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1.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(10): 654-662, dic. 2019.
Artigo em Espanhol | IBECS | ID: ibc-184793

RESUMO

Las enfermedades endocrinas están experimentando un importante incremento de su prevalencia, debido a causas de diversa índole, entre ellas la epidemia de obesidad y de desnutrición, el envejecimiento de la población, pero también el efecto de los disruptores endocrinos, entre otros. Por otra parte, las nuevas tecnologías, tanto a nivel de analítica molecular y genética, de imagen y de nuevos dispositivos terapéuticos, obligan a que la comunidad profesional endocrina en España tenga que estar en constante formación. La conexión con los pacientes a través de sus asociaciones, cada vez más activas, y con la sociedad civil en general, el compromiso profesional y la demanda de diversos colectivos sociales de una atención moderna y equitativa, y a llevar a cabo investigación que facilite la consecución de avances para los pacientes, obligan al especialista en Endocrinología y Nutrición, y a la Sociedad Española de Endocrinología y Nutrición (SEEN), a posicionarse y dar respuesta a todos estos retos. En el presente documento, la SEEN expone sus propuestas y su estrategia hasta el 2022


Endocrine diseases are experiencing an important increase in their prevalence, due to causes of various kinds, including the epidemic of obesity and malnutrition, the aging of the population, but also the effect of endocrine disruptors, among others. On the other hand, new technologies, both in terms of molecular and genetic analysis, image and new therapeutic devices, require that the endocrine professional community in Spain must be in constant training. The connection with patients through their associations, increasingly active, and with the civil society in general, the professional commitment and demand of various social groups for a modern and equitable care, and to carry out research that facilitates the achievement of advances for patients, forces the specialist in endocrinology and nutrition and the Spanish Society of Endocrinology and Nutrition (SEEN) to position themselves and respond to all these challenges. In this document, the SEEN presents its proposals and its strategy until 2022


Assuntos
Endocrinologia/organização & administração , Sociedades Médicas/organização & administração , Sociedades Médicas/tendências , Estratégias , Endocrinologia/tendências , Sistemas Nacionais de Saúde , Medicina/organização & administração , Promoção da Saúde , Espanha
2.
Autoimmunity ; 52(5-6): 220-227, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366254

RESUMO

Background: Graves' disease (GD) is characterized by the production of autoantibodies against the TSHR (TRAbs). With long-term treatment, serum concentrations of TRAbs decline but in some patients, despite being clinically stable, TRAbs persist for many years.Objective: To investigate whether GD patients with persistence of TRAbs constitute a subset of patients that could be identified by phenotypic analysis of circulating lymphocytes, suggesting disease heterogeneity.Materials and methods: Peripheral blood lymphocytes (including naïve, memory and effector T and B cells, Th17, regulatory T cells (Treg), recent thymic emigrants (RTEs) and double positive CD4+CD8+ (DP) cells) were analysed by flow cytometry in a cross-sectional study in 25 clinically stable GD patients, five patients at onset of GD disease and 40 healthy donors (HDs).Results: GD patients with persistence of TRAbs showed a lower percentage of Treg and lower absolute numbers of central and effector memory CD8+ T cells than HD. No differences in RTEs were found in peripheral blood from GD patients compared to HD. Stable GD patients had higher percentage of DP cells of effector phenotype than HD.Conclusions: Using extensive phenotypic analysis of lymphocyte subpopulations, it is possible to detect changes that help to identify patients with persistent TSHR antibodies and may contribute to understand why the autoimmune response is maintained.

3.
Endocrinol Diabetes Nutr ; 66(10): 654-662, 2019 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31272927

RESUMO

Endocrine diseases are experiencing an important increase in their prevalence, due to causes of various kinds, including the epidemic of obesity and malnutrition, the aging of the population, but also the effect of endocrine disruptors, among others. On the other hand, new technologies, both in terms of molecular and genetic analysis, image and new therapeutic devices, require that the endocrine professional community in Spain must be in constant training. The connection with patients through their associations, increasingly active, and with the civil society in general, the professional commitment and demand of various social groups for a modern and equitable care, and to carry out research that facilitates the achievement of advances for patients, forces the specialist in endocrinology and nutrition and the Spanish Society of Endocrinology and Nutrition (SEEN) to position themselves and respond to all these challenges. In this document, the SEEN presents its proposals and its strategy until 2022.

