RESUMEN
The aim of the study was to investigate the association of adipokines (resistin, leptin and adiponectin) with obesity, insulin resistance (IR) and inflammation in type 2 diabetes mellitus (T2DM). A total of 284 patients with T2DM were included. Concentrations of resistin, leptin, adiponectin, and inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)] were measured and homeostatic model assessment for IR (HOMA-IR) index was calculated. Resistin correlated negatively with estimated glomerular filtration rate (eGFR) and positively with hsCRP, TNF-α, IL-6, and white blood cell count (WBC). Leptin correlated positively with HOMA-IR, whereas adiponectin correlated negatively. Leptin also correlated positively with body mass index (BMI), waist circumference, IL-6, WBC and negatively with eGFR. Adiponectin correlated negatively with waist circumference, WBC, and eGFR. Multivariate logistic regression indicated lower eGFR and higher WBC and IL-6 as independent predictive factors of resistin concentration above the upper quartile (CAQ3), whereas female sex and higher BMI and HOMA-IR of leptin CAQ3, and lower HOMA-IR and older age of adiponectin CAQ3. In conclusion, in contrast to leptin and adiponectin, in T2DM patients, resistin is not associated with BMI and IR, but with inflammation and worse kidney function.
Asunto(s)
Biomarcadores/sangre , Diabetes Mellitus Tipo 2/complicaciones , Tasa de Filtración Glomerular , Inflamación/patología , Resistencia a la Insulina , Resistina/metabolismo , Adipoquinas/sangre , Adiponectina/genética , Adiponectina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Humanos , Inflamación/etiología , Inflamación/metabolismo , Pruebas de Función Renal , Leptina/genética , Leptina/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Resistina/genéticaRESUMEN
INTRODUCTION: The potential effect of adipokines on the development of AF is yet to be established. The aim of this study was to investigate the association of baseline serum adipokines with 1) the presence of AF at baseline and 2) future risk of AF development. MATERIAL AND METHODS: The current study is a sub-analysis of the prospective, randomised AVOCADO (Aspirin Vs./Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes) trial. The AVOCADO study included patients with type 2 DM burdened with at least two additional cardiovascular risk factors and receiving acetylsalicylic acid. In patients included in the current analysis adipokines and inflammatory biomarker levels were measured. Information on the subsequent AF diagnosis was collected after a median of 5.4 years of follow-up. RESULTS: A total of 273 patients with type 2 DM (median age 68 years; 52% male) were included in the initial analysis comparing patients with and without AF at baseline. Patients with diagnosed AF (12%) had higher levels of serum resistin [8.5 (5.8-10.5) vs. 6.9 (5.6-8.7) ng/mL; p = 0.034], adiponectin [6.9 (5.6-8.7) vs. 2.7 (1.8-4.2) ng/mL; p = 0.032], and N-terminal pro-B-type natriuretic peptide [336 (148-473) vs. 108 [45-217]; p < 0.001) than non-AF patients. There were no significant differences in serum leptin, IL-6, and TNF-alpha concentrations between the two groups. From subjects without known AF at study entry, 19% developed AF at follow-up. In logistic regression analysis, baseline adipokine levels did not predict AF development. CONCLUSION: In type 2 DM, patients with AF have higher resistin and adiponectin concentrations than patients with no AF. None of the studied adipokines proved a predictor of future AF development.
