Publications by authors named "Gemma Rojo-Martínez"

101 Publications

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity.

Theranostics 2021 12;11(14):6983-7004. Epub 2021 May 12.

Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucía-University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain.

We recently demonstrated that the 'Metabesity' factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-treated astrocytes. The impact of ORY1001, an inhibitor of the LSD1-CoREST complex, on HMG20A expression, reactive astrogliosis and glucose metabolism was evaluated and in high-fat high-sucrose fed mice. We show that is predominantly expressed in hypothalamic astrocytes, the main nutrient-sensing cell type of the brain. HMG20A expression was upregulated in diet-induced obesity and glucose intolerant mice, correlating with increased transcript levels of and indicative of inflammation and reactive astrogliosis. transcript levels were also increased in adipose tissue of obese non-diabetic individuals as compared to obese diabetic patients. HMG20A silencing in astrocytes resulted in repression of inflammatory, cholesterol biogenesis and epithelial-to-mesenchymal transition pathways which are hallmarks of reactive astrogliosis. Accordingly, HMG20A depleted astrocytes exhibited reduced mitochondrial bioenergetics and increased susceptibility to apoptosis. Neuron viability was also hindered in HMG20A-depleted astrocyte-derived conditioned media. ORY1001 treatment rescued expression of reactive astrogliosis-linked genes in HMG20A ablated astrocytes while enhancing cell surface area, GFAP intensity and STAT3 expression in healthy astrocytes, mimicking the effect of HMG20A. Furthermore, ORY1001 treatment protected against obesity-associated glucose intolerance in mice correlating with a regression of hypothalamic HMG20A expression, indicative of reactive astrogliosis attenuation with improved health status. HMG20A coordinates the astrocyte polarization state. Under physiological pressure such as obesity and insulin resistance that induces low grade inflammation, HMG20A expression is increased to induce reactive astrogliosis in an attempt to preserve the neuronal network and re-establish glucose homeostasis. Nonetheless, a chronic metabesity state or functional mutations will result in lower levels of HMG20A, failure to promote reactive astrogliosis and increase susceptibility of neurons to stress-induced apoptosis. Such effects could be reversed by ORY1001 treatment both and , paving the way for a new therapeutic approach for Type 2 Diabetes Mellitus.
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http://dx.doi.org/10.7150/thno.57237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171100PMC
May 2021

Dietary Macronutrient Composition in Relation to Circulating HDL and Non-HDL Cholesterol: A Federated Individual-Level Analysis of Cross-Sectional Data from Adolescents and Adults in 8 European Studies.

J Nutr 2021 Apr 13. Epub 2021 Apr 13.

Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.

Background: Associations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined.

Objective: We assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data.

Methods: Dietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13-80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI.

Results: The replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with -3.91 mg/dL (95% CI: -6.98, -0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically significant association in females. We observed no statistically significant interaction by age.

Conclusions: The replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in European adolescents and adults when fats were consumed as MUFAs or PUFAs but not as SFAs.
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http://dx.doi.org/10.1093/jn/nxab077DOI Listing
April 2021

Cardiovascular diseases in people with diabetes mellitus in Spain according to the Primary Care Clinical Database (BDCAP) in 2017.

Med Clin (Barc) 2021 Mar 30. Epub 2021 Mar 30.

Servicio de Endocrinología y Nutrición, Hospital Universitario Central de Asturias, Oviedo, Asturias, España; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, España.

Introduction And Objectives: Atherosclerotic cardiovascular disease and heart failure are the leading cause of morbidity and mortality in patients with diabetes. The objective of this work is to know the prevalence of atherosclerotic cardiovascular diseases and heart failure in people diagnosed with diabetes in Spain during 2017 and compare them with those not diagnosed with diabetes according to age and sex.

Methods: Data for diagnoses of diabetes mellitus (DM), acute myocardial infarction (AMI), stroke, peripheral artery disease (PAD) or heart failure (HF) for 2017 were obtained from the National Health System's Primary Care Clinical Database (BDCAP).

Results: Comparing people with diabetes and people without diabetes over 35 years of age, the Odds Ratio (OR) for being diagnosed with acute myocardial infarction, stroke, peripheral artery disease or heart failure is about 2 in those over 64 years of age and more than 4 in patients under that age. This OR is superior in females versus males for all diagnoses apart from peripheral artery disease.

Conclusions: This study shows the high cardiovascular comorbidity of patients with diabetes in Spain, with a greater excess of risk in patients under 65 years of age, more pronounced in women. We should offer more intensive treatment for DM2 in women.
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http://dx.doi.org/10.1016/j.medcli.2020.12.040DOI Listing
March 2021

Association between mental health comorbidity and health outcomes in type 2 diabetes mellitus patients.

Sci Rep 2020 11 11;10(1):19583. Epub 2020 Nov 11.

EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Aragón, Health Services Research On Chronic Patients Network (REDISSEC), Miguel Servet University Hospital, 50009, Zaragoza, Spain.

Type 2 diabetes mellitus (T2D) is often accompanied by chronic diseases, including mental health problems. We aimed at studying mental health comorbidity prevalence in T2D patients and its association with T2D outcomes through a retrospective, observational study of individuals of the EpiChron Cohort (Aragón, Spain) with prevalent T2D in 2011 (n = 63,365). Participants were categorized as having or not mental health comorbidity (i.e., depression, anxiety, schizophrenia, and/or substance use disorder). We performed logistic regression models, controlled for age, sex and comorbidities, to analyse the likelihood of 4-year mortality, 1-year all-cause hospitalization, T2D-hospitalization, and emergency room visit. Mental health comorbidity was observed in 19% of patients. Depression was the most frequent condition, especially in women (20.7% vs. 7.57%). Mortality risk was higher in patients with mental health comorbidity (odds ratio 1.24; 95% confidence interval 1.16-1.31), especially in those with substance use disorder (2.18; 1.84-2.57) and schizophrenia (1.82; 1.50-2.21). Mental health comorbidity also increased the likelihood of all-cause hospitalization (1.16; 1.10-1.23), T2D-hospitalization (1.51; 1.18-1.93) and emergency room visit (1.26; 1.21-1.32). These results suggest that T2D healthcare management should include specific strategies for the early detection and treatment of mental health problems to reduce its impact on health outcomes.
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http://dx.doi.org/10.1038/s41598-020-76546-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658226PMC
November 2020

Incidence and regression of metabolic syndrome in a representative sample of the Spanish population: results of the cohort [email protected] study.

