The Decreased Growth Hormone Response to Growth Hormone Releasing Hormone in Obesity Is Associated to Cardiometabolic Risk Factors

The aim of the present study was to evaluate the relationship between GHRH-induced GH secretion in obese premenopausal women and cardiovascular risk markers or insulin resistance. Premenopausal obese women, aged 35–52 years, were studied. GH secretion, IGF-I, serum cardiovascular risk markers, insulin, leptin, mid-waist and hip circumference, total body fat, and truncal fat were measured. Subjects were classified as meeting the criteria for GH deficiency (GHD) when peak GH after stimulation with GHRH was ≤3 μg/L. Mean total and LDL cholesterol, fasting insulin, and HOMA-IR were all higher, in subjects who would have been classified as GH-deficient compared with GH-sufficient. Peak GH secretion after stimulation was inversely associated with fasting insulin (R = −0.650, P = .012), HOMA-IR (R = −0.846, P = .001), total cholesterol (R = −0.532, P = .034), and LDL cholesterol (R = −0.692, P = .006) and positively associated with HDL cholesterol (R = 0.561, P = .037). These data strongly suggest a role for insulin resistance in the decreased GH secretion of obesity and that the blunted GH secretion of central obesity could be the pituitary expression of the metabolic syndrome

PYY1-36 and PYY3-36 secretory response after a mixed meal in healthy individuals

[Resumen] Introducción. El péptido YY (PYY) tiene 36 aminoácidos y lo sintetizan fundamentalmente las células L del intestino. El PYY aumenta tras las comidas y alcanza su nadir tras el ayuno. Tras la ingestión se liberan dos formas: PYY1-36 y PYY3-36. Se ha demostrado que el PYY3-36 reduce la ingesta en humanos y roedores. Hay poca información sobre los valores plasmáticos de PYY, especialmente de PYY3-36, en respuesta a la ingestión y su relación con la respuesta de ghrelina. Objetivos. Estudiar la respuesta secretora de PYY1-36 y PYY3-36 en sujetos normales tras ingerir una comida mixta y su relación con la secreción de ghrelina total y acilada. Sujetos y métodos. Estudiamos a 8 sujetos sanos, 4 mujeres y 4 varones, con una mediana de edad de 53 (intervalo, 36-59) años. Tras el ayuno nocturno, recibieron en 2 días diferentes y de forma aleatoria: una comida oral mixta estándar, que consistía en 400 ml de Isosource Energy (159 kcal/100 ml) o placebo por vía oral (400 ml de agua). Se obtuvieron muestras sanguíneas en los tiempos 0, 30, 45, 60 y 120 min para la determinación de PYY1-36, PYY3-36, ghrelina total y ghrelina acilada. Las comparaciones se realizaron mediante la prueba de Wilcoxon. Las correlaciones numéricas se analizaron mediante la prueba de correlación de Spearman. Se consideró significativo un valor de p ≤ 0,05. Resultados. Tras ingerir la comida, se produce un máximo de PYY1-36 (mediana [intervalo]) de 141,5 (81-198) pg/ml y no hay respuesta tras placebo, con un máximo de 92,5 (46-219) pg/ml (p = 0,04). Los valores del área bajo la curva (ABC) de PYY1-36 tras la ingesta fueron 14.865 (8.032-19.822) pg/ml/min y tras placebo, 8.992 (4.455- 21.382) pg/ml/min (p = 0,06). Tras ingerir la comida se produce un máximo de PYY3-36 de 92,5 (59-135) pg/ml y no hay respuesta tras placebo, con un máximo de 46,5 (30- 66) pg/ml (p = 0,02). Los valores del ABC de PYY3-36 tras la ingesta fueron 9.086 (6.412-14.970) pg/ml/min y tras placebo, 4.984 (3.142-6.772) pg/ml/min (p = 0,012). El cociente nadir de ghrelina total/máximo de PYY1-36 disminuye de forma marcada tras la ingestión; los valores preprandiales son 7,44 (3,64-14,56) y los posprandiales, 3,55 (1,64-7,16) (p = 