4.
AJR Am J Roentgenol ; : 1-6, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30973776

RESUMO

OBJECTIVE: Ultrasound-based stratification of the malignancy risk of thyroid nodules has potential variability. The purpose of this study is to evaluate the diagnostic effectiveness of the first commercially available system for computer-aided diagnosis (CADx) imaging analysis. MATERIALS AND METHODS: Ultrasound images of 300 thyroid nodules (135 of which were malignant) acquired before surgical treatment were retrospectively reviewed by a thyroid expert, and his classification of each image was then compared with the classification rendered by an image analysis program (AmCAD-UT, AmCAD Biomed). The American Thyroid Association (ATA) classification system, the European Thyroid Imaging Reporting and Data System (EU-TIRADS), and the classification system jointly proposed by American and Italian associations of clinical endocrinologists (the American Association of Clinical Endocrinologists [AACE], the American College of Endocrinology [ACE], and Associazione Medici Endocrinologi [AME]) were used for risk stratification. RESULTS: The diagnostic performance of the thyroid expert when the ATA system was used was as follows: sensitivity, 87.0%; specificity, 91.2%; positive predictive value, 90.5%; and negative predictive value, 90.9%. Compared with the expert, the CADx program, when used with the three classification systems, had a similar sensitivity but a lower specificity and positive predictive value. Regarding the negative predictive value, the results of the expert did not differ from those of the CADx program when it applied the ATA classification system (90.9% vs 86.3%; p = 0.07). The ROC AUC value was 0.88 for the expert clinician and 0.72 for the CADx program when the ATA classification system was used. CONCLUSION: The CADx ultrasound image analysis program described in the present study is useful for risk stratification of thyroid nodules, but it does not perform better than a sonography expert.

5.
Minerva Endocrinol ; 44(2): 169-175, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30531695

RESUMO

Acromegaly is a chronic disorder usually diagnosed late in the disease evolution, leading to substantial morbidity and mortality related to this long period of undiagnosed state as well as the difficulty in achieving normalization of GH hypersecretion and controlling tumor mass. First generation somatostatin analogues (SSA) are accepted as the first-line medical therapy or as second-line therapy in patients undergoing unsuccessful surgery. However, because a high percentage of patients experience SSA treatment failure, the inclusion of biomarkers associated with a successful or non-successful response to these drug (as well as to all classes of medical therapy) is necessary to better guide the choice of treatment, potentially allowing for a quicker achievement of disease control. The current treatment algorithms for acromegaly are based upon a "trial and error" approach with additional treatment options provided when disease is not controlled. In many other diseases, their therapeutic algorithms have been evolving towards personalizing treatment with medication that best matches individual disease characteristics, using biomarkers that identify therapeutic response, thus allowing the personalization of the therapy. It is time to introduce this approach to acromegaly treatment algorithms. This paper reviews the potential tools for doing so.


Assuntos
Acromegalia/tratamento farmacológico , Medicina de Precisão , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Humanos , Padrões de Prática Médica
6.
Diabetes Obes Metab ; 20(9): 2314-2318, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29785837

