Associação entre variantes do gene da adiponectina (ADIPOQ): -11391 G/A, -11377 C/G, 45T>G e I164T e os níveis circulantes de adiponectina de alto peso molecular e fatores de risco cardiometabólico

A adiponectina, um hormônio produzido pelo tecido adiposo, atua na regulação do metabolismo energético e interfere favoravelmente na sensibilidade à insulina através de suas ações no fígado e musculatura esquelética. Ao contrário da maioria das outras adipocitocinas, associa-se inversamente com a obesidade visceral, resistência à insulina, diabetes tipo 2 e doença cardiovascular. Inúmeros estudos demonstraram nos últimos anos os efeitos de variantes genéticas no gene ADIPOQ sobre os níveis circulantes de adiponectina, resistência à insulina, diabetes e obesidade. Entretanto, além de resultados contraditórios, a maior parte desses estudos foi realizada em populações Caucasianas e Asiáticas. Avaliar, em uma população multiétnica adulta do município do Rio de Janeiro, as possíveis associações das variantes genéticas (-11391 G>A, -11377C>G, +45T>G e T517G) no gene ADIPOQ com o fenótipo obeso, níveis circulantes de adiponectina de alto peso molecular e fatores de risco cardiometabólico. Trata-se de um estudo transversal. Foram estudados 100 indivíduos eutróficos (IMC 18,5 24,9 kg/m2, idade: 32,5 + 9,8 anos) e 100 obesos (IMC 30 58,2 kg/m2, idade 37,5 + 14,1 anos), igualmente divididos entre homens e mulheres. Os indivíduos obesos apresentaram valores significativamente maiores de circunferência abdominal, pressão arterial sistólica, diastólica e média, glicemia de jejum, triglicerídeos, LDL-colesterol, leptina, insulina, HOMA-IR e proteína C reativa, quando comparados aos eutróficos. Contrariamente, exibiram menores valores de adiponectina e HDL-colesterol. Análises de correlação mostraram relação inversa e significativa entre a adiponectina, circunferência abdominal, insulina, HOMA-IR e pressão arterial. Com os níveis de HDL-colesterol, a correlação foi positiva. Por meio de análise de regressão múltipla foi possível identificar os determinantes dos níveis séricos de adiponecinta. Sexo masculino, circunferência abdominal, HOMA-IR e a variante genética -11391G>A, foram os principais responsáveis por essa variação, com um R2 de 30%. Quanto à análise genética, não encontramos nenhuma associação entre essas variantes e o fenótipo obeso. Entretanto, os indivíduos carreadores do alelo mutante -11391A apresentaram menores valores de glicemia, pressão arterial e relação cintura-quadril e maiores concentrações sanguíneas de adiponectina, quando comparados aos indivíduos ditos selvagens. Ademais, os carreadores do alelo mutante -11377G apresentaram menores valores de pressão arterial sistólica, diastólica e média. Os resultados do presente estudo demonstram que níveis de adiponectina diferem entre eutróficos e obesos e que concentrações mais baixas dessa adipocitocina estão associadas a um pior perfil cardiometabólico. Variantes no gene ADIPOQ podem interferir nessa relação e alguns polimorfismos parecem ter um perfil protetor no risco cardiovascular.

Níveis circulantes de Grelina, índices de adiposidade e fatores de risco cardiovascular e metabólico relacionados, em população multiétnica do Estado do Rio de Janeiro

