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PURPOSE: Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy, with increasing prevalence worldwide and still unclear pathogenic mechanisms. Extracellular vesicles (EVs) are emerging as potential biomarkers of disease-specific pathways in metabolic disorders, but their potential role in GDM is not fully understood. Therefore, the main aim of this study was to evaluate the link between EVs and hyperglycaemia during pregnancy. METHODS: We assessed 50 GDM women and 50 controls at the third trimester of pregnancy in whom we collected demographic characteristics and clinical and anthropometric parameters. In addition, the circulating total EVs (tEVs) and their subpopulations were assessed using flow cytometry. RESULTS: The levels of tEVs and EVs subtypes, expressed as median and interquartile range, were not significantly different between two groups; however, adipocyte-derived EVs (aEVs) concentration, expressed as percentage, was higher in controls than in GDM women (p = 0.045). In addition, a significant correlation was observed between aEVs (%) and third trimester total cholesterol (p = 0.022) within the GDM group. Furthermore, a significant correlation between endothelial-derived EVs (eEVs) and platelet-derived EVs (pEVs) within both groups was found, as well as a significant relation between aEVs and pEVs. CONCLUSIONS: These data, although preliminary, represent the starting point for further studies to determine the role of circulating EVs in GDM.
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Biomarcadores/metabolismo , Índice de Masa Corporal , Diabetes Gestacional/fisiopatología , Vesículas Extracelulares/patología , Hiperglucemia/epidemiología , Adulto , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Hiperglucemia/metabolismo , Hiperglucemia/patología , Italia/epidemiología , Embarazo , Tercer Trimestre del Embarazo , PronósticoRESUMEN
The aim of this review is to provide general suggestions on physical activity (PA) in pre-gestational and gestational diabetes mellitus (GDM) and encourage women to take part in safe and effective activities throughout pregnancy, in the absence of other contraindications. PA before and during pregnancy and in postpartum has many positive effects on the mother, as it could reduce the risk of GDM, excessive weight gain and lower back pain and also prevents, in the postpartum, diabetes mellitus. It may also reduce the duration of labour and complications at childbirth, fatigue, stress, anxiety and depression, thereby leading to an improved sense of wellbeing. Clinically, it is thought to help prevent preeclampsia and premature birth even though RCTs provide conflicting evidence with regard to the prevention of GDM. The main reason for this rests on the fact that the majority of clinical trials have not been able to replicate the preventive effect of PA on the onset of GDM, such as the different adherence of the patient to PA. Herein, we survey the literature regarding exercise and PA on GDM prevention and treatment as well as on clinical outcomes in pre-GDM in pregnancy. On the basis of the current literature, we also present a series of general recommendations and suggestions on PA and exercise training in pregnancy among both diabetic patients and those at risk for GDM.
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Diabetes Gestacional/terapia , Terapia por Ejercicio/métodos , Ejercicio Físico , Estilo de Vida Saludable , Periodo Posparto , Embarazo en Diabéticas/terapia , Adulto , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Diabetes Gestacional/fisiopatología , Femenino , Humanos , Embarazo , Resultado del Embarazo , Embarazo en Diabéticas/diagnóstico , Embarazo en Diabéticas/epidemiología , Embarazo en Diabéticas/fisiopatología , Factores Protectores , Factores de Riesgo , Adulto JovenRESUMEN
PurposeTo study neuroretinal alterations in patients affected by type 2 diabetes with no diabetic retinopathy (DR) or mild nonproliferative diabetic retinopathy (NPDR) and without any sign of diabetic macular edema.Patients and methodsIn total, 150 type 2 diabetic patients with no (131 eyes) or mild NPDR (19 eyes) and 50 healthy controls were enrolled in our study. All underwent a complete ophthalmologic examination, including Spectral-Domain optical coherence tomography (SD-OCT). Ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL) thickness values were calculated after automated segmentation of SD-OCT scans.ResultsMean best-corrected visual acuity was 0.0±0.0 LogMAR in all the groups. Mean GC-IPL thickness was 80.6±8.1 µm in diabetic patients and 85.3±9.9 µm in healthy controls, respectively (P=0.001). Moreover, evaluating the two different diabetic groups, GC-IPL thickness was 80.7±8.1 µm and 79.7±8.8 µm in no-DR and mild-NPDR group (P=0.001 and P=0.022 compared with healthy controls, respectively). Average RNFL thickness was 86.1±10.1 µm in diabetes patients and 91.2±7.3 µm in controls, respectively (P=0.003). RNFL thickness was 86.4±10.2 µm in no-DR group and 84.1±9.4 µm in mild-NPDR group (P=0.007 and P=0.017 compared with healthy controls, respectively).ConclusionWe demonstrated a significantly reduced GC-IPL and RNFL thickness values in both no-DR and mild-NPDR groups compared with healthy controls. These data confirmed neuroretinal alterations are early in diabetes, preceding microvascular damages.