RESUMO

The present post hoc analysis of two 30-week clinical trials compared efficacy and hypoglycaemia outcomes at early study visits with iGlarLixi (insulin glargine U100 [iGlar] and lixisenatide) vs iGlar alone in patients with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs; LixiLan-O trial) or basal insulin (LixiLan-L trial). Time to control, defined as days to achieve glycated haemoglobin (HbA1c) <53 mmol/mol (<7%) or fasting plasma glucose (FPG) ≤7.2 mmol/L, was estimated using the Kaplan-Meier method. In the LixiLan-O and LixiLan-L trials, 60% and 46% of patients, respectively, reached HbA1c <53 mmol/mol (<7%) with iGlarLixi at 12 weeks, vs 45% and 24%, respectively, with iGlar. In the LixiLan-O trial, the median time to target HbA1c was approximately half with iGlarLixi vs iGlar (85.0 vs 166.0 days; P < .0001). In the LixiLan-L trial, the median time to target HbA1c was 153.0 days with iGlarLixi, while target HbA1c was never reached by 50% of patients with iGlar (P < .0001). Time-to-target FPG and hypoglycaemia outcomes were similar between treatments. In T2D uncontrolled on OADs or basal insulin, iGlarLixi resulted in glycaemic control in more patients than did iGlar at early treatment time points.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Peptídeos/administração & dosagem , Adulto , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Combinação de Medicamentos , Jejum/sangue , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
7.
Diabetes Obes Metab ; 19(10): 1408-1415, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28386990

RESUMO

AIMS: To assess the impact of baseline characteristics on clinical outcomes in the LixiLan-L trial, a randomized open-label trial designed to evaluate the efficacy and safety of iGlarLixi, a novel fixed-ratio combination of insulin glargine 100 U (iGlar) plus lixisenatide, in comparison with iGlar over 30 weeks in a population of patients with type 2 diabetes mellitus (T2DM) inadequately controlled on a previous regimen of basal insulin alone or in combination with 1 or 2 oral glucose-lowering drugs. MATERIALS AND METHODS: In this exploratory analysis of LixiLan-L (N = 736), efficacy outcomes were assessed within population subgroups derived from the following baseline characteristics: glycated haemoglobin [HbA1c; <8%, ≥8% (<64, ≥64 mmol/mol)]; duration of T2DM (<10, ≥10 years); body mass index (<30, ≥30 kg/m2 ). Furthermore, the incidence of symptomatic hypoglycaemia with plasma glucose ≤3.9 mmol/L (≤70 mg/dL) was also analysed according to the same subgroups. RESULTS: Compared with the iGlar treatment group, patients treated with iGlarLixi showed consistently greater reductions in HbA1c during the treatment period, with higher percentages of patients achieving the HbA1c target level of <7% (<53 mmol/mol) in all of the subpopulations tested (P < .0001 for all), having consistent mitigation of body weight gain and with no major differences in the incidence of hypoglycaemia. CONCLUSIONS: iGlarLixi consistently improved glycaemic control compared with iGlar in all baseline characteristic subgroups of patients with T2DM inadequately controlled with insulin, including difficult-to-treat subgroups of patients with long duration of diabetes, obesity and high HbA1c. Clinical trial number: NCT02058160 (clinicaltrials.gov).


Assuntos
Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Insulina Glargina/administração & dosagem , Peptídeos/administração & dosagem , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Combinação de Medicamentos , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
9.
Endocrinol. nutr. (Ed. impr.) ; 63(8): 397-408, oct. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-156269

RESUMO

Purpose. To describe real-world use of lanreotide combination therapy for acromegaly. Patients and methods. ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort). Results. Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1–6) and 2.1 years (0.4–6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15–505%) in the cabergoline cohort and 156% ULN (15–534%) in the pegvisomant cohort, and decreased to 104% ULN (13–557%) p<0.001 and 86% ULN (23–345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort. Conclusion. In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated (AU)


