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The authors regret that Alexandra Bargiota's name was spelt incorrectly in the author list. The details given in this correction are correct.
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OBJECTIVE: Growth hormone (GH) and insulin-like growth factor I (IGF-I) are the principal biomarkers used to assess disease activity in acromegaly, and any discrepancy between them renders interpretation of results inconclusive. Purpose of this study was to assess the frequency of this discrepancy and identify parameters that might affect its occurrence. DESIGN: A systematic review of MEDLINE and Scopus was performed (1987-2013) followed by a meta-analysis to address the frequency of discrepant results between GH and IGF-I levels. Meta-regression and subgroup analyses were performed assessing the effects of the year of publication, the different types of GH testing and GH assays used, as well as the impact of treatment with somatostatin analogues (SSAs) on the occurrence of this discrepancy. RESULTS: The analysis retrieved 39 eligible studies totalling 7071 patients. The pooled discordance rate between GH and IGF-I was 25·7% (95% CI: 22·3-29·4), and the predominant format was that of elevated IGF-I with normal GH levels (15·3%, 95% CI: 12·5-18·7). No significant correlation between the discordance rate and the year of publication was shown; whereas, the use of ultrasensitive GH assays resulted in higher discordance rates (30·7%, 95% CI: 25·9-35·9 vs 19·8%, 95% CI: 14·1-27·2, P = 0·04) as did treatment with SSAs (32·5%, 95% CI: 27·8-37·4) vs (21·6%, 95% CI: 17·8-25·6, P = 0·001). CONCLUSIONS: Discrepancy between GH and IGF-I results is encountered in a quarter of treated patients with acromegaly, especially when using ultrasensitive GH assays or in patients receiving SSAs, a fact that the clinician should take into consideration when making clinical decisions.
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Acromegalia/diagnóstico , Hormona del Crecimiento/análisis , Factor I del Crecimiento Similar a la Insulina/análisis , Biomarcadores/análisis , HumanosRESUMEN
AIMS: Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. METHODS: Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. RESULTS: Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. CONCLUSION: These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/uso terapéutico , Sistemas de Infusión de Insulina/estadística & datos numéricos , Insulina/uso terapéutico , Sistema de Registros , Adolescente , Adulto , Austria , Dinamarca , Diabetes Mellitus Tipo 1/metabolismo , Inglaterra , Femenino , Francia , Alemania , Grecia , Adhesión a Directriz , Humanos , Irlanda , Italia , Letonia , Masculino , Países Bajos , Nueva Zelanda , Irlanda del Norte , Noruega , Guías de Práctica Clínica como Asunto , Escocia , Suecia , Ucrania , Estados Unidos , Gales , Australia Occidental , Adulto JovenRESUMEN
OBJECTIVE: Somatic mutations in the GNAS1 gene, which encodes the alpha-subunit of G stimulatory proteins (gsp), are frequently detected in somatotroph pituitary tumors and have been associated to specific clinical and histopathological characteristics. However, the question whether the presence of a somatic gsp mutation affects the response to somatostatin analog treatment remains unresolved. DESIGN: Following a literature search, we performed a meta-analysis, including 8 eligible studies, in order to estimate the effect of gsp mutation on the percent reduction of growth hormone (GH) levels during an acute octreotide suppression test (OST). A total of 310 patients with acromegaly [126 gsp (+) and 184 gsp (-)] were included in the analysis. RESULTS: The presence of the gsp mutation was related with a greater reduction in GH levels on OST [Weighted Mean Difference (WMD): 9.08 % (95 % CI, 2.73, 15.42); p = 0.005; random effects model]. There was significant heterogeneity for this effect estimate (I(2) = 58 %, p value for heterogeneity = 0.02). A sensitivity analysis after exclusion of a study with different methodology of OST provided similar estimates [WMD: 6.93 % (95 % CI, 1.40, 12.46); p = 0.01], albeit with no significant heterogeneity (I(2) = 35 %, p value for heterogeneity = 0.16). CONCLUSIONS: The present meta-analysis suggests a role for gsp mutation as a prognostic factor of treatment response to somatostatin analogs.
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Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Neoplasias Hipofisarias/genética , Hormona del Crecimiento/metabolismo , Humanos , Mutación/genéticaRESUMEN
In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.