BMJ Open Diabetes Res Care 2020 10;8(1)

Endocrinologia y Nutricion, Hospital Clínico San Carlos, Madrid, Spain

Introduction: Metabolic syndrome (MetS) is an important predictor of cardiovascular mortality. Identification of occurrence and regression trends of MetS could permit elaboration of preventive strategies with new targets. The objective of this study was to analyze the occurrence and regression rates of MetS and its associated factors in the representative cohort of Spain of the [email protected] study.

Research Design And Methods: The [email protected] study is a prospective cohort where 5072 people representative of the Spanish population over 18 years of age were randomly selected between 2009 and 2010. Follow-up was a median of 7.5 (IQR 7.2-7.9) years, with 2408 (47%) participating subjects. A total of 1881 (78%) subjects had all the pertinent data available and were included in this study.

Results: Of the 1146 subjects without baseline criteria for MetS, 294 (25.7%) developed MetS during follow-up, while of the 735 patients with prior MetS, 148 (20.1%) presented regression. Adjusted MetS incidence per 1000 person-years was 38 (95% CI 32 to 44), while regression incidence was 36 (95% CI 31 to 41). Regression rate was independently higher than incidence rate in the following: women, subjects aged 18-45, university-degree holders, patients without central obesity, without hypertension, as well as those with body mass index of <25 kg/m. Lower progression and higher regression rates were observed with an adapted 14-point Mediterranean Diet adherence screener questionnaire score of >11 in both groups and with >500 and>2000 MET-min/week of physical activity, respectively.

Conclusions: This study provides MetS incidence and regression rates, and identifies the target population for intervention strategies in Spain and possibly in other countries.
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http://dx.doi.org/10.1136/bmjdrc-2020-001715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554469PMC
October 2020

Prevalence of diabetes mellitus in Spain in 2016 according to the Primary Care Clinical Database (BDCAP).

Endocrinol Diabetes Nutr (Engl Ed) 2021 Feb 26;68(2):109-115. Epub 2020 Sep 26.

Servicio de Endocrinología y Nutrición, Hospital Universitario Central de Asturias, Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, España.

The prevalence of type 2 diabetes mellitus is increasing worldwide, including in Spain, and this disease has become a major challenge for health care. In Spain, the computerization of medical records in primary care, in the Primary Care Clinical Database (BDCAP), has made possible the diagnoses of diabetes in a representative sample of the nation as a whole. This article analyzes the prevalence of diabetes recorded in this database and compares the data of the different autonomous communities. The prevalence of diabetes in Spain is 6.66% of the total population assigned to primary care in the National Health System, is higher in men than in women (7.27% vs. 6.06%), and increases with age up to 80 years. There are significant differences in the adjusted prevalence of diabetes between autonomous communities, with lower prevalence rates in North and Central Spain and higher rates in the South and East, as well as the islands. The lowest prevalence is seen in Castile and Leon (4.51%), and the highest in the Canary Islands (9.72%).
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http://dx.doi.org/10.1016/j.endinu.2019.12.004DOI Listing
February 2021

Iodine Deficiency and Mortality in Spanish Adults: [email protected] Study.

Thyroid 2021 01 17;31(1):106-114. Epub 2020 Sep 17.

Department of Endocrinology and Nutrition, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomedica de Málaga-IBIMA, Málaga, Spain.

Longitudinal data assessing the impact of iodine deficiency (ID) on mortality are scarce. We aimed to study the association between the state of iodine nutrition and the risk of total and cause-specific mortality in a representative sample of the Spanish adult population. We performed a longitudinal observational study to estimate mortality risk according to urinary iodine (UI) concentrations using a sample of 4370 subjects >18 years representative of the Spanish adult population participating in the nationwide study [email protected] (2008-2010). We used Cox regression to assess the association between UI at the start of the study (<50, 50-99, 100-199, 200-299, and ≥300 μg/L) and mortality during follow-up (National death registry-end of follow-up December 2016) in raw models, and adjusted for possible confounding variables: age, sex, educational level, hypertension, diabetes, obesity, chronic kidney disease, smoking, hypercholesterolemia, thyroid dysfunction, diagnosis of cardiovascular disease or cancer, area of residence, physical activity, adherence to Mediterranean diet, dairy and iodinated salt intake. A total of 254 deaths were recorded during an average follow-up period of 7.3 years. The causes of death were cardiovascular 71 (28%); cancer 85 (33.5%); and other causes 98 (38.5%). Compared with the reference category with adequate iodine nutrition (UI 100-300 μg/L), the hazard ratios (HRs) of all-cause mortality in the category with UI ≥300 μg/L were 1.04 (95% confidence interval [CI 0.54-1.98]); however, in the categories with 50-99 UI and <50 μg/L, the HRs were 1.29 [CI 0.97-1.70] and 1.71 [1.18-2.48], respectively ( for trend 0.004). Multivariate adjustment did not significantly modify the results. Our data indicate an excess mortality in individuals with moderate-severe ID adjusted for other possible confounding factors.
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http://dx.doi.org/10.1089/thy.2020.0131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840306PMC
January 2021

Standardized Map of Iodine Status in Europe.

Thyroid 2020 09 15;30(9):1346-1354. Epub 2020 Jul 15.

Department of Public Health, Dokuz Eylul University Medical Faculty, İzmir, Turkey.

Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 μg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 μg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 μg/L. We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.
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http://dx.doi.org/10.1089/thy.2019.0353DOI Listing
September 2020

The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease.

Front Endocrinol (Lausanne) 2020 6;11:103. Epub 2020 Mar 6.

UGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional de Málaga, Universidad de Málaga, Málaga, Spain.

The synthetic atypical cannabinoid Abn-CBD, a cannabidiol (CBD) derivative, has been recently shown to modulate the immune system in different organs, but its impact in obesity-related meta-inflammation remains unstudied. We investigated the effects of Abn-CBD on metabolic and inflammatory parameters utilizing a diet-induced obese (DIO) mouse model of prediabetes and non-alcoholic fatty liver disease (NAFLD). Ten-week-old C57Bl/6J mice were fed a high-fat diet for 15 weeks, following a 2-week treatment of daily intraperitoneal injections with Abn-CBD or vehicle. At week 15 mice were obese, prediabetic and developed NAFLD. Body weight and glucose homeostasis were monitored. Mice were euthanized and blood, liver, adipose tissue and pancreas were collected and processed for metabolic and inflammatory analysis. Body weight and triglycerides profiles in blood and liver were comparable between vehicle- and Abn-CBD-treated DIO mice. However, treatment with Abn-CBD reduced hyperinsulinemia and markers of systemic low-grade inflammation in plasma and fat, also promoting white adipose tissue browning. Pancreatic islets from Abn-CBD-treated mice showed lower apoptosis, inflammation and oxidative stress than vehicle-treated DIO mice, and beta cell proliferation was induced. Furthermore, Abn-CBD lowered hepatic fibrosis, inflammation and macrophage infiltration in the liver when compared to vehicle-treated DIO mice. Importantly, the balance between hepatocyte proliferation and apoptosis was improved in Abn-CBD-treated compared to vehicle-treated DIO mice. These results suggest that Abn-CBD exerts beneficial immunomodulatory actions in the liver, pancreas and adipose tissue of DIO prediabetic mice with NAFLD, thus protecting tissues. Therefore, Abn-CBD and related compounds could represent novel pharmacological strategies for managing obesity-related metabolic disorders.
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http://dx.doi.org/10.3389/fendo.2020.00103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067697PMC
February 2021

Oxidative and inflammatory effects of pulmonary rehabilitation in patients with bronchiectasis. A prospective, randomized study.

Nutr Hosp 2020 Feb;37(1):6-13

Hospital Regional Universitario de Málaga.

Introduction: Background: systemic inflammation and oxidative stress are important factors in the pathogenesis of bronchiectasis. Pulmonary rehabilitation (PR) is recommended for bronchiectasis, but there is no data about its effect on the inflammatory and REDOX status of these patients. Aims: to investigate the effect of PR in non-cystic-fibrosis bronchiectasis (NCFB) patients, and to compare it with the effect of PR plus a hyperproteic oral nutritional supplement (PRS) enriched with beta-hydroxy-beta-methylbutyrate (HMB) on serum inflammatory and oxidative biomarkers. Materials and methods: this was an open randomized, controlled trial. Thirty individuals (65 years old or younger with a body mass index over 18.5, older than 65 years with a body mass index over 20) were recruited from September 2013 to September 2014, and randomly assigned to receive PR or PRS. Total neutrophils, and inflammatory and oxidative biomarker levels were measured at baseline, and then at 3 and 6 months. Results: in the PRS group neutrophil levels were decreased from baseline at 6 months. A significantly different fold change was found between the PR and PRS groups. In the PR group, IL-6 and adiponectin were increased by the end of the study while TNFα levels were decreased from baseline at 6 months. REDOX biomarkers remained stable throughout the study except for 8-isoprostane levels, which were increased from baseline at 6 months in both groups of patients. Conclusions: a PR program induced a pro-oxidative effect accompanied by changes in circulating inflammatory cytokine levels in NCFB patients. Our results would also suggest a possible beneficial effect of the HMB enriched supplement on neutrophil level regulation in these patients. The information provided in this study could be useful for choosing the right therapeutic approach in the management of bronchiectasis.
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http://dx.doi.org/10.20960/nh.02763DOI Listing
February 2020

[The importance of dairy products in the diet: byond bone].

Nutr Hosp 2019 Jul;36(3):497-498

Instituto de Biomedicina de Málaga (IBIMA).

Introduction:
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http://dx.doi.org/10.20960/nh.02667DOI Listing
July 2019

Ambient temperature and prevalence of diabetes and insulin resistance in the Spanish population: [email protected] study.

Eur J Endocrinol 2019 May;180(5):273-280

Department of Endocrinology and Nutrition, Hospital Regional Universitario de Málaga/Universidad de Málaga, IBIMA, Málaga, Spain.

Objective The activity of brown adipose tissue is sensitive to changes in ambient temperature. A lower exposure to cold could result in an increased risk of developing diabetes at population level, although this factor has not yet been sufficiently studied. Design We studied 5072 subjects, participants in a national, cross-sectional population-based study representative of the Spanish adult population ([email protected] study). All subjects underwent a clinical, demographic and lifestyle survey, a physical examination and blood sampling (75 g oral glucose tolerance test). Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). The mean annual temperature (°C) in each individual municipality was collected from the Spanish National Meteorology Agency. Results Linear regression analysis showed a significant positive association between mean annual temperature and fasting plasma glucose (β: 0.087, P < 0.001), 2 h plasma glucose (β: 0.049, P = 0.008) and HOMA-IR (β: 0.046, P = 0.008) in multivariate adjusted models. Logistic regression analyses controlled by multiple socio-demographic variables, lifestyle, adiposity (BMI) and geographical elevation showed increasing odds ratios for prediabetes (WHO 1999), ORs 1, 1.26 (0.95-1.66), 1.08 (0.81-1.44) and 1.37 (1.01-1.85) P for trend = 0.086, diabetes (WHO 1999) ORs 1, 1.05 (0.79-1.39), 1.20 (0.91-1.59) and 1.39 (1.02-1.90) P = 0.037, and insulin resistance (HOMA-IR ≥75th percentile of the non-diabetic population): ORs 1, 1.03 (0.82-1.30), 1.22 (0.96-1.55), 1.26 (0.98-1.63) (P for trend = 0.046) as the mean annual temperature (into quartiles) rose. Conclusions Our study reports an association between ambient temperature and the prevalence of dysglycemia and insulin resistance in Spanish adults, consistent with the hypothesis that a lower exposure to cold could be associated with a higher risk of metabolic derangements.
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http://dx.doi.org/10.1530/EJE-18-0818DOI Listing
May 2019

Respiratory chain polymorphisms and obesity in the Spanish population, a cross-sectional study.

