RESUMEN
OBJECTIVES: Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear. METHODS: We investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of â¼4 years. RESULTS: A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child-Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800-1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50 × 103/µl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11-3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16-3.62; P=0.013) independently predicted overall bleeding events. CONCLUSIONS: Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.
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Hemorragia Gastrointestinal/epidemiología , Cirrosis Hepática/epidemiología , Trombocitopenia/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Hemorragia/epidemiología , Humanos , Relación Normalizada Internacional , Italia/epidemiología , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Tiempo de Protrombina , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: To assess the pattern of in-hospital changes in drug use in older patients from 2010 to 2016. METHODS: People aged 65 years or more acutely hospitalized in those internal medicine and geriatric wards that did continuously participate to the REgistro POliterapie Società Italiana di Medicina Interna register from 2010 to 2016 were selected. Drugs use were categorized as 0 to 1 drug (very low drug use), 2 to 4 drugs (low drug use), 5 to 9 drugs (polypharmacy), and 10 or more drugs (excessive polypharmacy). To assess whether or not prevalence of patients in relation to drug use distribution changed overtime, adjusted prevalence ratios (PRs) was estimated with log-binomial regression models. RESULTS: Among 2120 patients recruited in 27 wards continuously participating to data collection, 1882 were discharged alive and included in this analysis. The proportion of patients with very low drug use (0-1 drug) at hospital discharge increased overtime, from 2.7% in 2010 to 9.2% in 2016. Results from a log-logistic adjusted model confirmed the increasing PR of these very low drug users overtime (particularly in 2014 vs 2012, PR 1.83 95% CI 1.14-2.95). Moreover, from 2010 to 2016, there was an increasing number of patients who, on polypharmacy at hospital admission, abandoned it at hospital discharge, switching to the very low drug use group. CONCLUSION: This study shows that in internal medicine and geriatric wards continuously participating to the REgistro POliterapie Società Italiana di Medicina Interna register, the proportion of patients with a very low drug use at hospital discharge increased overtime, thus reducing the therapeutic burden in this at risk population.
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Prescripciones de Medicamentos/estadística & datos numéricos , Pacientes Internos , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Medicina Interna/normas , Italia , Masculino , Polifarmacia , Sistema de Registros , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: A link between increased blood viscosity and type 2 diabetes has been previously reported. Herein, we investigated the association of blood viscosity with prediabetes, identified by glycated hemoglobin A1c (HbA1c) according to the new American Diabetes Association criteria, and subclinical atherosclerosis. METHODS AND RESULTS: The study cohort includes 1136 non-diabetic adults submitted to anthropometrical evaluation, an oral glucose tolerance test and ultrasound measurement of carotid intima-media thickness (IMT). Whole blood viscosity was estimated using a validated formula based on hematocrit and total plasma proteins. After adjusting for age, and gender, individuals with HbA1c-defined prediabetes (HbA1c 5.7-6.4% [39-47 mmol/mol]) exhibited significantly higher values of hematocrit, and predicted blood viscosity as compared with controls. Increased levels of IMT were observed in subjects with HbA1c-defined prediabetes in comparison to controls. Predicted blood viscosity was positively correlated with age, waist circumference, blood pressure, cholesterol, triglycerides, fibrinogen, white blood cell, HbA1c, fasting and 2-h post-load glucose levels, fasting insulin, IMT and inversely correlated with HDL and Matsuda index of insulin sensitivity. Of the three glycemic parameters, i.e. HbA1c, fasting and 2-h post-load glucose, only HbA1c showed a significant correlation with predicted blood viscosity (ß = 0.054, P = 0.04) in a multivariate regression analysis model including multiple atherosclerosis risk factors. CONCLUSION: The study shows that individuals with HbA1c-defined prediabetes have increased predicted blood viscosity and IMT. The HbA1c criterion may be helpful to capture individuals with an increased risk of diabetes and cardiovascular disease who may benefit from an intensive lifestyle intervention.
