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Objectives: Knowledge, attitude, and practices (KAP) have been widely used during times of pandemic to quantify and locate gaps of care during pandemics. Using this tool, we can identify and target populations who underwent solid organ transplant (SOT) to bolster preventative practices in these patients during COVID-19. Materials and methods: An institution-based cross-sectional study was conducted between June 1, 2020 and June 30, 2021 on patients who underwent a liver and/or kidney transplant at Methodist Dallas Medical Center in Dallas, Texas, USA. A KAP questionnaire of 26 questions about COVID-19 was designed based on the clinical and community management guidelines published by the WHO. The participant's overall KAP was categorized using Bloom's cut-off point. A KAP domain was considered sufficient if the score was between 60 and 100% and insufficient if the score was <60%. The strength of association was assessed by using odds ratio (OR); only significant independent factors in each tested area were assessed. Results: Respondents with children in the household were less likely to have sufficient practices than those who did not [OR = 0.2491, 95% Confidence Interval (0.0893-0.6120), p = 0.001]. We also found that sufficient levels of knowledge correlated with higher likelihood of sufficient levels of practices [OR = 4.94, 95% CI (1.646-14.2159), p < 0.005]. Interestingly, we found that sufficient levels of attitude did not correlate with sufficient levels of practice (p = 0.201). Conclusion: Our study found that knowledge and having children in the household correlated with higher levels of practice.

Asunto(s)

COVID-19 , Trasplante de Órganos , COVID-19/epidemiología , Niño , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Pandemias , Estados Unidos

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Rocky Mountain spotted fever (RMSF) is a tick-borne illness caused by Rickettsia rickettsii. The classic triad of fever, rash, and a recent tick bite is rarely present at diagnosis. Less known, but more common initial presentations include gastrointestinal symptoms such as anorexia, nausea, vomiting, and abdominal pain. In endemic areas, a persistent fever with gastrointestinal symptoms should prompt screening and early initiation of antibiotics to prevent the development of fulminant RMSF and its associated high mortality. This case aims to educate about the gastrointestinal and hepatic manifestations of this diagnostic enigma.

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NEW FINDINGS: What is the central question of this study? Does short-duration, high-intensity exercise training that combines functional aerobic and resistance exercises into training sessions lasting 8-20 min benefit individuals with type 2 diabetes? What is the main finding and its importance? Functional high-intensity training improves insulin sensitivity and reduces cardiometabolic risk in individuals with type 2 diabetes. This type of exercise training may be an effective exercise mode for managing type 2 diabetes. The increase in insulin sensitivity addresses a key defect in type 2 diabetes. ABSTRACT: Functional high-intensity training (F-HIT) is a novel fitness paradigm that integrates simultaneous aerobic and resistance training in sets of constantly varied movements, based on real-world situational exercises, performed at high-intensity in workouts that range from ∼8 to 20 min per session. We hypothesized that F-HIT would be an effective exercise mode for reducing insulin resistance in type 2 diabetes (T2D). We recruited 13 overweight/obese adults (5 males, 8 females; 53 ± 7 years; BMI 34.5 ± 3.6 kg m-2 , means ± SD) with T2D to participate in a 6-week (3 days week-1 ) supervised F-HIT programme. An oral glucose tolerance test was used to derive measures of insulin sensitivity. F-HIT significantly reduced fat mass (43.8 ± 83.8 vs. 41.6 ± 7.9 kg; P < 0.01), diastolic blood pressure (80.2 ± 7.1 vs. 74.5 ± 5.8; P < 0.01), blood lipids (triglyceride and VLDL, both P < 0.05) and metabolic syndrome z-score (6.4 ± 4.5 vs. -0.2 ± 5.2 AU; P < 0.001), and increased basal fat oxidation (0.08 ± 0.03 vs. 0.10 ± 0.04 g min-1 ; P = 0.05), and high molecular mass adiponectin (214.4 ± 88.9 vs. 288.8 ± 127.4 ng mL-1 ; P < 0.01). Importantly, F-HIT also increased insulin sensitivity (0.037 ± 0.010 vs. 0.042 ± 0.010 AU; P < 0.05). Increases in high molecular mass adiponectin and basal fat oxidation correlated with the change in insulin sensitivity (ρ, 0.75, P < 0.05 and ρ, 0.81, P < 0.01, respectively). Compliance with the training programme was >95% and no injuries or adverse events were reported. These data suggest that F-HIT may be an effective exercise mode for managing T2D. The increase in insulin sensitivity addresses a key defect in T2D and is consistent with improvements observed after more traditional aerobic exercise programmes in overweight/obese adults with T2D.

