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Background: Our aim in this study was to investigate if Hip index (HI) improves the identification of cardiovascular risk (CVR) beyond that achieved with either the waist-to-height ratio (WHtR) or body mass index (BMI)-adjusted waist circumference (A body shape index [ABSI]) in the Spanish Caucasian population. Methods: Three thousand eight hundred forty-four subjects (1754 males, response rate 75.8%) were included. Anthropometric indices (AIs) included were HI, ABSI, and WHtR. CVR was estimated using the Framingham, Systematic COronary Risk Evaluation (SCORE), and American College of Cardiology/American Heart Association (ACC/AHA) charts. Areas under the receiver operating characteristic curve (AUC) were obtained to evaluate the performance of AIs in detecting CVR. We also estimated the AIs' standardized Z-scores and compared them against the CVR. Results: AUC demonstrated that the best AI in males to estimate higher CVR according to Framingham and ACC/AHA charts was WHtR. In females, WHtR also achieved good performance and showed higher prediction capacity than the other AIs. After transforming to Z-scores, ABSI was the best linear predictor for CVR according to SCORE and ACC/AHA, although WHtR also proved to be good. HI did not associate with the measures of CVR. Conclusions: HI does not predict high CVR in the Spanish Caucasian Population. However, ABSI is directly and linearly related to high CVR, with a higher performance than WHtR when standardized and evaluated as a linear predictor.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

Aim: To determine the association of body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtr) and Body Shape Index (ABSI) with high cardiovascular risk (CVR), as well as to determine whether how strong are these relationships., Material and Methods: A cross-sectional study was carried out in Spanish Caucasian adults. 3,456 subjects completed the study, 45.78% males, aged < 65 years and non-diabetic subjects. Anthropometric/biochemical variables were measured. We determined ABSI based on WC adjusted for height and weight. High CVR was defined as ≥ 20% according to the Framingham chart, ≥ 5% with the SCORE chart, and ≥ 7.5% with the ACC/AHA guide. Areas under the receiver operating characteristic curves (AUCs) were estimated for each anthropometric measure., Results: Most significant AUCs in males were: WHtr and ABSI for Framingham ≥ 20% and SCORE ≥ 5%. Also significant were WHtr, WC and ABSI for ACCA/AHA ≥ 7.5%. On the other hand, most significant AUCs in females were: WHtr and WC for Framingham ≥ 20%; and WHtr and WHR for SCORE ≥ 5%, WHtr, and WC for ACC/AHA guide ≥ 7.5%., Conclusions: Overall, the best anthropometric index identifying Spanish males and females who are at high risk for CV events is WHtr. ABSI was also found to be a good anthropometric index to predict high CVR in Spanish males according to FR, SCORE and ACC/AHA charts. For Spanish females, WC is a good anthropometric index according to FR and ACC/AHA guide, while WHR is better according to SCORE., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: MSR received grants funding from Eli Lilly Lab (2010-115-B99) & Bayer Pharmaceutical Co. (2005-115-B99), respectively. CFP also received partial support for this study from Fundación Mutua Madrileña (FMM-2008), Spain. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The prevalence and related factors of hypertensive subjects according to the resident area (rural versus urban) were investigated in two population-based studies from Spain. Medical questionnaires were administered and anthropometrics were measured, using standardized protocols. Hypertension was diagnosed in pharmacology treated subjects or those with blood pressure (BP) ≥140/90 mm Hg. Regarding BP control, it was defined as under control if BP was <140/90 or <140/85 mm Hg in type 2 diabetic subjects. Information on educational status, social class, smoking habit, and alcohol intake was obtained. 3,816 subjects (54.38 % women) were included. Prevalence of diagnosed hypertension was higher in women and showed no differences according to the living area (men: urban 21.88 versus rural 21.92 %, p = 0.986; women: urban 28.73 versus rural 30.01 %, p = 0.540). Women living in rural areas and men with secondary or tertiary education levels had a lower probability of being BP uncontrolled (OR (95 % CI): 0.501 (0.258-0.970)/p=0.040, 0.245 (0.092-0.654)/p=0.005, and 0.156 (0.044-0.549)/p=0.004, respectively). Urban young men (31-45 years) and medium aged women (46-60 years) were less BP controlled than their rural counterparts (41.30 versus 65.79 %/p=0.025 and 35.24 versus 53.27 %/p=0.002, respectively).

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., (© 2016 by the American Diabetes Association.)

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.

Introduction and Objectives: Di@bet.es 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., (Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Our aim was to investigate if genetic variations in the visfatin gene (SNPs rs7789066/ rs11977021/rs4730153) could modify the cardiovascular-risk (CV-risk) despite the metabolic phenotype (obesity and glucose tolerance). In addition, we investigated the relationship between insulin sensitivity and variations in visfatin gene., Material and Methods: A population-based study in rural and urban areas of the Province of Segovia, Spain, was carried out in the period of 2001-2003 years. A total of 587 individuals were included, 25.4% subjects were defined as obese (BMI ≥30 Kg/m2)., Results: Plasma visfatin levels were significantly higher in obese subjects with DM2 than in other categories of glucose tolerance. The genotype AA of the rs4730153 SNP was significantly associated with fasting glucose, fasting insulin and HOMA-IR (Homeostasis model assessment-insulin resistance) after adjustment for gender, age, BMI and waist circumference. The obese individuals carrying the CC genotype of the rs11977021 SNP showed higher circulating levels of fasting proinsulin after adjustment for the same variables. The genotype AA of the rs4730153 SNP seems to be protective from CV-risk either estimated by Framingham or SCORE charts in general population; and in obese and non-obese individuals. No associations with CV-risk were observed for other studied SNPs (rs11977021/rs7789066)., Conclusions: In summary, this is the first study which concludes that the genotype AA of the rs4730153 SNP appear to protect against CV-risk in obese and non-obese individuals, estimated by Framingham and SCORE charts. Our results confirm that the different polymorphisms in the visfatin gene might be influencing the glucose homeostasis in obese individuals.