Propósito. Describir el uso de lanreotida en combinación terapéutica en acromegalia en la práctica clínica. Pacientes y métodos. ACROCOMB es un estudio observacional, retrospectivo, de pacientes con acromegalia activa tratados en centros hospitalarios españoles con lanreotida en combinación con cabergolina o pegvisomant entre 2006 y 2011. Se revisaron los datos clínicos de 108 pacientes tratados en 44 departamentos de endocrinología: 61 pacientes recibieron lanreótido/cabergolina (cohorte cabergolina) y 47 lanreotida/pegvisomant (cohorte pegvisomant). Resultados. La edad mediana de los pacientes fue de 50,8 años en la cohorte de cabergolina y 42,7 años en la de pegvisomant. Los tratamientos médicos previos a la combinación con lanreótido fueron análogos de somatostatina (SSA) en monoterapia (40 [66%] pacientes) o agonistas de la dopamina (7 [11%] pacientes) en la cohorte de cabergolina y SSA (29 [62%] pacientes) y pegvisomant en monoterapia (16 [34%] pacientes) en la de pegvisomant. Doce pacientes no habían recibido tratamiento previo y en 4 pacientes se desconocía la terapia previa. La mediana de duración del tratamiento fue de 1,6 años (0,1-6) y 2,1 años (rango 0,4 a 6,3) en las cohortes de cabergolina y pegvisomant, respectivamente. Al inicio del estudio el valor mediano del factor de crecimiento de insulina-I era 149% el límite superior normal (LSN) (15-505%) en la cohorte de cabergolina y 156% LSN (15-534%) en la de pegvisomant. Al final del estudio se redujeron a 104% LSN (13-557%) p<0,001 y 86% LSN (23-345%) p<0,0001, respectivamente. Al final del estudio, se reportaron valores normales de factor de crecimiento de insulina-I ajustados por edad en el 48% de los pacientes tratados con lanreotida/cabergolina y 70% de los tratados con lanreotida/pegvisomant. No hubo cambios significativos en los parámetros hepáticos, cardíacos o glucémicos. Conclusión. En la práctica clínica las combinaciones con lanreotida son una opción útil en el tratamiento de pacientes con acromegalia que no está bien controlada en monoterapia, ya sea con SSA carbegolina o pegvisomant; particularmente, la combinación de lanreotida y pegvisomant tiene una alta eficacia y se tolera bien (AU)


Assuntos
Humanos , Acromegalia/tratamento farmacológico , Somatostatina/análogos & derivados , Agonistas de Dopamina/farmacocinética , Estudos Retrospectivos , Quimioterapia Combinada
10.
Endocrinol Nutr ; 63(8): 397-408, 2016 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27448708

RESUMO

PURPOSE: To describe real-world use of lanreotide combination therapy for acromegaly. PATIENTS AND METHODS: ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort). RESULTS: Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1-6) and 2.1 years (0.4-6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15-505%) in the cabergoline cohort and 156% ULN (15-534%) in the pegvisomant cohort, and decreased to 104% ULN (13-557%) p<0.001 and 86% ULN (23-345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort. CONCLUSION: In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated.


Assuntos
Acromegalia/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Ergolinas/farmacologia , Hormônio do Crescimento Humano/análogos & derivados , Fator de Crescimento Insulin-Like I/metabolismo , Peptídeos Cíclicos/farmacologia , Somatostatina/análogos & derivados , Cabergolina , Agonistas de Dopamina/administração & dosagem , Ergolinas/administração & dosagem , Ergolinas/química , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/química , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/química , Estudos Retrospectivos , Somatostatina/administração & dosagem , Somatostatina/química , Somatostatina/farmacologia
11.
Diabetes Care ; 39(9): 1614-20, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27281772

RESUMO

OBJECTIVE: We sought to examine the presence and severity of brain small vessel disease (SVD) in patients with type 2 diabetes and diabetic retinopathy (DR) compared with those without DR. RESEARCH DESIGN AND METHODS: We evaluated 312 patients with type 2 diabetes without previous cardiovascular disease (men 51%; mean age 57 years; age range 40-75 years); 153 patients (49%) had DR. MRI was performed to evaluate the presence and severity (age-related white matter changes scale) of white matter lesions (WMLs) and lacunes, and transcranial Doppler ultrasound was used to measure the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). RESULTS: The prevalence of lesions of cerebral SVD (WML and/or lacunes) was higher in patients with DR (40.2% vs. 30.1% without DR, P = 0.04). Age (P < 0.01) and systolic blood pressure (P = 0.02) were associated with the presence of SVD. The severity of SVD was associated with age and the presence of DR (P < 0.01 and P = 0.01, respectively). Patients with DR showed a higher MCA PI compared with those without DR (P < 0.01). Age, systolic and diastolic blood pressure, and retinopathy and its severity were associated with an increased MCA PI (P < 0.01 for all variables). A positive correlation was found between MCA PI values and the presence and severity of SVD (P < 0.01 for both variables). CONCLUSIONS: Patients with type 2 diabetes who have DR have an increased burden of cerebral SVD compared with those without DR. Our findings suggest that the brain is a target organ for microangiopathy, similar to other classic target organs, like the retina.