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Viscosidad Sanguínea , Enfermedades Cardiovasculares/etiología , Hemoglobina Glucada/análisis , Hemorreología , Estado Prediabético/sangre , Estado Prediabético/fisiopatología , Adulto , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/fisiopatología , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Hematócrito , Humanos , Masculino , Persona de Mediana Edad , Estado Prediabético/complicaciones , Estado Prediabético/diagnóstico , Valor Predictivo de las Pruebas , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: Recent data demonstrated that serum phosphorus, within the normal range, is an independent predictor of atherosclerotic cardiovascular disease, independently of renal function. Traditional cardiovascular risk factors are important mediators of endothelial dysfunction, the early step of atherosclerosis. We designed this study to evaluate a possible correlation between serum phosphorus and endothelium-dependent vasodilation, evaluated by the strain-gauge plethysmography, in naïve hypertensives. METHODS AND RESULTS: We investigated by strain-gauge plethysmography, the relationship between forearm blood flow (FBF) response to acetylcholine (ACh) and serum phosphorus in 500 patients with uncomplicated, never-treated, essential hypertension, divided by phosphorus tertiles. There were no significant differences among tertiles with the exclusion of forearm blood flow (FBF). Phosphorus (ß = -0.454; P = 0.0001), estimated-glomerular filtration rate (e-GFR, by CKD-EPI formula) (ß = 0.261; P = 0.0001), gender (ß = 0.215; P = 0.0001), BMI (ß = -0.086; P = 0.018), HDL-cholesterol (ß = 0.077; P = 0.036) were significantly related to endothelium-dependent vasodilation. In an additional analysis including serum high sensitivity C-reactive protein (hs-CRP) (measured in 400 patients) in the same model, the link between serum phosphorus and ACh-stimulated FBF did not change (ß = -0.422; P = 0.0001). Clinically relevant, 0.1 mg of phosphorus increase is associated with a reduction of 22% of ACh-stimulated FBF. On multiple logistic regression analysis, the risk of endothelial dysfunction was about twice higher in patients in the second (OR = 1.754, 95% CI = 1.055-2.915; P = 0.030) and three-fold higher in the third tertile (OR = 2.939, 95% CI = 1.598-5.408; P = 0.0001) in comparison with those in the first tertile of phosphorus. CONCLUSION: An impaired ACh-stimulated FBF is associated with serum phosphorus levels, within the normal range, in hypertensives.
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Endotelio Vascular/fisiopatología , Antebrazo/irrigación sanguínea , Hipertensión/sangre , Hipertensión/fisiopatología , Fósforo/sangre , Vasodilatación , Acetilcolina/administración & dosificación , Adulto , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Estudios Transversales , Diagnóstico Precoz , Endotelio Vascular/efectos de los fármacos , Femenino , Humanos , Hipertensión/diagnóstico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Pletismografía , Valor Predictivo de las Pruebas , Factores de Riesgo , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificaciónRESUMEN
BACKGROUND AND AIMS: To evaluate if complement C3 is associated with insulin secretion, as suggested by recent in vitro studies, independently of confounders including adiposity measures. METHODS AND RESULTS: 1010 nondiabetic subjects were stratified into quartiles according to complement C3 values. Insulin secretion was assessed using indexes derived from oral glucose tolerance test (OGTT) in the whole study group and from intravenous glucose tolerance test (IVGTT) in a subgroup (n = 110). Significant differences between quartiles of C3 were observed in body mass index (BMI), waist, fat mass, blood pressure, total cholesterol, high density lipoprotein (HDL), triglycerides, fasting and 2-h post-load glucose, fasting insulin, C reactive protein (hsCRP), fibrinogen, aspartate aminotransferase (AST), alanine aminotransferase (ALT), complement C4, and insulin sensitivity with C3 quartiles exhibiting graded increases in cardio-metabolic risk factors. Differences in insulin secretion indexes between C3 quartiles remained significant after adjustment for age, gender, BMI, insulin sensitivity, blood pressure, total cholesterol, HDL, triglycerides, hsCRP, fibrinogen, and complement C4 levels (P < 0.0001). A multivariable regression analysis revealed that complement C3 is a contributor of insulin secretion, explaining 2.4% and 1.9% of variation of the Stumvoll index for first-phase and second-phase insulin secretion, respectively, and 2.1% of variation of the InsAUC30/GluAUC30 index, independently of gender, age, BMI, waist, fat mass, blood pressure, total cholesterol, HDL, triglycerides, hsCRP, fibrinogen, AST, ALT. CONCLUSIONS: Complement C3 concentrations are associated with insulin secretion independently of important determinants of glucose homeostasis such as gender, age, adiposity, subclinical inflammation, and insulin sensitivity.