We examined the prevalence of metabolic syndrome (MetS), glucose tolerance categories and risk factors of cardiovascular-disease (CVD) in the general Spanish population. We studied 3844 randomly sampled subjects (46% males) aged 35-74 years. Glucose tolerance categories were defined according to the 2003 ADA and MetS according to the Harmonized Consensus Criteria with waist circumference (WC) cut-off-points previously reported in Spanish population (≥94.5/≥89.5cm for males/females). The prevalences of normoglycemia (NG), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG and IGT considered together (IFG/IGT), and diabetes mellitus (DM) were 67.6/16.6/5.0/3.3, and 7.5%, respectively. The overall prevalence of MetS was 31.2%. In subjects with NG, IFG, IGT, IFG/IGT, and DM the MetS prevalence's were 16.3/57.1/31.5/66.1, and 74.4% (p<0.001), respectively. MetS was more common in males, older subjects, smokers, and/or individuals with obesity, IFG, IFG/IGT, DM, or insulin resistance (HOMA-IR ≥3.8). MetS was less prevalent in individuals with low alcohol intake and/or high education level. Regarding the risk level of CVD estimated by Framingham and SCORE risk charts, IGT had higher estimated CVD-risk than IFG and IFG/IGT. The presence of MetS increases the risk 4.85 times by Framingham and 2.43 times by SCORE. Prevalence of prediabetes (IFG/IGT) and MetS were 25% and 31.2% respectively. Prevalence of MetS has not changed in the past decade in Spanish females, but has slightly increased in males. We found that subjects with IGT showed a higher risk of CVD than IFG and IFG/IGT according to the Framingham and SCORE. MetS increased the CVD-risk previously estimated by Framingham and SCORE., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Obesity is associated with numerous metabolic complications such as diabetes mellitus type 2, dyslipidemia, hypertension, cardiovascular diseases and several forms of cancer. Our goal was to compare different criteria to define the metabolically healthy obese (MHO) with metabolically unhealthy obese (MUHO) subjects. We applied Wildman (W), Wildman modified (WM) with insulin resistance (IR) with cut-off point ≥ 3.8 and levels of C- Reactive Protein (CRP) ≥ 3 mg/l; and Consensus Societies (CS) criteria. In these subjects cardiovascular-risk (CV-risk) was estimated by Framingham score and SCORE for MHO and MUHO., Methods: A cross-sectional study was conducted in Spanish Caucasian adults. A total of 3,844 subjects completed the study, 45% males, aged 35-74 years. Anthropometric/biochemical variables were measured. Obesity was defined as BMI: ≥ 30 Kg/m(2)., Results: The overall prevalence of obesity in our population was 27.5%, (23.7%/males and 30.2%/females). MHO prevalence according to W, WM, and CS definition criteria were: 9.65%, 16.29%, 39.94% respectively in obese participants. MHO has lower waist circumference (WC) measurements than MUHO. The estimated CV-risks by Framingham and SCORE Project charts were lower in MHO than MUHO subjects. WC showed high specificity and sensitivity in detecting high estimated CV risk by Framingham. However, WHR showed high specificity and sensitivity in detecting CV risk according to SCORE Project. MHO subjects as defined by any of the three criteria had higher adiponectin levels after adjustment by sex, age, WC, HOMA IR and Framingham or SCORE risks. This relationship was not found for CRP circulating levels neither leptin levels., Conclusions: MHO prevalence is highly dependent on the definition criteria used to define those individuals. Results showed that MHO subjects had less WC, and a lower estimated CV-risk than MUHO subjects. Additionally, the high adiponectin circulating levels in MHO may suggest a protective role against developing an unhealthy metabolic state.