0,03), mientras que no se modifica tras placebo. El cociente nadir de ghrelina acilada/máximo de PYY3-36 disminuye de forma marcada tras la ingestión, y los valores preprandiales son 2,03 (0,92-3) y los posprandiales, 0,73 (0,26-1,27) (p = 0,02), mientras que no se modifican tras placebo. Conclusiones. En sujetos normales, PYY1-36 y PYY3-36 aumentan de forma paralela tras ingerir una comida mixta; simultáneamente, los valores de ghrelina total y acilada disminuyen. El cociente entre el nadir de ghrelina acilada y el máximo de PYY3-36 disminuye tras ingerir una comida mixta. Este conjunto de datos indica su posible participación en la regulación aguda del apetito tras la comida.[Abstract] Background. Peptide YY (PYY) is a 36 amino acid peptide synthesized mostly by intestinal L cells. This peptide reaches its nadir during fasting and increases immediately after meals. After food intake, two molecular forms are released, PYY1-36 and PYY3-36. PYY3-36 reduces food intake in both humans and rodents. There is scarce information about plasmatic concentrations of PYY, especially of PYY3-36, after food ingestion, and their relationship to ghrelin. Objectives. To study PYY1-36 and PYY3-36 secretory response after a mixed meal, and its relationship to total and acylated ghrelin secretion in healthy subjects. Subjects and method. We studied eight healthy subjects, 4 women and 4 men, with a median age of 53 (range, 36-59) years. After an overnight fast, the subjects received either a mixed standard meal (400 ml Isosource Energy® [159 kcal/100 ml]) or placebo (400 ml of water) orally in random order on two different days. Blood samples were obtained at 0, 30, 45, 60 and 120 min for measurement of PYY1-36, PYY3-36, total ghrelin and acylated ghrelin. Comparisons were made by Wilcoxon's test. Numerical correlations were performed using Spearman's test. P-values ≤ 0.05 were considered significant. Results. After a mixed meal, PYY1-36 reached a peak of (median [range]) 141.5 (81-198) pg/ml. There was no response to placebo, with a peak of 92.5 (46-219) pg/ml (p = 0.04). The area under the curve (AUC) of PYY1-36 levels after a mixed meal were 14,865 (8,032-19,822) pg/ml/min and after placebo were 8,992 (4,455-21,382) pg/ml/min (p = 0.06). After ingestion of a mixed meal, PYY3-36 reached a peak of 92.5 (59-135) pg/ml, with no response to placebo (46.5 [30-66] pg/ml) (p = 0.02). The AUC of PYY3-36 levels after a mixed meal were 9,086 (6,412-14,970) pg/ml/min, and after placebo were 4,984 (3,142-6,772) pg/ml/min (p = 0.012). The quotient between nadir total ghrelin/peak PYY1-36 was markedly diminished after food ingestion, with preprandial values of 7.44 (3.64-14.56) and postprandial values of 3.55 (1.64-7.16) (p = 0.03). The former quotient was unmodified by placebo. The quotient between nadir acylated ghrelin/peak PYY3-36 was markedly diminished after ingestion of a mixed meal, with preprandial values of 2.03 (0.92-3) and postprandial values of 0.73 (0.26-1.27) (p = 0.02). This quotient was unmodified by placebo. Conclusions. In healthy subjects, blood levels of both PYY1-36 and PYY3-36 increase after ingestion of a mixed meal. Simultaneously, total and acylated ghrelin levels diminish. The quotient between nadir acylated ghrelin/peak PYY3-36 diminishes after a mixed meal. All these data suggest the possible contribution of these peptides to appetite regulation after ingestion.Instituto de Salud Carlos III, PI051024Instituto de Salud Carlos III, PI070413Xunta de Galicia, PGIDT05PXIC91605PNXunta de Galicia, PS07/1

Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART)