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Adiposidad , Complemento C3/análisis , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Obesidad/sangre , Sobrepeso/sangre , Adulto , Índice de Masa Corporal , Complemento C4/análisis , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Resistencia a la Insulina , Secreción de Insulina , Italia/epidemiología , Masculino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/etiología , Persona de Mediana Edad , Obesidad/inmunología , Obesidad/metabolismo , Obesidad/fisiopatología , Sobrepeso/inmunología , Sobrepeso/metabolismo , Sobrepeso/fisiopatología , Factores de Riesgo , Circunferencia de la CinturaRESUMEN
BACKGROUND AND AIMS: The A1C diagnostic criterion for identifying individuals at increased risk for diabetes, introduced by the American Diabetes Association in 2010, was not defined on the basis of the principal pathophysiological abnormalities responsible for the development and progression of type 2 diabetes; we therefore wished to gain a deeper insight into the metabolic abnormalities characterizing the group of at risk individuals with an A1C value of 5.7-6.4%. METHODS AND RESULTS: As many as 338 non-diabetic offspring of type 2 diabetic patients were consecutively recruited. Insulin secretion was assessed using both indexes derived from oral glucose tolerance test (OGTT), and intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. As compared with subjects with A1C <5.7%, individuals with A1C of 5.7-6.4% exhibited lower insulin sensitivity after adjusting for age, gender and body mass index (BMI). Insulin secretion estimated from the OGTT, did not differ between the two groups. By contrast, as compared with subjects with A1C <5.7%, the acute insulin response (AIR) during an IVGTT and both IVGTT-derived and OGTT-derived disposition indexes were reduced in individuals with A1C of 5.7-6.4% after adjusting for age, gender and BMI. As A1C increased to ≥ 5.7%, a sharp decrease in insulin sensitivity and ß-cell function, measured as disposition index, was observed. CONCLUSIONS: Caucasian individuals with A1C ≥ 5.7% exhibit both core pathophysiological defects of type 2 diabetes i.e. insulin resistance and ß-cell dysfunction.
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Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina Glucada/metabolismo , Resistencia a la Insulina/fisiología , Células Secretoras de Insulina/metabolismo , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Técnica de Clampeo de la Glucosa , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/metabolismo , Secreción de Insulina , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND AIMS: Normoglucosetolerants (NGT) are considered at low risk, even if a 1-h post-load glucose (PLG) value ≥ 155 mg dl(-1) identifies NGTs at high risk of type-2 diabetes (T2D) and sub-clinical organ damage. Specific dietary factors may affect insulin sensitivity and the risk of T2D. However, it is unknown whether dietary components affect 1-h PLG in hypertensive NGT. Therefore, we investigate the effect of dietary patterns on 1-h PLG. METHODS AND RESULTS: We selected 188 subjects (94 NGTs < 155 mg dl(-1) and 94 NGTs ≥ 155 mg dl(-1) PLG), well matched for age, gender and body mass index (BMI). Insulin sensitivity was evaluated using the Matsuda index. Dietary intake was quantified by a semiquantitative food frequency questionnaire (FEQ) validated in the European Investigation into Cancer and Nutrition (EPIC) study. The NGT ≥ 155 group had significantly reduced insulin sensitivity (40.3 ± 19.8 vs. 73.3 ± 28.8; P < 0.0001). With the exclusion of total calories, lipids, alcohol and fiber consumption we observed a significant difference, between groups, in starch (214.1 ± 52.4 vs. 268.8 ± 71.8 g; P < 0.0001), saturated (27.4 ± 8.7 vs. 24.1 ± 8.5 g; P = 0.009), monounsaturated (45.5 ± 8.9 vs. 48.8 ± 10.7 g; P = 0.023) and polyunsaturated fatty acids (FAs) (14.5 ± 4.0 vs. 16.8 ± 4.7 g; P < 0.0001), fructose (14.5 ± 5.3 vs. 11.2 ± 4.8 g; P < 0.0001), and oligosaccharides (103.2 ± 26.6 vs. 89.9 ± 29.2 g; P = 0.001) consumption. In the whole population, starch was the major predictor of 1-h PLG, explaining 23.2% of variation (P < 0.0001). In the NGT < 155 group, fructose was the strongest predictor, accounting for 15.4% of the variation; BMI, gender and polyunsaturated FAs added another 6.6%, 3.6% and 3.2%, respectively. In the NGT ≥ 155 group, saturated and polyunsaturated FAs were retained as the major predictors of 1-h PLG, explaining 18.2% and 11.4% of the variation. CONCLUSIONS: The present data demonstrate that dietary patterns affect 1-h PLG, remarking the importance of both quantitative and qualitative composition of a diet.