O objetivo deste estudo foi analisar o comportamento dos níveis plasmáticos de grelina, em relação aos fatores de risco cardiometabólico, em uma população multiétnica de eutróficos e de obesos..A grelina é um peptídeo produzido predominantemente pelas células oxínticas gástricas, que desempenha importante papel na homeostase energética, promovendo estímulo do apetite e aumento do peso corporal, além de participar do controle do metabolismo lipídico e glicídico, interagindo diretamente com os fatores de risco cardiometabólico. Este é um estudo transversal. Duzentos indivíduos entre 18 e 60 anos com diferentes graus de índice de massa corporal (IMC) compuseram a amostra, assim dividida: cem eutróficos (IMC < 25 kg/m2) e 100 obesos (IMC ≥ 30 kg/m2). Todos foram avaliados para parâmetros antropométricos, determinação da pressão arterial (aferida por método oscilométrico através de monitor automático) e variáveis metabólicas (métodos usuais certificados). A grelina acilada foi mensurada pela técnica de sanduíche ELISA; a leptina, pelo método Milliplex MAP. O marcador inflamatório proteína C reativa ultrassensível(PCRUS)foi estimado por nefelometria ultrassensível. A insulina foi determinada por quimioluminescência e o HOMA-IR calculado pelo produto insulinemia (U/ml) X níveis de glicemia de jejum (mmol/L) / 22.5. Foram excluídos do estudo aqueles com história de comorbidades crônicas, doenças inflamatórias agudas, dependência de drogas e em uso de medicação nos dez dias anteriores à entrada no estudo. As concentrações de grelina acilada mostraram tendência de redução ao longo dos graus de adiposidade (P<0,001); a leptina se comportou de maneira oposta (P<0,001). Os níveis de grelina se correlacionaram negativamente com IMC (r = -.36; P<0,001), circunferência da cintura (CC) (r=-.34; P<0,001), relação cintura/quadril (RCQ) (r=-.22; P=0,001), diâmetro abdominal sagital (DAS) (r=-.28; P<0,001), pressão arterial sistólica (PAS) (r=-.21; P=0,001), insulina (r=-.27; P<0,001), HOMA-IR (r=-.24; P=0,001) e PCRUS (r=-.29; P<0,001); e positivamente com o HDL-colesterol (r=.30; P<0,001).A PCRUS acompanhou o grau de resistência insulínica e os níveis de grelina também mostraram tendência de redução ao longo dos tercis de resistência insulínica (P=0,001). Em modelo de regressão linear múltipla as principais associações independentes da grelina acilada foram sexo feminino (P=0,005) e HDL-colesterol (P=0,008), ambos com associação positiva e IMC (P<0,001) (associação negativa). Esses achados apontam para uma associação da grelina acilada com melhor perfil metabólico, já que seus níveis se correlacionaram positivamente com HDL-colesterol e negativamente com indicadores de resistência insulínica e atividade inflamatória.

Avaliação volumétrica e funcional do músculo glúteo máximo submetido a gluteoplastia de aumento com implantes de silicone

A operação para aumento de glúteos com implantes teve início no fim da década de 1960, entretanto a técnica intramuscular, considerada padrão atualmente, foi descrita cerca de 30 anos depois. Cirurgiões e pacientes apresentam crescente interesse na realização do aumento de glúteos haja vista que sua frequência apresenta aumento nos últimos anos. A utilização de implantes intramusculares que superam o volume do músculo em mais de cinquenta por cento configura uma situação nova que deve ser estudada. O tecido muscular estriado esquelético apresenta grande suscetibilidade para atrofia secundariamente à compressão, e sendo o glúteo máximo um músculo importante na manutenção da postura ereta, deambulação, corrida e salto, é necessário pesquisar possíveis alterações musculares decorrentes da operação. O objetivo deste estudo é avaliar o volume e força do músculo glúteo máximo ao longo de 12 meses após a introdução de implantes intramusculares, o posicionamento destes implantes no interior da musculatura e mudanças antropométricas obtidas com a operação. Foram selecionadas 48 mulheres, 24 candidatas a gluteoplastia de aumento com implantes compuseram o grupo de estudo e 24 candidatas a mamoplastia de aumento compuseram o grupo controle de acordo com os critérios de inclusão e exclusão. As pacientes foram avaliadas em quatro momentos diferentes: pré-operatório e após três, seis e 12 meses da operação. Em todas as etapas foi realizada avaliação clínica nutricional, tomografia computadorizada com reconstrução 3D e teste isocinético. Todas as pacientes permaneceram afastadas de atividades físicas durante três meses após a operação. Foram utilizados implantes glúteos em gel coesivo de base oval e superfície lisa com volumes de 350 cm3 e 400 cm3. O nível de significância estatística foi mantido em 5%. As pacientes candidatas a gluteoplastia apresentaram valores da relação entre as medidas da cintura e do quadril maiores que aquelas do grupo controle. A operação de aumento glúteo com implantes demonstrou eficácia na melhora desta relação. Os implantes apresentaram posição obliqua com inclinação semelhante à das fibras musculares após três meses da operação, independente da posição em que foram inseridos. As pacientes do grupo de estudo apresentaram atrofia muscular após 12 meses em 6,14% à esquerda e 6,43% à direita, as pacientes do grupo controle não apresentaram atrofia. A força muscular apresentou redução do valor de torque máximo durante a flexão do quadril a 30 /s em ambos os grupos e aumento do torque máximo durante a adução a 60 /s apenas no grupo de estudo. Concluímos que a introdução de implante de silicone no interior do músculo glúteo máximo causa atrofia muscular após 12 meses. As variações na força deste músculo nesse período não podem ser atribuídas primariamente à operação ou à presença dos implantes em seu interior. Os implantes permaneceram em posição obliqua. O aumento de glúteos com implantes gera mudanças antropométricas nas mulheres submetidas a esta operação.

