RESUMEN
Interactions between the gut microbiota, diet, and the host potentially contribute to the development of metabolic diseases. Here, we identify imidazole propionate as a microbially produced histidine-derived metabolite that is present at higher concentrations in subjects with versus without type 2 diabetes. We show that imidazole propionate is produced from histidine in a gut simulator at higher concentrations when using fecal microbiota from subjects with versus without type 2 diabetes and that it impairs glucose tolerance when administered to mice. We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38γ MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). We also demonstrate increased activation of p62 and mTORC1 in liver from subjects with type 2 diabetes. Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes.
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Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal , Imidazoles/metabolismo , Insulina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Transducción de Señal , Animales , Células Cultivadas , Diabetes Mellitus Tipo 2/microbiología , Células HEK293 , Histidina/metabolismo , Humanos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína Sequestosoma-1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND AND AIMS: Bile acids (BA) are vital regulators of metabolism. BAs are AQ6 secreted in the small intestine, reabsorbed, and transported back to the liver, where they can modulate metabolic functions. There is a paucity of data regarding the portal BA composition in humans. This study aimed to address this knowledge gap by investigating portal BA composition and the relation with peripheral and fecal BA dynamics in conjunction with the gut microbiome. APPROACH AND RESULTS: Thirty-three individuals from the BARIA cohort were included. Portal plasma, peripheral plasma, and feces were collected. BA and C4 levels were measured employing mass spectrometry. FGF19 was measured using ELISA. Gut microbiota composition was determined through metagenomics analysis on stool samples. Considerable diversity in the portal BA composition was observed. The majority (n = 26) of individuals had a 9-fold higher portal than peripheral BA concentration. In contrast, 8 individuals showed lower portal BA concentration compared with peripheral and had higher levels of unconjugated and secondary BA in this compartment, suggesting more distal origin. The altered portal BA profile was associated with altered gut microbiota composition. In particular, taxa within Bacteroides were reduced in abundance in the feces of these individuals. CONCLUSIONS: Characterization of the portal BA composition in relation to peripheral and fecal BA increased insight into the dynamics of BA metabolism in individuals with obesity. Peripheral BA composition was much more diverse due to microbial metabolism. About 24% of the portal samples was surprisingly low in total BA; the underlying mechanism requires further exploration.
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AIM: To evaluate medical and surgical treatment of postbariatric hypoglycaemia (PBH) in daily practice. MATERIALS AND METHODS: Retrospective data were extracted from medical records from four hospitals. PBH was defined by neuroglycopenic symptoms together with a documented glucose <3.0 mmol/L in the postprandial setting after previous bariatric surgery. Data were scored semiquantitatively on efficacy and side effects by two reviewers independently. Duration of efficacy and of use were calculated. RESULTS: In total, 120 patients were included with a median follow-up of 27 months with a mean baseline age of 41 years, total weight loss of 33% and glucose nadir 2.3 mmol/L. Pharmacotherapy consisted of acarbose, diazoxide, short- and long-acting octreotide and glucagon-like peptide-1 receptor agonist analogues (liraglutide and semaglutide) with an overall efficacy in 45%-75% of patients. Combination therapy with two drugs was used by 30 (25%) patients. The addition of a second drug was successful in over half of the patients. Long-acting octreotide and the glucagon-like peptide-1 receptor agonist analogues scored best in terms of efficacy and side effects with a median duration of use of 35 months for octreotide. Finally, 23 (19%) patients were referred for surgical intervention. Efficacy of the surgical procedures, pouch banding, G-tube placement in remnant stomach and Roux-en-Y gastric bypass reversal, pooled together, was 79% with a median duration of initial effect of 13 months. CONCLUSIONS: In daily practice, pharmacotherapy for PBH was successful in half to three quarters of patients. Combination therapy was often of value. One in five patients finally needed a surgical procedure, with overall good results.