Asunto(s)

Diabetes Mellitus Tipo 2/metabolismo , Entrenamiento de Intervalos de Alta Intensidad , Resistencia a la Insulina/fisiología , Sobrepeso/metabolismo , Índice de Masa Corporal , Enfermedades Cardiovasculares/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Síndrome Metabólico/metabolismo , Persona de Mediana Edad , Obesidad/metabolismo , Factores de Riesgo

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Bariatric surgery provides significant and durable improvements in glycemic control and hepatic steatosis, but the underlying mechanisms that drive improvements in these metabolic parameters remain to be fully elucidated. Recently, alterations in mitochondrial morphology have shown a direct link to nutrient adaptations in obesity. Here, we evaluate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics in a diet-induced obesity Sprague-Dawley (SD) rat model. Livers were harvested from adult male SD rats 90-days after either Sham or RYGB surgery and continuous high-fat feeding. We assessed expression of mitochondrial proteins involved in fusion, fission, mitochondrial autophagy (mitophagy) and biogenesis, as well as differences in citrate synthase activity and markers of oxidative stress. Gene expression for mitochondrial fusion genes, mitofusin 1 (Mfn1; P < 0.05), mitofusin 2 (Mfn2; P < 0.01), and optic atrophy 1 (OPA1; P < 0.05) increased following RYGB surgery. Biogenesis regulators, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α; P < 0.01) and nuclear respiratory factor 1 (Nrf1; P < 0.05), also increased in the RYGB group, as well as mitophagy marker, BCL-2 interacting protein 3 (Bnip3; P < 0.01). Protein expression for Mfn1 (P < 0.001), PGC1α (P < 0.05), BNIP3 (P < 0.0001), and mitochondrial complexes I-V (P < 0.01) was also increased by RYGB, and Mfn1 expression negatively correlated with body weight, insulin resistance, and fasting plasma insulin. In the RYGB group, citrate synthase activity was increased (P < 0.02) and reactive oxygen species (ROS) was decreased compared to the Sham control group (P < 0.05), although total antioxidant capacity was unchanged between groups. These data are the first to show an association between RYGB surgery and improved markers of liver mitochondrial dynamics. These observed improvements may be related to weight loss and reduced energetic demand on the liver, which could facilitate normalization of glucose homeostasis and protect against hepatic steatosis.

Asunto(s)

Derivación Gástrica/efectos adversos , Mitocondrias Hepáticas/metabolismo , Dinámicas Mitocondriales , Mitofagia , Obesidad/cirugía , Animales , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Obesidad/etiología , Obesidad/metabolismo , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley

RESUMEN

BACKGROUND: Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE: We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS: A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ±â€¯2 y; BMI, 34.0 ±â€¯1.1 kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets. RESULTS: Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05). CONCLUSION: Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.

Asunto(s)

Glucosa/metabolismo , Resistencia a la Insulina/fisiología , Obesidad/dietoterapia , Granos Enteros , Adulto , Glucemia/metabolismo , Estudios Cruzados , Fibras de la Dieta , Método Doble Ciego , Femenino , Humanos , Masculino , Obesidad/metabolismo , Resultado del Tratamiento

RESUMEN

Type 2 diabetes (T2D) is characterized by reductions in ß-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve ß-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on ß-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on ß-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of ß-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the ß-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased ß-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat (R2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase (R2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving ß-cell function in adults with T2D.