Avaliação do efeito do chá verde sobre a pressão arterial, função endotelial, perfil metabólico, atividade inflamatória e adiposidade corporal em mulheres pré-hipertensas obesas

As doenças cardiovasculares são a principal causa de morte nos países ocidentais. Alguns estudos sugerem que o chá verde tem efeito benéfico sobre diferentes fatores de risco cardiovascular. No entanto, outros estudos não mostraram essa associação. Objetiva avaliar em mulheres pré-hipertensas obesas o efeito do consumo de chá verde sobre: a pressão arterial, a função endotelial, o perfil metabólico, a atividade inflamatória e a adiposidade corporal. Estudos clínico, randomizado, cruzado, duplo-cego e placebo-controlado. Durante 4 semanas as mulheres foram orientadas a ingerir 3 cápsulas de extrato de chá verde por dia (500mg extrato chá verde/cápsula) passando por 2 semanas de washout e posteriormente ingeriam por mais 4 semanas o placebo. As mulheres que iniciaram o estudo tomando placebo posteriormente utilizaram o chá verde. Ou seja, todas as pacientes receberam chá verde e placebo por um mesmo período. No início e final de cada tratamento foram analisadas as variáveis. Foram avaliadas 20 mulheres pré-hipertensas, obesidade grau I e II, idade entre 25 e 59 anos. O local do estudo foi o Laboratório da Disciplina de Fisiopatologia Clínica e Experimental Clinex. Universidade do Estado do Rio de Janeiro. As variáveis estudadas foram a pressão arterial, índice de hipertemia reativa (avaliada com Endo-PAT2000), proteína C reativa, interleucina-6, fator de necrose tumoral-α, molécula de adesão intercelular e molécula de adesão vascular celular, inibidor de ativador do plasminogênio, fator de crescimento endotelial vascular, E-selectina, adiponectina, colesterol total, LDL-colesterol, HDL-colesterol, triglicérides, glicemia, insulina, HOMA, índice de massa corporal, circunferência de cintura, circunferência de quadril, relação cintura quadril e percentual de gordura corporal. Como resultados, na avaliação da pressão arterial pela monitorização ambulatorial da pressão arterial, observou-se redução significativa da pressão arterial sistólica de 24 horas (pré 130,31,7 mmHg vs. pós 127,02,0 mmHg; p= 0,02), pressão arterial sistólica diurna (pré 134,01,7 mmHg vs. pós 130,72,0 mmHg; p= 0,04) e pressão arterial sistólica noturna (pré 122,21,8 mmHg vs. pós 118,42,2 mmHg; p= 0,02), após o consumo do chá verde, em comparação ao uso do placebo. Após o consumo do chá verde foi observado aumento, embora estatisticamente não significativo, no índice de hiperemia reativa (pré 1,980,10 vs. pós 2,220,14), além de redução expressiva na concentração da molécula de adesão intercelular (pré 91,88,0 ng/ml vs. pós 85,85,6 ng/ml) e do fator de crescimento endotelial vascular (pré 195,846,2 pg/ml vs. pós 158,638,7 pg/ml), porém sem significância estatística. As demais variáveis avaliadas não se modificaram de forma significativa após o consumo do chá verde, em comparação ao placebo. Foi observada forte correlação entre redução de pressão arterial sistólica e diastólica de 24hs, avaliada pela monitorização ambulatorial da pressão arterial, e o aumento do índice de hipertemia reativa (r= -0,47; r= -0,50, respectivamente). Os resultados do presente estudo sugerem que o chá verde tem efeito benéfico sobre a pressão arterial e possivelmente sobre a função endotelial.

