RESUMEN

We describe the clinical course of renal tubular acidosis (RTA) type 4 in pregnancy, which has not been previously published. Renal tubular acidosis type 4 is a condition associated with increased urinary ammonia secondary to hypoaldosteronism or pseudohypoaldosteronism. Pregnancy may worsen the hyperkalaemia and acidosis of renal tubular acidosis type 4, possibly through an antialdosterone effect. We advise regular monitoring of potassium and pH throughout pregnancy to ensure safe levels are maintained.

Asunto(s)

Aldosterona/metabolismo , Hipoaldosteronismo/complicaciones , Enfermedades Renales/complicaciones , Potasio/sangre , Complicaciones del Embarazo/metabolismo , Equilibrio Ácido-Base , Acidosis Tubular Renal/complicaciones , Adulto , Amoníaco/orina , Femenino , Humanos , Concentración de Iones de Hidrógeno , Hiperpotasemia/complicaciones , Enfermedades Renales/metabolismo , Túbulos Renales/metabolismo , Embarazo

RESUMEN

CONTEXT: The combination of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) has been proposed as a potential treatment for diabetes and obesity. However, the combined effects of these hormones, PYY(3-36) and GLP-1(7-36 amide), on glucose homeostasis are unknown. OBJECTIVE: This study sought to investigate the acute effects of PYY(3-36) and GLP-1(7-36) amide, individually and in combination, on insulin secretion and sensitivity. SETTING AND DESIGN: Using a frequently sampled iv glucose tolerance test (FSIVGTT) and minimal modeling, this study measured the effects of PYY(3-36) alone, GLP-1(7-36) amide alone, and a combination of PYY(3-36) and GLP-1(7-36) amide on acute insulin response to glucose (AIRg) and insulin sensitivity index (SI) in 14 overweight human volunteers, studied in a clinical research facility. RESULTS: PYY(3-36) alone caused a small but nonsignificant increase in AIRg. GLP-1(7-36) amide alone and the combination of PYY(3-36) and GLP-1(7-36) amide did increase AIRg significantly. No significant differences in SI were observed with any intervention. CONCLUSIONS: PYY(3-36) lacks any significant acute effects on first-phase insulin secretion or SI when tested using an FSIVGTT. Both GLP-1(7-36) amide alone and the combination of PYY3-36 and GLP-1(7-36) amide increase first-phase insulin secretion. There does not seem to be any additive or synergistic effect between PYY(3-36) and GLP-1(7-36) amide on first-phase insulin secretion. Neither hormone alone nor the combination had any significant effects on SI.

Asunto(s)

Péptido 1 Similar al Glucagón/farmacología , Glucosa/administración & dosificación , Insulina/sangre , Obesidad/sangre , Sobrepeso/sangre , Fragmentos de Péptidos/farmacología , Péptido YY/farmacología , Adulto , Glucemia , Femenino , Prueba de Tolerancia a la Glucosa , Homeostasis/efectos de los fármacos , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Adulto Joven

RESUMEN

Glucagon and glucagon-like peptide (GLP)-1 are the primary products of proglucagon processing from the pancreas and gut, respectively. Giving dual agonists with glucagon and GLP-1 activity to diabetic, obese mice causes enhanced weight loss and improves glucose tolerance by reduction of food intake and by increase in energy expenditure (EE). We aimed to observe the effect of a combination of glucagon and GLP-1 on resting EE and glycemia in healthy human volunteers. In a randomized, double-blinded crossover study, 10 overweight or obese volunteers without diabetes received placebo infusion, GLP-1 alone, glucagon alone, and GLP-1 plus glucagon simultaneously. Resting EE--measured using indirect calorimetry--was not affected by GLP-1 infusion but rose significantly with glucagon alone and to a similar degree with glucagon and GLP-1 together. Glucagon infusion was accompanied by a rise in plasma glucose levels, but addition of GLP-1 to glucagon rapidly reduced this excursion, due to a synergistic insulinotropic effect. The data indicate that drugs with glucagon and GLP-1 agonist activity may represent a useful treatment for type 2 diabetes and obesity. Long-term studies are required to demonstrate that this combination will reduce weight and improve glycemia in patients.

