Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

HDLs, diabetes, and metabolic syndrome.

The prevalence of type 2 diabetes mellitus and of the metabolic syndrome is rising worldwide and reaching epidemic proportions. These pathologies are associated with significant morbidity and mortality, in particular with an excess of cardiovascular deaths. Type 2 diabetes mellitus and the cluster of pathologies including insulin resistance, central obesity, high blood pressure, and hypertriglyceridemia that constitute the metabolic syndrome are associated with low levels of HDL cholesterol and the presence of dysfunctional HDLs. We here review the epidemiological evidence and the potential underlying mechanisms of this association. We first discuss the well-established association of type 2 diabetes mellitus and insulin resistance with alterations of lipid metabolism and how these alterations may lead to low levels of HDL cholesterol and the occurrence of dysfunctional HDLs. We then present and discuss the evidence showing that HDL modulates insulin sensitivity, insulin-independent glucose uptake, insulin secretion, and beta cell survival. A dysfunction in these actions could play a direct role in the pathogenesis of type 2 diabetes mellitus.

Screening premorbid metabolic syndrome in community pharmacies: a cross-sectional descriptive study

Background: Premorbid metabolic syndrome (pre-MetS) is a cluster of cardiometabolic risk factors characterised by central obesity, elevated fasting glucose, atherogenic dyslipidaemia and hypertension without established cardiovascular disease or diabetes. Community pharmacies are in an excellent position to develop screening programmes because of their direct contact with the population. The main aim of the study was to determine the prevalence of pre-MetS in people who visited community pharmacies for measurement of any of its five risk factors to detect the presence of other risk factors. The secondary aims were to study the presence of other cardiovascular risk factors and determine patients" cardiovascular risk. Methods: Cross-sectional, descriptive, multicentre study. Patients meeting selection criteria aged between 18 and 65 years who visited participating community pharmacies to check any of five pre-MetS diagnostic factors were included. The study involved 23 community pharmacies in Catalonia (Spain). Detection criteria for pre-MetS were based on the WHO proposal following IDF and AHA/NHBI consensus. Cardiovascular risk (CVR) was calculated by Regicor and Score methods. Other variables studied were smoking habit, physical activity, body mass index (BMI), and pharmacological treatment of dyslipidemia and hypertension. The data were collected and analysed with the SPSS programme. Comparisons of variables were carried out using the Student"s T-test, Chi-Squared test or ANOVA test. Level of significance was 5% (0.05). Results: The overall prevalence of pre-MetS was 21.9% [95% CI 18.7-25.2]. It was more prevalent in men, 25.5% [95% CI 22.1-28.9], than in women, 18.6% [95% CI 15.5-21.7], and distribution increased with age. The most common risk factors were high blood pressure and abdominal obesity. About 70% of people with pre-MetS were sedentary and over 85% had a BMI ≥25 Kg/m2 . Some 22.4% had two metabolic criteria and 27.2% of patients with pre-MetS had no previous diagnosis. Conclusions: The prevalence of pre-MetS in our study (21.9%) was similar to that found in other studies carried out in Primary Care in Spain. The results of this study confirm emergent cardiometabolic risk factors such as hypertension, obesity and physical inactivity. Our study highlights the strategic role of the community pharmacy in the detection of pre-MetS in the apparently healthy population.

Metabolic syndrome in young adults – prevalence, childhood predictors and association with subclinical atherosclerosis