Assuntos
Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Retinopatia Diabética/epidemiologia , Artéria Cerebral Média/diagnóstico por imagem , Adulto , Idoso , Pressão Sanguínea , Doenças Cardiovasculares , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Circulação Cerebrovascular , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fluxo Pulsátil , Índice de Gravidade de Doença , Ultrassonografia Doppler Transcraniana
12.
Clin Endocrinol (Oxf) ; 84(4): 540-50, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26662620

RESUMO

BACKGROUND: Efficacy of the GH-receptor antagonist pegvisomant (PEG) has differed between preclinical and observational studies mainly due to dose adjustment and IGF-I normalization criteria. An escape phenomenon has also been described, but its definition and underlying causes have not been fully established. OBJECTIVE: To re-evaluate the outcomes of long-term PEG in a series of previously published patients and analyse the escape phenomenon. METHODS: We reviewed all patients with acromegaly resistant to SSA in whom PEG was started as monotherapy, who had been included in a previous publication. We prospectively evaluated 64 (56·3% women) from six tertiary care referral hospitals in Spain, for whom data as of June 2014 were available. Escape to PEG was defined as confirmed loss of biochemical control (IGF-I >1·2xULN), after at least 6 months of previous control with a stable dose of PEG. RESULTS: Patients were followed up for 13·0 (5·9-34·8) years since diagnosis, and 9·0 (4·1-10·4) years since the first administration of PEG. Fifty-one (89·5%) patients had an adequate IGF-I control at the last follow-up visit, 9 of them without treatment. Tumour growth was reported in 6 of 64 cases (9·4%), none of whom had received prior radiotherapy (P = 0·011). Seven patients died during follow-up. We found 16 escapes in 10 patients (15·6%). We identified potential underlying causes in 9 cases (tumour regrowth, previous treatment modifications, concomitant menopause and change in testosterone administration). The reason was unknown in 7 escapes, which occurred in 6 patients (9·4%). All patients, except one, achieved subsequent biochemical control after treatment adjustment. CONCLUSIONS: We reassure the efficacy and safety of long-term PEG. An escape phenomenon may occur, but it can be overcome by adjusting therapy.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Acromegalia/metabolismo , Adulto , Idoso , Feminino , Seguimentos , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores da Somatotropina/antagonistas & inibidores , Receptores da Somatotropina/metabolismo , Espanha , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
13.
PLoS One ; 10(9): e0136931, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26375586

RESUMO

BACKGROUND: The role of genetic variations within the ghrelin gene on cardiometabolic profile and nutritional status is still not clear in humans, particularly in elderly people. OBJECTIVES: We investigated six SNPs of the ghrelin gene and their relationship with metabolic syndrome (MS) components. SUBJECTS AND METHODS: 824 subjects (413 men/411 women, age 77.31±5.04) participating in the Mataró aging study (n = 310) and the Hortega study (n = 514) were analyzed. Anthropometric variables, ghrelin, lipids, glucose and blood pressure levels were measured, and distribution of SNPs -994CT (rs26312), -604GA (rs27647), -501AC (rs26802), R51Q (rs34911341), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene evaluated. Genotypes were determined by multiplex PCR and SNaPshot minisequencing. MS (IDF criteria) was found in 54.9%. RESULTS: No association between any of the SNPs and levels of total fasting circulating ghrelin levels was found. C/A-A/A genotype of M72L was associated with increased risk of central obesity according to IDF criteria, while G/A-G/G genotypes of -604GA with reduced risk. A/A genotype of -501AC polymorphism was associated to decreased BMI. In relation to lipid profile, the same genotypes of -604GA were associated with increased total cholesterol and LDL-cholesterol and -501AC with reduced triglycerides. There were no associations with systolic or diastolic blood pressure levels or with hypertension, glucose levels or diabetes and ghrelin polymorphisms. However, G/G genotype of -604GA was associated with glucose >100 mg/dL. Haplotype analysis showed that only one haplotype is associated with increased risk of waist circumference and central obesity. The analysis of subjects by gender showed an important and different association of these polymorphisms regarding MS parameters. CONCLUSION: Ghrelin gene variants -604GA, -501AC and M72L are associated with certain components of MS, in particular to BMI and lipid profile in elderly Spanish subjects.