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Derivación Gástrica , Hipoglucemia , Obesidad Mórbida , Humanos , Adulto , Estudios Retrospectivos , Octreótido/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemia/etiología , Hipoglucemia/terapia , Derivación Gástrica/efectos adversos , Glucosa , Obesidad Mórbida/cirugía , Obesidad Mórbida/etiologíaRESUMEN
Over the past decades, the role of the intestinal microbiota in metabolic diseases has come forward. In this regard, both composition and function of our intestinal microbiota is highly variable and influenced by multiple factors, of which diet is one of the major elements. Between 1970 and 1990, diet composition has changed and consumption of dietary sugars has increased, of which fructose intake rose by more than 10-fold. This increased intake of sugars and fructose is considered as one of the major risk factors in the developments of obesity and several metabolic disturbances. In this review, we describe the association of dietary fructose intake with insulin resistance, nonalcoholic fatty liver disease (NAFLD) and lipid metabolism. Moreover, we will focus on the potential causality of this altered gut microbiota using fecal transplantation studies in human metabolic disease and whether fecal microbial transplant can reverse this phenotype.
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Fructosa , Enfermedad del Hígado Graso no Alcohólico , Dieta/efectos adversos , Fructosa/efectos adversos , Fructosa/metabolismo , Humanos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Factores de RiesgoRESUMEN
BACKGROUND: The aim was to evaluate the cost-effectiveness and cost-utility of ursodeoxycholic acid (UDCA) prophylaxis for the prevention of symptomatic gallstone disease after Roux-en-Y gastric bypass (RYGB) in patients without gallstones before surgery. METHODS: Data from a multicentre, double-blind, randomized placebo-controlled superiority trial were used. Patients scheduled for laparoscopic RYGB or sleeve gastrectomy were randomized to receive 900â mg UDCA or placebo for 6 months. Indicated by the clinical report, prophylactic prescription of UDCA was evaluated economically against placebo from a healthcare and societal perspective for the subgroup of patients without gallstones before surgery who underwent RYGB. Volumes and costs of in-hospital care, out-of-hospital care, out-of-pocket expenses, and productivity loss were assessed. Main outcomes were the costs per patient free from symptomatic gallstone disease and the costs per quality-adjusted life-year (QALY). RESULTS: Patients receiving UDCA prophylaxis were more likely to remain free from symptomatic gallstone disease (relative risk 1.06, 95 per cent c.i. 1.02 to 1.11; P = 0.002) compared with patients in the placebo group. The gain in QALYs, corrected for a baseline difference in health utility, was 0.047 (95 per cent bias-corrected and accelerated (Bca) c.i. 0.007 to 0.088) higher (P = 0.022). Differences in costs were -356 (95 per cent Bca c.i. -1573 to 761) from a healthcare perspective and -1392 (-3807 to 917) from a societal perspective including out-of-pocket expenses and productivity loss, both statistically non-significant, in favour of UDCA prophylaxis. The probability of UDCA prophylaxis being cost-effective was at least 0.872. CONCLUSION: UDCA prophylaxis after RYGB in patients without gallstones before surgery was cost-effective.
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Cálculos Biliares , Derivación Gástrica , Obesidad Mórbida , Análisis Costo-Beneficio , Cálculos Biliares/prevención & control , Cálculos Biliares/cirugía , Gastrectomía , Humanos , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
OBJECTIVE: Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota-immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT). DESIGN: Patients with recent-onset (<6 weeks) T1D (18-30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition. RESULTS: Stimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=-0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics. CONCLUSION: FMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D. TRIAL REGISTRATION NUMBER: NTR3697.
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Diabetes Mellitus Tipo 1/prevención & control , Trasplante de Microbiota Fecal/métodos , Adolescente , Adulto , Péptido C/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/microbiología , Duodeno/metabolismo , Duodeno/microbiología , Femenino , Microbioma Gastrointestinal , Humanos , Células Secretoras de Insulina/fisiología , Masculino , Trasplante Autólogo , Adulto JovenRESUMEN
AIM: To assess the effects of Roux-en-Y gastric bypass surgery (RYGB)-related changes in glucagon-like peptide-1 (GLP-1) on cerebral resting-state functioning in obese women. MATERIALS AND METHODS: In nine obese females aged 40-54 years in the fasted state, we studied the effects of RYGB and GLP-1 on five a priori selected networks implicated in food- and reward-related processes as well as environment monitoring (default mode, right frontoparietal, basal ganglia, insula/anterior cingulate and anterior cingulate/orbitofrontal networks). RESULTS: Before surgery, GLP-1 receptor blockade (using exendin9-39) was associated with increased right caudate nucleus (basal ganglia network) and decreased right middle frontal (right frontoparietal network) connectivity compared with placebo. RYGB resulted in decreased right orbitofrontal (insula/anterior cingulate network) connectivity. In the default mode network, after surgery, GLP-1 receptor blockade had a larger effect on connectivity in this region than GLP-1 receptor blockade before RYGB (all PFWE < .05). Results remained similar after correction for changes in body weight. Default mode and right frontoparietal network connectivity changes were related to changes in body mass index and food scores after RYGB. CONCLUSIONS: These findings suggest GLP-1 involvement in resting-state networks related to food and reward processes and monitoring of the internal and external environment, pointing to a potential role for GLP-1-induced changes in resting-state connectivity in RYGB-mediated weight loss and appetite control.