BMJ Open 2019 02 19;9(2):e027004. Epub 2019 Feb 19.

Genomic and Genetic Diagnosis Unit, Research Foundation of Valencia University Clinical Hospital-INCLIVA, Valencia, Spain.

Objective: To study the association of genes involved in the mitochondrial respiratory chain (MRC) pathway with body mass index (BMI) and obesity risk.

Design: This work studies three cross-sectional populations from Spain, representing three provinces: HORTEGA (Valladolid, Northwest/Centre), SEGOVIA (Segovia, Northwest/centre) and PIZARRA (Malaga,South).

Setting: Forty-eight single nucleotide polymorphisms (SNPs) from MRC genes were selected and genotyped by SNPlex method. Association studies with BMI and obesity risk were performed for each population. These associations were then verified by analysis of the studied population as a whole (3731 samples).

Participants: A total of 3731 Caucasian individuals: 1502 samples from HORTEGA, 988 from PIZARRA and 1241 from SEGOVIA.

Results: rs4600063 (), rs11205591 () and rs10891319 () SNPs were associated with BMI and obesity risk (p values for BMI were 0.04, 0.0011 and 0.0004, respectively, and for obesity risk, 0.0072, 0.039 and 0.0038). However, associations between rs4600063 and BMI and between these three SNPs and obesity risk are not significant if Bonferroni correction is considered. In addition, rs11205591 and rs10891319 polymorphisms showed an additive interaction with BMI and obesity risk.

Conclusions: Several polymorphisms from genes coding MRC proteins may be involved in BMI variability and could be related to the risk to become obese in the Spanish general population.
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http://dx.doi.org/10.1136/bmjopen-2018-027004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377525PMC
February 2019

Dairy Product Consumption and Metabolic Diseases in the [email protected] Study.

Nutrients 2019 Jan 24;11(2). Epub 2019 Jan 24.

Instituto de Investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain.

To date it is not clear what the role of dairy products is in metabolic diseases like diabetes, obesity, and hypertension. Therefore, the aim of this study is to test the association between dairy product consumption and those pathologies. A cross-sectional study was conducted with 5081 adults included in the [email protected] study, from 100 health centers around Spain. Food frequency questionnaires were carried out concerning consumption habits, which included dairy product consumption. Logistic regression models were used for the association analyses between the variables controlling confounding variables. Women had a higher consumption of milk, cheese, or yogurt than men ( < 0.0001), but men consumed more sugar dairy products ( < 0.001). People who live in the North of Spain consume more dairy products than those who live in the East. Dairy product consumption was inversely associated with the presence of hypertension regardless of age, sex, geographical region, and body mass index (BMI) (Odds Ratio (OR) 0.743; = 0.022). The presence of obesity was inversely associated with dairy consumption regardless of age, sex, and geographical region (OR 0.61; < 0.001). Milk consumption was not associated with diabetes. Our results show that consuming dairy products is associated with a better metabolic profile in the Spanish population.
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http://dx.doi.org/10.3390/nu11020262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412325PMC
January 2019

Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: [email protected] study.

Sci Rep 2018 04 26;8(1):6571. Epub 2018 Apr 26.

Department of Endocrinology and Nutrition, Hospital Regional Universitario de Málaga, IBIMA, Málaga, Spain.

Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30-100, 15-30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia (FT4 < 12.0 pmol/L p5): OR 1.5 [1.1-2.2] p = 0.024, and hypotriiodothyroninemia (FT3 < 3.9 pmol/L p5): OR 1.8 [1.3-2.6] p = 0.001 than the reference category with ferritin ≥30 µg/L. There was no significant heterogeneity of the results between men, pre-menopausal and post-menopausal women or according to the iodine nutrition status. Our results confirm an association between ID and hypothyroxinemia and hypotriiodothyroninemia in the general adult population without changes in TSH.
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http://dx.doi.org/10.1038/s41598-018-24352-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919900PMC
April 2018

Normative reference values for hand grip dynamometry in Spain. Association with lean mass.

Nutr Hosp 2018 Jan 16;35(1):98-103. Epub 2018 Jan 16.

Unidad de Gestión Clínica de Endocrinología y Nutrición. Hospital Regional Universitario de Málaga. Universidad de Málaga..

Background And Objectives: The objective of this study was to establish reference values for hand grip strength, compare the results obtained with Collin and Jamar type dynamometers and determine their association with anthropometric and lean mass measurements.

Material And Methods: This cross-sectional population-based study was undertaken in Pizarra (Málaga, Spain). The grip strength of the dominant hand was measured using Collin and Jamar dynamometers. Skinfolds (triceps, abdominal, biceps of dominant arm and subscapular) were measured, and body composition was estimated. Eight hundred seventeen adults randomly selected from the census were recruited. Dynamometry reference values are presented for the dominant hand, by gender and age groups.

Results: No determinations could be made with the Collin dynamometer in 69 women due to the difficulty in grasping the dynamometer. We found significant positive correlations between the measurements with Jamar and Collin dynamometers (r = 0.782; p < 0.001) and between grip strength and lean mass index (LMI), determined by both dynamometers (r = 0.538, p < 0.001 and r = 0.462, p < 0.001, respectively). Malnourished patients according to LMI had significantly lower grip strength than normally nourished patients (p < 0.001 for Jamar; p < 0.02 for Collin).

Conclusions: Dynamometry reference values in the Spanish population are presented. We recommend the use of the Jamar type dynamometer versus the Collin type dynamometer. Hand grip dynamometry is associated with lean mass, which confirms its usefulness in nutritional assessment.
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http://dx.doi.org/10.20960/nh.1052DOI Listing
January 2018

Joint Data Analysis in Nutritional Epidemiology: Identification of Observational Studies and Minimal Requirements.

