Murri M.,Biomedical Research Laboratory |
Leiva I.,Pediatric Endocrinology Service |
Gomez-Zumaquero J.M.,Molecular Biology Laboratory |
Tinahones F.J.,CIBER ISCIII |
And 6 more authors.
BMC Medicine | Year: 2013
Background: A recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1 diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level.Methods: A case-control study was carried out with 16 children with type 1 diabetes and 16 healthy children. The fecal bacteria composition was investigated by polymerase chain reaction-denaturing gradient gel electrophoresis and real-time quantitative polymerase chain reaction.Results: The mean similarity index was 47.39% for the healthy children and 37.56% for the children with diabetes, whereas the intergroup similarity index was 26.69%. In the children with diabetes, the bacterial number of Actinobacteria and Firmicutes, and the Firmicutes to Bacteroidetes ratio were all significantly decreased, with the quantity of Bacteroidetes significantly increased with respect to healthy children. At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes. We also found that the number of Bifidobacterium and Lactobacillus, and the Firmicutes to Bacteroidetes ratio correlated negatively and significantly with the plasma glucose level while the quantity of Clostridium correlated positively and significantly with the plasma glucose level in the diabetes group.Conclusions: This is the first study showing that type 1 diabetes is associated with compositional changes in gut microbiota. The significant differences in the number of Bifidobacterium, Lactobacillus and Clostridium and in the Firmicutes to Bacteroidetes ratio observed between the two groups could be related to the glycemic level in the group with diabetes. Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children. These findings could be useful for developing strategies to control the development of type 1 diabetes by modifying the gut microbiota. © 2013 Murri et al; licensee BioMed Central Ltd.
Prieto-Tenreiro A.,University of Santiago de Compostela |
Diaz-Guardiola P.,Endocrinology and Nutrition Service
Hormones | Year: 2010
Central Hypothyroidism (central H) is mainly due to acquired lesions, either in the pituitary, the hypothalamus or both, and in such cases it is usually associated with deficient secretion of other pituitary hormones. Isolated central hypothyroidism (I central H) remains a very rare disease. By the use of the serum thyroid stimulating Hormone (TSH) assay as an initial screening test for thyroid disease, the diagnosis of I, central H can be missed or delayed, since most of these patients have normal or even slightly high serum TSH concentrations. We present a 54-year-old woman with intense tiredness, in whom hypothyroidism was initially and persistently excluded because of normal TSH levels. Further investigations showed again a normal TSH with slightly low Free thyroxine (FT4), and central H was suspected. A thyrotropin releasing Hormone (TRH) stimulation test confirmed the diagnosis. No lesion was found by Magnetic resonance Imaging (MRI). No other pituitary hormone insufficiency was detected. Finally, after excluding, the intake of any drug affecting the hypothalamo-pituitary-thyroid axis and the presence of critical systemic illness, the unusual diagnosis of idiopathic isolated central H was made. When suspecting central H, both FT4 and TSH should be measured and if these values are low, TSH response to TRH is recommended to reach specific diagnosis.
Garcia-Serrano S.,CIBER ISCIII |
Moreno-Santos I.,IMABIS Foundation |
Garrido-Sanchez L.,CIBER ISCIII |
Gutierrez-Repiso C.,IMABIS Foundation |
And 14 more authors.
Molecular Medicine | Year: 2011
Animal studies have revealed the association between stearoyl-CoA desaturase 1 (SCD1) and obesity and insulin resistance. However, only a few studies have been undertaken in humans. We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation. The insulin resistance was calculated in 40 morbidly obese patients and 11 overweight controls. Measurements were made of VAT and SAT SCD1, SREBP-1 and ATPase p97 mRNA expression and protein levels. VAT and SAT SCD1 mRNA expression levels in the morbidly obese patients were ignificantly lower than in the controls (P = 0.006), whereas SCD1 protein levels were significantly higher (P < 0.001). In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007). However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05). Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97. In conclusion, these data suggest that the regulation of SCD1 is altered in individuals with morbid obesity and that the SCD1 protein has a different regulation in the two adipose tissues, as well as being closely linked to the degree of insulin resistance. © 2011 The Feinstein Institute for Medical Research.