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Diabetes Mellitus Tipo 2/inducido químicamente , Retinopatía Diabética/complicaciones , Fibras Nerviosas/patología , Disco Óptico/patología , Células Ganglionares de la Retina/patología , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Retinopatía Diabética/clasificación , Retinopatía Diabética/diagnóstico por imagen , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Óptico/diagnóstico por imagen , Enfermedades del Nervio Óptico/etiología , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
BACKGROUND AND AIMS: Costs associated with diabetes represent a large burden for patients and the health-care system. However, few studies examined the costs for diabetes treatment in adults with type 1 diabetes (T1DM). This analysis was aimed to assess the costs of treatment associated with T1DM among adults in Italy from the national health-care system perspective. METHODS AND RESULTS: Data were collected using a questionnaire assessing resource consumption retrospectively (drugs, visits, diagnostics, hospitalisations and self-monitoring of blood glucose (SMBG)). One-year costs were calculated for the 12 months preceding the survey. Cost estimation, referred to 2006, was carried out using univariate and multivariate Poisson regression models. Fifty-eight centres enrolled 1193 patients (49.5% women; aged between 18 and 55 years, average diabetes duration was 16.1 ± 9.8 years). The average annual cost for an adult patient with TDM1 was 2450 (95% confidence interval (CI): 2358-2544). Insulin therapy and SMBG accounted together for 71.2% of total costs (35.6% and 35.6%, respectively); the remainder was shared by hospitalisations (18%), visits (4.0%), diagnostics (3.9%) and other drugs (2.9%). Univariate analyses showed that the presence of complications was associated with excess of costs, mainly related to the hospitalisation and drugs. Multivariate analyses confirmed these results showing that the presence of micro-vascular plus macrovascular complications doubles the cost of treatment. CONCLUSION: Strategies of care for T1DM that can improve disease management and prevent or delay the onset of complications could represent the most important tool to reduce costs in the long term while improving clinical outcomes and quality of life.
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Costo de Enfermedad , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Angiopatías Diabéticas/terapia , Costos de la Atención en Salud , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Adolescente , Adulto , Automonitorización de la Glucosa Sanguínea/economía , Estudios de Casos y Controles , Costos y Análisis de Costo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/economía , Angiopatías Diabéticas/economía , Angiopatías Diabéticas/prevención & control , Costos de los Medicamentos , Femenino , Encuestas de Atención de la Salud , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/economía , Insulina/administración & dosificación , Insulina/economía , Sistemas de Infusión de Insulina/economía , Italia , Masculino , Persona de Mediana Edad , Distribución de Poisson , Estudios Retrospectivos , Adulto JovenRESUMEN
The DAWN (Diabetes Attitudes, Wishes and Needs) study is a survey promoted by the International Diabetes Federation to recognize the perceptions and attitudes of people suffering from diabetes mellitus. In this context, we evaluated the quality of life of Italian and immigrant women with gestational diabetes mellitus (GDM). Information was gathered using a structured questionnaire for patients' self-compilation. In a 3-month period, a 51-item questionnaire was submitted to 198 Italians and 88 immigrants (from 27 different foreign nationalities). Italian women were older and had higher education than the immigrants. 60% of the Italians and 38% of the immigrants had a family history of diabetes mellitus. In both groups, the diagnosis of GDM caused anxiety; one-third of women feared their child could contract diabetes at delivery and/or have congenital malformations. Some women had trouble in following treatment regimens: the major concern being dietary advice and blood glucose testing. Most women were satisfied (34%) or highly satisfied (60%) with the quality of care, although the degree of cooperation between diabetes specialists and gynaecologists was considered sometimes unsatisfactory. In order to optimize maternal and foetal outcomes, educational projects and improved communication between patients and the healthcare provider team are recommended.