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Derivación Gástrica , Receptor del Péptido 1 Similar al Glucagón , Adulto , Femenino , Péptido 1 Similar al Glucagón , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Obesidad/cirugíaRESUMEN
PURPOSE: Although diabetes care guidelines recommend paying attention to oral health, the effect on daily practice has been limited, and patients with diabetes have yet to benefit. We investigated whether implementation of an oral care protocol for general practitioners (GPs [family physicians]) can improve patient-centered outcomes for patients with type 2 diabetes. METHODS: Twenty-four GP offices were randomly assigned to the experimental or control group (12 offices each). In the experimental group, GPs and nurse practitioners implemented an oral care protocol. No extra attention was given to oral health in the control group. The primary outcome parameter was oral health-related quality of life (QoL) assessed with the 14-item Oral Health Impact Profile at baseline and 1 year later. Other outcomes were self-reported oral health complaints and general health-related QoL (36-item Short Form Health Survey). RESULTS: Of 764 patients with type 2 diabetes, 543 (71.1%) completed the 1-year follow-up. More patients reported improved oral health-related QoL in the experimental group (35.2%) compared to the control group (25.9%) (P = .046; Padj = .049). In a secondary post hoc analysis including GP offices with ≥60% patient follow-up (n = 18), improvement was 38.3% and 24.9%, respectively (P and Padj = .011). Improvement of self-reported oral health complaints did not differ between groups. The intervention had no effect on general health-related QoL, with the exception of the concept scale score for changes in health over time (Padj = .033). CONCLUSIONS: Implementation of an oral care protocol in primary diabetes care improved oral health-related QoL in patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Médicos Generales , Diabetes Mellitus Tipo 2/terapia , Humanos , Atención Primaria de Salud , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Bariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects. DESIGN: Subjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (2H2-glucose and 2H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks. RESULTS: We observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa. CONCLUSION: Allogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects. TRIAL REGISTRATION NUMBER: NTR4327.
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Trasplante de Microbiota Fecal , Derivación Gástrica , Glucosa/metabolismo , Resistencia a la Insulina , Síndrome Metabólico/metabolismo , Adulto , Anciano , Ácidos y Sales Biliares/análisis , Quimiocina CCL2/sangre , Quimiocina CCL2/genética , Metabolismo Energético , Ácidos Grasos Volátiles/análisis , Heces/química , Microbioma Gastrointestinal , Tránsito Gastrointestinal , Expresión Génica , Humanos , Lipólisis , Masculino , Síndrome Metabólico/fisiopatología , Síndrome Metabólico/terapia , Metabolómica , Persona de Mediana Edad , Grasa Subcutánea/metabolismo , Donantes de Tejidos , Adulto JovenRESUMEN
TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion <30 mg/24 hours and >300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM.
