A Body Shape Index (ABSI) and Hip Index (HI) Adjust Waist and Hip Circumferences for Body Mass Index, But Only ABSI Predicts High Cardiovascular Risk in the Spanish Caucasian Population.

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.

Body fat anthropometric indexes: Which of those identify better high cardiovascular risk subjects? A comparative study in Spanish population.

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.

Prevalence, Treatment, and Associated Factors of Hypertension in Spain: A Comparative Study between Populations.

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).

La pandemia de obesidad. Los vínculos fisiopatológicos: disfunción endócrina de la célula adiposa, inflamación y resistencia a la insulina / The obesity pandemic. The pathophysiological links: endocrine adipose cell dysfunction, inflammation and insulin resistance

La obesidad se define como un exceso de masa de tejido adiposo blanco como resultado de un desequilibrio energético. Las últimas décadas han favorecido tal desequilibrio energético debido a que la ingesta de energía excede al gasto de energía. La epidemia mundial de obesidad se ha convertido en un importante problema de salud, que contribuye a una mayor mortalidad debido a un mayor riesgo de enfermedades: cardiovasculares, diabetes mellitus tipo 2, y algunos tipos de cáncer. En nuestro trabajo hemos discutido los mecanismos ya establecidos a nivel sistémico, celular y molecular después de que la ‘expansión’ del tejido adiposo blanco exporte concentraciones elevadas de ácidos grasos libres causantes de lipotoxicidad a órganos específicos (p.ej.: músculo estriado, hígado). La resistencia a la insulina es la principal consecuencia fisiopatológica y mediadora de las características del estado lipotóxico. Otras alteraciones celulares incluyen la generación excesiva de radicales libres de oxígeno y por tanto la oxidación de las proteínas clave, así como la disfunción mitocondrial. La expansión del tejido adiposo blanco obeso estimula pronto el desarrollo de inflamación a través de una mayor actividad de los macrófagos situados en la célula adiposa y de otras fuentes, con liberación excesiva a la sangre (plasma / suero) de múltiples citocinas pro-inflamatorias (p.ej.: TNF, IL-6). Así se establece un estado de inflamación crónico y subclínico en la patogénesis de la obesidad. Estas nuevas vías de investigación todavía exigen más investigación, incluyendo la posibilidad de descubrir nuevos fármacos para el tratamiento de los pacientes obesos y el diseño de estrategias más eficaces de prevención de Obesidad, Diabetes Mellitus tipo 2 y otras de sus comorbilidades (AU)

Obesity is defined as an excessive of adipose tissue mass as a result of an energy imbalance. During the last decades have favoured the energy imbalance causing the energy intake exceeds energy expenditure. The worldwide obesity epidemic has become a major health concern, because it contributes to higher mortality due to an increased risk for diseases including cardiovascular diseases, type 2 diabetes mellitus, muscle skeletal disorders and some cancers. The lack of a complete understanding of the precise regulatory networks that control adipogenesis, energy expenditure, and inflammation is a fundamental problem in metabolic research. In our paper we discussed the already established systemic, cellular and molecular mechanisms following the expandability of the white adipose tissue exporting high levels concentrations of free fatty acids causing lipotoxicity in specific organs (e.g.: striated muscle, liver). Insulin resistance is, likely, the main physiopathological consequence and mediator of all features defining the ‘lipotoxic’ state. Also many other cellular alterations including the excessive generation of free radical and hence oxidation of key proteins as well as mitochondrial dysfunction are major alterations. Similarly expandability of the obese white adipose tissue stimulate early in this process. Stimulate the activity of inflammation through the enhanced activity of macrophages from inside the adipose cell and from other sources hence excessive liberation to the blood (plasma / serum) of multiple species of proinflammatory cytokines (e.g.: TNFα, IL6). Overall it ends up by establishing a chronic non-clinically overt inflammation (or para-inflammation) at the cores of obesity pathogenesis. These new avenues of research still demand more research including then possibility of discovering new pharmacological approaches for the treatment of the obese patients (AU)

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

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.

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

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.

Prevalencia, diagnóstico, tratamiento y control de la hipertensión arterial en España. Resultados del estudio Di@bet.es / Prevalence, diagnosis, treatment, and control of hypertension in Spain. Results of the Di@bet.es Study

Introducción y objetivos: El Di@bet.es es un estudio nacional diseñado con el objetivo de estimar la prevalencia de diabetes mellitus y otros factores de riesgo cardiovascular en la población adulta española. Se presenta la prevalencia de hipertensión arterial y en qué grado se reconoce, se trata y se controla. Métodos: Se incluye una muestra de la población española con 5.048 adultos de edad ≥ 18 años. Se realizó un interrogatorio clínico y una exploración que incluyó 3 lecturas de presión arterial en reposo y sedestación para calcular la media de las 3 lecturas. Se definió hipertensión como presión arterial sistólica ≥ 140 mmHg y/o presión arterial diastólica ≥ 90 mmHg y/o en tratamiento farmacológico antihipertensivo. Resultados: El 42,6% de la población adulta española de edad ≥ 18 años es hipertensa, más los varones (49,9%) que las mujeres (37,1%). La prevalencia fue superior entre los prediabéticos (67,9%) y diabéticos (79,4%). El 37,4% de los hipertensos están sin diagnosticar, más los varones (43,3%) que las mujeres (31,5%). Toman tratamiento farmacológico el 88,3% de los hipertensos conocidos y solo el 30% tiene la presión arterial controlada, más las mujeres (24,9%) que los varones (16%). Conclusiones: La prevalencia de hipertensión en España es alta y un importante porcentaje de pacientes hipertensos aún están sin diagnosticar. La hipertensión se asoció con diabetes y prediabetes, y aunque el tratamiento farmacológico es cada vez más frecuente, no logra mejorar el grado de control, que continúa siendo bajo. Es importante desarrollar y promocionar campañas poblacionales de prevención, detección y tratamiento de la hipertensión arterial (AU)