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Adipoquinas/sangre , Fibrilación Atrial/sangre , Diabetes Mellitus Tipo 2/sangre , Adiponectina/sangre , Anciano , Fibrilación Atrial/fisiopatología , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Humanos , Interleucina-6/sangre , Leptina/sangre , Masculino , Persona de Mediana Edad , Inhibidor 1 de Activador Plasminogénico/sangre , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resistina/sangreRESUMEN
OBJECTIVES: The aim of this study was to investigate the association of serum brain-derived neurotrophic factor (BDNF) levels with platelet reactivity and antidiabetes treatment, as well as serum adipocytokine concentrations. METHODS: This observational, open-label study enrolled 149 patients. Serum BDNF, hematologic, biochemical parameters and platelet reactivity were measured. Blood samples were taken after the last acetylsalicylic acid dose. RESULTS: Patients with high BDNF levels were younger (65.60±8.956 vs. 68.59±8.516) and smoked cigarettes more frequently (14.6% vs. 4.1%); they were more commonly being treated by metformin (77.3% vs. 54%); had higher platelet counts (245.81±68.85 103/mm3 vs. 206.61±44.48 103/mm3); had shorter collagen-adenosine diphosphate closure time (CADP-CT) values (104.88±69.73 s vs. 140.93±86.63 s); had higher triglyceride concentrations (140.73±67.5 vs. 121.76±60.49) and had higher concentrations of serum thromboxane B2 (0.938±1.59 vs. 0.364±0.76). In univariate linear regression analyses, predictive factors for serum BDNF levels above the median were metformin treatment, current smoking, platelet count, triglyceride concentration, total cholesterol concentration and CADP-CT >74 s. In multivariate backward stepwise analysis CADP-CT >141 s; adiponectin concentration >4.22 µg/mL; total cholesterol and low-density lipoprotein levels were independently associated with serum BDNF levels above the median. CONCLUSIONS: Our results suggest that BDNF may be associated with lipid metabolism and that increased production of BDNF may be related to metformin treatment. Moreover, we showed an association between BDNF levels and platelet reactivity; we found that serum BDNF levels in patients with type 2 diabetes who had high platelet reactivity were higher than in subjects with normal platelet reactivity despite antiplatelet therapy.
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Factor Neurotrófico Derivado del Encéfalo/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Activación Plaquetaria/efectos de los fármacos , Adulto , Anciano , Aspirina/farmacología , Aspirina/uso terapéutico , Biomarcadores/sangre , Femenino , Humanos , Hipoglucemiantes/farmacología , Masculino , Metformina/farmacología , Persona de Mediana Edad , Activación Plaquetaria/fisiología , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To investigate the association of leptin, resistin, and tumour necrosis factor α (TNF-α) with prognosis in type 2 diabetes (T2D). METHODS: Analysis included 284 T2D patients. Apart from routine laboratory parameters, baseline leptin, resistin, and TNF-α concentrations were measured. Patients were followed for a median of 5.4 years. The primary endpoint was all-cause death at follow-up. The secondary endpoint was a composite of death, acute coronary syndrome, and stroke or transient ischemic attack. RESULTS: At baseline, median age was 68 years, and 48% of patients were female. Data on the primary endpoint were obtained for all patients: 32 (11%) died during follow-up. Data on the secondary endpoint were available for 230 patients, of whom 45 (20%) reached the secondary endpoint. In univariate analyses, older age, heart failure, lower-glomerular filtration rate, and higher resistin, TNF-α and NT-proBNP concentrations were predictors of the study endpoints. Of these variables, only resistin remained an independent predictor of both study endpoints in multivariate models. In receiver-operating characteristic analysis, area under the curve for resistin was 0.7. Resistin concentration of greater than or equal to 11.4 ng/mL had sensitivity of 41% and specificity of 91% for prediction of death at follow-up (Youden's index). CONCLUSIONS: Higher resistin is associated with reduced survival in T2D, irrespectively of TNF-α. Resistin concentration of above 11 ng/mL indicates T2D patients at an increased risk of unfavourable outcomes. Leptin was not a prognostic factor. These results suggest that in T2D, association of resistin with unfavourable outcomes might, at least in part, result from its pro-inflammatory properties.