Background and Aim: Prevalence rates of "metabolically healthy obese" (MHO) subjects vary depending on the criteria used. This study examined the prevalence and characteristics of MHO subjects and metabolically abnormal normal-weight subjects and compared the findings with the NHANES 1999-2004 study. The aims of the present study were, first, to determine the prevalence rates of MHO and MNHNO subjects using the same criteria as those of the National Health and Nutrition Examination Survey (NHANES) (1999-2004) study, and second to compare the prevalence and correlates of obese subjects who are resistant to the development of adiposity-associated cardiometabolic abnormalities (CA) and normal-weight individuals who display cardiometabolic risk factor clustering between the Spanish and the US populations., Methods and Results: Di@bet.es study is a national, cross-sectional population-based survey of 5728 adults conducted in 2009-2010. Clinical, metabolic, sociodemographic, and anthropometric data and information about lifestyle habits, such as physical activity, smoking habit, alcohol intake and food consumption, were collected. Subjects were classified according to their body mass index (BMI) (normal-weight, <25 kg/m(2); overweight, 25-29.9 kg/m(2); and obese, >30 kg/m(2)). CA included elevated blood pressure; elevated levels of triglycerides, fasting glucose, and high-sensitivity C-reactive protein (hs-CRP); and elevated homeostasis model assessment of insulin resistance (HOMA-IR) value and low high-density lipoprotein cholesterol (HDL-c) level. Two phenotypes were defined: metabolically healthy phenotype (0-1 CA) and metabolically abnormal phenotype (≥2 CA). The prevalence of metabolically abnormal normal-weight phenotype was slightly lower in the Spanish population (6.5% vs. 8.1%). The prevalence of metabolically healthy overweight and MHO subjects was 20.9% and 7.0%, respectively, while in NHANES study it was 17.9% and 9.7%, respectively. Cigarette smoking was associated with CA in each phenotype, while moderate physical activity and moderate alcohol intake were associated with being metabolically healthy. Olive oil intake was negatively associated with the prevalence of CA., Conclusions: Smoking, physical activity level, and alcohol intake contribute to the explanation of the prevalence of CA in the Spanish population, as in the US population. However in Spain, olive oil intake contributes significantly to the explanation of the variance in the prevalence of CA., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aims: Retinal vein occlusion (RVO) is the most frequent retinal vascular disease after diabetic retinopathy in which arterial risk factors are much more relevant than venous factors. The objective was to evaluate the role of risk factors in the development of the first episode of RVO., Subjects and Methods: One hundred patients with RVO [mean age 56 years, 42% females and mean body mass index (BMI) 27.5 kg/m(2)] were recruited consecutively from the outpatient clinic of a tertiary hospital in Valencia (Spain). All subjects underwent clinical assessment including anthropometric and blood pressure measurements and laboratory test including homocysteine, antiphospholipid antibodies (aPLAs) and thrombophilia studies. In half of the subjects, a carotid ultrasonography was performed. Three control populations matched by age, sex and BMI from different population-based studies were used to compare the levels and prevalence of arterial risk factors. One cohort of young patients with venous thromboembolic disease was used to compare the venous risk factors., Results: Blood pressure levels and the prevalence of hypertension were significantly higher in the RVO population when compared with those for the general populations. There was also a large proportion of undiagnosed hypertension within the RVO group. Moreover, carotid evaluation revealed that a large proportion of patients with RVO had evidence of subclinical organ damage. In addition, homocysteine levels and prevalence of aPLAs were similar to the results obtained in our cohort of venous thromboembolic disease., Conclusions: The results indicate that hypertension is the key factor in the development of RVO, and that RVO can be the first manifestation of an undiagnosed hypertension. Furthermore, the majority of these patients had evidence of atherosclerotic disease. Among the venous factors, a thrombophilia study does not seem to be useful and only the prevalence of hyperhomocysteinaemia and aPLAs is higher than in the general population., (© 2014 John Wiley & Sons Ltd.)

Introduction: Dyslipidemia is a significant contributor to the elevated CVD risk observed in type 2 diabetes mellitus. We assessed the prevalence of dyslipidemia and its association with glucose metabolism status in a representative sample of the adult population in Spain and the percentage of subjects at guideline-recommended LDL-C goals., Material and Methods: The di@bet.es study is a national, cross-sectional population-based survey of 5728 adults., Results: A total of 4776 subjects were studied. Dyslipidemia was diagnosed in 56.8% of subjects; only 13.2% of subjects were treated with lipid lowering drugs. Lipid abnormalities were found in 56.8% of Spanish adults: 23.3% with high LDL-C, 21.5% high TG, 35.8% high non-HDL-C, and 17.2% low HDL-C. Most normal subjects showed an LDL-C ≤ 3.36 mmol/l. Pre-diabetics presented similar proportion when considering a goal of 3.36 mmol/l, but only 35% of them reached an LDL-C goal ≤ 2.6 mmol/l. Finally, 45.3% of diabetics had an LDL-C ≤ 2.6 mmol/l, and only 11.3% achieved an LDL-C ≤ 1.8 mmol/l., Conclusions: Our study demonstrates a high prevalence of dyslipidemia in the adult Spanish population, and a low use of lipid-lowering drugs. Moreover, the number of subjects achieving their corresponding LDL-C goal is small, particularly in subjects at high cardiovascular risk, such as diabetics., (Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.)

