RESUMEN
BACKGROUND: Adults with growth hormone (GH) deficiency (GHD) may experience physical and psychological disturbances, which can affect their quality of life (QOL). OBJECTIVES: To develop and validate a disease-specific module from the previously published QOL measure Questions on Life Satisfaction Modules (QLS(M)): the QLS(M)-H that specifically addressed the needs of patients with hypopituitarism. A second aim was for the questionnaire to be applicable across different cultural backgrounds in order to evaluate the efficacy of therapy in large, international clinical trials, thus providing additional clinical endpoints for these studies. DESIGN: A preliminary German language version of the QLS(M)-H was developed from 26 semi-structured interviews of adults with GHD. The questionnaire was then independently translated into five other languages and applied in open, non-controlled, multicentre, longitudinal studies to patient (n=717) and normative populations (n=2700). METHODS: A revised, nine-item version of the questionnaire was developed, based on previously defined criteria, and was evaluated for reliability and validity. Sensitivity to detect changes after GH replacement was also assessed. RESULTS: The 16 items of the preliminary questionnaire were reduced to nine items on the basis of the correlation of items/factors from initial patient interviews. Psychometric analysis revealed the reliability of the nine-item scale. The Cronbach's alpha scores ranged from 0.81 to 0.89 and the test-retest correlations ranged from 0.76 to 0.88, all of which indicate reliability over time. Mean scores increased significantly during GH replacement therapy, with observed changes greater than those seen with the non-specific modules of the QLS(M), indicating the sensitivity of the scale. CONCLUSIONS: The QLS(M)-H questionnaire is concise, easy to complete, and can be effectively applied across different cultural backgrounds. Psychometric evaluation of the questionnaire reveals that it is a valid, reliable and sensitive tool useful for assessing impaired life satisfaction in adult patients with GHD and also for monitoring the efficacy of GH therapy.
Asunto(s)
Hormona de Crecimiento Humana/deficiencia , Calidad de Vida , Encuestas y Cuestionarios , Adulto , Australia , Índice de Masa Corporal , Europa (Continente) , Femenino , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Hormonas Hipofisarias/deficiencia , Psicometría , Estados UnidosRESUMEN
BACKGROUND: The associations between leptin levels and the prevalence of a polymorphism in the beta 3-adrenergic receptor were studied in a cross-sectional analysis of 600 participants in a population-based study, which were stratified for glucose tolerance by an oral glucose tolerance test. METHODS: In a random sample of 600 participants in the Rotterdam study, aged 55-75 years at baseline (309 men, 291 women) the relationships were studied between the presence of Trp64 Arg mutation in the beta 3-adrenergic receptor gene and fasting leptin, glucose and insulin (fasting and after an oral glucose load), and other components of the insulin resistance syndrome. RESULTS: Mean age of the study population was 66.9 years (SD 5.7). Fasting serum leptin levels overall in men and women were 6.1 micrograms/l (SE 0.2) and 21.7 micrograms/l (0.9), respectively, (P < 0.001). These differences were independent of age, body mass index and waist to hip ratio. We identified 73/600 persons who were heterozygotes for the Trp64 Arg polymorphism (allelic frequency 6.1%), but failed to find an association between the presence of this polymorphism and leptin or any measured parameter indicative for obesity, impaired glucose tolerance or type 2 diabetes mellitus. CONCLUSION: Heterozygosity for the Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not accompanied by obesity, impaired glucose tolerance and type 2 diabetes mellitus in the general elderly Dutch population, and is also not associated with changes in circulating leptin levels.