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Nefropatías Diabéticas/metabolismo , Proteína S/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/orina , Femenino , Humanos , Glomérulos Renales/metabolismo , Masculino , Persona de Mediana Edad , Proteína S/orina , Proteínas Proto-Oncogénicas/sangre , Proteínas Proto-Oncogénicas/orina , Proteínas Tirosina Quinasas Receptoras/sangre , Proteínas Tirosina Quinasas Receptoras/orina , Tirosina Quinasa c-Mer , Tirosina Quinasa del Receptor AxlRESUMEN
Lower levels of free thyroxine (whether this is endogenous or exogenous) lead to a hypocoagulable state, and higher levels of free thyroxine lead to a hypercoagulable state. In this narrative review, the effects of different levels of thyroid hormones on clinical end points are described. Hypothyroidism is associated with an increased bleeding risk, whereas hyperthyroidism leads to an increased risk of venous thrombosis. Besides, effects of thyroid hormone on the heart may indirectly influence hemostasis. Hyperthyroidism leads to a higher incidence of atrial fibrillation and atrial flutter, and, at least partly by that mechanism, a higher risk of cerebral arterial thrombosis. In addition, compression effects of goiter on developing venous thrombosis are described. This is caused by local stasis of blood due to tumor expansion.
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Bocio , Hemostasis , Hipotiroidismo , Trombofilia , Trombosis de la Vena , Bocio/sangre , Bocio/complicaciones , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/complicaciones , Factores de Riesgo , Trombofilia/sangre , Trombofilia/etiología , Tiroxina/sangre , Trombosis de la Vena/sangre , Trombosis de la Vena/complicacionesRESUMEN
PURPOSE OF REVIEW: The objective of this review is to critically assess the contributing role of the gut microbiota in human obesity and type 2 diabetes (T2D). RECENT FINDINGS: Experiments in animal and human studies have produced growing evidence for the causality of the gut microbiome in developing obesity and T2D. The introduction of high-throughput sequencing technologies has provided novel insight into the interpersonal differences in microbiome composition and function. The intestinal microbiota is known to be associated with metabolic syndrome and related comorbidities. Associated diseases including obesity, T2D, and fatty liver disease (NAFLD/NASH) all seem to be linked to altered microbial composition; however, causality has not been proven yet. Elucidating the potential causal and personalized role of the human gut microbiota in obesity and T2D is highly prioritized.
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Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/terapia , Microbioma Gastrointestinal , Animales , Diabetes Mellitus Tipo 2/complicaciones , Ácidos Grasos/metabolismo , Humanos , Resistencia a la Insulina , Metabolismo de los Lípidos , Síndrome Metabólico/complicacionesRESUMEN
The aim of the present study was to compare the effectiveness and safety of add-on treatment with dapagliflozin to placebo in patients with prednisone-induced hyperglycaemia during treatment for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We enrolled 46 patients hospitalized for an AECOPD in a multicentre double-blind randomized controlled study in which add-on treatment with dapagliflozin 10 mg was compared with placebo. Glycaemic control and incidence of hypoglycaemia were measured through a blinded subcutaneous continuous glucose monitoring device. Participants in the dapagliflozin group spent 54 ± 27.7% of the time in target range (3.9-10 mmol/L) and participants in the placebo group spent 53.6 ± 23.4% of the time in target range (P = .96). The mean glucose concentration was 10.1 mmol/L in the dapagliflozin group and 10.4 mmol/L in the placebo group (P = .66). One participant using dapagliflozin and 2 participants using placebo experienced symptomatic hypoglycaemia. Treatment with dapagliflozin was safe and there was no difference in risk of hypoglycaemia compared with placebo. Dapagliflozin did not result in better glycaemic control compared with placebo in participants with prednisone-induced hyperglycaemia during AECOPD.