Asunto(s)

Diabetes Mellitus Tipo 2/rehabilitación , Terapia por Ejercicio/métodos , Células Secretoras de Insulina/metabolismo , Grasa Abdominal , Tejido Adiposo , Fosfatasa Alcalina/sangre , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina , Masculino , Persona de Mediana Edad , Proinsulina/sangre

RESUMEN

BACKGROUND: Increased dietary whole-grain intake may protect against cardiovascular disease (CVD). OBJECTIVE: The objective was to evaluate the efficacy of whole grains compared with refined grains on body composition, hypertension, and related mediators of CVD in overweight and obese adults. METHODS: We conducted a double-blind, randomized, controlled crossover trial in 40 overweight or obese men and women aged <50 y with no known history of CVD. Complete whole-grain and refined-grain diets were provided for two 8-wk periods, with a 10-wk washout between diets. Macronutrient composition was matched, except for the inclusion of either whole grains or refined grains (50 g/1000 kcal in each diet). Measurements included blood pressure, body composition, blood lipids and adiponectin, and markers of inflammation and glycemia. RESULTS: Thirty-three participants (6 men and 27 women) completed the trial [mean ± SD age: 39 ± 7 y; mean ± SD body mass index (in kg/m2): 33.1 ± 4.3]. Decreases in diastolic blood pressure were -5.8 mm Hg (95% CI: -7.7, -4.0 mm Hg) after the whole-grain diet and -1.6 mm Hg (95% CI: -4.4, 1.3 mm Hg) after the control diet (between effect, P = 0.01). Decreases in plasma adiponectin were -0.1 (95% CI: -0.9, 0.7) after the whole-grain diet and -1.4 (95% CI: -2.6, -0.3) after the control diet (between effect, P = 0.05). Decreases in diastolic blood pressure correlated with the circulating adiponectin concentration (r = 0.35, P = 0.04). Substantial reductions in body weight, fat loss, systolic blood pressure, total cholesterol, and LDL cholesterol were observed during both diet periods, with no relevant difference between them. CONCLUSIONS: The improvement in diastolic blood pressure was >3-fold greater in overweight and obese adults when they consumed a whole-grain compared with a refined-grain diet. Because diastolic blood pressure predicts mortality in adults aged <50 y, increased whole-grain intake may provide a functional approach to control hypertension. This may benefit patients at risk of vascular-related morbidity and mortality. This trial was registered at clinicaltrials.gov as NCT01411540.

Asunto(s)

Enfermedades Cardiovasculares/prevención & control , Dieta , Sobrepeso , Granos Enteros , Adulto , Glucemia , Presión Sanguínea , Composición Corporal , Método Doble Ciego , Femenino , Humanos , Resistencia a la Insulina , Lípidos/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo

RESUMEN

OBJECTIVE: High body mass index (BMI) is a risk factor for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Our aim was to determine if prevalence of dysplasia in BE varies by BMI and study the effect of BMI on progression to high-grade dysplasia (HGD) or EAC. MATERIALS AND METHODS: This is a retrospective review of patients with endoscopic evidence of BE confirmed by presence of intestinal metaplasia on histology from January 2000 to December 2012 at Cleveland Clinic. Patient demographics, BMI and endoscopic findings such as length of BE, dysplasia in BE and size of hiatal hernia were reviewed. Dysplasia was classified as no dysplasia (NDBE), low-grade dysplasia (LGD), HGD and EAC. RESULTS: In this cohort of 1239 patients, average BMI was 29.8 ± 6 kg/m(2). There were 228 (18.4%) in group with BMI <25, 236 (19%) in BMI group 25-27.4, 262 (21.1%) in BMI 27.5-29.9, 303 (24.5%) in BMI 30-34.9, 126 (10.2%) in BMI 35-39.9 and 86 (6.8%) in BMI ≥40. Lower BMI groups had lower prevalence of dysplasia while higher BMI groups had higher prevalence of dysplasia (p = 0.002). During mean follow up of 31.6 ± 26 months, there were 14 cases of HGD/EAC in NDBE group and 29 cases of HGD/EAC in LGD group. BMI or BMI change was not associated with progression to HGD/EAC in NDBE. CONCLUSIONS: High BMI was associated with higher prevalence of dysplasia in BE. But once in a surveillance program, higher BMI is not associated with progression of dysplasia in NDBE.