Hidalgo J.I.,Complutense University of Madrid |
Maqueda E.,Endocrinology and Nutrition Service |
Risco-Martin J.L.,Complutense University of Madrid |
Cuesta-Infante A.,Complutense University of Madrid |
And 2 more authors.
Journal of Biomedical Informatics | Year: 2014
Chronic patients must carry out a rigorous control of diverse factors in their lives. Diet, sport activity, medical analysis or blood glucose levels are some of them. This is a hard task, because some of these controls are performed very often, for instance some diabetics measure their glucose levels several times every day, or patients with chronic renal disease, a progressive loss in renal function, should strictly control their blood pressure and diet. In order to facilitate this task to both the patient and the physician, we have developed a web application for chronic diseases control which we have particularized to diabetes. This system, called glUCModel, improves the communication and interaction between patients and doctors, and eventually the quality of life of the former. Through a web application, patients can upload their personal and medical data, which are stored in a centralized database. In this way, doctors can consult this information and have a better control over patient records. glUCModel also presents three novelties in the disease management: a recommender system, an e-learning course and a module for automatic generation of glucose levels model. The recommender system uses Case Based Reasoning. It provides automatic recommendations to the patient, based on the recorded data and physician preferences, to improve their habits and knowledge about the disease. The e-learning course provides patients a space to consult information about the illness, and also to assess their own knowledge about the disease. Blood glucose levels are modeled by means of evolutionary computation, allowing to predict glucose levels using particular features of each patient. glUCModel was developed as a system where a web layer allows the access of the users from any device connected to the Internet, like desktop computers, tablets or mobile phones. © 2014 Elsevier Inc.
Beristain E.,Hospital Universitario Araba Txagorritxu |
Vicente M.-A.,Endocrinology and Nutrition Service |
Guerra I.,Hospital Universitario Araba Txagorritxu |
Gutierrez-Corres F.-B.,Hospital Universitario Araba Txagorritxu |
And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013
Context: Succinate dehydrogenase complex, subunit D (SDHD) mutations cause pheochromocytoma/paraganglioma syndrome. SDHD, located at chromosome 11q23, shows a parent-of-origin effect because the disease is observed almost exclusively when the mutation is transmitted from the father, although some cases of maternal transmission have been reported. Several hypotheses have been proposed for this peculiar inheritance pattern, but the underlying mechanisms have not yet been clearly elucidated. Objective: The objective of the study was to explain the parent-of-origin effect in a family, mainly affected by paternally transmitted paragangliomas, and with a maternally transmitted renal tumor. Patients: Peripheral blood DNA from 15 carriers and 7 tumor DNA samples from SDHD-p.Trp5* carriers were studied. Methods: We conducted mutation genotyping and microsatellite marker analysis in germline and tumor DNA and methylation status analysis in tumor DNA by methylation-specific multiplex ligation-dependent probe amplification. Results: Mutation genotyping and microsatellite marker analysis demonstrated loss of heterozygosity of the wild-type allele (maternal) in all studied tumors, except the renal tumor, which lost the mutated allele (maternal), and the prostate tumor, which had no loss of heterozygosity. The methylation-specific multiplex ligation-dependent probe amplification demonstrated that the methylation profile corresponded exclusively to the paternal chromosome without genomic loss, suggesting paternal uniparental disomy as the mechanism underlying the parent-of-origin effect in this SDHD family. Conclusions: The paternal uniparental disomy involves the loss of maternally imprinted cell cycle regulators and the overexpression of paternally imprinted growth activators, leading to tumorigenesis in this syndrome. Copyright © 2013 by The Endocrine Society.