Olga Giménez-Palop

A lesser postprandial suppression of plasma ghrelin in Prader-Willi syndrome is associated with low fasting and a blunted postprandial PYY response.

Objective  Ghrelin and polipeptide YY (PYY) are involved in the regulation of food intake. We evaluated these two peptides and their possible relationship in adult patients with Prader–Willi syndrome (PWS).

¿La diabetes mellitus es un equivalente de riesgo coronario? Resultados de un metaanálisis de estudios prospectivos

Introduccion y objetivos Varias guias sobre el tratamiento de los factores de riesgo cardiovascular basan sus recomendaciones en el concepto de que la diabetes mellitus (DM) es un equivalente de riesgo coronario o de riesgo cardiovascular. Hasta el presente no se ha realizado ninguna revision sistematica sobre los estudios en los que se sustenta dicho concepto. Metodos Se ha realizado una busqueda sistematica en PubMed hasta febrero de 2006 para localizar los estudios prospectivos que cumplian los siguientes criterios: a) periodo de seguimiento > 5 anos; b) incluir un grupo de pacientes con DM y sin enfermedad coronaria (DM+EC–), otro sin DM y con enfermedad coronaria (DM–EC+), y otro sin ninguno de los 2 factores de riesgo (DM–EC–), y c) proporcionar datos sobre mortalidad coronaria o cardiovascular. Se ha evaluado las caracteristicas de los estudios y se las ha combinado separadamente, segun el sexo, con un modelo de efectos aleatorios, y tomando el grupo DM–EC– como de referencia. Resultados Trece estudios han cumplido los criterios de inclusion. Los varones del grupo DM+EC– presentan una menor mortalidad coronaria y cardiovascular que los del grupo DM–EC+, pero las diferencias no son significativas (hazard ratio [intervalo de confianza del 95%]: mortalidad coronaria, 3,06 [2,45-3,83] frente a 4,28 [3,24-5,66], respectivamente, p = 0,066; mortalidad cardiovascular, 2,55 [2-3,26] frente a 3,61 [2,81-4,62], respectivamente, p = 0,051). Las mujeres no presentan diferencias significativas entre los dos grupos DM+EC– y DM–EC+ en relacion con la mortalidad coronaria (4,68 [3,40-6,45] frente a 3,51 [1,75-7,04], respectivamente; p = 0,42) y la cardiovascular (4,70 [4,23-5,22] frente a 3,39 [1,51-9,02], respectivamente; p = 0,59). Conclusiones Este metaanalisis apoya la idea de que las mujeres del grupo DM+EC– tienen una mortalidad coronaria y cardiovascular similar a la de las mujeres en el grupo DM–EC+, mientras que los varones del grupo DM+EC– tienen una tendencia no estadisticamente significativa a presentar una menor mortalidad coronaria y cardiovascular que los varones en el grupo DM–EC+.

Serum soluble transferrin receptor concentrations are increased in central obesity. Results from a screening programme for hereditary hemochromatosis in men with hyperferritinemia.

BACKGROUND A decrease in the serum concentrations of the soluble transferrin receptor (sTfR) is considered a good index of tissue iron. Because obesity is associated with hyperferritinemia and this is considered a sign of iron overload, a decrease in sTfR would be expected for the obese. We evaluated whether obese men with hyperferritinemia, detected in a genetic screening programme for hereditary hemochromatosis (HH), have lower serum concentrations of sTfR than their non-obese counterparts. METHODS 75 men (age: 55.4+/-12.4 years) with hyperferritinemia (serum ferritin--SF > 200 microg/L) and no known conditions of iron overload were evaluated for body mass index (BMI), waist circumference (WC), blood pressure, traditional indices of iron status, sTfR, fasting plasma glucose, lipid profile, insulin resistance (HOMA-IR), highly-sensitive C-reactive protein, hepatic enzymes and HFE gene mutations of HH. RESULTS sTfR correlated with BMI (r=0.289; p=0.014) and with WC (r=0.420; p<0.001). Thirty-two subjects were obese (BM > or = 30 kg/m(2)) and had a significantly higher sTfR (2.95 (2.22-3.28) vs 2.28 (1.88-2.91) mg/L; p=0.013), hemoglobin (157+/-12 vs 152+/-11 gr/L; p=0.049) and HOMA-IR (1.38 (1.04-2.69) vs 1.02 (0.60-1.55) mg/L; p=0.009) than the non-obese. WC explained separately more variability of the sTfR than BMI (r(2)=0.177; p=0.002 and r=0.077; p=0.042, respectively), after adjusting for potential confounders. CONCLUSION An increase in serum concentrations of sTfR is associated with central obesity in men with hyperferritinemia.