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Compuestos de Bencidrilo/uso terapéutico , Glucocorticoides/efectos adversos , Glucósidos/uso terapéutico , Hiperglucemia/inducido químicamente , Hiperglucemia/tratamiento farmacológico , Prednisona/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Compuestos de Bencidrilo/efectos adversos , Terapia Combinada/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Método Doble Ciego , Quimioterapia Combinada/efectos adversos , Femenino , Glucocorticoides/uso terapéutico , Glucosa/metabolismo , Glucósidos/efectos adversos , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina/uso terapéutico , Resistencia a la Insulina , Tiempo de Internación , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio , Prednisona/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Índice de Severidad de la Enfermedad , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Tejido Subcutáneo/metabolismoRESUMEN
BACKGROUND: The number of bariatric interventions for morbid obesity is increasing worldwide. Rapid weight loss is a major risk factor for gallstone development. Approximately 11 % of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. Gallstone disease can lead to severe complications and often requires hospitalization and surgery. Ursodeoxycholic acid (UDCA) prevents the formation of gallstones after bariatric surgery. However, randomized controlled trials with symptomatic gallstone disease as primary endpoint have not been conducted. Currently, major guidelines make no definite statement about postoperative UDCA prophylaxis and most bariatric centers do not prescribe UDCA. METHODS: A randomized, placebo-controlled, double-blind multicenter trial will be performed for which 980 patients will be included. The study population consists of consecutive patients scheduled to undergo Roux-en-Y gastric bypass or sleeve gastrectomy in three bariatric centers in the Netherlands. Patients will undergo a preoperative ultrasound and randomization will be stratified for pre-existing gallstones and for type of surgery. The intervention group will receive UDCA 900 mg once daily for six months. The placebo group will receive similar-looking placebo tablets. The primary endpoint is symptomatic gallstone disease after 24 months, defined as admission or hospital visit for symptomatic gallstone disease. Secondary endpoints consist of the development of gallstones on ultrasound at 24 months, number of cholecystectomies, side-effects of UDCA and quality of life. Furthermore, cost-effectiveness, cost-utility and budget impact analyses will be performed. DISCUSSION: The UPGRADE trial will answer the question whether UDCA reduces the incidence of symptomatic gallstone disease after Roux-en-Y gastric bypass or sleeve gastrectomy. Furthermore it will determine if treatment with UDCA is cost-effective. TRIAL REGISTRATION: Netherlands Trial Register (trialregister.nl) 6135 . Date registered: 21-Nov-2016.
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Colagogos y Coleréticos/uso terapéutico , Cálculos Biliares/prevención & control , Derivación Gástrica/efectos adversos , Complicaciones Posoperatorias/prevención & control , Ácido Ursodesoxicólico/uso terapéutico , Colagogos y Coleréticos/efectos adversos , Colagogos y Coleréticos/economía , Protocolos Clínicos , Análisis Costo-Beneficio , Método Doble Ciego , Estudios de Seguimiento , Cálculos Biliares/etiología , Humanos , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/etiología , Calidad de Vida , Ácido Ursodesoxicólico/efectos adversos , Ácido Ursodesoxicólico/economíaRESUMEN
AIM: To investigate the effect of basic periodontal therapy (BPT) with antimicrobials (AM) on the parameters of metabolic syndrome (MetS) (waist circumference, systolic/diastolic blood pressure [BP], HDL-cholesterol, triglycerides, glucose). METHODS: One hundred and ten periodontitis patients without known comorbidities and unaware of possible MetS were randomly assigned to BPT (n = 56) or BPT+AM (n = 54) and followed for 12 months post-therapy. Number of patients with undiagnosed MetS was also determined. RESULTS: In all patients, the periodontal condition improved; however, the BTP+AM group showed greater pocket depth reduction than the BPT group. Post-therapy, systolic BP (p < .05) and triglycerides (p < .05) reduced significantly during the follow-up period. No significant differences could be assessed between the BPT+AM and BPT group. Despite the absence of self-reported comorbidities, 27.2% (n = 30) periodontitis patients fulfilled the criteria of MetS at baseline. After therapy, this proportion changed to 14.5% at 3 months (p = .007), to 17.3% at 6 months (p = .017) and to 21.8% at 12-month follow-up (p = .383). CONCLUSION: Although a reduction in systolic BP and triglycerides and a temporarily improvement in the whole metabolic status were observed, the use of antimicrobials in conjunction with BTP does not yield any additional improvement in the parameters of MetS.