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BACKGROUND: Interindividual variability in response to aspirin has been popularized as 'resistance'. We hypothesized that faster recovery of platelet cyclooxygenase-1 activity may explain incomplete thromboxane (TX) inhibition during the 24-h dosing interval. OBJECTIVE: To characterize the kinetics and determinants of platelet cyclooxygenase-1 recovery in aspirin-treated diabetic and non-diabetic patients. PATIENTS/METHODS: One hundred type 2 diabetic and 73 non-diabetic patients on chronic aspirin 100 mg daily were studied. Serum TXB(2) was measured every 3 h, between 12 and 24 h after a witnessed aspirin intake, to characterize the kinetics of platelet cyclooxygenase-1 recovery. Patients with the fastest TXB(2) recovery were randomized to aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily, for 28 days and TXB(2) recovery was reassessed. RESULTS AND CONCLUSIONS: Platelet TXB(2) production was profoundly suppressed at 12 h in both groups. Serum TXB(2) recovered linearly, with a large interindividual variability in slope. Diabetic patients in the third tertile of recovery slopes (≥ 0.10 ng mL(-1) h(-1) ) showed significantly higher mean platelet volume and body mass index, and younger age. Higher body weight was the only independent predictor of a faster recovery in non-diabetics. Aspirin 100 mg twice daily completely reversed the abnormal TXB(2) recovery in both groups. Interindividual variability in the recovery of platelet cyclooxygenase activity during the dosing interval may limit the duration of the antiplatelet effect of low-dose aspirin in patients with and without diabetes. Inadequate thromboxane inhibition can be easily measured and corrected by a twice daily regimen.
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Aspirina/administración & dosificación , Plaquetas/enzimología , Ciclooxigenasa 1/sangre , Diabetes Mellitus Tipo 2/enzimología , Anciano , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Tromboxano B2/sangreRESUMEN
AIM: The best way to treat pregnant patients who have type 1 diabetes is still unclear. For this reason, the present study compared metabolic control and maternal-fetal outcomes in patients treated with continuous subcutaneous infusions of rapid-acting insulin analogues (CSII) or with insulin glargine and multiple daily injections of rapid-acting insulin analogues (glargine-MDI). METHODS: This retrospective multicentre study involved 144 women with type 1 diabetes, 100 of whom were using CSII and 44 glargine-MDI. Outcomes analyzed were metabolic control, diabetes complications, pregnancy outcome, perinatal morbidity and mortality, and fetal malformations. RESULTS: The two groups were comparable for age, prepregnancy BMI, primiparous rate and diabetes complications, although patients using CSII had longer duration of diabetes (P=0.03) and higher White classifications (P=0.04). In both groups, metabolic control improved during pregnancy, but good control was reached earlier among patients using CSII. At parturition, patients using CSII had lower HbA(1c) (6.2±0.7% vs 6.5±0.8%; P=0.02) and required less insulin (P<0.01). Weight gain was similar in both groups, and maternal-fetal outcomes did not differ. CONCLUSION: In pregnant patients with type 1 diabetes, MDI and CSII are equivalent in terms of metabolic control and fetal-maternal outcomes, although patients using CSII achieved good control earlier and with less insulin.