Assuntos
Grelina/genética , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Idoso , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Caracteres Sexuais , Espanha
14.
Int J Endocrinol ; 2015: 381415, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26089883

RESUMO

Type 2 diabetes (T2D) exists in 25-40% of hospitalized patients. Therapeutic inertia is the delay in the intensification of a treatment and it is frequent in T2D. The objectives of this study were to detect patients admitted to surgical wards with hyperglycaemia (HH; fasting glycaemia > 140 mg/dL) as well as those with T2D and suboptimal chronic glycaemic control (SCGC) and to assess the midterm impact of treatment modifications indicated at discharge. A total of 412 HH patients were detected in a period of 18 months; 86.6% (357) had a diagnosed T2D. Their preadmittance HbA1c was 7.7 ± 1.5%; 47% (189) had HbA1c ≥ 7.4% (SCGC) and were moved to the upper step in the therapeutic algorithm at discharge. Another 15 subjects (3.6% of the cohort) had T2D according to their current HbA1c. Ninety-four of the 189 SCGC patients were evaluated 3-6 months later. Their HbA1c before in-hospital-intervention was 8.6 ± 1.2% and 7.5 ± 1.2% at follow-up (P < 0.004). Active detection of hyperglycaemia in patients admitted in conventional surgical beds permits the identification of T2D patients with SCGC as well as previously unknown cases. A shift to the upper step in the therapeutic algorithm at discharge improves this control. Hospitalization is an opportunity to break therapeutic inertia.

15.
PLoS One ; 10(6): e0127057, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26039878

RESUMO

INTRODUCTION: The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow ß-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes. OBJECTIVE: To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to ß-cells in type 1 diabetes. METHODS: A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides. RESULTS: We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion. CONCLUSIONS: We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for autoimmune diseases.


Assuntos
Autoantígenos/imunologia , Autoimunidade , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/imunologia , Fosfatidilserinas/uso terapêutico , Animais , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular , Citocinas/metabolismo , Células Dendríticas/imunologia , Imunoterapia , Injeções Intraperitoneais , Insulina/uso terapêutico , Lipossomos , Camundongos Endogâmicos NOD , Fenótipo
16.
Med. clín (Ed. impr.) ; 144(12): 560-565, jun. 2015. tab
Artigo em Espanhol | IBECS | ID: ibc-141033

RESUMO

La creciente prevalencia de obesidad y de diabetes mellitus tipo 2 (DM2) comporta un interés ascendente en la investigación de nuevos procedimientos. El tratamiento de la DM2 se ha centrado hasta ahora en compensar la insulinopenia y la resistencia a la insulina. Sin embargo, en los últimos 10 años se han abierto nuevas líneas de investigación en el tratamiento de la DM2, cuyos estudios en fase preclínica parecen prometedores. La posibilidad de usar estos fármacos de forma combinada con los disponibles hasta ahora (sensibilizadores a la insulina o insulinotropos) permitirá potenciar el efecto antidiabético y favorecer la reducción ponderal con menos efectos secundarios. El seguimiento poscomercialización nos ayudará a conocer mejor su perfil de seguridad y sus potenciales efectos sobre las lesiones de los órganos diana (AU)


