Retinol-Binding Protein-4 in Women With Untreated Essential Hypertension

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Future Perspectives on GLP-1 Receptor Agonists and GLP-1/glucagon Receptor Co-agonists in the Treatment of NAFLD

Along the obesity pandemic, the prevalence of non-alcoholic fatty liver disease (NAFLD), often regarded as the hepatic manifestation of the metabolic syndrome, increases worldwide representing now the prevalent liver disease in western countries. No pharmacotherapy is approved for the treatment of NAFLD and, currently, the cornerstone treatment is lifestyle modifications focusing on bodyweight loss, notoriously difficult to obtain and even more difficult to maintain. Thus, novel therapeutic approaches are highly demanded. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are approved for the treatment of type 2 diabetes and obesity. They exert their body weight-lowering effect by reducing satiety and food intake. GLP-1RAs have also been shown to reduce liver inflammation and fibrosis. Furthermore, glucagon receptor agonism is being investigated for the treatment of NAFLD due to its appetite and food intake-reducing effects, as well as its ability to increase lipid oxidation and thermogenesis. Recent studies suggest that glucagon receptor signaling is disrupted in NAFLD, indicating that supra-physiological glucagon receptor agonism might represent a new NAFLD treatment target. The present review provides (1) an overview in the pathophysiology of NAFLD, including the potential involvement of GLP-1 and glucagon, (2) an introduction to the currently available GLP-1RAs and (3) outlines the potential of emerging GLP-1RAs and GLP-1/glucagon receptor co-agonists in the treatment of NAFLD

Effect of treatment of periodontitis on incretin axis in obese and non-obese individuals: A cohort study

CONTEXT: Periodontitis confers an increased risk of developing type 2 diabetes and, in patients with obesity, it might interfere with the incretin axis. The effect of periodontal treatment on glucoregulatory hormones remains unknown. OBJECTIVE: To evaluate the effect of periodontal treatment on incretin axis in obese and lean non-diabetic individuals. SETTING: King's College Dental Hospital and Institute, London, UK. PARTICIPANTS AND METHODS: The metabolic profile of obese and BMI-normal individuals affected by periodontitis was studied at baseline, 2 and 6 months after intensive periodontal treatment, by measuring plasma insulin, glucagon, GLP-1 and GIP and markers of systemic inflammation and oxidative stress. MAIN OUTCOME MEASURE(S): Circulating levels of incretins and inflammatory markers. RESULTS: At baseline, periodontal parameters were worse for obese than non-obese; this was accompanied by higher levels of circulating hs-CRP, insulin and GLP-1. The response to periodontal treatment was less favourable in the obese group, without significant variations of hs-CRP or malondialdehyde. Gluco-regulatory hormones changed differently after treatment: while insulin and glucagon did not vary at 2 and 6 months, GLP-1 and GIP significantly increased at 6 months in both groups. In particular, GLP-1 increased more rapidly in obese participants, while the increase of GIP followed similar trends across visits in both groups. CONCLUSIONS: Nonsurgical treatment of periodontitis is associated with increased GLP-1 and GIP levels in non-obese and obese patients; changes in GLP-1 were more rapid in obese participants. This might have positive implications for the metabolic risk of these individuals

Obesity reduces the pro-angiogenic potential of adipose tissue stem cell-derived extracellular vesicles (EVs) by impairing miR-126 content: impact on clinical applications

BACKGROUND/OBJECTIVES: Soluble factors and cell-derived extracellular vesicles (EVs) are crucial tissue repair mediators in cell-based therapy. In the present study, we investigate the therapeutic impact of EVs released by adipose tissue-derived stem cells (ASCs) recovered from obese subjects' visceral and subcutaneous tissues. METHODS: ASCs were recovered from 10 obese (oASCs) and 6 non-obese (nASCs) participants and characterized. In selected experiments, nASCs and oASCs were cultured with palmitic acid (PA) or high glucose (HG), respectively. EVs from obese (oEVs) and non-obese (nEVs) subjects' visceral and subcutaneous ASCs were collected after ultracentrifugation and analyzed for their cargo: microRNA-126 (miR-126), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 2 (MMP-2), and for their biological effects on endothelial cells (ECs). Western blotting analysis and loss- and gain-of function experiments were performed. RESULTS: oEVs show impaired angiogenic potential compared with nEVs. This effect depends on EV cargo: reduced content of VEGF, MMP-2 and, more importantly, miR-126. We demonstrate, using gain- and loss-of-function experiments, that this reduced miR-126 content leads to Spred1 upregulation and the inhibition of the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway in ECs. We also show that PA treatment of nASCs translates into the release of EVs that recapitulate oEV cargo. Moreover, HG treatment of oASCs further reduces miR-126 EV content and EV-mediated in vitro angiogenesis. Finally, impaired pro-angiogenic potential is also detected in EVs released from obese subcutaneous adipose tissue-derived ASCs. CONCLUSIONS: These results indicate that obesity impacts on EV pro-angiogenic potential and may raise concerns about the use of adipose tissue-derived EVs in cell-based therapy in the obese setting