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Glucemia/metabolismo , Conducta Alimentaria , Hipertensión/dietoterapia , Adulto , Presión Sanguínea , Índice de Masa Corporal , HDL-Colesterol/sangre , Creatinina/sangre , Diabetes Mellitus Tipo 2/prevención & control , Dieta , Fibras de la Dieta/administración & dosificación , Ingestión de Energía , Hipertensión Esencial , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Periodo Posprandial/fisiología , Encuestas y Cuestionarios , Población BlancaRESUMEN
BACKGROUND AND AIMS: Low insulin-like growth factor-1 (IGF-1) levels and high uric acid concentrations are associated with cardio-metabolic disorders. Acute IGF-1 infusion decreases uric acid concentration in healthy individuals. In this study, we aimed to examine the relationship between IGF-1 and uric acid levels. METHODS AND RESULTS: 1430 adult non diabetic subjects were stratified into quartiles according to their circulating IGF-1 values. Significant differences in uric acid concentration, measured by the URICASE/POD method were observed between low (quartile 1), intermediate (quartile 2 and 3), and high (quartile 4) IGF-1 levels groups after adjusting for age, gender, and body mass index (P = 0.02). These differences remained significant after adjustment for blood pressure, total cholesterol, high density lipoprotein, triglycerides, fasting and 2 h post-load glucose levels, HOMA-IR index (P = 0.005), liver enzymes (P = 0.03), glucose tolerance status (P = 0.02), growth hormone levels (GH) (P = 0.05), anti-hypertensive treatments (P = 0.04) or diuretics use (P = 0.04)). To clarify the molecular links between IGF-1 and uric acid, we performed an in vitro study, incubating human hepatoma cells with uric acid for 24 or 48 h in the presence of GH and observed a 21% and 26% decrease, respectively, in GH-stimulated IGF-1 mRNA expression (P = 0.02 and P = 0.012, respectively). This effect appears to be mediated by uric acid ability to down regulate GH intracellular signaling; in fact we observed a significant decrease of GH activated JAK2 and Stat5 phosphorylation. CONCLUSIONS: These data demonstrate an inverse relationship between IGF-1 and uric acid levels in adults and suggest that uric acid might affect hepatic IGF-1 synthesis.
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Factor I del Crecimiento Similar a la Insulina/metabolismo , Ácido Úrico/sangre , Adulto , Anciano , Antropometría , Glucemia/metabolismo , Línea Celular Tumoral , Estudios de Cohortes , Femenino , Prueba de Tolerancia a la Glucosa , Hormona de Crecimiento Humana/sangre , Humanos , Lípidos/sangre , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is linked with insulin resistance, however, if it is differentially associated with surrogate hepatic insulin resistance indexes is still undefined. We examined the relationship between these indexes, NAFLD and its related biomarkers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [GGT], alkaline phosphatase [ALK], high-sensitive C reactive protein [hsCRP], insulin-like growth factor-1 [IGF-1]). METHODS AND RESULTS: 473 Caucasians subjects underwent liver ultrasonography and oral glucose tolerance tests; homeostasis model assessment (HOMA), glucose(0-30) (area under the curve [AUC]) × insulin(0-30) (AUC) and liver insulin resistance (liver IR) indexes were computed. Liver IR index correlated more strongly than HOMA with GGT, ALK, hsCRP, ALT and AST and more strongly than glucose(0-30) (AUC) × insulin(0-30) (AUC) index with ALT, AST, GGT, ALK, hsCRP, and IGF-1. The ability of these indexes to identify NAFLD was evaluated by the area under the ROC curve; the ROC AUC for liver IR index was higher (0.733) than the ones for HOMA (0.685) and glucose(0-30) (AUC) × insulin(0-30) (AUC) (0.663) indexes. In a logistic regression model subjects in the highest quartile of the three indexes had a higher risk of having NAFLD than those in the lowest quartile (9.85-, 5.12- or 3.99-fold higher for liver IR index, HOMA, glucose(0-30) (AUC) × insulin(0-30) (AUC) index respectively). CONCLUSIONS: we documented significant cross-sectional associations of NAFLD and liver biomarkers with three validated indexes of hepatic insulin resistance, with liver IR index showing the stronger correlation.
