Núria Alonso

Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A.

OBJECTIVE GH deficiency (GHD) in adults is associated with adverse effects on metabolism and increased cardiovascular risk. Pregnancy-associated plasma protein-A (PAPP-A) is a protease that promotes IGF-I availability in vascular tissues. PAPP-A levels appear to correlate with carotid intima-media thickness and have been proposed as an early predictor of cardiac events. The aim of our study was to evaluate PAPP-A levels in GHD adults at baseline and after GH replacement and correlate them with changes in body composition, lipid profile, glucose homeostasis, inflammatory markers and in leptin and adiponectin. PATIENTS AND METHODS Fourteen GHD adults were evaluated at baseline and after 1 year of GH therapy. All patients were compared at baseline with 28 age-, sex- and body mass index (BMI)-matched control subjects. RESULTS At baseline, GHD adults showed higher PAPP-A levels (P=0.03) and higher leptin (P=0.04), fibrinogen (P=0.002) and highly sensitive C-reactive protein (P=0.01) values than controls. Therapy with GH reduced PAPP-A (P=0.03) and fibrinogen levels (P=0.002) while increased BMI (P=0.01) and reduced waist-hip ratio (WHR; P=0.05) were observed. Insulin and homeostasis model assessment of insulin resistance index increased after treatment (P<0.004/P=0.007), without changes in leptin or adiponectin levels. PAPP-A values correlated positively with BMI and WHR and negatively with adiponectin before and after treatment, with no correlation with glucose homeostasis parameters, lipid profile or leptin. CONCLUSIONS Our study suggests that PAPP-A expression is increased in GHD adults, and that 1 year of GH replacement therapy is able to reduce PAPP-A levels in this population. However, further studies are required to determine whether this decrease correlates with an improvement in atherosclerosis.

Diabetes mellitus y riesgo cardiovascular: recomendaciones del Grupo de Trabajo Diabetes y Enfermedad Cardiovascular de la Sociedad Española de Diabetes (SED, 2015)

The present paper updates the Clinical Practice Recommendations for the management of cardiovascular risk factors (CVRF) in diabetes mellitus. This is a medical consensus agreed by an independent panel of experts from the Spanish Society of Diabetes (SED). Several consensuses have been proposed by scientific and medical Societies to achieve clinical goals. However, the risk score for general population may lack sensitivity for individual assessment or for particular groups at risk, such as diabetics. Traditional risk factors together with non-traditional factors are reviewed throughout this paper. Intervention strategies for managing CVRF in the diabetic patient are reviewed in detail: balanced food intake, weight reduction, physical exercise, smoking cessation, reduction in HbA1c, therapy for high blood pressure, obesity, lipid disorders, and platelet anti-aggregation. It is hoped that these guidelines can help clinicians in the decisions of their clinical activity. This regular update by the SED Cardiovascular Disease Group of the most relevant concepts, and of greater practical and realistic clinical interest, is presented in order to reduce CVR of diabetics.

Regulatory T cells in diabetes and gastritis

Patients with Type 1 diabetes mellitus (T1D) have an increased prevalence of associated organ-specific autoimmune diseases such as pernicious anemia whose histological substrate is a chronic atrophic gastritis (CAG). Latent pernicious anemia precedes clinically-manifest pernicious anemia and may be difficult to detect solely on simple analytical grounds. We recently described an increased prevalence of clinically-latent pernicious anemia in T1D using low concentrations of pepsinogen I, a zymogen of pepsin present in gastric mucosa, as a useful additional diagnostic marker, besides parietal cell antibodies, for screening latent pernicious anemia in T1D. The failure of peripheral tolerance mechanisms such as regulatory T cells (Treg) might be involved in CAG development in T1D patients. Indeed, functional defects in Tregs have been described in T1D patients. To this end, the percentage of Tregs in peripheral blood of T1D-CAG patients was analyzed and compared with those of a group of T1D without associated autoantibodies and a healthy control group. Tregs levels were also analyzed in gastric biopsies of T1D-CAG patients. The results obtained have led to new questions regarding the pathogenic mechanisms implicated in the development of associated autoimmune diseases in T1D.

Ghrelin, glucose homeostasis, and carotid intima media thickness in kidney transplantation.