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Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/mortalidad , Leptina/metabolismo , Resistina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Anciano , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaAsunto(s)
Infecciones por Corynebacterium/diagnóstico , Corynebacterium/aislamiento & purificación , Marcapaso Artificial/microbiología , Sepsis/diagnóstico , Anciano , Infecciones por Corynebacterium/diagnóstico por imagen , Femenino , Humanos , Imagen Multimodal , Marcapaso Artificial/efectos adversos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sepsis/diagnóstico por imagenRESUMEN
Introduction Recent studies have shown that rhythm control does not provide additional benefit over rate control in terms of morbidity or mortality and is less cost effective in patients with atrial fibrillation (AF). It remains to be determined if any of the treatment strategies should be favored on the basis of the quality of life (QoL) or functional capacity. Objectives This HOT CAFE substudy was conducted to compare the functional status of patients with persistent AF assigned either to rate or rhythm control strategy. Patients and methods We enrolled 205 patients (mean [SD] age, 60.8 [11.2] years) with persistent AF who were randomly assigned either to rate or rhythm control strategies. The New York Heart Association (NYHA) functional classification, intensity of arrhythmiarelated symptoms, exercise tolerance, and QoL were analyzed. Results After a mean (SD) of 1.7 (0.4) years, the NYHA class and QoL improved in both groups. Both strategies lead to improvement in AFrelated symptoms. Treadmill test duration and maximal workload increased over time in both groups. In terms of NYHA class improvement, rhythm control was superior to rate control in patients with AF and hypertension (odds ratio [OR], 1.89; 95% CI, 0.98-3.65; P = 0.055) and in those with moderate HF (OR, 2.04; 95% CI, 1.03-4.06; P = 0.04). When success was considered as left ventricular function improvement, the rhythmcontrol strategy also proved to be superior in patients with hypertension (OR, 2.64; 95% CI, 1.21-5.74; P = 0.01) and those with NYHA class II or III (OR, 4.27; 95% CI, 1.25-9.85; P <0.001). Conclusions Rate- and rhythmcontrol strategies improved functional status in patients with persistent AF. However, rhythm control might be more appropriate for patients with AF and hypertension and those with moderate HF.
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Antiarrítmicos/uso terapéutico , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Cardioversión Eléctrica/métodos , Adulto , Anciano , Prueba de Esfuerzo , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Some cardiac implantable electronic device (CIED) implantation procedures require the use of X-rays, which is reflected by such parameters as total fluoroscopy time (TFT) and dose-area product (DAP - defined as the absorbed dose multiplied by the area irradiated). MATERIAL AND METHODS: This retrospective study evaluated 522 CIED implantation (424 de novo and 98 device upgrade and new lead placement) procedures in 176 women and 346 men (mean age 75±11 years) over the period 2012-2015. The recorded procedure-related parameters TFT and DAP were evaluated in the subgroups specified below. The group of 424 de novo procedures included 203 pacemaker (PM) and 171 implantable cardioverter-defibrillator (ICD) implantation procedures, separately stratified by single-chamber and dual-chamber systems. Another subgroup of de novo procedures involved 50 cardiac resynchronization therapy (CRT) devices. The evaluated parameters in the group of 98 upgrade procedures were compared between 2 subgroups: CRT only and combined PM and ICD implantation procedures. RESULTS: We observed differences in TFT and DAP values between procedure types, with PM-related procedures showing the lowest, ICD - intermediate (with values for single-chamber considerably lower than those for dual-chamber systems) and CRT implantation procedures - highest X-ray exposure. Upgrades to CRT were associated with 4 times higher TFT and DAP values in comparison to those during other upgrade procedures. Cardiac resynchronization therapy de novo implantation procedures and upgrades to CRT showed similar mean values of these evaluated parameters. CONCLUSIONS: Total fluoroscopy time and DAP values correlated progressively with CIED implantation procedure complexity, with CRT-related procedures showing the highest values of both parameters. Med Pr 2017;68(3):363-374.