Introduction and Objectives: To assess the patterns of use of 8 therapeutic drug groups for the treatment of diabetes mellitus and other cardiovascular risk factors, and to identify sociodemographic and health determinants of their use in the overall Spanish population., Methods: A representative sample of the Spanish population within the Di@bet.es study, a cross-sectional population-based survey, was included., Study Variables: sociodemographic, clinical, and lifestyle data; physical examination, and an oral glucose tolerance test in patients without known diabetes mellitus. Furthermore, patients were systematically queried about current medication use, and 8 pharmacotherapeutic groups were evaluated: lipid-lowering therapy, antihypertensives, oral hypoglycemic agents, insulin, thyroid hormone, uricosurics, psychoactive drugs, and nonsteroidal anti-inflammatory drugs., Results: Sixty-six percent of the Spanish population was taking at least one medication. Therapeutic drug use was associated with age, independently of the higher prevalence of diabetes mellitus, hypertension, or hyperlipidemia in older patients. Sex disparities were found in the use of lipid-lowering agents, allopurinol, levothyroxine, nonsteroidal anti-inflammatory drugs, and psychoactive drugs. Use of psychoactive drugs was related to education level, work status, physical activity, smoking, and alcohol consumption. Almost 30% of patients with diabetes mellitus were taking 6 or more medications daily. Diabetes mellitus was associated with greater use of antihypertensives, lipid-lowering agents, and nonsteroidal anti-inflammatory drugs., Conclusions: Age and sex are the most important factors determining therapeutic drug use. Lifestyle patterns and sociocultural factors have an impact only on psychoactive drug use. Diabetes mellitus is associated with greater use of antihypertensives, lipid-lowering agents, and nonsteroidal anti-inflammatory drugs., (Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Background and Aim: MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes, including complex metabolic processes, such as energy and lipid metabolism, which have been studied in the context of diabetes and obesity. Some particular microRNAs have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. The aim of this profiling study was to characterize the expression of miRNA in serum samples of obese, nonobese diabetic and obese diabetic individuals to determine whether miRNA expression was deregulated in these serum samples and to identify whether any observed deregulation was specific to either obesity or diabetes or obesity with diabetes., Patients and Methods: Thirteen patients with type 2 diabetes, 20 obese patients, 16 obese patients with type 2 diabetes and 20 healthy controls were selected for this study. MiRNA PCR panels were employed to screen serum levels of 739 miRNAs in pooled samples from these four groups. We compared the levels of circulating miRNAs between serum pools of each group. Individual validation of the twelve microRNAs selected as promising biomarkers was carried out using RT-qPCR., Results: Three serum microRNAs, miR-138, miR-15b and miR-376a, were found to have potential as predictive biomarkers in obesity. Use of miR-138 or miR-376a provides a powerful predictive tool for distinguishing obese patients from normal healthy controls, diabetic patients, and obese diabetic patients. In addition, the combination of miR-503 and miR-138 can distinguish diabetic from obese diabetic patients., Conclusion: This study is the first to show a panel of serum miRNAs for obesity, and compare them with miRNAs identified in serum for diabetes and obesity with diabetes. Our results support the use of some miRNAs extracted from serum samples as potential predictive tools for obesity and type 2 diabetes.

Background: We aimed to investigate the prevalence of metabolic syndrome in rural and urban areas in the province of Segovia, Spain, and its relationship to lifestyle habits, cardiovascular risk, and serum adiponectin concentrations., Methods: The study had a cross-sectional design and included 888 individual residents in the province of Segovia, Autonomous Community of Castilla-León., Results: The age/sex standardized prevalence of the metabolic syndrome was by: (1) American Heart Association/National Heart Lung and Blood Institute criteria (AHA/NHLBI), 17%; (2) International Diabetes Federation (IDF), 24.3%; and (3) Consensus Societies/Joint Interim Statement (CS), 27.8%. A high correlation was found between the different criteria. No formal education [odds ratio (OR) 6.9 (2.4-20.2)] and primary education [6.7 (2.8-15.9)] were independently associated with metabolic syndrome. An inverse association with metabolic syndrome was found for subjects doing a high level of exercise during work [0.4 (0.2-0.7)] as well as those who were mild drinkers [alcohol intake of less than 15 grams/daily, 0.4 (0.3-0.8)]. Among subjects with low estimated cardiovascular risk, adiponectin levels are higher in those who do not meet criteria of metabolic syndrome. A total of 29.7% of subjects meeting CS criteria had >20% 10-year predicted risk of cardiovascular disease (CVD) by the Framingham risk score criteria [4.5 (2.4-8.5)]., Conclusions: Our results show: (1) A higher estimated prevalence of metabolic syndrome according to IDF and CS criteria. (2) Low educational level was independently associated with metabolic syndrome. A high level of physical activity and a daily alcohol intake of less than 15 grams/day were inversely associated with metabolic syndrome. (3) Metabolic syndrome increases the predicted CVD risk. (4) Adiponectin levels are not inversely related to insulin resistance in subjects with high cardiovascular risk and metabolic syndrome.

The aim of the study is to assess the prevalence of metabolic syndrome (MetS) in Spain using specific cutoff points for waist circumference (WC) (>94.5 cm for men and >89.5 cm for women) and evaluating the influence of several socio-demographic and economic factors. Data on MetS were obtained from a national study of 4,727 subjects from 18 to 90 years of age, conducted in Spain between 2009 and 2010 (The di@bet.es study). MetS was defined applying the new Harmonized definition (evaluating the use of abdominal obesity (AO) as a obligatory criterion for MetS or not) as well as with other widely used criteria. Results were then compared with data from previous studies. Multiple logistic regression models were used to evaluate the influence of different social factors. The age-standardized MetS prevalence was 38.37 % (CI 35.74-40.99) in men and 29.62 % (CI 27.56-31.69) in women, when AO was required as a diagnostic criterion; 42.13 % (CI 39.37-44.89) and 32.31 % (CI 30.15-34.47) in men and women, respectively, if AO was not considered mandatory. Prevalence of MetS increased with age (p < 0.001 for trend). Women with a lower educational level were more likely to have MetS (OR 4.4; 95 % CI: 2.84-6.7) as compared with those with a higher educational level. Subjects with MetS had a worse physical quality of life. The combination of AO, hypertension and carbohydrate alterations was the most common MetS' pattern. A high prevalence of MetS was detected in the Spanish population especially in men, the elderly and women with a low educational level.