Is Diabetes Mellitus a Coronary Heart Disease Equivalent? Results of a Meta-Analysis of Prospective Studies

INTRODUCTION AND OBJECTIVES Several guidelines on the treatment of cardiovascular risk factors base their recommendations on the assertion that diabetes mellitus (DM) is a coronary heart disease (CHD) or cardiovascular disease (CVD) risk equivalent. To date, no systematic review of studies substantiating this assertion has been carried out. METHODS A systematic search of the PubMed database up to February 2006 was performed to identify prospective studies meeting the following criteria: a) follow-up was >5 years; b) groups of subjects with DM and without CHD (i.e., DM+CHD-), without DM and with CHD (DM-CHD+), and without either DM or CHD (DM-CHD-) were all included; and c) data on CHD or CVD mortality was reported. The characteristics of the studies were assessed, and data were combined separately for men and women using a random effects model and taking the DM-CHD- group as a reference. RESULTS In total, 13 studies met the inclusion criteria. Overall, CHD mortality was non-significantly lower in DM+CHD- men than in DM-CHD+ men, hazard ratio [HR] (95% confidence interval [CI]), 3.06 (2.45-3.83) vs 4.28 (3.24-5.66), respectively (P=.066); as was CVD mortality, HR (95% CI), 2.55 (2.00-3.26) vs 3.61 (2.81-4.62), respectively (P=.051). In women, there was no significant difference between the DM+CHD- and DM-CHD+ groups with regard to either CHD mortality, HR (95% CI), 4.68 (3.40-6.45) vs 3.51 (1.75-7.04), respectively (P=.42), or CVD mortality, HR (95% CI), 4.70 (4.23-5.22) vs 3.39 (1.51-9.02), respectively (P=.59). CONCLUSIONS The findings of this meta-analysis support the view that women in the DM+CHD- group have similar CHD and CVD mortality to those in the DM-CHD+ group, whereas men in the DM+CHD- group demonstrated a non-significant trend towards lower CHD and CVD mortality than those in the DM-CHD+ group.

Postprandial Adiponectin Levels Are Unlikely to Contribute to the Pathogenesis of Obesity in Prader-Willi Syndrome

Aim:To investigate fasting and postprandial adiponectin levels in PWS patients as compared to obese and lean subjects and whether they could contribute to the pathogenesis of obesity in this syndrome. Methods: We studied 7 patients with PWS, 16 obese patients and 42 lean subjects for the fasting study. From this group, we evaluated 7 patients with PWS, 7 age-sex-BMI-matched obese non-PWS patients and 7 age-sex-matched lean subjects before and after the administration of 3,139.5 kJ (750 kcal) of a standard liquid meal (53.2% carbohydrate, 30% fat, 16.7% protein) after an overnight fast. Blood samples were obtained every 15 min for the first hour and every 30 min thereafter until 6 h. Adiponectin, IGF-I, glucose, triglycerides, cholesterol, and insulin were measured. Results:Fasting plasma adiponectin levels were lower in PWS than in lean subjects (5.24 ± 2.56 vs. 8.28 ± 4.63 µg/ml, p = 0.041) but higher than in obese patients (4.01 ± 1.27 µg/ml, p = 0.047). After the meal, adiponectin concentrations mildly decreased in PWS at time point 240 min, while in obese and lean subjects no changes were observed. However, 6-hour postprandial AUC for adiponectin was similar in all three groups. Conclusion: Fasting adiponectin levels are low in PWS, but they are so mildly modulated postprandially that these changes do not seem significant for the pathogenesis of obesity in this syndrome.

Men with hyperferritinemia and diabetes in the Mediterranean area do not have a higher iron overload than those without diabetes

AIM To assess the role of iron overload in type 2 diabetic men with hyperferritinemia. METHODS 150 men were recruited from a genetic screening programme for hereditary hemocromatosis (HH) and were tested for type 2 diabetes, other components of the metabolic syndrome, beta cell function (BCF), insulin sensitivity, high-sensitivity C-reactive protein and iron overload. RESULTS Fifty-one men had type 2 diabetes. They were older (p=0.017) and 99 had lower BCF (p<0.001) than non-diabetic men. None of the iron overload indexes was associated with diabetes. CONCLUSIONS Our findings dispute a role of iron overload in the pathogenesis of type 2 diabetes.