Asunto(s)

Metabolismo Energético/efectos de los fármacos , Péptido 1 Similar al Glucagón/administración & dosificación , Glucagón/administración & dosificación , Hiperglucemia/tratamiento farmacológico , Adulto , Calorimetría Indirecta , Estudios Cruzados , Método Doble Ciego , Metabolismo Energético/fisiología , Femenino , Glucagón/farmacología , Péptido 1 Similar al Glucagón/farmacología , Humanos , Hiperglucemia/metabolismo , Infusiones Intravenosas , Masculino , Persona de Mediana Edad

RESUMEN

Hyperprolactinemia is a common consequence of treatment with an antipsychotic medication. It can result in hypogonadism due to the inhibitory effect of elevated prolactin levels on the hypothalamic-pituitary-gonadal hormonal axis. We present a case of hypogonadism secondary to hyperprolactinemia in a patient taking antipsychotic medication, with radiological evidence of a pituitary microadenoma. The relevance and investigation of hyperprolactinemia in patients being treated with antipsychotic medications are discussed.

Asunto(s)

Antipsicóticos/efectos adversos , Galactorrea/inducido químicamente , Hiperprolactinemia/inducido químicamente , Hipogonadismo/etiología , Neoplasias Hipofisarias/diagnóstico , Adulto , Femenino , Humanos , Hiperprolactinemia/complicaciones , Angiografía por Resonancia Magnética

RESUMEN

OBJECTIVE: Cabergoline is a highly effective medical treatment for patients with hyperprolactinaemia. There is an increased risk of valvular heart disease in patients receiving cabergoline for Parkinson's disease. This study examined whether cabergoline treatment of hyperprolactinaemia is associated with a greater prevalence of valvulopathy. DESIGN: Cross-sectional, two-dimensional echocardiographic study performed by a single echocardiographer. PATIENTS: Seventy-two patients (median age 36 years, 19 men) receiving cabergoline for hyperprolactinaemia, and 72 controls prospectively matched for age, sex and cardiovascular risk factors. Measurements Assessment of valvular mobility, regurgitation and morphology. RESULTS: Median cumulative dose exposure for cabergoline was 126 (58-258) mg, and patients had received cabergoline for 53 (26-96) months. The frequency of mild mitral regurgitation was identical (5/72, 7%) in patient and control groups. Mild aortic regurgitation was not significantly different between groups (4/72 [controls] vs 2/72 [patients], P = 0.681). There was only one case of tricuspid regurgitation, which was mild and observed in a cabergoline-treated patient. Nodular thickening of the right coronary cusp, noncoronary cusp or left coronary cusp of the aortic valve was observed at a similar frequency in both groups. There were no cases of extensive thickening of any valvular leaflet. CONCLUSION: Our data demonstrates that there is no association between cabergoline treatment for hyperprolactinaemia and valvulopathy. This study therefore supports continued use of low-dose cabergoline for patients with hyperprolactinaemia.

Asunto(s)

Ergolinas/uso terapéutico , Enfermedades de las Válvulas Cardíacas/fisiopatología , Válvulas Cardíacas/fisiopatología , Hiperprolactinemia/tratamiento farmacológico , Adulto , Antiparkinsonianos/efectos adversos , Antiparkinsonianos/uso terapéutico , Presión Sanguínea , Cabergolina , Estudios Transversales , Relación Dosis-Respuesta a Droga , Ecocardiografía , Ergolinas/efectos adversos , Femenino , Enfermedades de las Válvulas Cardíacas/inducido químicamente , Enfermedades de las Válvulas Cardíacas/diagnóstico , Válvulas Cardíacas/diagnóstico por imagen , Válvulas Cardíacas/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo/métodos , Función Ventricular Izquierda , Función Ventricular Derecha

RESUMEN

OBJECTIVE: Peptide YY(3-36) (PYY(3-36)), a Y2 receptor agonist, and oxyntomodulin, a glucagon-like peptide 1 (GLP-1) receptor agonist, are cosecreted by intestinal L-cells after each meal. Separately each hormone acts as an endogenous satiety signal and reduces appetite in humans when infused intravenously. The aim of the current study was to investigate whether the anorectic effects of PYY(3-36) and oxyntomodulin can be additive. RESEARCH DESIGN AND METHODS: Twelve overweight or obese human volunteers underwent a randomized, double-blinded, placebo-controlled study. An ad libitum test meal was used to measure energy intake during intravenous infusions of either PYY(3-36) or oxyntomodulin or combined PYY(3-36)/oxyntomodulin. RESULTS: Energy intake during coadministration of PYY(3-36) and oxyntomodulin was reduced by 42.7% in comparison with the saline control and was significantly lower than that during infusions of either hormone alone. CONCLUSIONS: The anorectic effects of PYY(3-36) and oxyntomodulin can be additive in overweight and obese humans. Coadministration of Y2 receptor agonists and GLP-1 receptor agonists may be a useful treatment strategy for obesity.