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 (AU)

Obesity and Cardiovascular Risk: Variations in Visfatin Gene Can Modify the Obesity Associated Cardiovascular Risk. Results from the Segovia Population Based-Study. Spain.

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.

Metabolic syndrome, glucose tolerance categories and the cardiovascular risk in Spanish population.

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.

Prevalence, Diagnosis, Treatment, and Control of Hypertension in Spain. Results of the Di@bet.es Study.

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.

Profile of individuals who are metabolically healthy obese using different definition criteria. A population-based analysis in the Spanish population.

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.

Variable patterns of obesity and cardiometabolic phenotypes and their association with lifestyle factors in the Di@bet.es study.

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.

Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers.

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.

Metabolic syndrome, adiponectin, and cardiovascular risk in Spain (the Segovia study): impact of consensus societies criteria.

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.

Functional characterization of TLR4 +3725 G/C polymorphism and association with protection against overweight.

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.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and ß-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Common variants of the liver fatty acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in 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.

Revised waist circumference cut-off points for the criteria of abdominal obesity in the Spanish population: Multicenter nationwide Spanish population based study / Revisión de los puntos de corte de la circunferencia de la cintura como criterio de obesidad abdominal en la población española: estudio nacional multicéntrico

Aims To investigate the optimal waist circumference (WC) cut-off points in the general Spanish-population and its relationships with insulin resistance (IR) and metabolic syndrome (MS) due to the disparity of values WC in the different regional areas. Methods A multicenter nationwide Spanish population based study on 3844 unrelated subjects, aged 35–74 years. Receiver operating characteristic (ROC) curve was analysed to identify the optimal WC cut-off points for detecting metabolic abnormalities related to the MS. Results The prevalence of MS, International Diabetes Federation (IDF) criteria: 29.1%/33.1% in males/females (P=.004), Adult Treatment Panel III (ATPIII) criteria: 23.5%/30.9% males/females (P<.001). Optimal WC cut-off to obtain the maximal sensitivity and specificity for detecting two or more of the other metabolic abnormalities associated with MS or IR was 94.5/89.5cm in males/females. According to these cut-off points, the prevalence of abdominal-obesity was 57.2%/61.3% in males/females, P=.011 and prevalence of MS was similar in both genders (males/females: 27.9%/28.9%, P=.527). The Spearman correlation coefficient relating WC to HOMA IR was 0.395. IR was similarly prevalent in males/females 24.1%/21.7% (P<.088). Prevalence of IR was 43% in subjects with MS by IDF criteria. Conclusions The new WC cut-off points found in our population were 94.5/89.5cm for males/females. For males, the cut-off points were lower than those defined by ATPIII but similar to IDF criteria. For females these cut-off points were higher than those proposed by ATPIII/IDF criteria (AU)

Objetivos Investigar los puntos de corte óptimos para la circumferencia de la cintura (CC) en la población general española y su relación con resistencia a la insulina (RI) y Síndrome Metabólico (SM), debido a la disparidad de valores de la CC en las diferentes áreas. Métodos Estudio multicéntrico a nivel nacional: se estudiaron 3,844 sujetos no relacionados, de 35-74 años. Se aplicó la curva COR (Curva de rendimiento diagnóstico) para identificar los puntos de corte óptimos para la CC para la detección de anormalidades metabólicas relacionadas con el SM. Resultados La prevalencia de SM, criterio IDF: 29.1%/33.1% varones/mujeres (p= 0.004), criterio ATPIII: 23.5%/30.9% varones/mujeres (p< 0.001). El punto de corte óptimo para la CC con máxima sensibilidad y especificidad para detectar 2 o más anormalidades metabólicas asociadas con SM o RI fue 94.5cm/89.5cm en varones/mujeres. De acuerdo con estos puntos de corte la prevalencia de obesidad-abdominal fue de 57.2%/61.3% en varones/mujeres, p= 0.011 y la prevalencia de SM fue similar en ambos sexos (varones/mujeres: 27.9%/28.9%, p = 0.527). El coeficiente de correlación de Spearman en relación a CC con RI fue 0.395. La prevalencia de RI fue similar en varones/mujeres: 24.1%/21.7% (p < 0.088). La prevalencia de RI en sujetos con SM por criterio IDF fue 43%. Conclusiones Los nuevos puntos de corte para la CC en nuestra población fueron 94.5/89.5cm para vaones/mujeres. Para varones los puntos de corte fueron más bajos que los definidos por criterio ATPIII, pero similar a los propuestos por criterio IDF. Para mujeres los puntos de corte fueron más elevados que los propuestos por criterios ATPIII/IDF (AU)

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired ß-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved ß-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.