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Resultado del Embarazo , Embarazo en Diabéticas/tratamiento farmacológico , Adulto , Complicaciones de la Diabetes/mortalidad , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Tipo 1/mortalidad , Femenino , Enfermedades Fetales/mortalidad , Enfermedades Fetales/prevención & control , Humanos , Recién Nacido , Infusiones Subcutáneas , Insulina Glargina , Sistemas de Infusión de Insulina , Morbilidad , Embarazo , Embarazo en Diabéticas/mortalidad , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: Aim of this study was to identify subgroups of adults with Type 1 Diabetes Mellitus (T1DM) treated with Continuous Subcutaneous Insulin Infusion (CSII) at higher risk of poor quality of life (QoL). A sample of consecutive patients completed the Diabetes Specific Quality of Life Scale (DSQOLS), investigating the daily burden and restrictions related to diabetes. Lower DSQOLS scores indicate worse QoL perception. METHODS AND RESULTS: The main results were obtained by using a regression-tree technique (RECursive Partitioning and AMalgamation - RECPAM) and multivariate logistic regression. Overall, 472 patients aged between 18 and 55 years were recruited by 43 Italian centers. RECPAM analysis led to the identification of 5 classes characterized by a marked difference in QoL. Male patients not reporting episodes of ketoacidosis and using CSII for >2 years had the lowest likelihood of scoring in the lower tertile of the DSQOLS summary score, and thus represented the reference category. Patients who reported > or =1 ketoacidosis episodes (OR = 5.4; 95% CI 2.4-12.1) and female patients with a duration of diabetes of <10 years (OR = 5.9; 95% CI 2.6-13.5) had the highest likelihood of reporting poor QoL, while females with longer diabetes duration (OR = 2.4; 95% CI 1.3-4.7) and males treated with CSII for < or =2 years (OR = 2.2; 95% CI 1.1-4.6) showed a two-fold risk of poor QoL. Patient age, diabetic complications and civil status were globally predictive variables associated with poor QoL. CONCLUSION: We identified subgroups of T1DM individuals treated with CSII showing a major impairment in QoL. Specific strategies are needed to help the patient cope with this therapeutic modality, especially during the initial phase of treatment.
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Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/psicología , Sistemas de Infusión de Insulina/psicología , Insulina/administración & dosificación , Calidad de Vida/psicología , Actividades Cotidianas , Adolescente , Adulto , Actitud Frente a la Salud , Costo de Enfermedad , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Cetoacidosis Diabética/psicología , Femenino , Humanos , Inyecciones Subcutáneas , Insulina/análogos & derivados , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Factores de Riesgo , Caracteres Sexuales , Estadística como Asunto , Encuestas y Cuestionarios , Factores de Tiempo , Adulto JovenRESUMEN
AIMS: Insulin glargine (IG), with its non-peaking action profile, might be useful in diabetic pregnancy. However, data on its safety are limited and its use during pregnancy is not recommended. This study focused on the effects of IG on perinatal outcome, particularly to estimate the rate of congenital anomalies and birthweight. METHODS: This retrospective study included women with pre-gestational diabetes who used IG before (at least 1 month) and during pregnancy. For all women we recorded data regarding maternal glycaemic control and pregnancy outcome. We also compared women treated with IG throughout pregnancy and women who stopped taking IG at an earlier stage. RESULTS: From 27 centres, 107 Type 1 diabetic pregnancies were identified. IG was started 10.3 +/- 6.9 months before conception and in 57.4% of cases was stopped during the first trimester; 42.6% of women continued using it until the end of pregnancy. There were six abortions (four spontaneous and two induced) and five newborns (4.9%) with congenital anomalies. Glycaemic control, birthweight and the prevalence of macrosomia and neonatal morbidity were similar in women who used IG for the full term compared with those who stopped IG earlier during pregnancy. CONCLUSIONS: This study, although limited, suggests that IG is safe and effective; the rate of congenital malformations was within the range expected for diabetic pregnancies treated with more traditional forms of insulin. IG used throughout pregnancy did not seem to influence birthweight or increase adverse outcomes.