The present study was undertaken to examine the prevalence of urinary ACR (albumin/creatinine ratio) >30 mg/g and the associated clinical and environmental factors in a representative sample of the population of Spain. Di@bet.es study is a national, cross-sectional population-based survey conducted in 2009-2010. Clinical, metabolic, socio-demographic, anthropometric data and information about lifestyle habit were collected. Those subjects without KDM (known diabetes mellitus) were given an OGTT (oral glucose tolerance test). Albumin and creatinine were measured in a urinary sample and ACR was calculated. The population prevalence of ACR >30 mg/g was 7.65% (adjusted for sex and age). The prevalence of ACR >30 mg/g increased with age (P<0.001). Subjects with carbohydrate metabolism disorders had a greater prevalence of ACR >30 mg/g but after being adjusted for age, sex and hypertension, was significant only in those subjects with UKDM (unknown diabetes mellitus) {OR (odd ratio), 2.07 [95% CI (confidence interval), 1.38-3.09]; P<0.001] and KDM [OR, 3.55 (95% CI, 2.63-4.80); P<0.001]. Prevalence of ACR >30 mg/g was associated with hypertension [OR, 1.48 (95% CI, 1.12-1.95); P=0.001], HOMA-IR (homoeostasis model assessment of insulin resistance) [OR, 1.47 (95% CI, 1.13-1.92); P≤0.01], metabolic syndrome [OR, 2.17 (95% CI, 1.72-2.72); P<0.001], smoking [OR, 1.40 (95% CI, 1.06-1.83); P≤0.05], physical activity [OR, 0.68 (95% CI, 0.54-0.88); P≤0.01] and consumption of fish [OR, 0.38 (95% CI, 0.18-0.78); P≤0.01]. This is the first study that reports the prevalence of ACR >30 mg/g in the Spanish population. The association between clinical variables and other potentially modifiable environmental variables contribute jointly, and sometimes interactively, to the explanation of prevalence of ACR >30 mg/g. Many of these risk factors are susceptible to intervention.

Background and Aims: Mediterranean diet (MedDiet) is causally related to diabetes and is a dietary pattern recommended to individuals with diabetes. We investigated MedDiet adherence in individuals with prediabetes and unknown (PREDM/UKDM) or known diabetes (KDM) compared to those with normal glucose metabolism (NORMAL)., Methods: This was a national, population-based, cross-sectional, cluster-sampling study. MedDiet adherence was scored (MedScore, mean ± SD 24 ± 5) using a qualitative food frequency questionnaire. Logistic regression was used to examine the association between MedScore and PREDM/UKDM or KDM versus control subjects., Results: We evaluated 5,076 individuals. Mean age was 50 years, 57% were female, 826 (582/244) were PREDM/UKDM, 478 were KDM and 3,772 were NORMAL. Mean age increased across MedScore tertiles (46, 51 and 56 years, p < 0.0001). Higher age-adjusted adherence to MedDiet (5-unit increment in the MedScore) was associated with lower and nondifferent odds (OR, 95% CI) of prevalent PREDM/UKDM (0.88, 0.81-0.96, p = 0.001) and KDM (0.97, 0.87-1.07, p = 0.279), respectively, compared to individuals in the NORMAL group., Conclusions: In a representative sample of the whole Spanish population, MedDiet adherence is independently associated with PREDM/UKDM. Therapeutic intervention may be, in part, responsible for the lack of differences in adherence observed between the KDM and NORMAL groups. However, reverse causation bias cannot be ruled out in cross-sectional studies., (Copyright © 2013 S. Karger AG, Basel.)