The increasing prevalence of obesity and type 2 diabetes mellitus (T2DM) has led to a growing interest in the investigation of new therapies. Treatment of T2DM has focused on the insulinopenia and insulin resistance. However, in the last 10 years, new lines of research have emerged for the treatment of T2DM and preclinical studies appear promising. The possibility of using these drugs in combination with other currently available drugs will enhance the antidiabetic effect and promote weight loss with fewer side effects. The data provided by post-marketing monitoring will help us to better understand their safety profile and potential long-term effects on target organs, especially the cardiovascular risk (AU)


Assuntos
Feminino , Humanos , Masculino , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Terapêutica/métodos , Terapêutica/enfermagem , Insulina/administração & dosagem , Insulina/sangue , Pesquisa Biomédica/métodos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Terapêutica/instrumentação , Terapêutica/normas , Insulina , Insulina/metabolismo , Pesquisa Biomédica
17.
Clin Endocrinol (Oxf) ; 83(1): 3-14, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25640882

RESUMO

Acromegaly is a chronic disorder usually diagnosed late in the disease evolution. Such delayed diagnosis, together with the inability to achieve the treatment goals of normalizing biochemical disease markers and controlling tumour mass may result in substantial morbidity and mortality. Somatostatin analogues (SSA) are accepted as first-line medical therapy or as second-line therapy in patients undergoing unsuccessful surgery and are considered a cornerstone in the treatment of acromegaly. However, because a high percentage of patients experience SSA medical treatment failure, the identification of biomarkers associated with a successful or unsuccessful response to all classes of medical therapy would help in the choice of treatment and potentially allow for a quicker normalization of biochemical parameters. The current treatment algorithms for acromegaly are based upon a "trial-and-error" approach with additional treatment options provided when disease is not controlled. In many other diseases, therapeutic algorithms have been evolving towards personalized treatment with the medication that best matches individual disease characteristics, using biomarkers that identify therapeutic response. Additionally, a personalized approach to complementary treatment of comorbidities present in the acromegalic patient is also required. This review will discuss the development of a potential treatment algorithm for acromegaly addressing the biochemical control of the disease as well of its associated comorbidities, under a personalized approach based upon markers of prognostic and predictive significance, such as tumour size, MRI adenoma signal, GH value after acute octreotide test, granular adenoma pattern, Ki-67, somatostatin receptor phenotype, aryl hydrocarbon-interacting protein expression, gsp mutations, RAF kinase activity, E-cadherin and beta-arrestin-1.


Assuntos
Adenoma/terapia , Algoritmos , Antineoplásicos Hormonais/uso terapêutico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Procedimentos Neurocirúrgicos , Medicina de Precisão , Somatostatina/análogos & derivados , Adenoma/genética , Adenoma/patologia , Arrestinas/metabolismo , Caderinas/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Antígeno Ki-67/metabolismo , Mutação , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Prognóstico , Receptores Acoplados a Proteínas-G/genética , Receptores de Somatostatina/metabolismo , Somatostatina/uso terapêutico , Falha de Tratamento , Resultado do Tratamento , Carga Tumoral , beta-Arrestina 1 , beta-Arrestinas , Quinases raf/metabolismo
18.
Med Clin (Barc) ; 144(12): 560-5, 2015 Jun 22.
Artigo em Espanhol | MEDLINE | ID: mdl-25194974

RESUMO

The increasing prevalence of obesity and type 2 diabetes mellitus (T2DM) has led to a growing interest in the investigation of new therapies. Treatment of T2DM has focused on the insulinopenia and insulin resistance. However, in the last 10 years, new lines of research have emerged for the treatment of T2DM and preclinical studies appear promising. The possibility of using these drugs in combination with other currently available drugs will enhance the antidiabetic effect and promote weight loss with fewer side effects. The data provided by post-marketing monitoring will help us to better understand their safety profile and potential long-term effects on target organs, especially the cardiovascular risk.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Terapia de Alvo Molecular , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Dipeptidil Peptidase 4/efeitos dos fármacos , Quimioterapia Combinada , Drogas em Investigação/efeitos adversos , Drogas em Investigação/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Glucagon/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucoquinase/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Glucose/farmacocinética , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/classificação , Hipoglicemiantes/farmacologia , Incretinas , Resistência à Insulina , Insulina de Ação Prolongada/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Fosfofrutoquinase-2/antagonistas & inibidores , Proteínas de Transporte de Sódio-Glucose/antagonistas & inibidores , Perda de Peso
19.
J Investig Med ; 62(8): 968-74, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25361053