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Anomalías Inducidas por Medicamentos/etiología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Insulina/análogos & derivados , Embarazo en Diabéticas/tratamiento farmacológico , Adulto , Peso al Nacer/efectos de los fármacos , Glucemia/efectos de los fármacos , Estudios de Casos y Controles , Femenino , Macrosomía Fetal/inducido químicamente , Humanos , Mortalidad Infantil , Recién Nacido , Insulina/efectos adversos , Insulina Glargina , Insulina de Acción Prolongada , Italia , Embarazo , Resultado del Embarazo , Estudios RetrospectivosRESUMEN
AIMS: The aim of this case-control study was to compare quality of life (QoL) and treatment satisfaction in adults with Type 1 diabetes (T1DM) treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). METHODS: Consecutive patients aged between 18 and 55 years, and attending diabetes clinics for a routine visit, completed the Diabetes-Specific Quality-of-Life Scale (DSQOLS), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the SF-36 Health Survey (SF-36). Case (CSII) and control subjects (MDI) were recruited in a 1 : 2 ratio. RESULTS: Overall, 1341 individuals were enrolled by 62 diabetes clinics; 481 were cases and 860 control subjects. Cases had a longer diabetes duration and were more likely to have eye and renal complications. Age, school education, occupation and HbA(1c) were similar. Of control subjects, 90% followed glargine-based MDI regimens and 10% used NPH-based MDI regimens. On multivariate analysis, after adjusting for socioeconomic and clinical characteristics, scores in the following areas of the DSQOLS were higher in cases than control subjects: diet restrictions (beta = 5.96; P < 0.0001), daily hassles (beta = 3.57; P = 0.01) and fears about hypoglycaemia (beta = 3.88; P = 0.006). Treatment with CSII was also associated with a markedly higher DTSQ score (beta = 4.13; P < 0.0001) compared with MDI. Results were similar when CSII was compared separately with glargine- or NPH-based MDI regimens. CONCLUSIONS: This large, non-randomized, case-control study suggests quality of life gains deriving from greater lifestyle flexibility, less fear of hypoglycaemia, and higher treatment satisfaction, when CSII is compared with either glargine-based or NPH-based MDI regimens.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/análogos & derivados , Calidad de Vida/psicología , Adulto , Métodos Epidemiológicos , Femenino , Humanos , Inyecciones Subcutáneas , Insulina/administración & dosificación , Insulina Glargina , Sistemas de Infusión de Insulina , Insulina de Acción Prolongada , Masculino , Persona de Mediana Edad , Satisfacción del PacienteRESUMEN
Triflusal is an antiplatelet drug related to aspirin, with different pharmacological properties and a lower haemorrhagic risk. We aimed at comparing their effects on platelet and endothelial activation in type 2 diabetes mellitus (T2DM). In a randomized, double-blind, parallel group study, we compared the effects of three daily regimens (300, 600, and 900 mg) of triflusal, and aspirin (100mg/day) on urinary 11-dehydro-thromboxane (TX)B(2), index of in vivo platelet activation, ex vivo platelet function using the analyzer PFA-100, plasma von Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite and nitrate (NO(2)(-)+NO(3)(-)) in 60 T2DM patients. Triflusal induced a dose-dependent reduction in 11-dehydro-TXB(2) and a prolongation of closure time in the presence of collagen plus epinephrine (Coll/Epi-CT). The effects of the highest triflusal dose were not different from those of aspirin. The closure time in the presence of collagen plus ADP (Coll/ADP-CT), ICAM-1, VCAM-1, and NO(2)(-)+NO(3)(-) were not modified either by triflusal or aspirin. Plasma P-selectin and vWF were reduced by triflusal but not by aspirin. In T2DM triflusal causes a profound inhibition of platelet TXA(2) biosynthesis in vivo, acting on different targets involved in the platelet-endothelial cell interactions.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Salicilatos/uso terapéutico , Tromboxano B2/análogos & derivados , Adulto , Anciano , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Biomarcadores/sangre , Biomarcadores/orina , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/orina , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Selectina-P/efectos de los fármacos , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Radioinmunoensayo , Estudios Retrospectivos , Salicilatos/administración & dosificación , Tromboxano B2/antagonistas & inhibidores , Tromboxano B2/biosíntesis , Tromboxano B2/orina , Factor de von Willebrand/efectos de los fármacos , Factor de von Willebrand/metabolismoRESUMEN