Asunto(s)

Adenocarcinoma/diagnóstico , Esófago de Barrett/patología , Índice de Masa Corporal , Neoplasias Esofágicas/diagnóstico , Metaplasia/patología , Lesiones Precancerosas/patología , Anciano , Progresión de la Enfermedad , Endoscopía , Esófago/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo

RESUMEN

Obesity-related nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease. Exercise and diet are uniformly prescribed treatments for NAFLD; however, there are limited empirical data on the effects of exercise training on metabolic function in these patients. The purpose of this study was to investigate the fasting and glucose-stimulated adaptation of gut peptides to short-term aerobic exercise training in patients with NAFLD. Twenty-two obese subjects, 16 with NAFLD [body mass index (BMI), 33.2 ± 1.1 (SE) kg/m(2)] and 6 obese controls (BMI, 31.3 ± 1.2 kg/m(2)), were enrolled in a supervised aerobic exercise program (60 min/day, 85% of their heart rate maximum, for 7 days). Fasting and glucose-stimulated glucagon-like peptide-1 (GLP-17-36) and peptide tyrosine tyrosine (PYYTotal) concentrations in plasma were assessed before and after the exercise program. Initially, the NAFLD group had higher fasting PYY (NAFLD = 117 ± 18.6, control = 47.2 ± 6.4 pg/ml, P < 0.05) and GLP-1 (NAFLD = 12.4 ± 2.2, control = 6.2 ± 0.2 pg/ml, P < 0.05) and did not significantly increase GLP-1 or PYY in response to glucose ingestion. After the exercise program, fasting GLP-1 was reduced in the NAFLD group (10.7 ± 2.0 pg/ml, P < 0.05). Furthermore, exercise training led to significant increase in the acute (0-30 min) PYY and GLP-1 responses to glucose in the NAFLD group, while the total area under the glucose-stimulated GLP-1 response curve was reduced in both NAFLD and controls (P < 0.05). In summary, 7 days of vigorous aerobic exercise normalized the dynamic PYY and GLP-1 responses to nutrient stimulation and reduced the GLP-1 response in NAFLD, suggesting that exercise positively modulates gut hormone regulation in obese adults with NAFLD.

Asunto(s)

Ejercicio Físico/fisiología , Tracto Gastrointestinal/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Péptido YY/metabolismo , Glucemia/metabolismo , Glucemia/fisiología , Ayuno/metabolismo , Ayuno/fisiología , Femenino , Péptido 1 Similar al Glucagón/metabolismo , Glucosa/metabolismo , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Obesidad/fisiopatología

RESUMEN

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an advanced and aggressive form of non-alcoholic fatty liver disease (NAFLD), which remains difficult to diagnose without a liver biopsy. Hyperferritinemia has increasingly been associated with the presence of NASH. Hence, we sought to explore the relationship between ferritin and NASH and to develop a composite model based on ferritin to predict the presence of NASH. METHODS: A total of 405 patients with biopsy-proven NAFLD were enrolled in the study. Comparison was explored to assess differences between patients with and without NASH, upon which a scoring model was established using variables found to be independent predictors of NASH. RESULTS: Among all patients with NAFLD, 291 (72%) had biopsy-proven NASH, and 114 (28%) had non-NASH. Mean age was 48 ± 12 years, and 56% were female. Ferritin was significantly higher in NASH compared with non-NASH patients (184 vs 126, respectively; P < 0.001) but lacked diagnostic accuracy for predicting NASH alone (area under the curve [AUC 0.62]). The addition of other significant variables such as aspartate aminotransferase, body mass index, platelet count, diabetes, and hypertension to ferritin improved the prediction of NASH with an AUC 0.81 (95% confidence interval: 0.76-0.86). Internal validation of the model using imputed data sets demonstrated that AUC did not change materially. CONCLUSIONS: While higher ferritin was significantly associated with NASH, ferritin alone lacked diagnostic accuracy to predict NASH. However, incorporating several easily obtainable variables with ferritin allowed the construction of a novel scoring system that can be easily applied in the clinical setting to guide management of NAFLD.