Background. Abnormalities in glucose homeostasis (AGH) frequently occur in kidney transplantation and favor vascular lesions. The purpose of this study was to analyze whether C-reactive protein (CRP), adiponectin, and ghrelin are markers of AGH and indicators of carotid atherosclerosis in kidney transplant patients with fasting plasma glucose below 126 mg/dL. Methods. This was a cross-sectional study of 85 kidney transplant patients (59 men; mean age: 52.4±11.6 years; median posttransplant follow-up 31 (range 3–61) months). All patients underwent an oral glucose tolerance test. Abnormalities in glucose homeostasis were diagnosed following American Diabetes Association criteria. CRP, adiponectin, and ghrelin levels were determined. Doppler ultrasound of the carotid artery was performed to determine intima media thickness (IMT) and atheromatous plaque. Results. A total of 50.5% of patients had AGH (12.9% were diagnosed with new-onset diabetes mellitus after transplantation and 37.7% had impaired glucose tolerance or impaired fasting glucose), whereas 49.4% were normoglycemic. Patients with AGH were older (P=0.002), had greater carotid IMT (P=0.022), and lower ghrelin concentrations (P=0.017) than normoglycemic patients. Logistic regression analyses showed ghrelin to be an independent marker for AGH (P=0.012) and AGH to be related to greater IMT (P=0.041). No differences in adiponectin or CRP were found in relation to AGH or atherosclerosis; however, there was a positive correlation between adiponectin levels and prednisone dose (r=0.240; P=0.044). Conclusions. A total of 50.5% of the study patients had abnormalities in glucose homeostasis. Patients with AGH had a higher percentage of preclinical atherosclerosis (greater carotid IMT). Ghrelin is an independent marker for abnormalities in glucose homeostasis.

No benefit from the obesity paradox for diabetic patients with heart failure

Paradoxically, obesity is associated with survival in heart failure (HF). Whether this is true for HF patients with comorbid type‐2 diabetes (T2D) remains uncertain. Our aim was to address this issue in diabetic patients by collecting correlates for body mass index (BMI) and long‐term mortality.

A prospective study of T- and B-lymphocyte subpopulations, CD81 expression levels on B cells and regulatory CD4+CD25+CD127low/−FoxP3+ T cells in patients with chronic HCV infection during pegylated interferon-alpha2a plus ribavirin treatment

Summary.  Resolution of hepatitis C virus (HCV) infection requires a complex interplay between innate and adaptative immune responses. The role of lymphocyte subpopulations during combined antiviral treatment remains to be defined. This study was conducted to assess the effect of pegylated interferon‐alpha2a (pegIFN‐α2a) and ribavirin treatment on peripheral blood lymphocytes, mainly on CD81 expression on B cells and CD4+CD25+CD127low/−FoxP3+ regulatory T cells (Tregs) in patients with chronic HCV infection. Thirty‐five patients with chronic HCV infection who started pegIFN‐α2a and ribavirin treatment were enrolled. Peripheral blood mononuclear cells (PBMC) were obtained at baseline before treatment (BT), mid‐treatment (MT), the end of treatment (ET) and 24 weeks post‐treatment (PT). During combined antiviral treatment, a significant decrease in the percentage of CD3+, CD8+, CD3+gamma/delta (γδ)+, CD19+ lymphocyte subpopulations and Tregs was observed. There was also a significant increase in the percentage of the CD4+ lymphocyte subpopulation and in CD81 expression levels on CD19+ B cells when BT was compared with ET (all P < 0.05). Seventeen patients were nonresponders (NR) and 18 had a sustained virological response (SVR). At baseline, NR patients had higher CD81 expression levels on CD19+ B cells (P = 0.017) and a higher Tregs percentage (P = 0.025) than SVR patients. Our results suggest that immunomodulation fluctuates during antiviral treatment and that percentage CD81 expression levels on B cells and Tregs might be useful as an immunological prognostic factor for pegIFN‐α2a and ribavirin treatment response in chronic HCV infection.

Frozen section in a cytological diagnosis of thyroid follicular neoplasm.

Objective/Hypothesis Fine‐needle aspiration biopsy is the most accurate diagnostic test for thyroid nodules, its only limitation being the diagnosis of follicular neoplasm that does not distinguish between benign and malignant follicular lesions.

Plasma ghrelin concentrations in type 1 diabetic patients with autoimmune atrophic gastritis.