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Biomarcadores/sangre , Hígado Graso/sangre , Hígado Graso/fisiopatología , Resistencia a la Insulina , Hígado/metabolismo , Adulto , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Área Bajo la Curva , Aspartato Aminotransferasas/sangre , Glucemia/metabolismo , Composición Corporal , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Ultrasonografía , Circunferencia de la Cintura , Población Blanca , gamma-Glutamiltransferasa/sangreRESUMEN
BACKGROUND AND AIMS: The American Diabetes Association (ADA) has revised criteria for diagnosis of type 2 diabetes recommending an A1C cut point of ≥6.5% in addition to criteria based on glucose levels. We compared A1C, fasting plasma glucose (FPG) or 2-h post-challenge glucose (2-hPG) criteria for the diagnosis of diabetes in a cohort of Italian Caucasians. METHODS AND RESULTS: A total of 1019 individuals without known diabetes completed an oral glucose tolerance test (OGTT) and had A1C measured. Moderate agreement existed for A1C and FPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.522), with 85.5% of individuals classified as not having diabetes by both A1C and FPG criteria, and 5.8% classified as having diabetes by both A1C and FPG criteria. Discordant classifications occurred for 5.5% of individuals who had an A1C ≥ 6.5% and FPG <126 mg dl(-1), and for 3.2% who had an A1C <6.5% and FPG ≥126 mg dl(-1). Modest agreement existed for A1C and 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.427), with 81.8% of individuals classified as not having diabetes by both A1C and 2-hPG criteria, and 6.0% classified as having diabetes by both A1C and 2-hPG criteria. The area under the receiver operating characteristic curve of A1C for identifying subjects with diabetes according to FPG or 2-hPG criteria was 0.856 and 0.794, respectively. Modest agreement existed for A1C and FPG and/or 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.446). CONCLUSIONS: A1C ≥ 6.5% demonstrates a moderate agreement with fasting glucose and 2-hPG for diagnosing diabetes among adult Italian Caucasians subjects.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina Glucada/análisis , Población Blanca , Adulto , Cromatografía Líquida de Alta Presión , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Ayuno , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Curva ROC , Factores de RiesgoAsunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/etiología , Prueba de Tolerancia a la Glucosa , Hiperglucemia/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Progresión de la Enfermedad , Femenino , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/complicaciones , Intolerancia a la Glucosa/diagnóstico , Humanos , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease, characterized by insulin resistance, has been correlated with several clinical and pathological manifestations, such as intima-media thickness. At present, no data are available regarding endothelial dysfunction, the first step in atherosclerosis, and non-alcoholic fatty liver disease. The aim of this study was to test a possible association between non-alcoholic fatty liver disease and endothelium-dependent vasodilation in a group of hypertensive patients. METHODS AND RESULTS: A total of 40 never-treated uncomplicated hypertensive outpatients were enrolled. Patients underwent a complete clinical and biochemical work-up including ultrasonographic scanning to detect liver steatosis. Insulin sensitivity was estimated by using the homeostasis model assessment (HOMA) index. Endothelial function was assessed by strain-gauge plethysmography during intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside. Endothelium-dependent vasodilation was significantly reduced in hypertensive patients with liver steatosis in comparison with those without. Statistical analysis demonstrated that the HOMA index was the strongest predictor of both endothelium-dependent vasodilation and liver steatosis. In particular, one point of HOMA accounts for 37.9% of forearm blood flow variation, and increases the risk of liver steatosis by 86.4%. CONCLUSION: Our data demonstrate that hypertensive patients with liver steatosis have a reduced endothelium-dependent vasodilation and highest insulin resistance. In keeping with this, it is possible to hypothesize that liver steatosis may be considered a marker of vascular damage in essential hypertension.
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Aterosclerosis/etiología , Endotelio Vascular/fisiopatología , Hígado Graso/etiología , Hipertensión/fisiopatología , Acetilcolina/farmacología , Adulto , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Biomarcadores , Estudios Transversales , Relación Dosis-Respuesta a Droga , Diagnóstico Precoz , Endotelio Vascular/efectos de los fármacos , Hígado Graso/diagnóstico por imagen , Femenino , Humanos , Hipertensión/complicaciones , Resistencia a la Insulina , Italia/epidemiología , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Nitroprusiato/farmacología , Pletismografía , Factores de Riesgo , Ultrasonografía , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND AND AIMS: Metabolically healthy but obese (MHO) subjects have a favourable cardio-metabolic risk profile, but whether they are also at lower risk for kidney dysfunction is still questionable. METHODS AND RESULTS: A total of 106 MHO, 122 normal-weight and 212 insulin-resistant obese (IRO) subjects were stratified on the basis of their insulin sensitivity and body mass index (BMI). The CKD-EPI equation was used to estimate glomerular filtration rate (eGFR) and ISI index was used to estimate insulin sensitivity. eGFR was significantly lower in IRO as compared to MHO subjects after adjusting for age, gender and BMI (P = 0.008). In a logistic regression model adjusted for age, gender and BMI, IRO subjects showed an increased risk of having eGFR in the lowest quartile (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.01-3.58; P = 0.04) as compared with MHO subjects. This association was maintained when waist, lean body mass, blood pressure, HDL cholesterol, triglyceride, fasting glucose and insulin levels were additionally included into the model (OR 2.49, 95%CI 1.17-5.27; P = 0.01), but its independence was not retained with further inclusion of insulin-like growth factor-1 (IGF-1) levels (OR 2.16, 95%CI 0.93-5.04; P = 0.07) No differences in eGFR were observed between non-obese and MHO individuals. CONCLUSIONS: These results indicate that heterogeneity in obese phenotypes may account for conflicting evidence regarding the significance of obesity as a risk factor for chronic kidney disease. Our findings suggest that obesity is associated with lower kidney function only when insulin sensitivity is reduced, and that plasma IGF-1 is likely to be an important mechanism linking the IRO phenotype with reduced eGFR.
