and body weight reduction and may represent one of the key mechanisms by which liraglutide is able to reduce cardiovascular events. Trial Registration: ClinicalTrials.gov: NCT01715428

Multiscenario flood hazard assessment using probabilistic runoff hydrograph estimation and 2D hydrodynamic modelling

In this paper, we aim to define a procedure of flood hazard assessment applicable to large river basins in which flood events can be induced/sustained by the full basin area or by fractions of the total area as functions of the extent of the triggering precipitation event. The proposed procedure is based on a combined approach accounting for (1) the reconstruction of intensity–duration–frequency curves expressing the magnitude in terms of intensity for multiple return periods; (2) the application of the soil conservation service method for runoff estimation from a selected rainfall scenario considering some characteristics of the basin (i.e. soil type, land use/treatment, surface condition, and antecedent moisture conditions); (3) 2D hydrodynamic modelling conducted by the HEC-RAS model using runoff hydrographs as hydrological input data; (4) the reconstruction of flood hazard maps by overlaying multiple inundation maps depicting flood extent for different return periods. To account for the variability in the extent of the triggering precipitation event and the resulting input hydrograph, multiple contributing areas are considered. The procedure is tested at the archaeological site of Sybaris in southern Italy, which is periodically involved in flood events of variable magnitude. The obtained results highlight that the variable extent of the floodable area is strongly conditioned by the extent of the contributing area and return period, as expected. The archaeological site is always involved in the simulated flooding process, except for the smallest contributing area for which only a 300-year event involves this part of the site. Our findings may be useful for developing and supporting flood risk management plans in the area. The developed procedure might be easily exported and tested in other fluvial contexts in which evaluations of multiple flood hazard scenarios, due to the basin geometry and extent, are needed

How cardiologists can manage excess body weight and related cardiovascular risk. An expert opinion

Obesity is an important independent cardiovascular (CV) risk factor and a chronic inflammatory disease related to the development of insulin resistance, type 2 diabetes, dyslipidaemia, coronary artery disease, hypertension, heart failure, atrial fibrillation and obstructive sleep apnoea. Body Mass Index (BMI) values &gt;27 kg/m2 are associated with an exponential increase in the risk for Major Adverse Cardiac Events (MACE). On the other hand, weight reduction can significantly reduce metabolic, CV and oncological risk. Orlistat, bupropion/naltrexone, liraglutide and semaglutide, combined with lifestyle changes, have proven to be effective in weight loss; the last two have been tested in randomized clinical trials (RCTs) with CV outcomes only in diabetic patients, and not in obese patients. To fill a fundamental gap of knowledge, the SELECT trial on patients with obesity and CV disease treated with semaglutide is ongoing, aiming at MACE as the primary endpoint. The battle against the social and clinical stigma towards obesity must be counteracted by promoting an awareness that elevates obesity to a complex chronic disease. Several actions should be implemented to improve the management of obesity, and cardiologists have a key role for achieving a global approach to patients with excess weight also through the correct implementation of available treatment strategies

Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

<p>Abstract</p> <p>Background</p> <p>Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n = 21) were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined.</p> <p>Methods</p> <p>LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1). ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p < 0.01 each). Differences between LAT and HAT group were almost exclusively in SC tissue, with little difference in OM tissue. Increased C5L2 (p < 0.01), an ASP receptor, in HAT suggests a compensatory ASP pathway, associated with increased TG storage.</p> <p>Results</p> <p>HAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL), lipolysis (HSL, CES1, perilipin), fatty acid binding proteins (FABP1, FABP3) and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ). By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7). HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p < 0.025.</p> <p>Conclusion</p> <p>Taken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG.</p

Racial difference in Acylation Stimulating Protein (ASP) correlates to triglyceride in non-obese and obese African American and Caucasian women

© 2009 Scantlebury-Manning et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Bilateral dilation of the urinary tract due to iliopsoas pyomyositis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pyomyositis is an acute bacterial infection of the skeletal muscles that arises from hematogenous spread and is caused predominantly by Gram-positive cocci.</p> <p>Case presentation</p> <p>We report a case of iliopsoas pyomyositis in a 25-year-old Greek Caucasian woman with a history of intravenous drug use. Her condition was complicated by bilateral dilation of the ureters and renal calyces as a result of mechanical pressure from inflammation and edema of the involved muscle. The patient did not present aggravation of renal function and was treated successfully solely with intravenous antibiotics, without surgical intervention. This is the first case report describing iliopsoas pyomyositis with reversible bilateral dilation of the urinary tract that was treated successfully with intravenous antibiotics, without surgical intervention.</p> <p>Conclusion</p> <p>We present the first described case of iliopsoas pyomyositis with reversible bilateral hydroureteronephrosis that was treated successfully with intravenous antibiotics, without the necessity of surgical intervention. To our knowledge, this is the first report of its kind in the literature regarding an unexpected event in the course of treating a patient with iliopsoas pyomyositis, and it should be of particular interest to different clinical medical specialties such as internal medicine, infectious disease and urology.</p

Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification

Multipotent adult resident cardiac stem cells (CSCs) were first identified by the expression of c-kit, the stem cell factor receptor. However, in the adult myocardium c-kit alone cannot distinguish CSCs from other c-kit-expressing (c-kitpos) cells. The adult heart indeed contains a heterogeneous mixture of c-kitpos cells, mainly composed of mast and endothelial/progenitor cells. This heterogeneity of cardiac c-kitpos cells has generated confusion and controversy about the existence and role of CSCs in the adult heart. Here, to unravel CSC identity within the heterogeneous c-kit-expressing cardiac cell population, c-kitpos cardiac cells were separated through CD45-positive or -negative sorting followed by c-kitpos sorting. The blood/endothelial lineage-committed (Lineagepos) CD45posc-kitpos cardiac cells were compared to CD45neg(Lineageneg/Linneg) c-kitpos cardiac cells for stemness and myogenic properties in vitro and in vivo. The majority (~90%) of the resident c-kitpos cardiac cells are blood/endothelial lineage-committed CD45posCD31posc-kitpos cells. In contrast, the LinnegCD45negc-kitpos cardiac cell cohort, which represents 10% of the total c-kitpos cells, contain all the cardiac cells with the properties of adult multipotent CSCs. These characteristics are absent from the c-kitneg and the blood/endothelial lineage-committed c-kitpos cardiac cells. Single Linnegc-kitpos cell-derived clones, which represent only 1–2% of total c-kitpos myocardial cells, when stimulated with TGF-β/Wnt molecules, acquire full transcriptome and protein expression, sarcomere organisation, spontaneous contraction and electrophysiological properties of differentiated cardiomyocytes (CMs). Genetically tagged cloned progeny of one Linnegc-kitpos cell when injected into the infarcted myocardium, results in significant regeneration of new CMs, arterioles and capillaries, derived from the injected cells. The CSC’s myogenic regenerative capacity is dependent on commitment to the CM lineage through activation of the SMAD2 pathway. Such regeneration was not apparent when blood/endothelial lineage-committed c-kitpos cardiac cells were injected. Thus, among the cardiac c-kitpos cell cohort only a very small fraction has the phenotype and the differentiation/regenerative potential characteristics of true multipotent CSCs