Asunto(s)

Técnicas de Apoyo para la Decisión , Ferritinas/sangre , Indicadores de Salud , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Biopsia , Estudios Transversales , Progresión de la Enfermedad , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Regulación hacia Arriba

RESUMEN

BACKGROUND: While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patients with diabetes mellitus (DM), less is known about NAFLD in non-DM patients. We investigated the clinical characteristics of NAFLD patients with and without DM and accuracy of the NAFLD fibrosis score (NFS) in these two NAFLD groups. METHODS: Clinical, biochemical and histological variables were evaluated in this prospective cross-sectional study of 503 patients with biopsy proven NAFLD. Comparisons between patients with and without DM were analysed. NFS was correlated with liver histology to assess its robustness in patients with and without DM. RESULTS: There were 503 biopsy proven NAFLD patients with 48% of the cohort being diabetic. Relative to patients without DM, patients with DM were older (52 vs. 46 years, p < 0.001), with higher proportion of females (70% vs. 54%, p < 0.001), higher BMI (37 vs. 35, p = 0.009), higher prevalence of hypertension (73% vs. 44%, p < 0.001), higher prevalence of NASH (80.2% vs. 64.4%; p < 0.001) and advanced fibrosis (40.3% vs. 17.0%; p < 0.001). A considerable amount of patients without DM still had NASH (64%) and advanced fibrosis (17%). The clinical utility of the NFS differed between NAFLD patients with and without DM, with sensitivity to exclude advanced fibrosis being 90% of NAFLD patients with DM but only 58% of patients without DM. CONCLUSION: Patients with DM have more severe NAFLD based on histology. However, NASH and advanced fibrosis also occur in a considerable proportion of NAFLD patients without DM. The lower utility of the NFS in NAFLD patients without DM emphasises the heterogeneous nature of the NAFLD phenotype.

RESUMEN

BACKGROUND AND AIM: While histological differences have been reported between pediatric and adult nonalcoholic fatty liver disease (NAFLD), potential age-related changes in serum transaminases and liver histology remain largely unexplored. Our study sought to investigate the clinical and histological characteristics of NAFLD across age. METHODS: This was a prospective cross-sectional study of 502 biopsy-proven NAFLD patients. Clinical data were evaluated and compared among different age groups; group A (ages 18-44), B (ages 45-64), and C (≥ ages 65). RESULTS: 34.9, 56.0, and 9.1 % of the cohort were distributed among group A, B, and C, respectively. While the prevalence of nonalcoholic steatohepatitis (NASH) was comparable across age groups, the prevalence of advanced fibrosis increased with age (p = 0.000). Although the mean ALT progressively decreased with age; 87, 64, 56 U/L in group A, B, and C, respectively (p = 0.000), there was no difference in mean AST (p = 0.939) across age. The AST:ALT ratio (AAR) progressively increased from 0.7, 0.9, and 1.1 in group A, B, and C, respectively (p = 0.000). In group C, an AAR ≥ 1 was found in 74 and 40 % of patients with and without advanced fibrosis. CONCLUSION: With advancing age, ALT levels progressively declined while AST levels remained stable, leading to a higher AAR. Although higher AAR is often used as a surrogate measure of advanced fibrosis, advancing age can also contribute to increased AAR. In fact, an AAR ≥ 1 was found in significant number of elderly patients without advanced fibrosis. Consequently, an increased AAR may be a function of decreasing ALT with age in addition to progressive fibrosis.