Fatty liver at ultrasounds, with/ without raised plasma levels of hepatic enzymes, is common in obesity. In most cases, it is the hallmark of non-alcoholic fatty liver disease (NAFLD), a potentially progressive disease associated with insulin resistance and the metabolic syndrome (MS). We tested the hypothesis that insulin resistance per se might be associated with hepatocellular necrosis. Alanine and aspartate aminotransferases (ALT and AST; no.=799) and gamma-glutamyltranspeptidase (GGT; no.=459) were analyzed in a group of treatment-seeking obese patients recruited in 12 Italian medical centers. Insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR; no.=522). Median ALT and AST increased with increasing obesity class (p=0.001 and p=0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased with the obesity class (p<0.0001), and was higher in subjects with elevated ALT (median, 4.93 vs 2.89; p<0.0001). A significant correlation was observed between HOMA-IR and ALT (R2=0.208; p<0.0001), as well as between HOMA-IR and AST or GGT (R2=0.112 and R2=0.080; p<0.0001). The correlation was maintained when cases with elevated enzyme levels were omitted from analysis. Diabetes and hypertriglyceridemia were the features of the MS most commonly associated with raised liver enzymes. In logistic regression, after correction for age, gender, BMI and features of the MS, HOMA-IR maintained a highly predictive value for raised ALT, AST and GGT. We conclude that in obesity insulin resistance is a risk factor for raised liver enzyme levels, possibly related to NAFLD.
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Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Hígado Graso/etiología , Hígado Graso/fisiopatología , Resistencia a la Insulina , Síndrome Metabólico/fisiopatología , Obesidad/complicaciones , gamma-Glutamiltransferasa/sangre , Adulto , Anciano , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Hígado/enzimología , Hígado/patología , Masculino , Persona de Mediana Edad , Necrosis , Obesidad/fisiopatología , Análisis de Regresión , Factores de RiesgoRESUMEN
AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.
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Acetamidas/farmacocinética , Ácidos y Sales Biliares/sangre , Hepatitis Crónica/diagnóstico , Cirrosis Hepática/diagnóstico , Hígado/metabolismo , Fenilalanina/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Pruebas Respiratorias , Isótopos de Carbono/efectos adversos , Femenino , Hepatitis Crónica/metabolismo , Hepatitis Crónica/patología , Humanos , Hígado/patología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Pronóstico , Sensibilidad y EspecificidadRESUMEN
Evaluation of liver function is crucial in the overall management of patients with liver disease. In particular, patients with end-stage liver disease need accurate prognostic indicators to plan liver transplantation, and in this case, to manage their presence in the waiting list. Availability of predictors of clinical outcome is further essential after liver transplant, mainly to correctly diagnose and adequately treat complications, such as acute rejection, drug toxicity, liver dysfunction. Breath tests using labelled substrates selectively metabolized within the liver may represent an accurate diagnostic and prognostic tool in these clinical conditions, possibly with an adjuntive role to the most commonly used prognostic models (Child-Pugh and MELD scores). Promising results have been in fact recently obtained by the use of different substrates (aminopyrine, methacetin, erythromycin, methionine) which explore different metabolic function of the hepatocyte. The usefulness of breath tests has been documented in liver disease patients both before and after liver transplantation, in the early as well as in the late phase.