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Tasa de Filtración Glomerular , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/análisis , Obesidad/sangre , Obesidad/metabolismo , Insuficiencia Renal/etiología , Adulto , Anciano , Algoritmos , Índice de Masa Corporal , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Italia/epidemiología , Riñón/fisiopatología , Modelos Logísticos , Masculino , Síndrome Metabólico/etiología , Persona de Mediana Edad , Obesidad/fisiopatología , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: Glucose-tolerant subjects who have 1-h post-load glucose levels ≥155 mg dl(-1) (normal glucose tolerance (NGT)-1h-high) are at an increased risk of developing type 2 diabetes. Prospectively conducted studies indicated that high levels of liver enzymes are predictors of a tendency to develop type 2 diabetes; however, it is unknown whether the NGT-1h-high subjects are at increased risk for secreting higher levels of liver biomarkers. METHODS AND RESULTS: In this study, oral glucose tolerance tests (OGTTs) were performed in a cohort of 1000 non-diabetic Caucasians and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were measured in these subjects. The NGT-1h-high subjects had increased levels of ALT and GGT, but not AST, as compared with the NGT-1h-low. Following adjustment for age and gender, the ALT, AST and GGT levels were all found to be significantly correlated with body mass index (BMI), waist circumference, blood pressure, triglycerides as well as fasting and post-challenge glucose and insulin levels. In a logistic regression analysis adjusted for age and gender, NGT-1h-high subjects were found to be at increased risk of having ALT levels in the highest quartile as compared with NGT-1h-low subjects (odds ratio (OR) = 1.71; 95% confidence interval (CI): 1.16-2.52). In addition, NGT-1 h-high subjects exhibited an increased risk for having GGT levels in the highest quartile (OR = 1.50; 95%CI: 1.02-2.17). These associations remained significant after adjustment for BMI, blood pressure and lipids, but were not significant following further adjustment for an insulin sensitivity index. NGT-1h-high subjects were at increased risk of having AST levels in the highest quartile as compared with NGT-1h-low subjects (OR = 1.51; 95%CI: 1.04-2.22). This association ceased to be significant following adjustment for BMI, blood pressure and lipids. CONCLUSIONS: These data suggest that a 1hPG ≥ 155 mg dl(-1) cut-off may facilitate the identification of NGT individuals at risk of developing liver abnormalities.
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Glucemia/análisis , Hígado/enzimología , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Índice de Masa Corporal , Estudios Transversales , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Triglicéridos/sangre , Población Blanca , gamma-Glutamiltransferasa/sangreRESUMEN
BACKGROUND AND AIM: Weight gain is associated with a decline in insulin sensitivity and a compensatory increase in insulin secretion. IGF-1 is a plausible candidate to explain these divergent phenomena. In this cross-sectional study, we analyzed the relationship between IGF-1 levels, insulin sensitivity and secretion in 110 nondiabetic subjects with a wide range of BMI to verify this hypothesis. METHODS AND RESULTS: Subjects underwent OGTT, IVGTT and euglycemic-hyperinsulinemic clamp. HOMA-beta, IVGTT-derived and OGTT-derived indexes for first-phase and second-phase insulin secretion were higher in obese as compared with overweight and normal-weight groups, while glucose disposal was lower. IGF-1 levels were negatively correlated with IVGTT-derived and OGTT-derived indexes first-phase and second-phase insulin secretion, and positively correlated with glucose disposal. These correlations were no longer significant after adjustment for BMI. In a multivariate analysis, the variables associated with glucose disposal were IGF-1, age, triglycerides, and 2-h post-load glucose accounting for 23.4% of its variation. When BMI was entered into the model, the variables associated with glucose disposal were triglycerides, 2-h post-load glucose and BMI accounting for 27.2% of variation. In a multivariate analysis, the only variable associated with IVGTT-derived first-phase and second-phase insulin secretion was IGF-1 accounting for 10.4% and 15.1% of variation, respectively. When BMI was entered into the model, it became the only variable associated with both first-phase and second-phase insulin secretion accounting for 25.7% and 37.6% of variation, respectively. CONCLUSION: These data suggest that progressive reduction in IGF-1 levels may be involved in obesity-related changes in both insulin sensitivity and secretion.