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Diabetes Mellitus/metabolismo , Enfermedades del Sistema Endocrino/inducido químicamente , Enfermedades del Sistema Endocrino/patología , Sistema Endocrino/patología , Endocrinología/métodos , Animales , Diabetes Mellitus/diagnóstico , Sistema Endocrino/efectos de los fármacos , HumanosRESUMEN
Although partnership issues are thought to be implicated in female psychology and sexual life, no data exist on the relationship between dissatisfaction with male sexual performance and female sexual dysfunction (FSD) in women with type 1 diabetes mellitus (DM-1). We studied 70 women with uncomplicated DM-1 and 100 nondiabetic women using Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS) and a Likert Scale to evaluate sexual function, sexual distress and the degree of satisfaction derived from the male partner's sexual performance. Compared with healthy controls, DM-1 women had significantly worse sexual function, higher sexual distress and higher FSD frequency. No significant difference in dissatisfaction with partner's sexual performance was found between diabetic and control group (CG). Moreover, dissatisfied diabetic and control women were comparable in sexual functioning, sexual distress and FSD frequency. In the CG, dissatisfied women had significantly worse total FSFI score compared with the satisfied ones. In addition, dissatisfaction with male sexual performance led to significantly worse FSDS score and higher FSD frequency in both diabetic and CGs. Therefore, our findings reveal a negative association between dissatisfaction with male partner's sexual performance and female sexual functioning, regardless of the presence of diabetes.
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Diabetes Mellitus Tipo 1/fisiopatología , Disfunciones Sexuales Fisiológicas/psicología , Disfunciones Sexuales Psicológicas/psicología , Parejas Sexuales/psicología , Adulto , Diabetes Mellitus Tipo 1/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción Personal , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Poststroke hyperglycemia has been associated with unfavorable outcome. Several trials investigated the use of intravenous insulin to control hyperglycemia in acute stroke. This meta-analysis summarizes all available evidence from randomized controlled trials in order to assess its efficacy and safety. METHODS: We searched PubMed until 15/02/2013 for randomized clinical trials using the following search items: 'intravenous insulin' or 'hyperglycemia', and 'stroke'. Eligible studies had to be randomized controlled trials of intravenous insulin in hyperglycemic patients with acute stroke. Analysis was performed on intention-to-treat basis using the Peto fixed-effects method. The efficacy outcomes were mortality and favorable functional outcome. The safety outcomes were mortality, any hypoglycemia (symptomatic or asymptomatic), and symptomatic hypoglycemia. RESULTS: Among 462 potentially eligible articles, nine studies with 1491 patients were included in the meta-analysis. There was no statistically significant difference in mortality between patients who were treated with intravenous insulin and controls (odds ratio: 1.16, 95% confidence interval: 0.89-1.49). Similarly, the rate of favorable functional outcome was not statistically different (odds ratio: 1.01, 95% confidence interval: 0.81-1.26). The rates of any hypoglycemia (odds ratio: 8.19, 95% confidence interval: 5.60-11.98) and of symptomatic hypoglycemia (odds ratio: 6.15, 95% confidence interval: 1.88-20.15) were higher in patients treated with intravenous insulin. There was no heterogeneity across the included trials in any of the outcomes studied. CONCLUSIONS: This meta-analysis of randomized controlled trials does not support the use of intravenous insulin in hyperglycemic stroke patients to improve mortality or functional outcome. The risk of hypoglycemia is increased, however.
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Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/tratamiento farmacológico , Administración Intravenosa , HumanosRESUMEN
AIMS/HYPOTHESIS: Familial partial lipodystrophy (FPLD) and obesity are both associated with increased risks of type 2 diabetes and cardiovascular disease. Although adipokines have been implicated, few data exist in subjects with FPLD; therefore we investigated a family with FPLD due to a lamin A/C mutation in order to determine how abnormalities of the plasma adipokine profile relate to insulin resistance and the metabolic syndrome. METHODS: Plasma levels of adiponectin, leptin, resistin, IL-1beta, IL-6 and TNF-alpha in 30 subjects (ten patients, 20 controls) were correlated with indices of metabolic syndrome. RESULTS: Compared with controls, FPLD patients had significantly lower plasma levels of adiponectin (3.7+/-1.0 in FDLP cases vs 7.1+/-0.72 mug/ml in controls, p=0.02), leptin (1.23+/-0.4 vs 9.0+/-1.3 ng/ml, p=0.002) and IL-6 (0.59+/-0.12 vs 1.04+/-0.17 pg/ml, p=0.047) and elevated TNF-alpha (34.8+/-8.1 vs 13.7+/-2.7 pg/ml, p=0.028), whereas IL-1beta and resistin were unchanged. In both groups, adiponectin levels were inversely correlated with body fat mass (controls, r=-0.44, p=0.036; FDLP, r=-0.67, p=0.025), insulin resistance (controls, r=-0.62, p=0.003; FDLP, r=-0.70, p=0.025) and other features of the metabolic syndrome. TNF-alpha concentrations were positively related to fat mass (controls, r=0.68, p=0.001; FDLP, r=0.64, p=0.048) and insulin resistance (controls, r=0.86, p=0.001; FDLP, r=0.75, p=0.013). IL-6, IL-1beta and resistin did not demonstrate any correlations with the metabolic syndrome in either group. CONCLUSIONS/INTERPRETATION: Low adiponectin and leptin and high TNF-alpha were identified as the major plasma adipokine abnormalities in FPLD, consistent with the hypothesis that low adiponectin and high TNF-alpha production may be mechanistically related, and perhaps responsible for the development of insulin resistance and cardiovascular disease in FPLD.