Background: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including central obesity, insulin resistance, impaired glucose tolerance, hypertension and dyslipidemia. The prevalence of MetS is increasing worldwide in all age groups. MetS is associated with increased risk of cardiovascular disease and type 2 diabetes mellitus. Aims: The aim of the present study was to investigate the prevalence, secular trends and childhood predictors of MetS in young adults. Furthermore, the relations between MetS and subclinical atherosclerosis were studied and whether apolipoproteins (apo) B and A-I, C-reactive protein (CRP) and type II secretory phospholipase A2 (sPLA2) were associated with MetS, and to what extent the atherogenicity of MetS was explained by these factors. Participants and Methods: The present thesis is part of the large scale population-based, prospective study, the Cardiovascular Risk in Young Finns Study. The first cross-sectional study was conducted in 1980 and included 3,596 participants aged 3-18 years. Carotid and brachial ultrasound studies were performed for 2,283 of these participants in 2001 and 2,200 of these participants in 2007. Results: The overall prevalence of MetS in young adults aged 24-39 years in 2001 was 10-15 % and 6 years later in 30-45 year-old adults it was 15-23 % depending on the MetS definition used. Between the years 1986 and 2001, MetS prevalence increased from 1.0 % to 7.5 % (p<0.0001) in 24-year-old participants that was mostly driven by the increased central obesity. Participants with MetS had increased carotid intima-media thickness (cIMT) and decreased carotid elasticity compared to those without the syndrome. Impaired brachial flow-mediated dilatation (FMD) was not related to MetS but it modified the relationship between MetS and cIMT (P for interaction 0.023). High levels of apoB, CRP, sPLA2 and low levels of apoA-I associated with MetS in young adults. In prospective analysis both MetS and high apoB predicted (P<0.0001) incident high cIMT, defined as cIMT>90th percentile and/or plaque. The association between MetS and incident high cIMT was attenuated by ~40 % after adjustment with apoB. Conclusions: MetS is common in young adults and increases with age. Screening for risk factors, especially obesity, at an early life stage could help identify children and adolescents at increased risk of developing MetS and cardiovascular disease later in life. MetS identifies a population of young adults with evidence of increased subclinical atherosclerosis. Impaired brachial endothelial response is not a hallmark of MetS in young adults, but the status of endothelial function modifies the association between metabolic risk factors and atherosclerosis. In addition, the atherogenicity of MetS in this population assessed by incident high cIMT appears to be substantially mediated by elevated apoB.

Glutamic acid decarboxylase antibodies are indicators of the course, but not of the onset, of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities Study

To efficiently examine the association of glutamic acid decarboxylase antibody (GADA) positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65) were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (³1 U/mL) was 7.3%. Baseline risk factors, with the exception of smoking and interleukin-6 (P £ 0.02), were generally similar between GADA-positive and -negative individuals. GADA positivity did not predict incident diabetes in multiply adjusted (HR = 1.04; 95%CI = 0.55, 1.96) proportional hazard analyses. However, a small non-significant adjusted risk (HR = 1.29; 95%CI = 0.58, 2.88) was seen for those in the highest tertile (³2.38 U/mL) of positivity. GADA-positive and GADA-negative non-diabetic individuals had similar risk profiles for diabetes, with central obesity and elevated inflammation markers, aside from glucose, being the main predictors. Among diabetes cases at study's end, progression to insulin treatment increased monotonically as a function of baseline GADA level. Overall, being GADA positive increased risk of progression to insulin use almost 10 times (HR = 9.9; 95%CI = 3.4, 28.5). In conclusion, in initially non-diabetic middle-aged adults, GADA positivity did not increase diabetes risk, and the overall baseline profile of risk factors was similar for positive and negative individuals. Among middle-aged adults, with the possible exception of those with the highest GADA levels, autoimmune pathophysiology reflected by GADA may become clinically relevant only after diabetes onset.

Association between diet quality and metabolic syndrome in overweight and obese postmenopausal women