Asunto(s)

Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Adolescente , Adulto , Factores de Edad , Anciano , Biomarcadores/sangre , Biopsia , Estudios Transversales , Femenino , Humanos , Cirrosis Hepática/epidemiología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Factores de Riesgo

RESUMEN

BACKGROUND & AIMS: Therapeutic options are limited for patients with non-alcoholic fatty liver disease (NAFLD). One promising approach is the attenuation of necroinflammation and fibrosis by inhibition of the renin-angiotensin system (RAS). We explored whether the risk of fibrosis was associated with the use of commonly used medications in NAFLD patients with hypertension. Specifically, we sought to determine the association between RAS blocking agents and severity of hepatic fibrosis in NAFLD patients with hypertension. METHODS: Cross-sectional study where clinical information including demographics, anthropometry, medical history, concomitant medication use, biochemical and histological features were ascertained in 290 hypertensive patients with biopsy proven NAFLD followed at two hepatology outpatient clinics. Stage of hepatic fibrosis was compared in patients with and without RAS blocker use. Other risk factors for fibrosis were evaluated from the electronic medical records and patient follow-up. RESULTS: Baseline characteristics of hypertensive patients treated with and without RAS blockers were similar except for less ballooning (1.02 vs. 1.31, P = 0.001) and lower fibrosis stage (1.63 vs. 2.16, P = 0.002) in patients on RAS blockers On multivariate analysis, advancing age (OR: 1.04; 95%CI: 1.01-1.06, P = 0.012) and presence of diabetes (OR: 2.55; 95%CI: 1.28-5.09, P = 0.008) had an independent positive association, while use of RAS blockers (OR: 0.37; 95%CI: 0.21-0.65, P = 0.001) and statins (OR: 0.52; 95%CI: 0.29-0.93, P = 0.029) had a negative association with advanced fibrosis. CONCLUSION: Hypertensive patients with NAFLD on baseline RAS blockers had less advanced hepatic fibrosis suggesting a beneficial effect of RAS blockers in NAFLD.

Asunto(s)

Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Hipertensión/tratamiento farmacológico , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Adulto , Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Estudios de Cohortes , Estudios Transversales , Femenino , Fibrosis , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Sistema Renina-Angiotensina/efectos de los fármacos

Asunto(s)

Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Hipertensión/tratamiento farmacológico , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Femenino , Humanos , Masculino

RESUMEN

BACKGROUND & AIMS: Current consensus suggests CD to be a multi-systemic disease that could affect any organ system including the liver. It remains under-diagnosed in the US and its prevalence and management in cirrhotic patients has not been studied. Our aim was (1) to estimate the prevalence of CD in cirrhosis, (2) to characterize cirrhotic patients with abnormal celiac serology and normal small bowel biopsy and (3) to evaluate the effect of a GFD on the liver. METHODS: A total of 204 consecutive patients with biopsy proven cirrhosis scheduled for an upper endoscopy (EGD) to assess and treat gastro-esophageal varices (GEV) at the Cleveland Clinic between 5/1/2008 and 5/30/2010 were enrolled in the study and followed for 2 years. RESULTS: CD affects 2.5% of cirrhotic patients and more than twice the prevalence in the general population. Abnormal EMA >1/10 and high hTTG levels >20 IU can be used to diagnose CD in cirrhosis. Sensitivities and specificities are 100% for EMA and 80% and 94% for hTTG, respectively. After a GFD, patients with CD showed a return to normal levels of their celiac serology, small bowel biopsy and liver enzyme abnormalities. CONCLUSIONS: CD is at least twice more common in cirrhotic patients than in the general population and GFD improves liver tests. CD can occur coincidentally with other liver disorders and screening may be warranted during the evaluation of patients with cirrhosis. Abnormal EMA and high hTTG levels can be used to diagnose CD in cirrhosis.

Asunto(s)

Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/epidemiología , Dieta Sin Gluten , Cirrosis Hepática/complicaciones , Cirrosis Hepática/dietoterapia , Adulto , Anciano , Biopsia , Enfermedad Celíaca/inmunología , Femenino , Humanos , Inmunoglobulina A/sangre , Intestino Delgado/patología , Hígado/enzimología , Cirrosis Hepática/enzimología , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Transglutaminasas/inmunología , Resultado del Tratamiento