Asunto(s)

Ingestión de Alimentos/efectos de los fármacos , Ingestión de Energía/efectos de los fármacos , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Oxintomodulina/administración & dosificación , Péptido YY/administración & dosificación , Adulto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Obesidad/metabolismo , Sobrepeso/metabolismo , Oxintomodulina/metabolismo , Selección de Paciente , Fragmentos de Péptidos , Péptido YY/metabolismo , Encuestas y Cuestionarios

RESUMEN

The glucagon-like peptide-1 (GLP-1) agonist drugs have attractions as a treatment for type 2 diabetes since they positively alter a number of key pathophysiological defects. These include increasing insulin release, reducing glucagon release, slowing gastric emptying and reducing food intake. In numerous clinical trials these agents have been shown to reduce DCCT-aligned HbA(1c) between 0.8% and 1.1% in patients with moderately controlled type 2 diabetes, whilst also being associated with some weight loss. Whilst medium-term safety and side-effect profiles are now well established, there are as yet no long-term studies on the safety of this group of drugs. The place of the GLP-1 agonists in the treatment paradigm for type 2 diabetes will evolve over the next decade.

RESUMEN

PURPOSE OF REVIEW: Complex physiological mechanisms have evolved to control food intake in mammals, which in health ensure the relative stability of body weight in adults. Central brain centres, gut-derived peptides and adipose-derived signals result in an integrative response to defend against starvation. Enteroendocrine cells throughout the gut and pancreas secrete a number of peptides with activity on gut motility, gut secretions and appetite. Understanding the interactions between different gut peptides has produced a rewardingly active research field with many unanswered questions. RECENT FINDINGS: Many gut peptides are now in translational research programmes to investigate their potential in human physiology and disease. Ghrelin has been shown in short-term human studies to both increase appetite and body weight. Oxyntomodulin has been shown to reduce weight and food intake in a 4 week study in humans. Anorectic activity of peptide YY(3-36) has been confirmed in a number of animal models. Obestatin has been identified as a novel gut peptide. Increasing evidence points to the effect of gastric-bypass surgery on body weight, including alteration of gut peptide activity. SUMMARY: Gut peptides, or gut-peptide mimetics, show great promise for use as therapeutic agents for the treatment of obesity and cachexia.

Asunto(s)

Regulación del Apetito/efectos de los fármacos , Hormonas Gastrointestinales/farmacología , Animales , Humanos , Obesidad/fisiopatología , Obesidad/prevención & control

RESUMEN

Extremely low concentrations of high density lipoprotein (HDL)-cholesterol and apolipoprotein (apo) AI are features of Tangier disease caused by autosomal recessive mutations in ATP-binding cassette transporter A1 (ABCA1). Less deleterious, but dominantly inherited mutations cause HDL deficiency. We investigated causes of severe HDL deficiency in a 42-year-old female with progressive coronary disease. ApoAI-mediated efflux of cholesterol from the proband's fibroblasts was less than 10% of normal and nucleotide sequencing revealed inheritance of two novel mutations in ABCAI, V1704D and L1379F. ABCA1 mRNA was approximately 3-fold higher in the proband's cells than in control cells; preincubation with cholesterol increased it 5-fold in control and 8-fold in the proband's cells, but similar amounts of ABCA1 protein were present in control and mutant cells. When transiently transfected into HEK293 cells, confocal microscopy revealed that both mutant proteins were retained in the endoplasmic reticulum, while wild-type ABCA1 was located at the plasma membrane. Severe HDL deficiency in the proband was caused by two novel autosomal recessive mutations in ABCA1, one (V1704D) predicted to lie in a transmembrane segment and the other (L1379F) in a large extracellular loop. Both mutations prevent normal trafficking of ABCA1, thereby explaining their inability to mediate apoA1-dependent lipid efflux.

Asunto(s)

Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Genes Recesivos/genética , Lipoproteínas HDL/deficiencia , Lipoproteínas HDL/genética , Mutación Missense/genética , Transportador 1 de Casete de Unión a ATP , Transportadoras de Casetes de Unión a ATP/química , Adolescente , Adulto , Anciano , Secuencia de Aminoácidos , Animales , Apolipoproteína A-I/genética , Células Cultivadas , Exones/genética , Femenino , Fibroblastos , Regulación de la Expresión Génica , Humanos , Lipoproteínas HDL/metabolismo , Masculino , Datos de Secuencia Molecular , Linaje , Transporte de Proteínas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Alineación de Secuencia