<p>Abstract</p> <p>Aim</p> <p>Familial hypercholesterolemia (FH) patients are at high risk for premature coronary heart disease (CHD). Despite the use of statins, most patients do not achieve an optimal LDL-cholesterol goal. The aims of this study are to describe baseline characteristics and to evaluate Lipid Lowering Therapy (LLT) in FH patients recruited in SAFEHEART.</p> <p>Methods and Results</p> <p>A cross-sectional analysis of cases recruited in the Spanish FH cohort at inclusion was performed. Demographic, lifestyle, medical and therapeutic data were collected by specific surveys. Blood samples for lipid profile and DNA were obtained. Genetic test for FH was performed through DNA-microarray. Data from 1852 subjects (47.5% males) over 19 years old were analyzed: 1262 (68.1%, mean age 45.6 years) had genetic diagnosis of FH and 590 (31.9%, mean age 41.3 years) were non-FH. Cardiovascular disease was present in 14% of FH and in 3.2% of non-FH subjects (P < 0.001), and was significantly higher in patients carrying a null mutation compared with those carrying a defective mutation (14.87% vs. 10.6%, respectively, P < 0.05). Prevalence of current smokers was 28.4% in FH subjects. Most FH cases were receiving LLT (84%). Although 51.5% were receiving treatment expected to reduce LDL-c levels at least 50%, only 13.6% were on maximum statin dose combined with ezetimibe. Mean LDL-c level in treated FH cases was 186.5 mg/dl (SD: 65.6) and only 3.4% of patients reached and LDL-c under 100 mg/dl. The best predictor for LDL-c goal attainment was the use of combined therapy with statin and ezetimibe.</p> <p>Conclusion</p> <p>Although most of this high risk population is receiving LLT, prevalence of cardiovascular disease and LDL-c levels are still high and far from the optimum LDL-c therapeutic goal. However, LDL-c levels could be reduced by using more intensive LLT such as combined therapy with maximum statin dose and ezetimibe.</p

Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART)

<p>Abstract</p> <p>Aim</p> <p>Familial hypercholesterolemia (FH) patients are at high risk for premature coronary heart disease (CHD). Despite the use of statins, most patients do not achieve an optimal LDL-cholesterol goal. The aims of this study are to describe baseline characteristics and to evaluate Lipid Lowering Therapy (LLT) in FH patients recruited in SAFEHEART.</p> <p>Methods and Results</p> <p>A cross-sectional analysis of cases recruited in the Spanish FH cohort at inclusion was performed. Demographic, lifestyle, medical and therapeutic data were collected by specific surveys. Blood samples for lipid profile and DNA were obtained. Genetic test for FH was performed through DNA-microarray. Data from 1852 subjects (47.5% males) over 19 years old were analyzed: 1262 (68.1%, mean age 45.6 years) had genetic diagnosis of FH and 590 (31.9%, mean age 41.3 years) were non-FH. Cardiovascular disease was present in 14% of FH and in 3.2% of non-FH subjects (P < 0.001), and was significantly higher in patients carrying a null mutation compared with those carrying a defective mutation (14.87% vs. 10.6%, respectively, P < 0.05). Prevalence of current smokers was 28.4% in FH subjects. Most FH cases were receiving LLT (84%). Although 51.5% were receiving treatment expected to reduce LDL-c levels at least 50%, only 13.6% were on maximum statin dose combined with ezetimibe. Mean LDL-c level in treated FH cases was 186.5 mg/dl (SD: 65.6) and only 3.4% of patients reached and LDL-c under 100 mg/dl. The best predictor for LDL-c goal attainment was the use of combined therapy with statin and ezetimibe.</p> <p>Conclusion</p> <p>Although most of this high risk population is receiving LLT, prevalence of cardiovascular disease and LDL-c levels are still high and far from the optimum LDL-c therapeutic goal. However, LDL-c levels could be reduced by using more intensive LLT such as combined therapy with maximum statin dose and ezetimibe.</p

Altered fasting and postprandial plasma ghrelin levels in patients with liver failure are normalized after liver transplantation