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Adiposidad , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/análisis , Insulina/metabolismo , Adulto , Anciano , Envejecimiento , Glucemia/análisis , Índice de Masa Corporal , Estudios Transversales , Femenino , Técnica de Clampeo de la Glucosa , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Secreción de Insulina , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Sobrepeso/sangre , Sobrepeso/complicaciones , Triglicéridos/sangre , Población Blanca , Adulto JovenRESUMEN
BACKGROUND: Pneumonia causes more deaths than any other infectious disease, especially in older patients with multiple chronic diseases. Recent studies identified a low functional status as prognostic factor for mortality in elderly patients with pneumonia while contrasting data are available about the role of diabetes. The aim of this study was to evaluate the in-hospital, 3-month and 1-year mortality in elderly subjects affected by pneumonia enrolled in the RePoSi register. METHODS: We retrospectively analyzed the data collected on hospitalized elderly patients in the frame of the REPOSI project. We analyzed the socio-demographic, laboratory and clinical characteristics of subjects with pneumonia. Multivariate logistic analysis was used to explore the relationship between variables and mortality. RESULTS: Among 4714 patients 284 had pneumonia. 52.8% were males and the mean age was 80â¯years old. 19.8% of these patients had a Barthel Index ≤40 (pâ¯Ëâ¯0.0001), as well as 43.2% had a short blessed test ≥10 (pâ¯Ëâ¯0.0117). In these subjects a significant CIRS for the evaluation of severity and comorbidity indexes (pâ¯Ëâ¯0.0001) were present. Although a higher fasting glucose level was identified in people with pneumonia, in the multivariate logistic analysis diabetes was not independently associated with in-hospital, 3-month and 1-year mortality, whereas patients with lower Barthel Index had a higher mortality risk (odds ratio being 9.45, 6.84, 19.55 in hospital, at 3 and 12â¯months). CONCLUSION: Elderly hospitalized patients affected by pneumonia with a clinically significant disability had a higher mortality risk while diabetes does not represent an important determinant of short and long-term outcome.
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Personas con Discapacidad/estadística & datos numéricos , Evaluación Geriátrica/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Neumonía/mortalidad , Anciano , Anciano de 80 o más Años , Comorbilidad , Diabetes Mellitus/epidemiología , Femenino , Humanos , Italia/epidemiología , Modelos Logísticos , Masculino , Análisis Multivariante , Neumonía/etiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by "Federico II" University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF.
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Enfermedades Carenciales/metabolismo , Insuficiencia Cardíaca/metabolismo , Enfermedades Metabólicas/metabolismo , Anciano , Biomarcadores/metabolismo , Enfermedad Crónica , Progresión de la Enfermedad , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de RegistrosRESUMEN
BACKGROUND: Recent randomized trials on hormone replacement therapy in postmenopausal women raised many doubts about their role in cardiovascular disease prevention. Therefore the role of other sex hormones needed to be investigated. In particular androgens seem to have a protective role on atherosclerosis. The present study was performed to assess the role of endogenous sex hormones on carotid atherosclerosis in postmenopausal women. METHODS AND RESULTS: We consecutively enrolled 101 postmenopausal women aged 45-75 (mean age 57.4) years referred to our University hospital menopausal health-screening clinic. The subjects underwent a medical history, a physical examination and biochemical analysis. Extracranial carotid arteries were assessed by ultrasound. Fifty percent of our sample had carotid plaques. On the multivariate logistic regression analysis age, glycaemia (positively) and testosterone (negatively) (P=0.02) were significantly correlated to carotid atherosclerosis. In non-obese subjects we found that participants in the third tertile had a significantly lower prevalence of carotid atherosclerosis (P=0.02) compared to those in the first tertile of testosterone. CONCLUSIONS: These results suggest a possible protective role of endogenous androgens at least on carotid atherosclerosis. Of course these preliminary results should be supported by prospective studies. Also the different role of these hormones on obese and non-obese subjects needs to be clarified.