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Desfibriladores Implantables/efectos adversos , Exposición a Riesgos Ambientales , Marcapaso Artificial/efectos adversos , Rayos X , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
AIMS: Genetic polymorphisms may contribute to platelet reactivity in diabetic patients; however, the information on their influence on long-term antiplatelet therapy is lacking. Our aim was to evaluate the role of previously described genetic variants and platelet reactivity on risk of all-cause mortality and cardiovascular events. METHODS: Blood samples were obtained from 303 Caucasian patients. Genome-wide genotyping was performed using Illumina Human Omni 2.5-Quad microarrays, and individual genotyping of selected SNPs was performed using a custom Sequenom iPLEX assay in conjunction with the Mass ARRAY platform. Platelet reactivity was measured with VerifyNow Aspirin Assay and PFA-100 Assay. Univariate and multivariate Cox regression analyses were performed to determine the impact of genetic variants and platelets reactivity on risk of all-cause mortality and cardiovascular events. RESULTS: Among the 237 patients included in the follow-up, death from any cause occurred in 34 (14.3%) patients and cardiovascular events occurred in 51 (21.5%) patients within a median observation time of 71 months (5.9 years). In univariate analyses, significant association in the presence of minor alleles in TXBA2R (rs1131882) with primary (HR 2.54, 95% CI 1.15-5.60, p = 0.021) and secondary endpoint (HR 2.06, 95% CI 1.06-4.04, p = 0.034) was observed. In addition, multivariate analyses revealed the impact of this polymorphism on primary (HR 2.34, 95% CI 1.09-5.00, p = 0.029) and secondary endpoint (HR 1.89, 95% CI 1.00-3.57, p = 0.048). CONCLUSIONS: Results of the study demonstrate for the first time an association between genetic polymorphism within TXBA2R gene encoding platelet's surface receptor and long-term survival of diabetic patients treated with ASA.
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Aspirina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/mortalidad , Activación Plaquetaria/genética , Polimorfismo de Nucleótido Simple , Receptores de Tromboxano A2 y Prostaglandina H2/genética , Anciano , Alelos , Aspirina/farmacología , Plaquetas/efectos de los fármacos , Plaquetas/fisiología , Clopidogrel , Diabetes Mellitus Tipo 2/sangre , Femenino , Genotipo , Humanos , Inflamación/sangre , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/mortalidad , Masculino , Persona de Mediana Edad , Activación Plaquetaria/efectos de los fármacos , Análisis de Supervivencia , Ticlopidina/análogos & derivados , Ticlopidina/farmacología , Ticlopidina/uso terapéuticoRESUMEN
Reversible complete atrioventricular block in patient with Wegener's granulomatosis - a report on a positive outcome with long term follow-up. Atrioventricular (AV) block is a rare complication of Wegener's granulomatosis (WG), thus there are no standards of management in such cases. We present a case of a patient with a dual-chamber pacemaker (DDD) implanted due to complete AV block in the course of Wegener's granulomatosis (WG). An immunosuppressive therapy resulted in the resolution of non-cardiac and AV conduction disorders. The diagnostic functions of the pacemaker enabled us to evaluate AV conduction over a five-year follow-up period. The resolution of AV conduction disorders, which accompanied WG remission, suggests that careful monitoring with temporary cardiac pacing may be considered in some patients before permanent pacemaker implantation.
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Bloqueo Atrioventricular/etiología , Granulomatosis con Poliangitis/complicaciones , Terapia de Inmunosupresión , Marcapaso Artificial , Bloqueo Atrioventricular/inmunología , Bloqueo Atrioventricular/terapia , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana EdadRESUMEN
INTRODUCTION: The vast majority of cardiac implantable electronic device (CIED) recipients require transvenous lead insertion, which may be hindered by the presence of venous anomalies. The aim of this study was to determine the prevalence and variations of persistent left superior vena cava (PLSVC) and to conduct subsequent outpatient follow-up in terms of device function and the clinical condition of the recipients using data from CIED placement procedures conducted over a 12-year period. METHODS: The study population included patients undergoing first-time transvenous implantation of cardiac pacemakers and implantable cardioverter-defibrillators (ICDs). The presence of PLSVC was determined based on intra-procedure venography. Outpatient follow-up involved assessments of patient condition, radiological imaging, and CIED function. RESULTS: Of a total of 4708 CIED recipients, PLSVC was detected in eight patients (mean age 65.5±13.9); five of them had double superior vena cava (DSVC), including three cases in which the vessels were bridged with a brachiocephalic vein (BCV). Three patients presented PLSVC associated with the absence of the right superior vena cava (RSVC), a very rare anomaly. Seven patients remain under observation, for a total of 78.4±48.4 months of follow-up. CONCLUSIONS: The rate of venous anomalies in the form of PLSVC detected in the evaluated population was 0.17%. These PLSVC cases were asymptomatic, which hindered their earlier detection. The presence of these anomalies made the procedures more challenging for the operator and increased the perioperative complication rates; however, neither patient condition nor CIED function was affected based on the long-term outpatient follow-up.