Background & Aims: To date no nation-wide study has yet been undertaken in Spain to estimate the iodine deficiency. The aim was to evaluate iodine intake and its conditioning factors in a representative sample of the whole adult population., Methods: The Di@bet.es Study is a national, cross-sectional, population-based survey conducted in 2009-2010 in Spain., Results: The median urinary iodine (UI) was 117.2 μg/L. Iodized salt (IS) was consumed by 43.9% of the population. The median UI in those who consumed IS and in those who did not consume IS was 131.1 and 110.8 μg/L respectively (p<0.0001). The likelihood of having UI levels above 100 μg/L was significantly associated with the intake of IS (OR=1.47) and milk at least once a day (OR=1.22). Within each individual autonomous communities, the median UI levels in those who consumed IS correlated significantly with the median levels of those who did not consume IS (r=0.76, p=0.001)., Conclusions: Though strictly speaking, Spain should be considered within the category of a country having an adequate iodine intake, the current value is too close to the cut point and does not guarantee that those groups with a greater need for iodine will have the required intake of iodine., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Aims: We evaluated the relations between surrogate indices of insulin resistance and waist circumference, metabolic syndrome and coronary heart disease risk across Hispanic and non-Hispanic white populations., Methods: The study was a cross-sectional analysis of participants without diabetes in the San Antonio Heart Study, Mexico City Diabetes Study and Spanish Insulin Resistance Study. We evaluated commonly used indices of insulin resistance, including homeostasis model assessment, McAuley's index, Gutt's insulin sensitivity index, Avignon's insulin sensitivity index and the Stumvoll index with and without demographics, the modified Matsuda index and the product of the triglycerides and glucose index. The metabolic syndrome was defined by American Heart Association/National Heart, Lung, and Blood Institute criteria and coronary heart disease risk by Framingham risk scores., Results: The Stumvoll index with demographics and the Avignon's insulin sensitivity index had the strongest correlations with waist circumference across populations. The triglycerides and glucose and McAuley's indices had the most robust correlations with Framingham risk score. The triglycerides and glucose index had the greatest ability to detect individuals with the metabolic syndrome and ≥ 10% coronary heart disease risk. Some indices display significant variability in the strength of the relationship with adiposity and coronary heart disease risk across populations., Conclusions: There are significant differences between insulin resistance indices regarding the ability to detect the metabolic syndrome and coronary heart disease risk across populations. Studies may need to consider the index of insulin resistance that best suits the objectives., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/ 47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2-2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26-2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

Aims/hypothesis: The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation., Methods: A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75 g)., Results: Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG-IGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age (p < 0.0001), and was higher in men than in women (p < 0.001)., Conclusions/interpretation: The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population.

Summary: The main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated., Methods: 1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model., Results: One polymorphism (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population., Conclusions: The study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians.

Subclinical low-grade systemic inflammation has been associated with obesity, insulin resistance and metabolic syndrome (MS). Recent studies have highlighted the role of gut microbiota in these disorders. The toll-like receptor 4 (TLR4) plays a key role in the innate immune response activation. We studied two polymorphisms (+3725G/C and 11350G/C) in the 3' untranslated region (3'UTR) of the TLR4 gene that may alter its expression and their association with metabolic disorders related to systemic inflammation. We cloned the 3'UTR into a luciferase reporter system and compared wild-type 3'UTR (WT) and +3725C variant (MUT) constructs luciferase activities. MUT construct reduced the reporter gene activity by 30% compared to WT (P = 0.0001). To evaluate the association between these polymorphisms with biochemical and clinical overweight related variables, we conducted a population cross-sectional study in 966 men of Argentine general population. Considering smoking as a confounding variable that causes systemic inflammation, we studied these possible effects in both, smokers and nonsmokers. The 11350G/C polymorphism was not detected in our sample whereas the CC genotype of +3725 polymorphism was associated with lean subjects (p = 0.011) and higher Adiponectin levels (p = 0.021). Subjects without any NCEP/ATP III MS component were associated with this genotype as well (p = 0.001). These results were strengthened in nonsmokers, in which CC genotype was associated with lean subjects (p = 0.003) and compared with G carriers showed significantly lower BMI (25.53 vs. 28.60 kg/m2; p = 0.023) and waist circumference (89.27 vs. 97.51 cm; p = 0.025). None of these associations were found in smokers. These results showed that +3725C variant has a functional effect down-regulating gene expression and it could be considered as a predictive factor against overweight, particularly in nonsmokers. Considering the role of TLR4 in inflammation, these findings would suggest that the presence of +3725C variant could predict a lower prevalence of chronic metabolic disorders.

Objective: The metabolic syndrome (MS) is a cluster of cardiometabolic factors, which predisposes to diabetes and cardiovascular disease (CVD). Early detection of high-risk individuals for MS using accurate measures of insulin resistance (IR) could improve detection and prevention of CVD and diabetes. The aim of this study was to explore the ability of lipid accumulation product (LAP), compared with traditional measures of IR, to identify MS., Design: In total, 768 Spanish adults were recruited. MS was assessed using the revised criteria of National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) and International Diabetes Federation (IDF). Measures of IR such as homeostasis model assessment of IR and LAP, an index of lipid accumulation based on a combination of waist circumference and serum triglycerides, were calculated. Receiver operating characteristic analysis was performed in order to detect the parameter with the best predictive capability for MS., Results: The prevalence of MS-NCEP/ATP III and MS-IDF was 15.1 and 20.5% for men respectively, and 15.4 and 17.5% for women. LAP showed the highest diagnostic accuracy for MS-NCEP/ATP III (area under the curve 0.91 and 0.90 among males and females) and MS-IDF (0.88 for both males and females). This was confirmed by internal validation using 20 000 bootstrap samples. Among males and females, different LAP cut-off values exhibited high sensitivity (78-85%) and specificity (78-85%) for MS-NCEP/ATP III and MS-IDF identification with elevated efficiency (proportion of positives and negatives classified correctly by the test=78-85%). When the sample was stratified according to decades of life, LAP exhibited a slightly lower performance among women than men, especially for MS-IDF detection., Conclusions: In non-diabetic adults LAP has a strong and reliable diagnostic accuracy for MS-IDF and, especially, MS-NCEP/ATP III among females and, in particular, among males from Spain.