Résumé Objectifs : Le syndrome métabolique (MetS) est un ensemble de composantes (obésité, résistance à l'insuline, intolérance au glucose, dyslipidémie, hypertension) qui sont associées à une augmentation du risque de diabète de type 2 et de maladies cardiovasculaires. Aux États-Unis, la fréquence du MetS atteint des proportions épidémiques avec une prévalence de 25% de la population. Les études nutritionnelles traditionnelles se sont concentrées sur l’effet d’un nutriment alors que les études plus récentes ont déterminé l’effet global de la qualité alimentaire sur les facteurs de risque. Cependant, peu d'études ont examiné la relation entre la qualité alimentaire et le MetS. Objectif: Déterminer l'association entre la qualité alimentaire et le MetS et ses composantes. Méthodes: La présence du MetS a été déterminée chez 88 femmes post-ménopausées en surpoids ou obèses, selon la définition du National Cholesterol Education Program Adult treatment Panel III alors que la qualité alimentaire a été évaluée selon le Healthy Eating Index (HEI). La sensibilité à l’insuline, la composition corporelle et le métabolisme énergétique ont été mesurés. Résultats: Le HEI corrélait négativement avec la plupart des mesures de masse grasse et du poids mais pas avec la sensibilité à l'insuline, l’hypertension et la plupart des marqueurs lipidiques. Cependant, l’HEI corrélait positivement avec LDL-C/ApoB et négativement avec le métabolisme énergétique. Conclusion: Les résultats démontrent que l’HEI est associé avec les mesures de gras corporel et la grosseur des LDL. Mots clés: Obésité, qualité alimentaire, métabolisme lipidique, syndrome métabolique.

Risque cardiométabolique et habitudes de vie des adultes atteints de diabète de type 1

Les patients atteints de diabète de type 1 (DbT1) présentent un risque accru de maladies cardiovasculaires. De plus, sous l’influence sociétale et iatrogénique, leur profil de risque cardiométabolique a défavorablement évolué au cours des dernières décennies. Cette population aurait aussi davantage de barrières à l’adoption d’un mode de vie sain. L’objectif de ce mémoire visait à explorer le mode de vie des adultes DbT1 et sa relation avec les facteurs de risque cardiométabolique. Une étude transversale observationnelle menée auprès de 124 adultes DbT1 a permis d’obtenir une caractérisation de leur profil cardiométabolique et de leurs habitudes de vie. Les résultats démontrent que la majorité des adultes atteints de DbT1 n'adoptent pas les saines habitudes de vie recommandées (bonne qualité alimentaire, pratique régulière d’activité physique, non fumeur) et que ceux-ci présentent un profil cardiométabolique altéré comparativement aux adultes DbT1 qui les adoptent. De plus, il y aurait une relation proportionnelle entre l’adoption d’un plus grand nombre de saines habitudes de vie et l’amélioration du profil cardiométabolique. Des études d’interventions ciblant les patients DbT1 et visant à améliorer ces trois grandes composantes des habitudes de vie sont nécessaires.

Valores del índice cintura/cadera en población escolar de Bogotá, Colombia: Estudio

Objetivo: Determinar los valores del índice cintura/cadera (ICC) en una población escolar de Bogotá, Colombia, pertenecientes al estudio FUPRECOL. Métodos: Estudio descriptivo y transversal, realizado en 3.005 niños y 2.916 adolescentes de entre 9 y 17,9 años de edad, pertenecientes a 24 instituciones educativas oficiales de Bogotá, Colombia. Se tomaron medidas de peso, talla, circunferencia de cintura, circunferencia de cadera. El estado de maduración sexual se recogió por auto-reporte. Se calcularon los percentiles (P3, P10, P25, P50, P75, P90 y P97) según sexo y edad y se realizó una comparación entre los valores del ICC observados con estándares internacionales. Resultados: De la población general (n=5.921), el 57,0% eran mujeres (promedio de edad 12,7 ± 2,3 años). En todas las edades el ICC fue mayor en los varones que en las mujeres, observándose un descenso en la media de los valores obtenidos desde los 9 hasta los 17,9 años. En varones, los valores del ICC mayores del P90 (asociados a riesgo cardiovascular) estuvieron en el rango 0,87 y 0,93 y en las mujeres entre 0,85 y 0,89. Al comparar los resultados de este estudio, por grupos de edad y sexo, con trabajos internacionales de niños y adolescentes de Europa, Suramérica, Asia y África, se observa que los valores del ICC fueron menores en este estudio en ambos sexos, con excepción de los escolares originarios de Grecia y Venezuela. Conclusiones: Se presentan percentiles del ICC según edad y sexo que podrán ser usados de referencia en la evaluación del estado nutricional y en la predicción del riesgo cardiovascular desde edades tempranas en población de Bogotá, Colombia.