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Marcapaso Artificial/estadística & datos numéricos , Malformaciones Vasculares/epidemiología , Vena Cava Superior/anomalías , Adulto , Anciano , Anciano de 80 o más Años , Electrodos Implantados/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Centros de Atención TerciariaRESUMEN
The aim of the present study was to investigate a possible association between the accumulation of rare coding variants in the genes for arachidonate 5-lipoxygenase (ALOX5) and ALOX5-activating protein (ALOX5AP), and corresponding production of leukotrienes (LTs) in patients with type 2 diabetes mellitus (T2DM) receiving acetylsalicylic therapy. Twenty exons and corresponding introns of the selected genes were resequenced in 303 DNA samples from patients with T2DM using pooled polymerase chain reaction amplification and next-generation sequencing, using an Illumina HiSeq 2000 sequencing system. The observed non-synonymous variants were further confirmed by individual genotyping of DNA samples comprising of all individuals from the original discovery pools. The association between the investigated phenotypes was based on LTB4 and LTE4 concentrations, and the accumulation of rare missense variants (genetic burden) in investigated genes was evaluated using statistical collapsing tests. A total of 10 exonic variants were identified for each resequenced gene, including 5 missense and 5 synonymous variants. The rare missense variants did not exhibit statistically significant differences in the accumulation pattern between the patients with low and high LTs concentrations. As the present study only included patients with T2DM, it is unclear whether the absence of observed association between the accumulation of rare missense variants in investigated genes and LT production is associated with diabetic populations only or may also be applied to other populations.
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Desfibriladores Implantables/efectos adversos , Remoción de Dispositivos , Endocarditis/etiología , Anciano , Diagnóstico Diferencial , Endocarditis/diagnóstico , Endocarditis/cirugía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The aim of this study was to investigate the association between serum concentrations of the brain-derived neurotrophic factor (BDNF), platelet reactivity and inflammatory markers, as well as its association with BDNF encoding gene variants in type 2 diabetic patients (T2DM) during acetylsalicylic acid (ASA) therapy. MATERIAL/METHODS: This retrospective, open-label study enrolled 91 patients. Serum BDNF, genotype variants, hematological, biochemical, and inflammatory markers were measured. Blood samples were taken in the morning 2-3 h after the last ASA dose. The BDNF genotypes for selected variants were analyzed by use of the iPLEX Sequenom assay. RESULTS: In multivariate linear regression analysis, CADP-CT >74 sec (p<0.001) and sP-selectin concentration (p=0.03) were predictive of high serum BDNF. In multivariate logistic regression analysis, CADP-CT >74 sec (p=0.02) and IL-6 concentration (p=0.03) were risk factors for serum BDNF above the median. Non-significant differences were observed between intronic SNP rs925946, missense SNP rs6265, and intronic SNP rs4923463 allelic groups and BDNF concentrations in the investigated cohort. CONCLUSIONS: Chronic inflammatory condition and enhanced immune system are associated with the production of BDNF, which may be why the serum BDNF level in T2DM patients with high platelet reactivity was higher compared to subjects with normal platelet reactivity in this study.
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Plaquetas/citología , Factor Neurotrófico Derivado del Encéfalo/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleótido Simple , Anciano , Alelos , Aspirina/uso terapéutico , Femenino , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inflamación/sangre , Interleucina-6/sangre , Intrones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación Missense , Selectina-P/sangre , Activación Plaquetaria , Pruebas de Función Plaquetaria , Estudios Prospectivos , Control de Calidad , Estudios RetrospectivosRESUMEN
Reversible complete atrioventricular block in patient with Wegener's granulomatosis - a report on a positive outcome with long term follow-up. Atrioventricular (AV) block is a rare complication of Wegener's granulomatosis (WG), thus there are no standards of management in such cases. We present a case of a patient with a dual-chamber pacemaker (DDD) implanted due to complete AV block in the course of Wegener's granulomatosis (WG). An immunosuppressive therapy resulted in the resolution of non-cardiac and AV conduction disorders. The diagnostic functions of the pacemaker enabled us to evaluate AV conduction over a five-year follow-up period. The resolution of AV conduction disorders, which accompanied WG remission, suggests that careful monitoring with temporary cardiac pacing may be considered in some patients before permanent pacemaker implantation.