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Pruebas Respiratorias , Hepatopatías/diagnóstico , Hepatopatías/cirugía , Trasplante de Hígado/fisiología , Enfermedad Crónica , Humanos , Isótopos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/cirugía , Hepatopatías/mortalidad , Trasplante de Hígado/mortalidad , Pronóstico , Factores de Riesgo , Listas de EsperaRESUMEN
Sleep-related breathing disorders are recognized as major health problems in obesity. They are involved in both hypertension and Type 2 diabetes, through mechanisms possibly related to increased sympathetic tone. We studied the association of habitual snoring with diabetes, hypertension, weight cycling and physical activity in a large Italian database of treatment-seeking obese subjects. Clinical and behavioral data were assessed by standardized questionnaires. Consecutive data of 1890 obese patients were analyzed [average body mass index (BMI), 38.2 kg/m2, median age: 46 yr, 78% females], from 25 obesity Italian centers, with low prevalence of clinical manifestations of cardiovascular disease. Habitual snoring was reported in 56% of the cases, and was associated with day-time sleepiness. The prevalence increased with obesity class and waist circumference, and was positively associated with weight cycling and weight gain since the age of 20, and smoking. Regular physical activity had a protective effect. Snoring was associated with diabetes and hypertension at univariate analysis, but in multivariate analysis an independent effect was only observed for hypertension. After adjustment for age, gender and BMI, physical activity maintained an independent, protective effect on both snoring (odds ratio 0.65, 95% confidence interval 0.49-0.84; p=0.001), diabetes (0.50, 0.30-0.86; p=0.011) and hypertension (0.71, 0.53-0.95; p=0.023). We conclude that in treatment-seeking, obese subjects with low prevalence of cardiovascular disease, snoring independently increases the risk of hypertension, whereas physical activity exerts a protection on both snoring and complications. These data underline the importance of lifestyle interventions to limit the burden of obesity and associated diseases.
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Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus/fisiopatología , Ejercicio Físico , Hipertensión/fisiopatología , Obesidad , Ronquido/fisiopatología , Adulto , Anciano , Índice de Masa Corporal , Bases de Datos Factuales , Complicaciones de la Diabetes , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Hipertensión/etiología , Italia , Masculino , Persona de Mediana Edad , Prevalencia , Ronquido/complicaciones , Ronquido/epidemiología , Encuestas y Cuestionarios , Aumento de PesoRESUMEN
Diabetes mellitus (DM) is associated with enhanced lipid oxidation and persistent platelet activation. We investigated whether oxidant stress (OS) also affects circulating proteins and is associated with an abnormal coagulative pattern. In 72 type 2 DM (T2DM) patients, urinary 8-iso-prostaglandin (PG) F2alpha and 11-dehydro-thromboxane B2 (TXM) were measured as markers of lipid peroxidation and platelet activation, respectively. The carbonyl content of plasma proteins (PCARB) was measured as global index of protein oxidation. 8-Iso-PGF2alpha and PCARB levels were higher in DM patients than in controls (P < 0.05). Likewise, both TXM and prothrombin F1+2 levels were higher in diabetics (P < 0.05). By contrast, anticoagulant markers, such as activated protein C, protein C activation peptide, and soluble thrombomodulin (TM) were depressed in T2DM (P < 0.05). In conclusion, OS in T2DM involves circulating proteins and is associated with an unbalanced promotion of procoagulant reactions. These effects in concert with platelet activation may contribute to atherothrombotic complications in T2DM.