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Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Testosterona/sangre , Factores de Edad , Anciano , Glucemia/metabolismo , Estrógenos/sangre , Estrógenos/fisiología , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Posmenopausia/sangre , Factores de Riesgo , Testosterona/fisiología , UltrasonografíaRESUMEN
PURPOSE: To compare the effect of liraglutide, sitagliptin and insulin glargine added to standard therapy on left ventricular function in post-ischemic type-2 diabetes mellitus patients. METHODS: We evaluated 32 type-2 diabetes mellitus Caucasians with history of post-ischemic chronic heart failure NYHA class II/III and/or left ventricular ejection fraction ≤45 %. Participants underwent laboratory determinations, electrocardiogram, echocardiogram, Minnesota Living with Heart Failure questionnaire and 6 min walking test at baseline and following 52 weeks treatment. Patients were treated with standard therapy for chronic heart failure and were randomized to receive liraglutide, sitagliptin and glargine in addition to metformin and/or sulfonylurea. RESULTS: Liraglutide treatment induced an improvement in left ventricular ejection fraction from 41.5 ± 2.2 to 46.3 ± 3 %; P = 0.001). On the contrary, treatment with sitagliptin and glargine induced no changes in left ventricular ejection fraction (41.8 ± 2.6 vs. 42.5 ± 2.5 % and 42 ± 1.5 vs. 42 ± 1.6 %, respectively; P = NS). Indexed end-systolic LV volume was reduced only in liraglutide-treated patients (51 ± 9 vs. 43 ± 8 ml/m2; P < 0.05). Liraglutide treatment induced also a significant increase in the anterograde stroke volume (39 ± 9 vs. 49 ± 11 ml; P < 0.05), whereas no differences were observed in the other two groups. Cardiac output and cardiac index showed a significant increase only in liraglutide-treated patients (4.4 ± 0.5 vs. 5.0 ± 0.6 L/min; P < 0.05 and 1.23 ± 0.26 vs. 1.62 ± 0.29 L/m2; P = 0.005, respectively). Liraglutide treatment was also associated with an improvement of functional capacity and an improvement of quality of life. CONCLUSIONS: These data provide evidence that treatment with liraglutide is associated with improvement of cardiac function and functional capacity in failing post-ischemic type-2 diabetes mellitus patients.
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Cardiotónicos/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cardiomiopatías Diabéticas/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Corazón/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Anciano , Biomarcadores/sangre , Cardiotónicos/efectos adversos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Cardiomiopatías Diabéticas/sangre , Cardiomiopatías Diabéticas/fisiopatología , Quimioterapia Combinada/efectos adversos , Femenino , Corazón/fisiopatología , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Humanos , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Incretinas/efectos adversos , Incretinas/uso terapéutico , Insulina Glargina/efectos adversos , Insulina Glargina/uso terapéutico , Liraglutida/efectos adversos , Masculino , Metformina/efectos adversos , Metformina/uso terapéutico , Persona de Mediana Edad , Proyectos Piloto , Calidad de Vida , Fosfato de Sitagliptina/efectos adversos , Fosfato de Sitagliptina/uso terapéutico , Volumen Sistólico/efectos de los fármacos , Compuestos de Sulfonilurea/efectos adversos , Compuestos de Sulfonilurea/uso terapéutico , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/tratamiento farmacológico , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: Hypertensive patients are characterized by development of both left ventricular hypertrophy (LVH) and endothelial dysfunction METHODS AND RESULTS: We enrolled 65 never-treated hypertensive patients (36 men and 29 women aged 45.6+/-6.0 years) to assess the possible relationship between echocardiographic left ventricular mass (LVM) and endothelium-dependent vasodilation. Left ventricular measurements were performed at end diastole and end systole according to the recommendations of the American Society of Echocardiography and the Penn Convention. LVM was calculated with the Devereux formula and indexed by body surface area and height raised to the 2.7th power. The endothelial function was tested as responses of forearm vasculature to acetylcholine (ACh), an endothelium-dependent vasodilator (7.5, 15, and 30 microg. mL-1. min-1, each for 5 minutes), and sodium nitroprusside (SNP), an endothelium-independent vasodilator (0.8, 1.6, and 3.2 microg. mL-1. min-1, each for 5 minutes). Drugs were infused into the brachial artery, and forearm blood flow (FBF) was measured by strain-gauge plethysmography. A negative significant relationship between indexed LVM and peak of increase in FBF was found during ACh infusions (r=-0. 554; P<0.0001). In addition, hypertrophic patients had a significantly lower responsive to ACh than patients without LVH (the peak increase in FBF was 9.9+/-3.7 versus 16.1+/-8.1 mL per 100 mL of tissue per minute; P<0.0001). No significant correlation was observed between LVM and FBF during SNP infusion. CONCLUSIONS: Our data provide the first evidence that echocardiographic LVM in hypertensive patients is inversely related to FBF responses to the endothelium-dependent vasodilating agent ACh, but it is likely that both endothelium and LVM are damaged by hypertension.