Search

Background & aims: Peripheral white blood cells (PWBC) may allow for the development of obesity biomarkers. We aimed to investigate the existence of gene expression and DNA methylation changes in PWBC after a very low calorie diet (VLCD) followed by a laparoscopic sleeve gastrectomy (LSG), and its correlation with surgical outcomes. Methods: From July 2013 to June 2014, 35 consecutive bariatric patients and 33 healthy lean volunteers were recruited. Molecular data was obtained once on the control group and at 3 different times on the LSG group: 1) at baseline; 2) after 2 weeks of VLCD, right before LSG; and 3) 6 months after LSG. The expression of 12 genes in PWBC was analyzed by quantitative real-time polymerase chain reaction: ghrelin (GHRL), visfatin (NAMPT), insulin receptor substrate 1 (IRS1), fat mass and obesity-related gene (FTO), leptin (LEP), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), fatty acid synthase (FASN), melanocortin 4 receptor (MC4R), fas cell surface death receptor (FAS), tumor necrosis factor alpha (TNF) and chemokine (C-C motif) ligand 2 (CCL2). Moreover, DNA methylation of GHRL, NAMPT and FAS promoters was analyzed in PWBC by bisulfite pyrosequencing. Results: Seven genes (GHRL, NAMPT, IRS1, FTO, FAS, TNF and CCL2) had detectable expression in PWBC. FTO expression at baseline was lower in patients than in controls (p = 0.042), equalizing after LSG. In patients, FAS expression decreased after VLCD (p = 0.01) and stayed low after LSG (p = 0.015). Also, CCL2 expression decreased 50% after LSG compared to pre-surgical levels (p = 0.016). All studied CpG sites in the GHRL gene promoter followed a consistent pattern of DNA methylationidemethylation. No direct correlation between these molecular changes and surgical outcomes was found at 1-year follow-up. Conclusions: FTO expression increased and FAS and CCL2 expression decreased in PWBC after LSG. Molecular changes did not correlate with surgical outcomes. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

A cromegaly is a rare disease caused by excess growth hormone (GH) secretion leading to an insulin-like growth factor-1 (IGF-I) which is the major mediator of GH action. Biochemical diagnosis of GH excess is accomplished by the combined measurement of baseline serum IGF-I concentration and the response of GH on an oral glucose tolerance test (OGTT). Several drawbacks regarding the interpretation of biochemical tests that include measurement of GH have been widely described in the literature, including different protocols for obtaining serum samples, great differences in the results obtained by different immunoassays, different cut-off points used to differentiate the normal status of the hypersecretion of GH. Clinical guidelines related to the diagnosis and management of patients with acromegaly state that "normal" IGF-I concentrations, (within an established age- and sex-reference range), excludes the diagnosis of active acromegaly, and mean disease control in patients who have received treatment. But many factors may exert influence over IGF-I measurement or interpretation and limit its value as a biological marker of disease activity. Major drawbacks of IGF-I measurements derive both from its own physiology, to the divergences in results obtained from different biochemical methods used for their quantification, to the heterogeneous ways of expressing the results obtained and to the lack of uniformity of the cut-offs to define treatment effectiveness. All these issues make it difficult to compare the results obtained by different authors. We will focus on the issues regarding the measurement and interpretation of IGF-I concentrations in the management of acromegaly patients.

Scientific knowledge to understand the biological basis of sex development was prompted by the observation of variants different from the 2 most frequent body types, and this became one of the fields first studied by modern pediatric endocrinology. The clinical observation was supported by professionals working in different areas of laboratory sciences which led to the description of adrenal and gonadal steroidogenesis, the enzymes involved, and the different deficiencies. Steroid hormone measurements evolved from colorimetry to radioimmunoassay (RIA) and automated immunoassays, although gas and liquid chromatography coupled to mass spectrometry are now the gold standard techniques for steroid measurements. Peptide hormones and growth factors were purified, and their measurement evolved from RIA to automated immunoassays. Hormone action mechanisms were described, and their specific receptors were characterized and assayed in experimental materials and in patient tissues and cell cultures. The discovery of the genetic basis for variant sex developments began with the description of the sex chromosomes. Molecular technology allowed cloning of genes coding for the different proteins involved in sex determination and development. Experimental animal models aided in verifying the roles of proteins and also suggested new genes to be investigated. New candidate genes continue to be described based on experimental models and on next-generation sequencing of patient DNAs. (c) 2017 S. Karger AG, Basel

Nutritional deficiencies are common after bariatric surgery, but data are scarce after sleeve gastrectomy (SG) at long term. We performed a prospective nutritional status evaluation before and at 2 and 5 years after SG in morbid obese patients receiving mulvitamin and mineral supplementation at a Spanish university hospital. One hundred seventy-six patients (49.3 +/- 9.1 years and 46.7 +/- 7.4 kg/m(2)) were evaluated; 51 of them were followed during 5 years. Anthropometric, compliance supplementation intake, and micronutrient evaluation were performed. Baseline concentrations were below normal values for 25(OH) vitamin D (73%), folic acid (16.5%), cobalamin (6.9%), pyridoxine (12%), thiamine (3.4%), and copper (0.5%). Anemia was found in 23%. In 49% of the subjects, at least one micronutrient deficiency was found at 2 years after SG. Vitamin D deficiency persisted at 2 and 5 years higher than 30% of patients. Frequencies of deficiencies for folic acid, B12, B6, and B1 vitamins decreased significantly after 2 years with normalization at 5 years. Copper deficiency increased between 1 and 2 years and it persisted at 5 years after SG. Vitamin supplementation compliance decreased progressively from the first year after surgery (94.8 to 81% at 2 years and to 53% 5 years after surgery). Vitamin D deficiency is the most prevalent long-term nutritional deficiency after SG. About half of patients show some micronutrient deficiency at medium long term, despite supplementation. A proactive follow-up is required to ensure a personalized and adequate supplementation in all surgically treated obese patients including those in which SG has been performed.

The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT). Methods: We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50 +/- 13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria. Results: Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (1427) mu g/mL. An inverse correlation was found between ADP and HOMA index (r =-0.432; p < 0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p < 0.05). Patients with c-IMT > 0.6 mm had more AGH (p = 0.012) and lower ADP levels (p = 0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT >= 0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT. Conclusions: Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis.

Background: Androgen receptor (AR) gene mutations are the most frequent cause of 46, XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). Objective: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46, XY DSD in a series of Spanish patients. Setting: We studied a series of 133 index patients with 46, XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. Methods: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. Results: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. Conclusions: AR gene mutation is the most frequent cause of 46, XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel. (J Clin Endocrinol Metab 95: 1876-1888, 2010)