Safety of Cabergoline in the Management of Pituitary Prolactin-Induced Symptoms with Patients Treated with Atypical Neuroleptics

UNLABELLED Atypical antipsychotic-induced hyperprolactinemia can cause important clinical symptoms, particularly in young women and also in men, such as impotence, loss of libido, gynecomastia, anovulation and galactorrhea. METHODS Observational over one-year follow-up of six patients (four women and two men, mean age of 31.1 years, range 26-37), treated with different atypical antipsychotics in an outpatient psychiatric device, who had clinical complications associated to high prolactin serum levels. All of them were treated with standard doses of cabergoline. RESULTS Most patients experienced significant clinical improvement after treatment with standard doses of cabergoline (mean dosage 1.08 mg/week), maintained for a mean of 18 month. Normal prolactin levels were achieved after the first months of treatment with cabergoline. No side effects or worsening of psychotic or behavioral symptoms were observed. CONCLUSIONS Long-term treatment with cabergoline seems to be safe in atypical antipsychotic-treated patients.

Lack of confirmation of thyroid endophenotype in Bipolar Disorder Type I and their first-degree relatives

BACKGROUND Among the biological factors associated with the development and outcomes in Bipolar Disorder Type I (BD-I), previous studies have highlighted the involvement of both thyroid function and/or auto-immunity, proposing a thyroid endophenotype. The objective of this study was to determine the presence of thyroid alterations in BD-I and their first-degree relatives (FDR). METHODOLOGY Unselected, cross-sectional case-control study with parallel analysis of individuals affected by BD-I (239), their FD-R (131), and 108 healthy controls. Thyroidal functional abnormalities (TSH and free T4) and thyroidal antibodies (thyroglobulin and thyroperoxidase antibodies) were studied. Assessments were carried out in parallel. The sample was described using arithmetic means, standard deviations, percentages and ranges. Chi-square, Student-t tests, ANOVA and Pearson correlation coefficients were used when indicated. RESULTS BD-I on actual and/or ever treated with lithium showed significant thyroidal functional abnormalities as compared to their FD-R and healthy controls. This BD-I subgroup showed a significant greater proportion of subjects suffering from subclinical hypothyroidism (22%). The role of gender/lithium interactions was relevant. The groups did not show differences in terms of positivization of thyroidal antibodies. LIMITATIONS The crosssectional design and the lack of determination of dietary iodine deficiencies and/or thyroidal ecographical controls may be a drawback. CONCLUSIONS The present study supports previous findings on the effect of lithium treatment on thyroidal functional, but did not support previous findings related to a familial association or endophenotype. In addition, the present study did not support a familial aggregation of thyroidal antibodies positivization in pedegrees of BD-I.

Tratamiento con hormona de crecimiento en el síndrome de Prader-Willi

INTRODUCTION The Prader-Willi syndrome (PWS) is a rare genetic disorder caused by absence of expression of the paternal alleles in región 15q11.2-q13. Obesity and hormonal deficiencies, especially of growth hormone (GH), are the most important signs from the therapeutic viewpoint. Recombinant GH (rGH) is effective in children and represents the mainstay in treatment; by contrast, little evidence in available in adult patients. OBJECTIVE To review the reported evidence on the beneficial and adverse effects of treatment with rGH in children and adults. DESIGN A review was made of 62 original articles published between 2000 and 2017 using the PubMed database. RESULTS In pediatric and adult PWS, rGH improves body morphology and composition, physical performance, cognition, psychomotor development, respiratory function, and quality of life with few adverse effects. CONCLUSIONS Treatment with rGH is effective and safe and improves quality of life in both children and adults with PWS.

Topiramate as a Cause of False Positive in the Overnight 1-mg Dexamethasone Suppression Test

OBJECTIVE To describe that topiramate may cause a false positive in an overnight 1-mg dexamethasone suppression test (DST) for hypercortisolism screening. METHODS We present a case in which topiramate induced dexamethasone metabolism, leading to a false positive on the DST. RESULTS A 44-year-old female with an incidentally found adenoma in the right adrenal gland underwent a DST for hypercortisolism screening. The patient was taking topiramate prescribed by a psychiatrist for an affective disorder, and insufficient cortisol suppression (11.9 mcg/dL) was observed. Her free cortisol in 24-hour urine was normal, and insufficient suppression was established in a second determination (9.3 mcg/dL). Finally, her psychiatrist switched her treatment from topiramate to bupropion, and the measurements were repeated. When she was not taking topiramate, correct suppression with 1 mg of dexamethasone was obtained (1.7 mcg/dL), and her free cortisol in 24-hour urine was again normal, thereby excluding the presence of hypercortisolism. On reviewing the literature, topiramate was not found to have been previously described as a cause of a false positive on DST, but it was proposed as a cause of hypoadrenalism in a patient taking oral corticosteroid replacement due to its capacity to induce dexamethasone metabolism. CONCLUSION Topiramate treatment may well be a cause of false positives in DSTs, and its presence should be taken into consideration when screening for hypercortisolism.