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Adiponectina/sangre , Diabetes Mellitus Lipoatrófica/fisiopatología , Resistencia a la Insulina/fisiología , Laminina/genética , Factor de Necrosis Tumoral alfa/análisis , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Lipoatrófica/sangre , Diabetes Mellitus Lipoatrófica/genética , Femenino , Homeostasis , Humanos , Interleucina-1/sangre , Interleucina-6/sangre , Laminina/fisiología , Leptina/sangre , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Análisis Multivariante , Mutación , Obesidad/sangre , Obesidad/fisiopatología , Resistina/sangreRESUMEN
OBJECTIVE: The assay of dried blood spots on filter paper to determine blood glucose concentration has been used to detect hypoglycaemia in out patients. We assessed the accuracy of this approach in assaying blood glucose concentrations in the hypoglycaemic range. DESIGN: Volunteers were rendered hypoglycaemic by intravenous infusion of insulin. The glucose concentration in simultaneously taken blood samples was measured either fresh or after drying on filter paper. PATIENTS: Twenty-four healthy young volunteers and 9 patients with insulin-dependent diabetes were studied. MEASUREMENTS: Plasma glucose concentrations were measured using a standard auto analyser glucose oxidase method. Whole blood taken simultaneously was placed on prepared filter paper and allowed to dry; glucose concentration was then measured using a well-established technique. A correction factor was applied to convert the glucose concentration of plasma to that of whole blood. The relationship between glucose concentrations measured by the two methods was determined by regression coefficient. RESULTS: In the unequivocally hypoglycaemic range (plasma < or = 2.5 mmol/l), corrected dried blood spot glucose concentrations significantly correlated with standard plasma glucose concentrations (r = 0.81; P < 0.001). The dried blood spot method had a sensitivity of 91%. In the range designated probable hypoglycaemia (plasma < or = 3.3 mmol/l), there was also significant correlation (r = 0.90; P < 0.001) and the sensitivity was 96%. The specificity of the dried blood spot method was 100% in both ranges. CONCLUSIONS: Measurement of glucose concentrations in dried blood spots is specific and sensitive in the hypoglycaemic range. The present study indicates that hypoglycaemia may be excluded or confirmed respectively when levels in excess of 3.7 or below 2.8 mmol/l are found in uncorrected dried blood spot analysis.
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Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Hipoglucemia/diagnóstico , Adulto , Atención Ambulatoria , Manchas de Sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Sensibilidad y EspecificidadRESUMEN
Superior mesenteric artery blood flow increases significantly after hypoglycaemia in healthy humans. Glucagon has vasoactive properties but its role in hypoglycaemic hyperaemia is unclear. To assess this role, we studied the superior mesenteric artery blood flow response to hypoglycaemia of patients with uncomplicated Type 1 (insulin-dependent) diabetes mellitus of at least 10 years duration; a group known to have defective glucagon response to hypoglycaemia. Hypoglycaemia was induced using an intravenous infusion of soluble human insulin (2.5 m-units.min-1.kg-1) discontinued at a plasma glucose of 2.5 mmol/l. Superior mesenteric artery blood flow was measured using transcutaneous duplex Doppler ultrasound. Plasma samples were assayed for glucose, insulin, glucagon, catecholamines, growth hormone and cortisol. Plasma glucose concentration fell to a nadir of 1.8 (0.3) mmol/l in patients and 1.4 (0.1) mmol/l in controls. Plasma glucagon concentration was unchanged in patients from a baseline level of 111.7 (13.1) ng/l but rose in controls from 105 (8.5) to a peak of 239 (3.1) ng/l (P<0.001). Superior mesenteric artery blood flow increased in both groups: from 385 (29) to 921 (100) ml/min (140% increase; P<0.05) in patients and from 517 (50) to 790 (67) (53% increase; P<0.001) in controls. This study shows that patients with Type 1 diabetes have a normal splanchnic vascular hyperaemic response to hypoglycaemia despite defective glucagon counter-regulation. These results support our previous work suggesting that glucagon is not a major mediator of this response; it seems likely that circulating adrenaline is the major regulatory mechanism.