Asunto(s)
Bloqueo Atrioventricular/complicaciones , Granulomatosis con Poliangitis/complicaciones , Estudios de Seguimiento , Humanos , Terapia de Inmunosupresión , Marcapaso ArtificialRESUMEN
The objective of this study was to investigate whether rare missense genetic variants in several genes related to platelet functions and acetylsalicylic acid (ASA) response are associated with the platelet reactivity in patients with diabetes type 2 (T2D) on ASA therapy. Fifty eight exons and corresponding introns of eight selected genes, including PTGS1, PTGS2, TXBAS1, PTGIS, ADRA2A, ADRA2B, TXBA2R, and P2RY1 were re-sequenced in 230 DNA samples from T2D patients by using a pooled PCR amplification and next-generation sequencing by Illumina HiSeq2000. The observed non-synonymous variants were confirmed by individual genotyping of 384 DNA samples comprising of the individuals from the original discovery pools and additional verification cohort of 154 ASA-treated T2DM patients. The association between investigated phenotypes (ASA induced changes in platelets reactivity by PFA-100, VerifyNow and serum thromboxane B2 level [sTxB2]), and accumulation of rare missense variants (genetic burden) in investigated genes was tested using statistical collapsing tests. We identified a total of 35 exonic variants, including 3 common missense variants, 15 rare missense variants, and 17 synonymous variants in 8 investigated genes. The rare missense variants exhibited statistically significant difference in the accumulation pattern between a group of patients with increased and normal platelet reactivity based on PFA-100 assay. Our study suggests that genetic burden of the rare functional variants in eight genes may contribute to differences in the platelet reactivity measured with the PFA-100 assay in the T2DM patients treated with ASA.
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Aspirina/farmacología , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Activación Plaquetaria/efectos de los fármacos , Activación Plaquetaria/genética , Inhibidores de Agregación Plaquetaria/farmacología , Anciano , Alelos , Biomarcadores , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exones , Femenino , Frecuencia de los Genes , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Polimorfismo de Nucleótido Simple , Factores de RiesgoAsunto(s)
Foramen Oval Permeable/complicaciones , Embolia Pulmonar/etiología , Accidente Cerebrovascular/etiología , Trombosis/complicaciones , Anciano , Femenino , Foramen Oval Permeable/diagnóstico , Humanos , Embolia Pulmonar/diagnóstico , Accidente Cerebrovascular/diagnóstico , Trombosis/diagnóstico , Trombosis/tratamiento farmacológicoRESUMEN
INTRODUCTION: Data regarding the effect of certain adipokines on lipid metabolism are equivocal. OBJECTIVES: The aim of this study was to evaluate the association of lipid control with adipokines and inflammatory markers in patients with type 2 diabetes. PATIENTS AND METHODS: The analysis included 195 patients with type 2 diabetes. The achievement of treatment targets in terms of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides was assessed in accordance with the current guidelines. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index as well as concentrations of highmolecular-weight (HMW) adiponectin, leptin, resistin, high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor α (TNF-α) were measured in all patients. Logistic regression analyses were performed to determine the risk factors for inadequate lipid control. RESULTS: Optimal control in terms of total cholesterol, LDL, HDL, and triglycerides was achieved in 61%, 43%, 53%, and 68% of the patients, respectively. In multivariate analyses, female sex, lower resistin concentrations, and the absence of statin treatment were predictors of total cholesterol levels above the treatment target; older age and lower statin dose--of LDL cholesterol levels above the treatment targets; female sex, higher HOMA-IR index, lower HMW adiponectin concentrations, and higher TNF-α concentration-o-f HDL levels below the treatment targets; and higher HOMA-IR, lower HMW adiponectin concentration, and the absence of statin treatment--of triglycerides above the treatment target. CONCLUSIONS: In type 2 diabetes, lower HMW adiponectin concentrations are associated with inadequate triglyceride and HDL control; higher TNF-α, with inadequate HDL control, and lower resistin concentrations, with inadequate total cholesterol control.