RESUMEN

Fetuin-A is synthesized in the liver and may be associated with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Lifestyle-induced weight loss reduces fetuin-A, but the effect of exercise alone is unknown. We determined the effect of short-term exercise training on plasma fetuin-A in 13 (50.5 ± 3.4 yr) obese adults (body mass index, 33.3 ± 0.9 kg/m(2)) with clinically diagnosed NAFLD. Subjects participated in 7 days of supervised exercise training (60 min/day at ∼85% maximum heart rate) and were instructed to maintain their normal caloric and macronutrient intake. Insulin resistance was assessed by an oral glucose tolerance test. Hepatic triglyceride content (HTGC) was determined by proton MRI. We used C2C12 skeletal muscle cells to examine the direct effect of fetuin-A on 2-deoxyglucose uptake, insulin signaling [phosphorylation of Akt and AS160 (pAkt and pAS160, respectively)], and glucose transporter-4 (GLUT-4) translocation. Insulin resistance was reduced by 29% (P < 0.05), and glucose area under the curve (AUC) was decreased by 13% (P < 0.01) after the 7 days of exercise. Furthermore, circulating fetuin-A was decreased by 11% (4.2 ± 03 vs. 3.6 ± 0.2 nM; P < 0.02), and this change correlated with reduced insulin resistance (r = 0.62; P < 0.04) and glucose AUC (r = 0.58; P < 0.04). Importantly, the exercise program did not change body weight (P = 0.12), HTGC (P = 0.73), or aerobic capacity (P = 0.14). In vitro experiments revealed that fetuin-A decreased skeletal muscle glucose uptake by downregulating pAkt and pAS160 and subsequent GLUT-4 translocation to the plasma membrane. Together, our findings highlight a role for fetuin-A in skeletal muscle insulin resistance and suggest that part of the exercise-induced improvement in glucose tolerance in patients with NAFLD may be due to lowering fetuin-A.

Asunto(s)

Glucemia/metabolismo , Ejercicio Físico/fisiología , Hígado Graso/metabolismo , Hígado Graso/fisiopatología , alfa-2-Glicoproteína-HS/metabolismo , Índice de Masa Corporal , Peso Corporal/fisiología , Células Cultivadas , Desoxiglucosa/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa/métodos , Transportador de Glucosa de Tipo 4/metabolismo , Humanos , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Células Musculares/metabolismo , Células Musculares/fisiología , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Enfermedad del Hígado Graso no Alcohólico , Obesidad/metabolismo , Obesidad/fisiopatología , Triglicéridos/metabolismo

RESUMEN

Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.

Asunto(s)

Colitis Colagenosa/diagnóstico , Colitis Linfocítica/diagnóstico , Colitis Ulcerosa/diagnóstico , Colon/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Colitis Colagenosa/clasificación , Colitis Colagenosa/patología , Colitis Colagenosa/terapia , Colitis Linfocítica/clasificación , Colitis Linfocítica/patología , Colitis Linfocítica/terapia , Colitis Ulcerosa/clasificación , Colitis Ulcerosa/patología , Colitis Ulcerosa/terapia , Colonoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Inducción de Remisión , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

CONTEXT: Hepatic steatosis, insulin resistance, inflammation, low levels of polyunsaturated lipids, and adiponectin are implicated in the development and progression of nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: We examined the effects of short-term aerobic exercise on these metabolic risk factors. DESIGN AND PARTICIPANTS: Obese individuals (N = 17, 34.3 ± 1.0 kg/m²) with clinically confirmed NAFLD were enrolled in a short-term aerobic exercise program that consisted of 7 consecutive days of treadmill walking at ~85% of maximal heart rate for 60 minutes per day. Preintervention and postintervention measures included hepatic triglyceride content, and a lipid saturation index and polyunsaturated lipid index (PUI) of the liver, obtained by (1)H magnetic resonance spectroscopy (N = 14). Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT), and mononuclear cells were isolated to assess reactive oxygen species production during the OGTT. Circulating glucose, insulin, and high molecular weight (HMW) adiponectin were determined from plasma. MAIN OUTCOME: Short-term aerobic exercise training improved hepatic lipid composition in patients with NAFLD. RESULTS: Exercise training resulted in an increase in liver PUI (P < .05), increased insulin sensitivity (Matsuda Index: P < .05), HMW adiponectin (P < .05), and maximal oxygen consumption (P < .05). Reactive oxygen species production during the OGTT was reduced following exercise training (P < .05). HMW adiponectin was increased after the exercise program and the increase was positively correlated with the increase in liver PUI (r = 0.52, P = .05). Body weight remained stable during the program (P > .05). CONCLUSION: Short-term exercise can target hepatic lipid composition, which may reduce the risk of NAFLD progression. The improvement in hepatic lipid composition may be driven by adiponectin.