J Nutr 2018 02;148(2):285-297

Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.

Background: Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease.

Objective: The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) Consortium, as well as minimal requirements for joint data analysis.

Methods: A predefined template containing information on study design, exposure measurements (dietary intake, alcohol and tobacco consumption, physical activity, sedentary behavior, anthropometric measures, and sociodemographic and health status), main health-related outcomes, and laboratory measurements (traditional and omics biomarkers) was developed and circulated to those European research groups participating in the ENPADASI under the strategic research area of "diet-related chronic diseases." Information about raw data disposition and metadata sharing was requested. A set of minimal requirements was abstracted from the gathered information.

Results: Studies (12 cohort, 12 cross-sectional, and 2 case-control) were identified. Two studies recruited children only and the rest recruited adults. All studies included dietary intake data. Twenty studies collected blood samples. Data on traditional biomarkers were available for 20 studies, of which 17 measured lipoproteins, glucose, and insulin and 13 measured inflammatory biomarkers. Metabolomics, proteomics, and genomics or transcriptomics data were available in 5, 3, and 12 studies, respectively. Although the study authors were willing to share metadata, most refused, were hesitant, or had legal or ethical issues related to sharing raw data. Forty-one descriptors of minimal requirements for the study data were identified to facilitate data integration.

Conclusions: Combining study data sets will enable sufficiently powered, refined investigations to increase the knowledge and understanding of the relation between food, nutrition, and human health. Furthermore, the minimal requirements for study data may encourage more efficient secondary usage of existing data and provide sufficient information for researchers to draft future multicenter research proposals in nutrition.
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http://dx.doi.org/10.1093/jn/nxx037DOI Listing
February 2018

The type 2 diabetes-associated HMG20A gene is mandatory for islet beta cell functional maturity.

Cell Death Dis 2018 02 15;9(3):279. Epub 2018 Feb 15.

Department of Cell Regeneration and Advanced Therapies, Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain.

HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither expression nor function of this T2DM candidate gene in islets is known. Herein we demonstrate that HMG20A is expressed in both human and mouse islets and that levels are decreased in islets of T2DM donors as compared to islets from non-diabetic donors. In vitro studies in mouse and human islets demonstrated that glucose transiently increased HMG20A transcript levels, a result also observed in islets of gestating mice. In contrast, HMG20A expression was not altered in islets from diet-induced obese and pre-diabetic mice. The T2DM-associated rs7119 SNP, located in the 3' UTR of the HMG20A transcript reduced the luciferase activity of a reporter construct in the human beta 1.1E7 cell line. Depletion of Hmg20a in the rat INS-1E cell line resulted in decreased expression levels of its neuronal target gene NeuroD whereas Rest and Pax4 were increased. Chromatin immunoprecipitation confirmed the interaction of HMG20A with the Pax4 gene promoter. Expression levels of Mafa, Glucokinase, and Insulin were also inhibited. Furthermore, glucose-induced insulin secretion was blunted in HMG20A-depleted islets. In summary, our data demonstrate that HMG20A expression in islet is essential for metabolism-insulin secretion coupling via the coordinated regulation of key islet-enriched genes such as NeuroD and Mafa and that depletion induces expression of genes such as Pax4 and Rest implicated in beta cell de-differentiation. More importantly we assign to the T2DM-linked rs7119 SNP the functional consequence of reducing HMG20A expression likely translating to impaired beta cell mature function.
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http://dx.doi.org/10.1038/s41419-018-0272-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833347PMC
February 2018

Altered Expression of miR-181a-5p and miR-23a-3p Is Associated With Obesity and TNFα-Induced Insulin Resistance.

J Clin Endocrinol Metab 2018 04;103(4):1447-1458

Joan XXIII University Hospital, IISPV, Tarragona, Spain.

Context: The proinflammatory cytokine TNFα is a key player in insulin resistance (IR). The role of miRNAs in inflammation associated with IR is poorly understood.

Objective: To investigate miR-181a-5p and miR-23a-3p expression profiles in obesity and to study their role in TNFα-induced IR in adipocytes.

Design: Two separate cohorts were used. Cohort 1 was used in adipose tissue (AT) expression studies and included 28 subjects with body mass index (BMI) <30 kg/m2 and 30 with BMI ≥30 kg/m2. Cohort 2 was used in circulating serum miRNA studies and included 101 subjects with 4 years of follow-up (48 case subjects and 53 control subjects). miR-181a-5p and miR-23a-3p expression was assessed in subcutaneous and visceral AT. Functional analysis was performed in adipocytes, using miRNA mimics and inhibitors. Key molecules of the insulin pathway, AKT, PTEN, AS160, and S6K, were analyzed.

Results: Expression of miR-181a-5p and miR-23a-3p was reduced in adipose tissue from obese and diabetic subjects and was inversely correlated to adiposity and homeostasis model assessment of IR index. Overexpression of miR-181a-5p and miR-23a-3p in adipocytes upregulated insulin-stimulated AKT activation and reduced TNFα-induced IR, regulating PTEN and S6K expression. Serum levels of miR-181a-5p were reduced in case vs control subjects at baseline, suggesting a prognostic value. Variable importance in projection scores revealed miR-181a-5p had more effect on the model than insulin or glucose at 120 minutes.

Conclusion: miR-181a-5p and miR-23a-3p may prevent TNFα-induced IR in adipocytes through modulation of PTEN and S6K expression.
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http://dx.doi.org/10.1210/jc.2017-01909DOI Listing
April 2018

Comparison of the Effects of Goat Dairy and Cow Dairy Based Breakfasts on Satiety, Appetite Hormones, and Metabolic Profile.

Nutrients 2017 Aug 15;9(8). Epub 2017 Aug 15.

UGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Regional de Málaga/Universidad de Málaga, 29009 Malaga, Spain.