Objective: Glycated hemoglobin (HbA₁(c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA₁(c). We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA₁(c) levels., Research Design and Methods: We studied associations with HbA₁(c) in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA₁(c) loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening., Results: Ten loci reached genome-wide significant association with HbA(1c), including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10⁻²⁶), HFE (rs1800562/P = 2.6 × 10⁻²⁰), TMPRSS6 (rs855791/P = 2.7 × 10⁻¹⁴), ANK1 (rs4737009/P = 6.1 × 10⁻¹²), SPTA1 (rs2779116/P = 2.8 × 10⁻⁹) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10⁻⁹), and four known HbA₁(c) loci: HK1 (rs16926246/P = 3.1 × 10⁻⁵⁴), MTNR1B (rs1387153/P = 4.0 × 10⁻¹¹), GCK (rs1799884/P = 1.5 × 10⁻²⁰) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10⁻¹⁸). We show that associations with HbA₁(c) are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA₁(c)) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA₁(c)., Conclusions: GWAS identified 10 genetic loci reproducibly associated with HbA₁(c). Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA₁(c) levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA₁(c).

Background: Altered lipid profile, and in particular low HDL and high triglyceride (TG) plasma levels, are within the major determinants of cardiovascular diseases. The identification of quantitative trait loci (QTL) affecting these lipid levels is a relevant issue for predictive purposes. The WWOX gene has been recently associated with HDL levels. This gene is located at chromosome 16q23, a region previously linked to familial combined hyperlipidemia (FCHL) and HDL. Our objective is to perform a genetic association analysis at the WWOX gene region with HDL, TG and TG/HDL ratio., Methods: A quantitative association analysis performed in 801 individuals selected from the Spanish general population., Results: For HDL levels, two regions of intron 8 display clustering of positive signals (p < 0.05) but none of them was associated in the haplotypic analysis (0.07 ≤ p ≤ 0.165). For TG levels not only intron 8 but also a 27 kb region spanning from the promoter region to intron 4 are associated in this study. For the TG/HDL genetic association analysis, positive signals are coincident with those of the isolated traits. Interestingly, haplotypic analysis at the 5' region showed that variation in this region modified both HDL and TG levels, especially the latter (p = 0.003)., Conclusions: Our results suggest that WWOX is a QTL for both TG and HDL.

Background: Genetic admixture is a common caveat for genetic association analysis. Therefore, it is important to characterize the genetic structure of the population under study to control for this kind of potential bias., Results: In this study we have sampled over 800 unrelated individuals from the population of Spain, and have genotyped them with a genome-wide coverage. We have carried out linkage disequilibrium, haplotype, population structure and copy-number variation (CNV) analyses, and have compared these estimates of the Spanish population with existing data from similar efforts., Conclusions: In general, the Spanish population is similar to the Western and Northern Europeans, but has a more diverse haplotypic structure. Moreover, the Spanish population is also largely homogeneous within itself, although patterns of micro-structure may be able to predict locations of origin from distant regions. Finally, we also present the first characterization of a CNV map of the Spanish population. These results and original data are made available to the scientific community.

Toll-like receptor 4 (TLR4) plays a key role in the activation of innate immune responses. Loss-of-function mutations in TLR4 prevent diet-induced obesity and insulin resistance (IR). We conducted a population cross-sectional study to evaluate whether Asp299Gly (rs4986790) TLR4 gene polymorphism is associated with metabolic syndrome (MS), surrogates of IR, and syndromes of lipid accumulation (SLAs) in Argentinean healthy male subjects. rs4986790 was genotyped in 621 healthy unrelated male blood donors. National Cholesterol Education Program/Adult Treatment Panel III-MS (NCEP/ATP III-MS); SLAs such as enlarged waist elevated triglyceride syndrome (EWET), hypertriglyceridemic waist (HW), and overweight-lipid syndrome (OLS); and surrogates of IR were assessed. The prevalence of MS, OLS, and EWET was significantly higher among Asp299Asp carriers (P < .05). These findings were confirmed using 32 000 bootstrap samples. Surrogate markers of IR were also significantly higher in Asp299Asp carriers (P < .05). Most findings were especially strengthened among individuals with C-reactive protein below the 95th percentile and/or total cholesterol to high-density lipoprotein cholesterol ratio >or=5. This is the first report to find, in Argentinean healthy male blood donors, associations between the Asp299Asp genotype of rs4986790 TLR4 gene polymorphism and high risk for NCEP/ATP III-MS, SLAs, and surrogates of IR. These findings are consistent with previous functional and observational studies showing that Asp299 allele, in comparison with Gly299, is associated with increased TLR4 activation, higher levels of inflammatory cytokines, acute-phase reactants and soluble adhesion molecules, and higher risk of atherosclerosis.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Objective: Recently independent studies, including genome-wide scans, have shown that variation in the fat mass and obesity associated gene (FTO) were significantly associated with obesity in populations of European origin., Design and Methods: In this study we examined the association between rs9939609 FTO variant and obesity related parameters in a population based-study of 732 unrelated individuals (46.9% males and 53.1% females; ages 35-74 years) from the province of Segovia in Central Spain (Castille)., Results: The AA genotype was significantly more frequent in obese individuals (defined as body mass index >or= 30 kg/m(2), n = 207; 80 males and 127 females) than in non-obese (19.9%vs. 13.7%, P = 0.026). In addition to increased obesity, AA homozygous individuals had higher waist circumference than individuals with AT heterozygous and TT homozygous genotypes. The minor A-allele of rs9939609 was associated with an increased odds ratio (OR) for obesity [OR 1.51, 95% confidence interval (CI) 1.10-2.12] as compared to the TT genotype. This difference was also statistically significant even after the adjustment for sex and age (OR 1.46, 95% CI 1.02-2.07)., Conclusions: Our results support the association of FTO gene variants with obesity, including parameters of visceral (abdominal) obesity, in an adult general population from Spain. Overall we confirm the previously reported association studies between variants in FTO gene and the risk of obesity.