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Antiinfecciosos/uso terapéutico , Síndrome Metabólico/prevención & control , Enfermedades Periodontales/microbiología , Enfermedades Periodontales/terapia , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIM: Systematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. MATERIAL AND METHODS: Literature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials, including also a non-intervention group. Data were extracted and meta-analyses were performed. RESULTS: From 3928 screened studies, 25 trials met the eligibility criteria. These trials enrolled 1748 periodontitis patients. Seven trials enrolled periodontitis patients that were otherwise healthy, 18 trials recruited periodontal patients with various co-morbidities, such as CVD or diabetes. None of the trials used hard clinical endpoints of CVD. However, improvement of endothelial function has been consistently reported. Meta-analyses demonstrated significant weighted mean difference (WMD) for hsCRP (-0.50 mg/l, 95% CI:-0.78; -0.22), IL-6 (-0.48 ng/l, 95% CI: -0.90; -0.06), TNF-α (-0.75 pg/ml, 95% CI: -1.34; -0.17), fibrinogen (-0.47 g/l, 95% CI: -0.76; -0.17), total cholesterol (-0.11 mmol/l, 95% CI: -0.21; -0.01) and HDL-C (0.04 mmol/l, 95% CI: 0.03; 0.06) favouring periodontal intervention. Importantly, periodontitis patients with co-morbidity benefitted most from periodontal therapy; significant WMD were observed for levels of hsCRP (-0.71 mg/l, 95% CI: -1.05; -0.36), IL-6 (-0.87 ng/l, 95% CI: -0.97; -0.78), triglycerides (-0.24 mmol/l, 95% CI: -0.26; -0.22), total cholesterol (-0.15 mmol/l, 95% CI: -0.29; -0.01), HDL-C (0.05 mmol/l, 95% CI: 0.03; 0.06) and HbA1c (-0.43%, 95% CI: -0.60; -0.25). CONCLUSIONS: This systematic review and meta-analyses demonstrate that periodontal treatment improves endothelial function and reduces biomarkers of atherosclerotic disease, especially in those already suffering from CVD and/or diabetes.
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Aterosclerosis/fisiopatología , Periodontitis/terapia , Aterosclerosis/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus/sangre , Diabetes Mellitus/fisiopatología , Endotelio Vascular/fisiopatología , Humanos , Factores de RiesgoRESUMEN
AIMS: Patients with idiopathic venous thromboembolism (VTE) have a high recurrence risk during and after stopping anticoagulant treatment. Several studies suggest that treatment with statins reduces the incidence of a first episode of VTE, but data on the effects in patients with a previous episode are lacking. We examined the effect of statin therapy on the risk of recurrent pulmonary embolism (PE). METHODS AND RESULTS: Using the PHARMO Record Linkage System, a Dutch population-based registry of pharmacy records linked with hospital discharge records, patients hospitalized with an acute episode of PE were identified between 1998 and 2008. Prescription-based use of statins and vitamin K antagonist (VKA) were identified starting at hospital discharge and during follow-up. The association between statin use (time-varying) and the incidence of recurrences, cardiovascular events, and death was assessed using Cox regression analysis. The mean (standard deviation) age was 61 (17) years. The median (range) duration of VKA treatment after acute PE was 199 (45-3793) days. Twenty-four per cent of the patients (n = 737) had at least one prescription of statins during the follow-up period and the median duration of statin therapy was 1557 (5-4055) days. During a median follow-up of 1529 (1-4155) days, 285 (9.2%) patients experienced a recurrence. Treatment with statins was associated with a reduced risk of recurrent PE [adjusted hazard ratio (HR) 0.50, 95% CI: 0.36-0.70], both during and after stopping VKA treatment. A dose-response relationship was shown for potency, with the largest reduction in those with the most potent statins. Finally, statin treatment also reduced the risk for cardiovascular events and all-cause mortality. CONCLUSION: Statin treatment decreases the risk of recurrent PE, irrespective of VKA treatment. Treatment with statins may be an attractive alternative for anticoagulant treatment in the long-term treatment of PE.
Asunto(s)
Anticoagulantes/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Embolia Pulmonar/prevención & control , Vitamina K/antagonistas & inhibidores , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/mortalidad , Sistema de Registros , Análisis de Regresión , Factores de Riesgo , Prevención Secundaria , Resultado del TratamientoRESUMEN
This study examines whether patients self-reported attachment representations and levels of depression and anxiety influenced psychologists' evaluations of morbidly obese patients applying for bariatric surgery. A sample of 250 patients (mean age 44, 84 % female) who were referred for bariatric surgery completed questionnaires to measure adult attachment and levels of depression and anxiety. Psychologists rated patients' suitability for bariatric surgery using the Cleveland Clinic Behavioural Rating System (CCBRS), unaware of the results of the completed questionnaires. Attachment anxiety (OR = 2.50, p = .01) and attachment avoidance (OR = 3.13, p = .001) were found to be associated with less positive evaluations on the CCBRS by the psychologists, and symptoms of depression and anxiety mediated this association. This study strongly supports the notion that patients' attachment representations influence a psychologist's evaluation in an indirect way by influencing the symptoms of depression and anxiety patients report during an assessment interview. The clinical implications of these findings are discussed.