RESUMO

PURPOSE: Type 2 diabetes mellitus (type 2 DM) and maturity-onset diabetes of the young present some similar clinical and biochemical characteristics that make them difficult to differentiate. Currently, the polymorphism T130I (rs1800961) in the HNF4A (hepatocyte nuclear factor 4A) gene has been described as a risk factor to type 2 DM and shows an autosomal dominant inheritance pattern associated to ß-cell function decrease. The aim of the present work was to characterize the phenotypic profile of the T130I carrier and noncarrier relatives included in 3 unrelated families. METHODS: We studied GCK, HNF1A, and HNF4A genes by polymerase chain reaction and sequencing in 3 unrelated subjects from Valladolid, Spain, in which maturity-onset diabetes of the young was suspected. We collected genetic, clinical, and biochemical data from these subjects and their relatives in order to check the presence of the T130I polymorphism. RESULTS: The heterozygous T130I mutation was the unique functional gene variation that could explain diabetes phenotype. We observed significant differences in glucose metabolism, lipid profile, and Homeostasis Model Assessment index when we compared T130I mutation carriers and noncarriers. Diabetes diagnosed in T130I mutation carriers was related to stressful situations in an earlier age and tightly associated with gestational diabetes. Fasting plasma glucose and HbA(1c) levels increased with age in all carriers (r = 0.69 and r = 0.66, P < 0.01), respectively. CONCLUSIONS: Our study supports the T130I variant in HNF4A as a major susceptibility genotype associated with early-onset type 2 DM. Healthy carriers of this mutation require a stricter control in the population of central Spain.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Fator 4 Nuclear de Hepatócito/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idade de Início , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Família , Feminino , Hemoglobina A Glicada/metabolismo , Heterozigoto , Humanos , Masculino , Mutação/genética , Linhagem , Espanha
20.
PLoS One ; 9(7): e101616, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24988226

RESUMO

Autoimmune polyglandular syndrome type 1 (APS-1, OMIM 240300) is a rare autosomal recessive disorder, characterized by the presence of at least two of three major diseases: hypoparathyroidism, Addison's disease, and chronic mucocutaneous candidiasis. We aim to identify the molecular defects and investigate the clinical and mutational characteristics in an index case and other members of a consanguineous family. We identified a novel homozygous mutation in the splice site acceptor (SSA) of intron 5 (c.653-1G>A) in two siblings with different clinical outcomes of APS-1. Coding DNA sequencing revealed that this AIRE mutation potentially compromised the recognition of the constitutive SSA of intron 5, splicing upstream onto a nearby cryptic SSA in intron 5. Surprisingly, the use of an alternative SSA entails the uncovering of a cryptic donor splice site in exon 5. This new transcript generates a truncated protein (p.A214fs67X) containing the first 213 amino acids and followed by 68 aberrant amino acids. The mutation affects the proper splicing, not only at the acceptor but also at the donor splice site, highlighting the complexity of recognizing suitable splicing sites and the importance of sequencing the intron-exon junctions for a more precise molecular diagnosis and correct genetic counseling. As both siblings were carrying the same mutation but exhibited a different APS-1 onset, and one of the brothers was not clinically diagnosed, our finding highlights the possibility to suspect mutations in the AIRE gene in cases of childhood chronic candidiasis and/or hypoparathyroidism otherwise unexplained, especially when the phenotype is associated with other autoimmune diseases.


Assuntos
Mutação , Poliendocrinopatias Autoimunes/genética , Sítios de Splice de RNA , Fatores de Transcrição/genética , Sequência de Bases , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Dados de Sequência Molecular
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