The satiating effects of cow dairy have been thoroughly investigated; however, the effects of goat dairy on appetite have not been reported so far. Our study investigates the satiating effect of two breakfasts based on goat or cow dairy and their association with appetite related hormones and metabolic profile. Healthy adults consumed two breakfasts based on goat (G-Breakfast) or cow (C-Breakfast) dairy products. Blood samples were taken and VAS tests were performed at different time points. Blood metabolites were measured and Combined Satiety Index (CSI) and areas under the curves (AUC) were calculated. Desire to eat rating was significantly lower (breakfast & time interaction < 0.01) and hunger rating tended to be lower (breakfast & time interaction = 0.06) after the G-breakfast. None of the blood parameters studied were different between breakfasts; however, AUC was inversely associated with the AUC and AUC after the G-Breakfast, whereas triglyceride levels were directly associated with AUC after the C-Breakfast. Our results suggest a slightly higher satiating effect of goat dairy when compared to cow dairy products, and pointed to a potential association of GLP-1 and triglyceride levels with the mechanisms by which dairy products might affect satiety after the G-Breakfast and C-Breakfast, respectively.
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http://dx.doi.org/10.3390/nu9080877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579670PMC
August 2017

Dietary fatty acids modulate adipocyte TNFa production via regulation of its DNA promoter methylation levels.

J Nutr Biochem 2017 09 25;47:106-112. Epub 2017 May 25.

UGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Regional de Malaga, Malaga, Spain; CIBER of the Instituto de Salud Carlos III (CIBERDEM CB07/08/0019), Málaga, Spain.

The factors regulating TNF alpha (TNFa) levels could be considered therapeutic targets against metabolic syndrome development. DNA methylation is a potent regulator of gene expression and may be associated with protein levels. In this study we investigate whether the effect of dietary fatty acids on TNFa released from adipocytes might be associated with modifications of the TNFa promoter DNA methylation status. A group of rats was assigned to three diets with a different composition of saturated, monounsaturated and polyunsaturated fatty acids. Samples of visceral adipose tissues were taken for adipocyte isolation, in which released TNFa levels were measured, and for methylation and expression studies. In addition, 3 T3-L1 cells were treated with palmitic, oleic and linoleic acids, with and without 5-Azacitydine (5-AZA). After treatments, cells and supernatants were included in the same analyses as rat samples. TNFa promoter methylation levels, gene expression and secretion were different according to the diets and fatty acid treatments associated with them. Cells treated with 5-AZA displayed higher TNFa levels than in the absence of 5-AZA, without differences between fatty acids. According to our results, dietary fatty acid regulation of adipocyte TNFa levels may be mediated by epigenetic modifications of the TNFa promoter DNA methylation levels.
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http://dx.doi.org/10.1016/j.jnutbio.2017.05.006DOI Listing
September 2017

Changes in SCD gene DNA methylation after bariatric surgery in morbidly obese patients are associated with free fatty acids.

Sci Rep 2017 04 10;7:46292. Epub 2017 Apr 10.

CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Málaga, Spain.

Stearoyl CoA Desaturase-1 (SCD) is considered as playing an important role in the explanation of obesity. The aim of this study was to evaluate whether the DNA methylation SCD gene promoter is associated with the metabolic improvement in morbidly obese patients after bariatric surgery. The study included 120 subjects with morbid obesity who underwent a laparoscopic Roux-en Y gastric by-pass (RYGB) and a control group of 30 obese subjects with a similar body mass index (BMI) to that found in morbidly obese subjects six months after RYGB. Fasting blood samples were obtained before and at six months after RYGB. DNA methylation was measured by pyrosequencing technology. DNA methylation levels of the SCD gene promoter were lower in morbidly obese subjects before bariatric surgery but increased after RYGB to levels similar to those found in the control group. Changes of DNA methylation SCD gene were associated with the changes of free fatty acids levels (r = -0.442, p = 0.006) and HOMA-IR (r = -0.249, p = 0.035) after surgery. RYGB produces an increase in the low SCD methylation promoter levels found in morbidly obese subjects. This change of SCD methylation levels is associated with changes in FFA and HOMA-IR.
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http://dx.doi.org/10.1038/srep46292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385880PMC
April 2017

Reference values for TSH may be inadequate to define hypothyroidism in persons with morbid obesity: [email protected] study.

Obesity (Silver Spring) 2017 04 9;25(4):788-793. Epub 2017 Mar 9.

Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.

Objective: To analyze the reference range of thyroid-stimulating hormone (TSH) in different BMI categories and its impact on the classification of hypothyroidism.

Methods: The study included 3,928 individuals free of thyroid disease (without previous thyroid disease, no interfering medications, TSH <10 µUI/mL and thyroid peroxidase antibodies [TPO Abs] <50 IU/mL) who participated in a national, cross-sectional, population-based study and were representative of the adult population of Spain. Data gathered included clinical and demographic characteristics, physical examination, and blood and urine sampling. TSH, free thyroxine, free triiodothyronine, and TPO Ab were analyzed by electrochemiluminescence (E170, Roche Diagnostics, Basel, Switzerland).

Results: The reference range (p2.5-97.5) for TSH was estimated as 0.6 to 4.8 µUI/mL in the underweight category (BMI<20 kg/m ), 0.6 to 5.5 µUI/mL in the normal-weight category (BMI 20-24.9 kg/m ), 0.6 to 5.5 µUI/mL in the overweight category (BMI 25-29.9 kg/m ), 0.5 to 5.9 µUI/mL in the obesity category (BMI 30-39.9 kg/m ), and 0.7 to 7.5 µUI/mL in the morbid obesity category (BMI ≥40). By using the reference criteria for the normal-weight population, the prevalence of high TSH levels increased threefold in the morbid obesity category (P < 0.01).

Conclusions: Persons with morbid obesity might be inappropriately classified if the standard ranges of normality of TSH for the normal-weight population are applied to them.
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http://dx.doi.org/10.1002/oby.21796DOI Listing
April 2017

Population-Based National Prevalence of Thyroid Dysfunction in Spain and Associated Factors: [email protected] Study.

Thyroid 2017 02 4;27(2):156-166. Epub 2017 Jan 4.

1 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III , Madrid, Spain .