Dietary PUFA and the metabolic syndrome in Indian Asians living in the UK

Indian Asians living in the UK have a 50% higher CHD mortality rate compared with the indigenous Caucasian population, which cannot be attributed to traditional risk factors. Instead, features of the metabolic syndrome, including raised plasma triacylglycerol, reduced HDL-cholesterol (HDL-C) and an increased proportion of small dense LDL particles, together with insulin resistance and central obesity, are prevalent among this population. The present review examines evidence to support the hypothesis that an imbalance in dietary PUFA intake, specifically a higher intake of n-6 PUFA in combination with a lower intake of the long-chain (LC) n-3 PUFA, plays an important role in the prevalence of the metabolic syndrome observed in Indian Asians. Data are presented to illustrate the impact of manipulation of the background n-6 PUFA intake (moderate or high n-6 PUFA) and the subsequent response to supplementation with LC n-3 PUFA on blood lipids and insulin action in a group of Indian Asian volunteers. The results demonstrate that supplementation with LC n-3 PUFA had no impact on insulin action in those subjects consuming either the moderate-or high-n-6 PUFA diet. In the postprandial phase reductions in plasma triacylglycerol concentrations were greater in those consuming the high-n-6 PUFA background diet subsequent to fish oil supplementation. The present study concludes that, contrary to the central hypothesis, the prevalence of metabolic abnormalities in Indian Asians compared with Caucasians may not be attributable to differences in intakes of n-6 and n-3 PUFA.

High density lipoprotein: guardian of the vascular system?

The role of low-density lipoprotein in the development of coronary heart disease (CHD) is well recognised. There is also growing evidence that high-density lipoprotein cholesterol (HDL-C) is a powerful inverse predictor for premature CHD and that maintaining a high HDL-C level may guard against atherosclerosis. Patients with low HDL-C levels often also have central obesity, insulin resistance and other features of the metabolic syndrome. This syndrome is both increasingly common and strongly implicated in the growing worldwide epidemic of type 2 diabetes. HDL-C may be increased by lifestyle changes, e.g. weight loss, physical activity and smoking cessation. Pharmacological agents such as fibrates, niacin and statins have also been shown significantly to elevate HDL-C. Although current guidelines are beginning to recognise the protective role of HDL-C level in preventing coronary events, HDL-C should be adopted soon as a target for intervention in its own right.

Effects of a ferment soy product on the adipocyte area reduction and dyslipidemia control in hypercholesterolemic adult male rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da cinemática do complexo tóracoabdominal durante repouso e endurance muscular respiratória em obesos

Background: Obesity may affect the respiratory system, causing changes in respiratory function and in the pulmonary volumes and flows. Objectives: To evaluate the influence of obesity in the movement of thoracoabdominal complex at rest and during maximal voluntary ventilation (MVV), and the contribution between the different compartments of this complex and the volume changes of chest wall between obese and non-obese patients. Materials and Methods: We studied 16 patients divided into two groups: the obese group (n = 8) and group non-obese (n = 8). The two groups were homogeneous in terms of spirometric characteristics (FVC mean: 4.97 ± 0.6 L - 92.91 ± 10.17% predicted, and 4.52 ± 0.6 L - 93.59 ± 8.05%), age 25.6 ± 5.0 and 26.8 ± 4.9 years, in non-obese and obese respectively. BMI was 24.93 ± 3.0 and 39.18 ± 4.3 kg/m2 in the groups investigated. All subjects performed breathing calm and slow and maneuver MVV, during registration for optoelectronic plethysmography. Statistical analysis: we used the unpaired t test and Mann-Whitney. Results: Obese individuals had a lower percentage contribution of the rib cage abdominal (RCa) during breathing at rest and VVM. The variation of end expiratory (EELV) and end inspiratory (EILV) lung volumes were lower in obese subjects. It has been found asynchrony and higher distortion between compartments of thoracoabdominal complex in obese subjects when compared to non-obese. Conclusions: Central obesity impairs the ventilation lung, reducing to adaptation efforts and increasing the ventilatory work