Asunto(s)
Trastornos de Ansiedad/psicología , Cirugía Bariátrica/psicología , Trastorno Depresivo/psicología , Obesidad Mórbida/psicología , Apego a Objetos , Adulto , Trastornos de Ansiedad/complicaciones , Trastorno Depresivo/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Oportunidad Relativa , Encuestas y CuestionariosRESUMEN
BACKGROUND: Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking. METHODS: In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort. FINDINGS: We observed that total fasting plasma bile acid levels increased, and faecal excretion of bile acids decreased after surgery suggesting increased reabsorption of bile acids. Consistent with increased bile acid levels after surgery we observed increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4, suggesting increased FXR activation in the gut. We also noted that a subset of bile acids had altered postprandial responses before and after surgery. Finally, fasting plasma levels of 6α-hydroxylated bile acids, which are TGR5 agonists and associated with improved glucose metabolism, were increased after surgery and one of them, HDCA, covaried with diabetes remission in an independent cohort. INTERPRETATION: Our findings provide new insights regarding bile acid kinetics and suggest that bariatric surgery in humans alters bile acid profiles leading to activation of FXR and TGR5, which may contribute to weight loss, improvements in glucose metabolism, and diabetes remission. FUNDING: Novo Nordisk Fonden, Leducq Foundation, Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, the ALF-agreement, ZonMw.
Asunto(s)
Cirugía Bariátrica , Ácidos y Sales Biliares , Diabetes Mellitus Tipo 2 , Factores de Crecimiento de Fibroblastos , Obesidad , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/cirugía , Diabetes Mellitus Tipo 2/sangre , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/sangre , Cirugía Bariátrica/métodos , Femenino , Masculino , Obesidad/cirugía , Obesidad/metabolismo , Obesidad/sangre , Persona de Mediana Edad , Adulto , Factores de Crecimiento de Fibroblastos/sangre , Factores de Crecimiento de Fibroblastos/metabolismo , Periodo Posprandial , Biomarcadores , Heces/química , Cinética , AyunoRESUMEN
BACKGROUND: Glycemic control is an important goal of bariatric surgery in patients with type 2 diabetes mellitus (T2DM) and obesity. The laparoscopic one-anastomosis gastric bypass (OAGB) has potential metabolic benefits over the laparoscopic Roux-en-Y gastric bypass (RYGB). Aim of this study is to examine whether RYGB or OAGB grants better glycemic control 12 months post-surgery. METHODS: For this retrospective cohort study, patients with T2DM and obesity, who underwent primary OAGB between 2008 and 2017 were reviewed. For each OAGB patient, three primary RYGB patients were matched for age, gender and body mass index (BMI). Glycemic control was expressed by the glycated hemoglobin (HbA1c), which was measured pre- and 12 months post-operatively. Weight loss was reported in percentage total weight loss (%TWL). RESULTS: A total of 152 patients, of whom 38 had OAGB and 114 RYGB, were included. Mean (standard deviation (SD)) HbA1c was 7.49 (1.51)% in the OAGB group and 7.56(1.23)% in the RYGB group at baseline. Twelve months after surgery the mean (SD) HbA1c dropped to 5.73 (0.71)% after OAGB and 6.09 (0.76)% after RYGB (adjusted p = 0.011). The mean (SD) BMI was reduced from 42.5(6.3) kg/m2 to 29.6(4.7) kg/m2 after OAGB and 42.3(5.8) kg/m2 to 29.9 (4.5) kg/m2 after RYGB; reflecting 30.3 (6.8) %TWL post-OAGB and 29.0 (7.3) %TWL post-RYGB (p = 0.34). CONCLUSION: This study indicates that OAGB leads to lower HbA1c one year after surgery compared to RYGB, without a difference in weight loss. Prospective (randomized) studies are needed to ascertain the most optimal metabolic treatment for patients with obesity and T2DM.