Background: The aim of this study was to investigate the national prevalence of thyroid dysfunction in Spain and its association with various clinical, environmental, and demographic variables.

Methods: The study included 4554 subjects (42.4% men) with a mean age of 50 years (range 18-93 years), who were participants in a national, cross-sectional, population-based survey conducted in 2009-2010. Data gathered included clinical and demographic characteristics, physical examination, and blood sampling. Thyrotropin, free thyroxine, free triiodothyronine, and thyroid peroxidase antibody (TPOAb) concentrations were analyzed by electrochemiluminescence. Urinary iodine (UI) levels were measured in an isolated urine sample.

Results: The prevalence of treated hypothyroidism, untreated subclinical hypothyroidism, and untreated clinical hypothyroidism was 4.2% [confidence interval (CI) 3.6-4.9%], 4.6% [CI 4.0-5.2%], and 0.3% [CI 0.1-0.5%], respectively. The prevalence of total hypothyroidism (including all fractions) was 9.1% [CI 8.2-10.0%]. The prevalence of total hyperthyroidism was 0.8% [CI 0.6-1.1]. A total of 7.5% [CI 6.7-8.3%] of the population tested positive for TPOAbs (≥50 IU/mL). In multivariate logistic regression models, TPOAbs were strongly associated with both hypothyroidism (p < 0.001) and hyperthyroidism (p = 0.005), whereas high UI levels (>200 μg/g creatinine) were associated with hypothyroidism (p < 0.001). The positive association between UI and hypothyroidism remained for both treated (p < 0.001) and untreated (p < 0.05) hypothyroidism, whereas it was especially significant for non-autoimmune (TPOAbs negative) forms (p < 0.001). At UI levels ≥200 μg/g, there was a positive correlation between UI and thyrotropin levels (β = 0.152, p < 0.001) and a negative correlation between UI and free triiodothyronine levels (β = -0.134, p = 0.001).

Conclusion: According to the data, a large proportion (10%) of the Spanish population has some evidence of thyroid dysfunction. High TPOAb concentrations were associated with both hypo- and hyperthyroidism, whereas high UI concentrations were associated with hypothyroidism.
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http://dx.doi.org/10.1089/thy.2016.0353DOI Listing
February 2017

Low Physical Activity and Its Association with Diabetes and Other Cardiovascular Risk Factors: A Nationwide, Population-Based Study.

PLoS One 2016 17;11(8):e0160959. Epub 2016 Aug 17.

CIBEROBN-Spanish Biomedical Research Centre in Physiopathology of Obesity.

Low physical activity (PA), or sedentary lifestyle, is associated with the development of several chronic diseases. We aimed to investigate current prevalence of sedentariness and its association with diabetes and other cardiovascular risk factors. PA was evaluated in a population-based, cross-sectional, randomly sampled study conducted in 2009-2010 in Spain. International Physical Activity Questionnaire (SF-IPAQ) was used to assess PA. 4991 individuals (median age 50 years, 57% women) were studied. Prevalence of sedentariness was 32.3% for men and 39% for women (p < 0.0001). Sex differences were particularly notable (age*sex interaction, p = 0.0024) at early and older ages. Sedentary individuals had higher BMI (28 vs. 27 kg/m2) and obesity prevalence (37 vs. 26%). Low PA was present in 44, 43, and 38% of individuals with known diabetes (KDM), prediabetes/unknown-diabetes (PREDM/UKDM), and normal glucose regulation (p = 0.0014), respectively. No difference between KDM and PREDM/UKDM (p = 0.72) was found. Variables independently associated (p < 0.05) with sedentariness were age, sex, BMI, central obesity, Mediterranean diet adherence, smoking habit, HDL-cholesterol, triglycerides and dyslipidemia. Low PA is on the rise in Spain, especially among women. Sedentariness is associated with several cardiovascular risk factors and may be responsible for the increasing prevalence of obesity and diabetes in this country.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160959PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988632PMC
July 2017

Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.

Diabetes 2016 10 14;65(10):3200-11. Epub 2016 Jul 14.

Cardiovascular Health Research Unit, University of Washington, Seattle, WA Department of Biostatistics, University of Washington, Seattle, WA.

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.
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http://dx.doi.org/10.2337/db16-0199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033262PMC
October 2016

Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial.

Lipids Health Dis 2016 Apr 18;15:78. Epub 2016 Apr 18.

CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.

Background: Nutrition therapy is the cornerstone of treating diabetes mellitus. The inclusion of fish (particularly oily fish) at least two times per week is recommended by current international dietary guidelines for type 2 diabetes. In contrast to a large number of human studies examining the effects of oily fish on different cardiovascular risk factors, little research on this topic is available in patients with type 2 diabetes. The aims of this pilot study were to investigate the effects of a sardine-enriched diet on metabolic control, adiponectin, inflammatory markers, erythrocyte membrane fatty acid (EMFA) composition, and gut microbiota in drug-naïve patients with type 2 diabetes.

Methods: 35 drug-naïve patients with type 2 diabetes were randomized to follow either a type 2 diabetes standard diet (control group: CG), or a standard diet enriched with 100 g of sardines 5 days a week (sardine group: SG) for 6 months. Anthropometric, dietary information, fasting glycated hemoglobin, glucose, insulin, adiponectin, inflammatory markers, EMFA and specific bacterial strains were determined before and after intervention.

Results: There were no significant differences in glycemic control between groups at the end of the study. Both groups decreased plasma insulin (SG: -35.3%, P = 0.01, CG: -22.6%, P = 0.02) and homeostasis model of assessment--insulin resistance (HOMA-IR) (SG: -39.2%, P = 0.007, CG: -21.8%, P = 0.04) at 6-months from baseline. However only SG increased adiponectin in plasma compared to baseline level (+40.7%, P = 0.04). The omega-3 index increased 2.6% in the SG compared to 0.6% in the CG (P = 0.001). Both dietary interventions decreased phylum Firmicutes (SG and CG: P = 0.04) and increased E. coli concentrations (SG: P = 0.01, CG: P = 0.03) at the end of the study from baseline, whereas SG decreased Firmicutes/Bacteroidetes ratio (P = 0.04) and increased Bacteroides-Prevotella (P = 0.004) compared to baseline.