Accuracy of sagittal abdominal diameter as predictor of abdominal fat among Brazilian adults: a comparation with waist circumference

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Circunferências medidas em diferentes locais do tronco e fatores de risco cardiometabólico

Os objetivos deste estudo foram comparar medidas de circunferências da cintura e abdominal e analisar suas relações com fatores de risco cardiometabólico em servidores de uma universidade da Bahia. Para tanto, cinquenta e cinco homens e setenta e uma mulheres (36,4 ± 11,2 anos) foram submetidos à avaliação antropométrica bem como medidas das pressões arteriais sistólica e diastólica, glicemia, triglicerídeos, colesterol total e frações HDL e LDL. Apesar das fortes correlações (P < 0.01) entre as diferentes medidas (r > 0,93), a circunferência da cintura foi significativamente menor que a circunferência abdominal em ambos os sexos, sendo a diferença média entre locais maior em mulheres (8,6 ± 4,1 vs 3,8 ± 4,2 cm; P < 0,01). A circunferência da cintura foi significativamente relacionada a dois e quatro fatores de risco em homens e mulheres, respectivamente. Por outro lado, a circunferência abdominal foi significativamente relacionada a um fator em homens e cinco em mulheres. Não foram observadas diferenças significativas (P > 0,05) entre coeficientes de correlação nos casos em que ambas as circunferências se relacionaram significativamente a um fator de risco. Esses resultados sugerem que o local de mensuração tem influência substancial sobre a circunferência tomada na região inferior do tronco, particularmente, em mulheres, porém, não evidenciam clara superioridade de uma das medidas quanto às relações com fatores de risco cardiometabólico tradicionais em amostra brasileira. Estudos devem ser conduzidos, buscando comparar a capacidade preditiva de diferentes medidas de circunferência para o desenvolvimento de fatores de risco e doenças cardiovasculares em diferentes populações.

Síndrome metabólica em mulheres na pós-menopausa tratadas de câncer de mama

PURPOSE: To assess the occurrence of metabolic syndrome (MetS) in postmenopausal breast cancer survivors. METHODS: A total of 158 breast cancer survivors were included in this cross-sectional study. Eligibility criteria were: women with amenorrhea >12 months and age ≥45 years, treated for breast cancer and no metastasis for at least five years. Clinical history and anthropometric indicator data (body mass index (BMI), and waist circumference, (WC) were collected. Biochemical parameters, including total cholesterol, HDL, LDL, triglycerides (TG), glucose and C-reactive protein (CRP), were measured. MetS was diagnosed as the presence of at least three of the following diagnostic criteria: WC>88 cm, blood pressure≥130/85 mmHg, triglycerides≥150 mg/dl, HDL <50 mg/dL,and glucose≥100 mg/dL. The Student's t-test and χ 2 test were used for statistical analysis. RESULTS: The mean age of breast cancer survivors was 63.1±8.6 years, with a mean follow-up of 9.1±4.0 years. MetS was diagnosed in 48.1% (76/158) and the most prevalent diagnostic criterion was abdominal obesity (WC>88 cm), affecting 54.4% (86/158) of the women. The patients without MetS had a longer follow-up compared those with MetS (p<0.05). Regarding the current BMI, PN average, those without MetS were overweight, and those with MetS were obese (p<0.05). Among the latter, comparison of BMI at the time of cancer diagnosis and current BMI (27.8±5.4 versus 33.4±5.4 kg/m2) showed a significant weight gain (p<0.05). Mean CRP values were higher in women with MetS (p<0.05). In the comparison of tumor characteristics and cancer treatments there was no difference between groups (p>0.05). CONCLUSION: Postmenopausal breast cancer survivors had a higher risk of developing metabolic syndrome and central obesity.