A randomized, double blind, cross-over, placebo-controlled clinical trial to assess the effects of Candesartan on the insulin sensitivity on non diabetic, non hypertense subjects with dysglyce mia and abdominal obesity. "ARAMIA"

BACKGROUND: The raising prevalence of type-2 diabetes mellitus and obesity has been recognized as a major problem for public health, affecting both developed and developing countries. Impaired fasting plasma glucose has been previously associated with endothelial dysfunction, higher levels of inflammatory markers and increased risk of developing insulin resistance and cardiovascular events. Besides life-style changes, the blockade of the renin-angiotensin system has been proposed as a useful alternative intervention to improve insulin resistance and decrease the number of new type-2 diabetes cases. The aim of this clinical trial is to study the effect of the treatment with Candesartan, an angiotensin II receptor antagonist, on the insulin resistance, the plasma levels of adipoquines, oxidative stress and prothrombotic markers, in a group of non diabetic, non hypertensive, dysglycemic and obese subjects. METHODS AND DESIGN: A randomized, double blind, cross-over, placebo-controlled, clinical trial was designed to assess the effects of Candesartan (up to 32 mg/day during 6 months) on the Homeostasis Model Assessment (HOMA) index, lipid profile, protrombotic state, oxidative stress and plasma levels of inflammatory markers. The participants will be recruited in the "Fundación Cardiovascular de Colombia". Subjects who fullfil selection criteria will receive permanent educational, nutritional and exercise support during their participation in the study. After a 15 days-run-in period with placebo and life-style recommendations, the patients who have a treatment compliance equal or greater than 80% will be randomlly assigned to one of the treatment groups. Group A will receive Candesartan during 6 months and placebo during 6 months. Group B will receive placebo during the first 6 months, and then, Candesartan during the last 6 months. Control visits will be programed monthly and all parameters of interest will be evaluated every 6 months. HYPOTHESIS: Treatment with Candesartan, could improve the HOMA index, the response to the oral glucose tolerance test and reduce the plasma levels of adipoquines, oxidative stress and prothrombotic markers, in non diabetic, non hypertense subjects with dysglycemia and abdominal obesity, recruited from a population at high risk of developing insulin resistance. These effects are independent of the changes in arterial blood pressure. Trial registration: NCT0031920

Neoplasia endocrina múltiple tipo-2B

La neoplasia endocrina multiple tipo 2 comprende tres sindromes : la neoplasia endocrina múltiple 2A con predisposición genética para desarrollar carcinoma medular del tiroides, feocromocitoma e hiperplasia primaria de paratiroides. La neoplasia endocrina múltiple 2B, desorden autosómico dominante con feocromocitoma y carcinoma medular del tiroides que generalmente se presenta a una edad más temprana y es más agresivo que la de tipo 2A, por lo que su diagnóstico precoz es crítico; estos pacientes, que también presentan neuromas mucosos, ganglioneuromas intestinales y hábito marfanoide, no desarrollan hiperparatiroidismo. Y el carcinoma medular familiar del tiroides, sin ninguna otra manifestación clínica de neoplasia endocrina múltiple 2A o 2B. Se han identificado mutaciones activadoras del proto-oncogene RET en todas las variantes de la neoplasia endocrina múltiple tipo 2. Las mutaciones del RET en la neoplasia endocrina múltiple 2B ocurren principalmente (95%) en las regiones que codifican para el dominio de tirosina cinasa, en los codones 883 y 918. No obstante las múltiples modalidades de tratamiento para los cánceres tiroideos, especialmente para el carcinoma medular, la sobrevida de los pacientes afectados no ha mejorado. Por tanto el desarrollo de nuevas estrategias de tratamiento, incluída la terapia génica, parece esperanzador para estos pacientes. La clonación de los cotrasportadores sodio-yoduro, ha abierto una nueva puerta para la terapia génica citorreductiva basada en la transferencia genética de los cotrasportadores, seguida por la ablación con yodo radiactivo (131I). Presentamos un caso esporádico de neoplasia  endocrina múltiple 2B en una niña asociado a una mutación en el codón 918 del exón 16 del proto-oncogene RET