OBJECTIVE Type 1 diabetes mellitus patients (DM1) show increased prevalence of pernicious anaemia, the histological substrate of which is type A chronic atrophic gastritis (CAG) in the stomach corpus, the main source of ghrelin. We aimed to compare plasma ghrelin concentrations in DM1 patients with type A CAG (DM1-CAG), DM1 patients without type A CAG and healthy controls and in DM1-CAG group, to ascertain a possible relationship between ghrelin and biochemical markers of gastric mucosa atrophy and/or neuroendocrine (NE) cell hyperplasia and histological gastric biopsy findings. DESIGN AND METHODS Fifteen DM1-CAG patients were matched for age, sex and body mass index with 15 DM1 patients without type A CAG and 15 controls. Pepsinogen I, pepsinogen II, gastrin, parietal cell antibodies, chromogranin A (CgA) and ghrelin were determined in all subjects. In DM1-CAG patients, immunohistochemical analysis of gastric biopsies using antibodies to CgA and ghrelin was performed. RESULTS Ghrelin concentrations differed among groups; however, paired comparisons between groups were not significant. In DM1-CAG, no correlation was found between ghrelin and gastric body atrophy markers, pepsinogen I and the pepsinogen I/II ratio. Immunohistochemical studies of DMI-CAG patients showed CgA staining in 12 and ghrelin staining in 6, which was confined to the foci of NE cell hyperplasia. Those patients who stained positive for ghrelin had higher ghrelin concentrations when compared with the negative patients. CONCLUSIONS Ghrelin concentrations are not decreased in DM1-CAG patients; thus, our data suggest that ghrelin is not a good marker of gastric mucosa atrophy in these patients, given the possible ghrelin synthesis in hyperplastic gastric endocrine/enterochromaffin-like cells.

Low Prevalence of Subclinical Atherosclerosis in Asymptomatic Patients With Type 1 Diabetes in a European Mediterranean Population

OBJECTIVE To evaluate the presence of early carotid and coronary atherosclerosis in asymptomatic patients with type 1 diabetes with no history of ischemic heart disease. RESEARCH DESIGN AND METHODS One hundred and fifty patients with type 1 diabetes (58% males; 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution; HbA1c 8.1 ± 2.3%; 52% nonsmokers; 26% retinopathy; 9% microalbuminuria) and 50 nondiabetic control subjects age and sex matched were studied. Carotid ultrasonography to determine common carotid artery intima-media thickness (c-IMT) and the presence of atheroma plaques and cardiac computed tomography for calcium analysis and quantification (coronary artery calcium score [CACS]) were performed. RESULTS Most patients with type 1 diabetes and control subjects displayed a CACS of 0 (82 vs. 92%). Patients with type 1 diabetes with CACS ≥1 were older and had higher HbA1c (44.5 ± 5.1 vs. 36.7 ± 8.1 years [P < 0.001] and 8.5 ± 1.1 vs. 7.8 ± 1.0% [P < 0.003], respectively) and longer evolution of diabetes (25.4 ± 9.2 vs. 19.3 ± 7.4 years, P < 0.005) and mean c-IMT (0.67 ± 0.18 vs. 0.53 ± 0.11 mm, P < 0.001) compared with patients with CACS of 0. Smoking (P < 0.02), nephropathy (P < 0.05), retinopathy (P < 0.05), and male sex (P < 0.03) were significantly and positively associated with CACS ≥1. Mean c-IMT was significantly higher in patients with type 1 diabetes (0.55 ± 0.14 vs. 0.48 ± 0.14 mm, P < 0.01), and 11% of them presented atheroma plaques (8% of control subjects). Multivariant logistic regression analysis showed that c-IMT was related to CACS (β = 6.87, P < 0.001). CONCLUSIONS A small percentage of patients with type 1 diabetes showed data suggestive of subclinical atherosclerosis. Universal screening of coronary disease in this population is not justified. Carotid ultrasonography may be useful for screening in the subset of patients with cardiovascular risk factors and long disease evolution.

Diabetes mellitus y riesgo cardiovascular: recomendaciones del Grupo de Trabajo Diabetes y Enfermedad Cardiovascular de la Sociedad Española de Diabetes (SED, 2015) ☆

Resumen El presente documento actualiza las recomendaciones de práctica clínica del manejo de los factores de riesgo cardiovascular (FRCV) en la diabetes mellitus (DM). Es un consenso médico realizado por un panel de expertos independiente de la Sociedad Española de Diabetes (SED). Se han propuesto y actualizado varios consensos de diferentes sociedades científicas o médicas con el fin de mejorar los resultados terapéuticos. La valoración del RCV en la población general puede carecer de sensibilidad para la evaluación individual en determinados grupos de riesgo como los diabéticos. Se revisan los factores de riesgo tradicionales y no tradicionales, así como las estrategias de intervención para el control de los FRCV en los pacientes diabéticos como la dieta, el control ponderal, el ejercicio físico, los hábitos tóxicos, el control glucémico, tensional y lipídico, así como la antiagregación plaquetaria. Confiamos en que estas pautas ayuden a los médicos en la toma de decisiones en su actividad asistencial. Se expone una actualización de los conceptos más relevantes y de mayor interés clínico-práctico y, a su vez realista, para reducir el RCV de los diabéticos como se venía haciendo regularmente por parte del Grupo de Enfermedad Cardiovascular de la SED.