Conclusions: Although enriching diet with 100 g of sardines 5 days a week during 6 months to a type 2 diabetes standard diet seems to have neutral effects on glycemic control in drug-naïve patients with type 2 diabetes, this nutritional intervention could have beneficial effects on cardiovascular risk. Furthermore, both dietary interventions decreased HOMA-IR and altered gut microbiota composition of drug-naïve patients with type 2 diabetes.

Trial Registration: Trial number and name of the registry: NCT02294526, ClinicalTrials.gov.
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http://dx.doi.org/10.1186/s12944-016-0245-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836051PMC
April 2016

Prevalence, Diagnosis, Treatment, and Control of Hypertension in Spain. Results of the [email protected] Study.

Rev Esp Cardiol (Engl Ed) 2016 Jun 12;69(6):572-8. Epub 2016 Mar 12.

Servicio de Endocrinología y Nutrición, Hospital Universitario Carlos Haya (IBIMA), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Málaga, Spain.

Introduction And Objectives: [email protected] is a national study designed to estimate the prevalence of diabetes mellitus and other cardiovascular risk factors in the Spanish adult population. The prevalence of hypertension and the degree to which it is recognized, treated, and controlled are described.

Methods: The study included a sample of the Spanish population with 5048 adults aged ≥ 18 years. Patients were questioned and examined, with 3 blood pressure readings while seated and at rest to calculate the mean of the 3 readings. Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or prescription for antihypertensive drug therapy.

Results: Hypertension was found in 42.6% of the Spanish adult population aged ≥ 18 years and was more common among men (49.9%) than women (37.1%). The prevalence was higher among prediabetics (67.9%) and diabetics (79.4%). Undiagnosed hypertension was identified in 37.4% of patients and was more common in men (43.3%) than in women (31.5%). Among patients with known hypertension, 88.3% were receiving drug therapy. Well-controlled blood pressure was found in only 30% and was more common among women (24.9%) than men (16%).

Conclusions: The prevalence of hypertension in Spain is high, and a considerable percentage of hypertensive patients have still not been diagnosed. Hypertension is associated with diabetes and prediabetes, and although drug therapy is increasingly common, the degree of control has not improved and remains low. Population campaigns should be developed and promoted for hypertension prevention, detection, and treatment.
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http://dx.doi.org/10.1016/j.rec.2015.11.034DOI Listing
June 2016

The Calculating Boluses on Multiple Daily Injections (CBMDI) study: A randomized controlled trial on the effect on metabolic control of adding a bolus calculator to multiple daily injections in people with type 1 diabetes.

J Diabetes 2017 Jan 13;9(1):24-33. Epub 2016 Apr 13.

Endocrinology and Nutrition Department, Málaga Institute of Biomedical Investigation (IBIMA), Málaga Regional University Hospital, Barcelona, Spain.

Background: Although the insulin bolus calculator is increasingly being used by people with type 1 diabetes (T1D) on multiple daily injection (MDI) therapy, few studies have investigated its effects on glycemic control. The aim of this study was to determine whether adding this device to therapeutic intensification could further improve metabolic control.

Methods: A 4-month randomized controlled clinical trial was performed comparing subjects undergoing therapeutic intensification and either using the bolus calculator (Cb group) or not (active control [Co] group). Metabolic control, fear of hypoglycemia, and treatment acceptance were evaluated.

Results: In all, 70 people completed the study (42 in the Cb group, 28 in the Co group). There was a significant decrease in HbA1c in both the Cb and Co groups (-7 mmol/mol [-0.7 %] vs -4 mmol/mol [-0.4 %], respectively). There were no significant differences in HbA1c at baseline or the end of the study, or in the decrease in HbA1c, glycemia, or changes in blood glucose levels at the end of the study between the two groups. There was a significant increase in the number of participants with good metabolic control (HbA1c <58 mmol/mol [7.5 %]) in the Cb group (from 16.7 % to 40.5 %), but not in the Co group. The incidence of hypoglycemic events was reduced slightly but significantly only in the Cb group. There was no change in the fear of hypoglycemia at the end of the study. The bolus calculator was well accepted.

Conclusions: In T1D, adding a bolus calculator to intensive MDI resulted in a significant improvement in metabolic control and slightly decreased the number of hypoglycemic episodes. Metabolic control also improved in the Co group.
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http://dx.doi.org/10.1111/1753-0407.12382DOI Listing
January 2017

Methylation patterns of Vegfb promoter are associated with gene and protein expression levels: the effects of dietary fatty acids.

Eur J Nutr 2017 Mar 26;56(2):715-726. Epub 2015 Dec 26.

UGC Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Málaga, Spain.

Purpose: We have investigated the epigenetic regulation by dietary fatty acids of Vegfb levels in rats' white adipose tissue and 3T3-L1 cells.

Methods: A group of rats were assigned to three diets, each one with a different composition of saturated, monounsaturated and polyunsaturated fatty acids. Samples of white adipose tissues were taken for the methylation and expression studies. Additionally, 3T3-L1 cells were treated with palmitic, oleic, and linoleic fatty acids. After treatment, cells were harvested and genetic material was extracted for the analysis of Vegfb levels.

Results: We report evidence of changes in the methylation levels of the CpG island at the Vegfb promoter and in the Vegfb expression levels in vivo and in vitro by dietary fatty acid, with the main contribution of the linoleic fatty acid. Vegfb promoter methylation levels were closely related to the Vegfb gene expression.

Conclusion: According to our results, the regulation of Vegfb gene expression by dietary fatty acids may be mediated, at least in part, by epigenetic modifications on Vegfb promoter methylation. Considering the deep association between angiogenesis and tissue growth, we suggest the nutriepigenetic regulation of Vegfb as a key target in the control of the adipose tissue expansion.
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http://dx.doi.org/10.1007/s00394-015-1115-7DOI Listing
March 2017