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Glucosa/metabolismo , Resistencia a la Insulina , Polimorfismo Genético , Proteínas/metabolismo , Receptores Adrenérgicos beta/genética , Anciano , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Heterocigoto , Humanos , Resistencia a la Insulina/genética , Leptina , Masculino , Persona de Mediana Edad , Prevalencia , Receptores Adrenérgicos beta 3 , Receptores de Leptina , Análisis de RegresiónAsunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Infertilidad/fisiopatología , Obesidad/fisiopatología , Proteínas/fisiología , Tejido Adiposo/fisiología , Adolescente , Adulto , Andrógenos/fisiología , Niño , Femenino , Humanos , Leptina , Masculino , Valores de ReferenciaRESUMEN
OBJECTIVE: To investigate the acute effect of dexamethasone administration on serum leptin levels and the relationships between dehydroepiandrosterone (DHEAS), androstenedione, testosterone and the IGF-I/IGFBP system and leptin levels in healthy elderly humans. METHODS: In 209 healthy elderly individuals (95 men, 114 women, aged 55-80 years) measurements were made in the fasting state (0800 h) and after an overnight dexamethasone suppression test (1 mg p.o. at 2300 h. RESULTS: Mean leptin levels increased from 6.2 +/- 0.4 (SE) micrograms/l to 7.3 +/- 0.5 (SE) micrograms/l in men and from 18.9 +/- 1.4 (SE) micrograms/l to 23.9 +/- 1.8 (SE) micrograms/l in women after 1 mg dexamethasone overnight ('post treatment')(P < 0.001 for both sexes). There was a significant relationship between post-treatment leptin and dexamethasone levels (men: P = 0.002; women: P < 0.001). The increase in leptin levels after dexamethasone administration was only partially related to the increase in plasma insulin concentrations. Cortisol levels were not related to leptin. In multivariate analyses the relationship between post-treatment leptin and dexamethasone levels remained after adjustment for post-treatment insulin levels, BMI, waist:hip ratio (WHR) and age (men: P < 0.001; women: P = 0.001). Plasma (free and total) IGF-I and IGFBP-3 levels were not related to leptin levels in men or women. IGFBP-1 levels were inversely related to leptin levels (P = 0.02), but this relationship was lost after adjustment for insulin, and/or BMI. In multivariate analyses the relationship between leptin and DHEAS was inverse in women (P = 0.04) (after adjustment for BMI, WHR, insulin and glucose), while there was no relationship between leptin and DHEAS in men. CONCLUSIONS: Administration of dexamethasone acutely increased leptin levels within 9 h in this elderly population. This increase was only partly related to changes in circulating insulin concentrations, but was independent of BMI and waist:hip ratio. No relation existed between leptin and (free or total) IGF-I and IGFBP-3 in men or women. Dehydroepiandrosterone was inversely related to leptin in women. These findings suggest a contributory regulatory role for corticosteroids in modulating circulating leptin concentrations in elderly healthy individuals of both sexes, which is at least in part independent of insulin, BMI and waist:hip ratio. Dehydroepiandrosterone might play a role in the gender-specific differences in serum leptin levels.
Asunto(s)
Dexametasona/farmacología , Ayuno/sangre , Glucocorticoides/farmacología , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Proteínas/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Androstenodiona/sangre , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Humanos , Insulina/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Leptina , Masculino , Persona de Mediana Edad , Análisis Multivariante , Proteínas/metabolismo , Factores Sexuales , Estimulación Química , Testosterona/sangreRESUMEN
Leptin, the product of the ob gene, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine changes, leptin levels and various hormonal parameters were investigated in a large cohort of healthy children and adolescents (312 males, 401 females, age 5.8-19.9 yr). For this purpose, a specific and sensitive RIA was developed that allowed the accurate measurement of low leptin levels in young lean children. With this assay, leptin proved to be a comparatively stable protein under common conditions of blood sampling and storage. Leptin levels increased in girls with age (r = 0.47, P < 0.0001), but decreased in boys (r = -0.34, P < 0.0001). An analysis according to pubertal stage showed a steady increase in girls between 2.51 micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5. In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential relationship was observed for leptin levels with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This relationship was similar between boys and girls at Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a given BMI with further progression of puberty that was much less pronounced in girls. Although the relative increase of leptin with BMI and percent body fat was the same in both genders, the absolute values at a given BMI or percent body fat were significantly lower in boys in late puberty and in adolescents. In boys, but not in girls, there was an inverse correlation with testosterone concentrations (r = -0.43, P < 0.0001), which explained 10.5% of the variation of leptin levels in a multiple regression model. Since BMI proved to be the major influencing variable, reference ranges were constructed using a best-fit regression line of the form leptin = a*e(b*BMI) and stratifying ranges according to gender and pubertal stage. In conclusion, these data suggest that 1) plasma leptin levels increase in girls and decrease in boys after Tanner stage 2 as the pubertal development proceeds; 2) they show a significant gender difference especially in late puberty and adolescence, even after adjustment for BMI or percent body fat; 3) the lower levels in males may be explained at least in part by a suppressive effect of androgens; 4) reference ranges with BMI as the independent variable should be stratified according to gender and pubertal stage.