Periodontitis affects glucoregulatory hormones in severely obese individuals

OBJECTIVE: To evaluate the effect of periodontitis (PD) on glucoregulatory hormones in obesity, never explored so far, a cross-sectional study was conducted in 110 severely obese, non-diabetic individuals. // METHODS: We collected clinical periodontal parameters, including probing pocket depth (PPD), bleeding on probing (BOP), clinical attachment level (CAL). Insulin, glucagon, GLP-1 and GIP were measured after 3 days of standardized diet. // RESULTS: Forty-seven subjects had periodontitis (PD+) and 63 did not (PD-). PD+ showed 30.3% of gingival sites with PPD > 4 mm, 55.2% of BOP sites and a mean CAL loss of 4.1 mm. Compared with PD-, PD+ had higher glucagon (26.60 [25.22] vs 3.93 [7.50] ng/l, p < 0.0001) and GIP levels (10.56 [13.30] vs 6.43 [8.43] pmol/l, p < 0.001), while GLP-1 was reduced (11.78 [10.07] vs 23.34 [16.80] pmol/l, p < 0.0001). Insulin did not differ. In PD+, after adjustment for confounders, PPD was positively related to glucagon (β = 0.424, p = 0.002) and inversely to GLP-1 (β = -0.159, p = 0.044). // CONCLUSIONS: We describe for the first time an impaired incretin axis coupled with a relative hyperglucagonemia in obese non-diabetic individuals with PD, that might contribute to deteriorate their glucose tolerance and partially explain the higher risk of diabetes observed in these patients

HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: The renal insufficiency and cardiovascular events (RIACE) Italian Multicenter Study

OBJECTIVE: To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. RESEARCH DESIGN AND METHODS: Serial (3-5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 \ub1 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. RESULTS: Median and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86-8.38) and 0.46% (0.29-0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1-2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3-5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD. CONCLUSIONS: In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications

TIMP3 Is Reduced in Atherosclerotic Plaques From Subjects With Type 2 Diabetes and Increased by SirT1

Atherosclerosis is accelerated in subjects with type 2 diabetes by unknown mechanisms. We identified tissue inhibitor of metalloproteinase 3 (TIMP3), the endogenous inhibitor of A disintegrin and metalloprotease domain 17 (ADAM17) and other matrix metalloproteinases (MMPs), as a gene modifier for insulin resistance and vascular inflammation in mice. We tested its association with atherosclerosis in subjects with type 2 diabetes and identified Sirtuin 1 (SirT1) as a major regulator of TIMP3 expression

Influencia de las nuevas tecnologías de la información y la comunicación para mejorar el aprendizaje en el área de Ciencia y Ambiente, en los estudiantes del Sexto Grado de Educación Primaria de la Institución Educativa N° 16173, Santa Rosa -Jaén - 2014

El estudio realizado buscó determinar la influencia de las Tecnologías de la información y comunicación en el aprendizaje del área de ciencia y ambiente, objetivo que se consolidó con la propuesta, nuevas tecnologías para desarrollar aprendizajes significativos, en el área de Ciencia y Ambiente, en estudiantes del sexto grado de Educación Primaria de la Institución Educativa Nª 16173, Santa Rosa- Jaén. El tipo de estudio fue de tipo mixto de diseño cuasi experimental. La población y muestra de estudio estuvo conformada por 22 estudiantes comprendidos entre los 6 y 12 años de edad, de los cuales el 55% fue de sexo femenino y 45% masculino. El instrumento estuvo basado en un cuestionario para medir conocimiento, conformado por 8 preguntas; aplicación, organizada en 4 preguntas y el razonamiento mediante 4 interrogantes y con un coeficiente de fiabilidad determinada por el alfa de Crombach de 0,889, también se recurrió a medidas de tendencias central: media aritmética, moda, mediana. Finalmente, se concluye, asumiendo que el programa “nuevas tecnologías de la información”, incidió significativamente en el desarrollo de un conjunto de capacidades en los estudiantes del sexto grado de educación primaria, tales como: selecciona medios o herramientas tic para generar redes de interaprendizaje, selecciona y organiza información, organiza conceptos y teorías, comprende y fundamenta conocimientos científicos, problematiza situaciones y analiza datos en función de las implicancia del saber y hacer científico.Tesi

Correspondence between the international diabetes federation criteria for metabolic syndrome and insulin resistance in a cohort of Italian nondiabetic caucasians: The GISIR database [4]

[No abstract available