Background: Obesity has emerged as one of the most serious public health concerns in the twenty-first century. the fat mass and obesity associated gene (FTO) has been found to contribute to the risk of obesity in humans. Our aims in this study were to investigate the association of rs9939609 single nucleotide polymorphism (SNP) of the FTO gene with different obesity-related parameters, to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese and its correlations with other adipocytokine gene expressions., Methods: The association between the rs9939609 FTO gene variant and obesity related parameters in 75 obese/morbidly obese adult patients and 180 subjects with body mass index (BMI) < 30 kg/m(2) (control group) was examined. Gene expression analyses: subcutaneous adipose tissue samples were obtained from 52 morbidly obese and five subjects with BMI < 30 kg/m(2). Visceral adipose tissue was also obtained from 35 morbidly obese patients. Weight, height, BMI, SBP, DBP, fasting glucose, lipid profile, proinsulin, insulin, leptin, and adiponectin (RIA) of patients were also obtained. Insulin resistance by HOMA(IR). rs9939609 of FTO genotyping using allele discrimination in real-time PCR. Genomic study of RNA extraction of adipose tissue and real-time PCR (RT-PCR) of adipocytokines and a housekeeping gene were quantified using TaqMan probes. Relative quantification was calculated using the DeltaDelta Ct formula., Results: The minor-(A) allele frequency of rs9939609 FTO gene in the whole population was 0.39. A strong association between this A allele and obesity was found, even after age-sex adjustment (p = 0.013). We found higher levels of FTO mRNA in subcutaneous adipose tissue from morbidly obese than in the control group (p = 0.021). FTO gene expression was lower in visceral than in subcutaneous adipose depot. However, this finding did not reach the level of statistical significance. A negative correlation between subcutaneous FTO gene expression and serum triglyceride levels and a positive correlation with leptin, perilipin, and visfatin gene expressions was found. In the visceral adipose tissue, these positive correlations were statistically significant only for perilipin., Conclusions: Our results show: (1) A strong association between rs9939609 SNP of the FTO gene variant and obesity in Spanish morbidly obese adult patients; (2) positive correlations between FTO mRNA and leptin, perilipin, and visfatin gene expressions in subcutaneous adipose tissue; (3) FTO and perilipin gene expressions were positively correlated in visceral fat depot. Overall these results may suggest a role of FTO in the regulation of lipolysis as well as in total body fat rather in fat distribution patterns.

Aims/hypothesis: The gene encoding transcription factor 7-like 2 (TCF7L2) has been related to type 2 diabetes in multiple ethnic groups. Here, we investigate whether three single nucleotide polymorphisms (SNPs) in the TCF7L2 gene are associated with an impaired proinsulin:insulin ratio., Methods: In this study we examined the associations between SNPs rs7901695, rs7903146 and rs12255372 in the TCF7L2 gene and metabolic variables affecting type 2 diabetes in a population-based study of 706 unrelated individuals (47% men and 53% women; aged 35-74 years) from the province of Segovia in central Spain (Castille), including 180 individuals with type 2 diabetes., Results: The minor allele frequency of rs7901695, rs7903146 and rs12255372 was significantly higher in diabetic patients compared with that in non-diabetic individuals. The T (minor) allele of the variant rs7903146 was significantly associated with a greater OR for type 2 diabetes adjusted for age, sex and BMI in logistic regression analysis: OR 1.29 (95% CI 1.06-1.57, p = 0.01). This risk allele was also associated with an increased proinsulin:insulin ratio after OGTT. Similar results were obtained for the other TCF7L2 SNPs., Conclusions/interpretation: Our results provide further evidence supporting the belief that the TCF7L2 gene is a major determinant of type 2 diabetes risk in Spain, as in other southern European populations. The association with increased proinsulin:insulin ratio after an OGTT suggests that TCF7L2 might be involved in insulin synthesis and processing.

Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10) has been associated with type 2 diabetes (T2DM), a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS) in T2DM and in polycystic ovary syndrome (PCOS). In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF) diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

Context: Obesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed., Objective: To investigate the possibility of the existence of a crosstalk between the CALPAIN 10 homologue CALPAIN 5 and nuclear receptors of the peroxisome proliferator-activated receptors family., Design: Cross-sectional, genetic association study and gene-gene interaction analysis., Subjects: The study sample comprise 1953 individuals, 725 obese (defined as body mass index > or = 30) and 1228 non obese subjects., Results: In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04-1.97], p = 0.027). In addition, we have found a significant interaction between CAPN5 and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%., Conclusion: Our results suggest that CAPN5 and PPARD gene products may also interact in vivo.