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Proteínas Sanguíneas/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Dinoprost/análogos & derivados , Peroxidación de Lípido , Trombosis/etiología , Tromboxano B2/análogos & derivados , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Biomarcadores/orina , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , F2-Isoprostanos/orina , Femenino , Hemostasis , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estrés Oxidativo , Activación Plaquetaria , Trombosis/sangre , Trombosis/metabolismo , Tromboxano B2/orinaRESUMEN
Plasma plasminogen activator inhibitor type 1 (PAI-1) increases in diabetes, and this might contribute to decreased fibrinolysis and accelerated atherosclerosis. Increased PAI-1 levels in the vessel wall could decrease local fibrinolysis and elevate thrombus formation and the unfavorable evolution of atherosclerotic plaques. High glucose increases PAI-1 synthesis in arterial wall cells in culture, and aortic wall PAI-1 levels have been found to be elevated in diabetic animals. However, arterial wall PAI-1 levels have not been investigated in diabetic subjects. Therefore, the aim of this study was to determine the effect of diabetes on PAI-1 levels in the arterial wall. Blood samples and small tissue specimens from the mammary artery were obtained from 11 diabetic and 10 nondiabetic subjects who underwent coronary artery bypass graft surgery. PAI-1 antigen localization in the arterial wall was obtained by immunohistochemistry and was read by laser scanning confocal microscopy; plasma fibrinolytic activity was measured by lysis of fibrin plates; and PAI-1 activity was assessed by a chromogenic method. PAI-1-related immunofluorescence was increased in the arterial wall of diabetic patients, whereas plasma fibrinolysis was reduced. These data provide evidence that diabetes is associated with increased PAI-1 in the arterial wall. This might be an important factor for increased cardiovascular risk and unfavorable plaque evolution in diabetes.
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Arterias/metabolismo , Arteriosclerosis/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatías Diabéticas/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , Anciano , Arterias/patología , Arteriosclerosis/patología , Angiopatías Diabéticas/patología , Femenino , Fibrinólisis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIMS: To validate a newly developed questionnaire for the measurement of patients' knowledge and practices, with particular attention to its ability in predicting HbA1c levels. RESEARCH DESIGN AND METHODS: The Knowledge and Practices Diabetes Questionnaire (KPDQ) is a questionnaire composed of two scales, investigating patient knowledge and practices. Twenty-two questions, 12 dealing with patients' knowledge and 10 relative to patients' practices, were initially identified. Factor analysis and reliability analysis were used to validate the questionnaire. The ability of the two scales in predicting metabolic control was then evaluated. The questionnaire was administered to a population of Type 1 diabetic subjects intensively treated and regularly attending the diabetes outpatient clinic of Pescara General Hospital. The mean of all HbA1c measurements performed after patients were taken in charge by the clinic was used as an indicator of metabolic control. RESULTS: Out of 133 Type 1 patients identified, 77 (58 %) filled in the questionnaire. Respondents had a mean age (+/- SD) of 37 +/- 13 years and a mean diabetes duration of 13 +/- 9 years. The application of factor and reliability analyses led to the definition of two final scales composed of 10 (Knowledge Score, KS) and 5 items (Practice Score, PS), respectively. Item-scale correlation was > or = 0.40 for all the items investigated. Cronbach's alpha coefficient exceeded the value of 0.70 for both scales. The mean number of HbA1c determinations during a median period of observation of 4 years was of 11 +/- 5. The mean HbA1c value for the whole population was of 7.0% +/- 1.4, while the proportion of patients with values < or = 7.0% was of 57%. After adjusting for clinical and patient-related characteristics, the KS was the only independent predictor of metabolic control. Patients in the lowest quartile of the KS showed a more than 20-fold increased risk of having mean HbA1c values > or = 7.0% as opposed to those in the highest quartile (odds ratio, OR=23.3;p=0.009). No association emerged between metabolic control and PS. CONCLUSIONS: The KPDQ presents excellent psychometric properties. The KS also shows a very impressive association with the mean HbA1c values over a period of 4 years. These findings are particularly remarkable in that many studies have failed in documenting such a relationship. The KS can thus be considered as a quick and efficient screening tool to be used in an ambulatory setting to monitor the level of practice-oriented knowledge of patients with Type 1 diabetes as well as to identify those subjects who need individualized educational interventions.