[Abstract] Context Anorexia is a problem of paramount importance in patients with advanced liver failure. Ghrelin has important actions on feeding and weight homeostasis. Experimental data exist, which suggest that ghrelin could protect hepatic tissue. Both fasting and post-oral glucose tolerance test (OGTT) ghrelin concentrations are controversial in liver cirrhosis and are unknown after liver transplantation. Objective Our aim was to study fasting ghrelin concentrations and their response to an OGTT in liver failure patients before and after liver transplantation. Design and methods We included 21 patients with severe liver failure studied before (pretransplantation, PreT) and 6 months after liver transplantation (posttransplantation, PostT), and 10 age- and body mass index-matched healthy or overweight subjects as the control group (Cont). After an overnight fast, 75 g of oral glucose were administered; glucose, insulin, and ghrelin were obtained at baseline and at times 30, 60, 90, and 120 min. Results Fasting ghrelin (median and range, pg/ml) levels were lower in PreT: 539 (309–1262) than in Cont: 643 (523–2163), P=0.045. Fasting ghrelin levels increased after liver transplantation, 539 (309–1262) vs 910 (426–3305), for PreT and PostT respectively, P=0.001. The area under the curve (AUC) of ghrelin (pg/ml min) was lower in PreT: 63 900 (37 260–148 410) than in Cont: 76 560 (56 160–206 385), P=0.027. The AUC of ghrelin increased in PostT, 63 900 (37 260–148 410) vs 107 595 (59 535–357 465), for PreT and PostT respectively, P=0.001. Fasting levels and the AUC of ghrelin were similar in PosT and Cont. Conclusions Decreased fasting and post-OGTT ghrelin levels in liver failure patients were normalized after liver transplantation.Instituto de Salud Carlos III; PI051024Instituto de Salud Carlos III; PI070413Xunta de Galicia; PS07/12Galicia. Consellería de Innovación, Industria e Comercio; PGIDT05PXIC91605PNGalicia. Consellería de Economía e Industria; INCITE08ENA916110E

Guía de buen uso de tiras de autoanálisis de la glucemia capilar en la Diabetes Mellitus

Texto en gallego y españo

A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide

There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical-molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort. TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers

Fasting and postprandial plasma ghrelin levels are decreased in patients with liver failure previous to liver transplantation

[Abstract] Anorexia is a problem of paramount importance in patients with advanced liver failure. Ghrelin has important actions on feeding and weight homeostasis. Concentrations of ghrelin are controversial in liver cirrhosis. Our aim was to study fasting ghrelin and their response to an oral glucose tolerance test (OGTT) in liver failure patients and normal subjects. Methods We included 16 patients with severe liver failure prior to liver transplantation. As a control group we included 10 age- and BMI-matched healthy subjects. After an overnight fast, 75 g of oral glucose were administered; glucose, insulin, and ghrelin were obtained at baseline and at times 30, 60, 90, and 120 min, respectively. Results Fasting ghrelin (median and range) were statistically significantly lower for patients compared to the controls, 527 (377–971) pg/ml vs. 643 (523–2163) pg/ml, P = 0.045, for patients and controls, respectively. The area under the curve for total ghrelin post-OGTT were lower in end-stage liver failure patients than in the control group, 58815 (44730–87420) pg/ml min vs. 76560 (56160–206385) pg/ml min, for patients and controls, respectively, P = 0.027. Conclusions Ghrelin levels are significantly decreased both fasting and post-OGTT in patients with liver failure candidates for transplantation. Decreased ghrelin levels could contribute to anorexia in patients with cirrhosis.Instituto de Salud Carlos III; PI051024Instituto de Salud Carlos III; PI070413Xunta de Galicia; PS07/12Xunta de Galicia; PGIDT05PXIC91605PNXunta de Galicia; INCITE08ENA916110E

Principio de funcionamiento de la máquina de corriente contínua

Tesis (Ingeniero Electricista)--Universidad Autónoma de Occidente, 1990PregradoIngeniero(a) Electricist