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Adipoquinas/sangre , Proteína C-Reactiva/análisis , Diabetes Mellitus Tipo 2/sangre , Metabolismo de los Lípidos , Factor de Necrosis Tumoral alfa/sangre , Anciano , Biomarcadores/sangre , Colesterol/sangre , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Inflamación , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Persona de Mediana Edad , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder, which affects more than 300 million people globally. The common effect of uncontrolled diabetes is the state of hyperglycemia, which results from beta-cell dysfunction as well as insulin resistance, which is accompanied with microvascular and macrovascular complications. As hyperglycemia defines diabetes, glycemic control is fundamental to the management of diabetes. Sodium glucose co-transporter 2 inhibitors (SGLT2) are a new group of oral antidiabetic medications that act by blocking the reabsorption of glucose, causing it to be excreted in the urine. Canagliflozin was the first SGLT2 inhibitor to be approved in the US by the Food and Drug Administration for the treatment and control of T2DM and on September 19, 2013, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Invokana(®). Canagliflozin is a SGLT2 inhibitor, which acts upon the proximal tubules of the kidneys and reduces the renal threshold for glucose. It is highly selective, binding 250 times more potently to SGLT2 than sodium glucose co-transporter 1 inhibitor. This action allows a higher amount of glucose to be excreted within the urine, causing the patient's plasma glucose level to be decreased and indirectly causing weight loss. Among the most common adverse events are hypoglycemia, headache, nausea, female genital and urinary tract infections, nasopharyngitis, and transient postural dizziness. Given its high efficacy in reducing hyperglycemia and good safety profile as either monotherapy or an add-on treatment to metformin, sulfonylureas, or insulin, canagliflozin seems to be a promising antihyperglycemic drug. Nevertheless, further large-scale and long-term studies should be conducted to evaluate the impact of canagliflozin on cardiovascular risk in T2DM patients.
RESUMEN
BACKGROUND: Evidence from the literature suggests diminished acetylsalicylic acid (ASA) treatment efficacy in type 2 diabetes (DM2). High on-aspirin platelet reactivity (HAPR) in DM2 has been linked to poor glycemic and lipid control. However, there are no consistent data on the association between HAPR and insulin resistance or adipose tissue metabolic activity. The aim of this study was to assess the relationship between laboratory response to ASA and metabolic control, insulin resistance and adipokines in DM2. METHODS: A total of 186 DM2 patients treated with oral antidiabetic drugs and receiving 75 mg ASA daily were included in the analysis. Response to ASA was assessed by measuring serum thromboxane B2 (TXB2) concentration and expressed as quartiles of TXB2 level. The achievement of treatment targets in terms of glycemic and lipid control, insulin resistance parameters (including Homeostatic Model Assessment-Insulin Resistance, HOMA-IR, index), and serum concentrations of high-molecular weight (HMW) adiponectin, leptin and resistin, were evaluated in all patients. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors of serum TXB2 concentration above the upper quartile and above the median. RESULTS: Significant trends in age, body mass index (BMI), HOMA-IR, HMW adiponectin concentration, C-reactive protein concentration and the frequency of achieving target triglyceride levels were observed across increasing quartiles of TXB2. In a multivariate analysis, only younger age and higher BMI were independent predictors of TXB2 concentration above the upper quartile, while younger age and lower HMW adiponectin concentration were predictors of TXB2 concentration above the median. CONCLUSIONS: These results suggest that in DM2, the most important predictor of HAPR is younger age. Younger DM2 patients may therefore require total daily ASA doses higher than 75 mg, preferably as a twice-daily regimen, to achieve full therapeutic effect. Higher BMI and lower HMW adiponectin concentration were also associated with less potent ASA effect. This is the first study to demonstrate an association of lower adiponectin concentration with higher serum TXB2 level in patients treated with ASA.