Asunto(s)

Hígado Graso/prevención & control , Metabolismo de los Lípidos , Hígado/metabolismo , Actividad Motora , Obesidad/terapia , Estrés Oxidativo , Adiponectina/sangre , Adiponectina/química , Adiponectina/metabolismo , Biomarcadores/sangre , Índice de Masa Corporal , Ejercicio Físico , Hígado Graso/epidemiología , Hígado Graso/etiología , Femenino , Humanos , Resistencia a la Insulina , Grasa Intraabdominal/inmunología , Grasa Intraabdominal/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Hígado/inmunología , Masculino , Persona de Mediana Edad , Peso Molecular , Enfermedad del Hígado Graso no Alcohólico , Obesidad/inmunología , Obesidad/metabolismo , Obesidad/fisiopatología , Ohio/epidemiología , Factores de Riesgo , Triglicéridos/metabolismo , Caminata

RESUMEN

BACKGROUND & AIMS: Celiac disease is underdiagnosed, with nonspecific symptoms and high morbidity. New diagnostic factors are needed. We aimed to estimate the frequency at which adult patients with positive results from serology tests are referred for small-bowel biopsies and to identify factors that improve the diagnosis of celiac disease. METHODS: We performed a retrospective analysis of data from 2477 subjects who received serology tests for celiac disease between 2005 and 2007. We analyzed results for total levels of IgA, IgA against human tissue transglutaminase (hTTG), IgA and IgG against gliadin, as well as dilution titers of IgA against endomysial antibodies (EMA). Biopsy samples were analyzed by pathologists experienced in detecting mucosal changes associated with celiac disease and graded according to the Marsh system. RESULTS: Of the 2477 patients, 610 (25%) had abnormal results from serology tests, and 39% of these patients (240 of 610) underwent small-bowel biopsy analyses. Of these patients, 50 (21%) had biopsy findings consistent with celiac disease (Marsh 3 lesions) and were placed on gluten-free diets. Titers of IgA hTTG greater than 118 U identified patients with celiac disease with a 2% false-positive rate. Titers of 21 to 118 U, in combination with an EMA dilution titer of 1:160 or greater, had a positive predictive value of 83% for celiac disease. IgA hTTG levels less than 20 U, in combination with an EMA dilution titer less than 1:10, had a negative predictive value of 92% for celiac disease. CONCLUSIONS: Serum levels of IgA hTTG greater than 118 U, or 21 to 118 U in combination with an EMA dilution titer of 1:160 or greater, can be used to identify adult symptomatic patients with celiac disease, in the absence of a small-bowel biopsy.

Asunto(s)

Enfermedad Celíaca/diagnóstico , Adulto , Anciano , Autoanticuerpos/sangre , Femenino , Gliadina/inmunología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Pruebas Serológicas/métodos , Transglutaminasas/inmunología

RESUMEN

Patients with nonalcoholic fatty liver (NAFLD) are typically obese and confounded by the metabolic syndrome. The body mass index (BMI) is often used as a surrogate marker of obesity defined as a BMI >30 λkg/m(2). However, it is now apparent that it is the distribution of body fat (not total fat) that is associated with NAFLD. Many patients (as many as 25%) with NAFLD are nonobese. This is particularly true in Asians who have a significantly increased risk of cardiovascular disease and diabetes even among those with a normal BMI. It is important for clinicians to be aware that these "metabolically obese" NAFLD patients should be monitored for the metabolic syndrome and its associated adverse outcomes irrespective of their BMI.

Asunto(s)

Pueblo Asiatico/estadística & datos numéricos , Índice de Masa Corporal , Hígado Graso/epidemiología , Síndrome Metabólico/epidemiología , Obesidad/epidemiología , Femenino , Humanos , Masculino , Enfermedad del Hígado Graso no Alcohólico