Longitudinal study of changes in body mass index, anthropometric measures, dietary intake and physical activity in cohorts of school-going Irish adolescents

The prevalence of obesity worldwide has increased dramatically over the last few decades. Poor dietary habits and low levels of exercise in adolescence are often maintained into adulthood where they can impact on the incidence of obesity and chronic diseases. A 3-year longitudinal study of anthropometric, dietary and exercise parameters was carried out annually (2005 - 2007) in 3 Irish secondary schools. Anthropometric measurements were taken in each year and analysed longitudinally. Overweight and obesity were at relatively low levels in these adolescents. Height, weight, BMI, waist and hip circumferences and TST increased significantly over the 3 years. Waist-to-hip ratio (WHR) decreased significantly over time. Boys were significantly taller than girls across the 3 years. A 3-day weighed food diary was used to assess food intake by the adolescents. Analysis of dietary intake data was determined using WISP©. Mean daily energy and nutrient intakes were reported. Mean daily energy and macronutrient intakes were analysed longitudinally. The adolescents’ diet was characterised by relatively high saturated fat intakes and insufficient fruit and vegetable consumption. The dietary pattern did not change significantly over the 3 years. Boys consumed more energy than girls over the study period. A validated questionnaire was used to assess physical activity and sedentary activity levels. Boys were substantially more active and had higher energy expenditure estimates than girls throughout the study. A significant longitudinal decrease in physical activity levels among the adolescents was observed. Both genders spent more than the recommended amount of time (hrs/day) pursing sedentary activities. The dietary pattern in these Irish adolescents is relatively poor. Of additional concern is the overall longitudinal decrease in physical activity levels. Promoting consumption of a balanced diet and increased exercise levels among adolescents will help to reduce future public health care costs due to weight-related diseases.

A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study

Objective: The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma.

Design: Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIHeAARP cohort.

Results: 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric
cardia adenocarcinoma risk (highest ($35 kg/m2) vs referent (18.5e<25 kg/m2); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5e<25 kg/m2). Mutual adjustment of WHR and BMI attenuated
both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia.

Conclusion Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI

Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes patients

Aim: To determine if serum pigment epithelium-derived factor (PEDF) levels in Type 2 diabetes are related to vascular risk factors and renal function. Methods: PEDF was quantified by ELISA in a cross-sectional study of 857 male Veterans Affairs Diabetes Trial (VADT) subjects, and associations with cardiovascular risk factors and renal function were determined. In a subset (n = 246) in whom serum was obtained early in the VADT (2.0 ± 0.3 years post-randomization), PEDF was related to longitudinal changes in renal function over 3.1 years. Results: Cross-sectional study: In multivariate regression models, PEDF was positively associated with serum triglycerides, waist-to-hip ratio, serum creatinine, use of ACE inhibitors or angiotensin receptor blockers, and use of lipid-lowering agents; it was negatively associated with HDL-C (all p < 0.05). Longitudinal study: PEDF was not associated with changes in renal function over 3.1 years (p > 0.09). Conclusions: Serum PEDF in Type 2 diabetic men was cross-sectionally associated with dyslipidemia, body habitus, use of common drugs for blood pressure and dyslipidemia, and indices of renal function; however, PEDF was not associated with renal decline over 3.1 years.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

A Prospective Cohort Study of Body Size and Risk of Head and Neck Cancers in the NIH-AARP Diet and Health Study

Background: The association between body size and head and neck cancers (HNCA) is unclear, partly because of the biases in case–control studies. Methods: In the prospective NIH–AARP cohort study, 218,854 participants (132,288 men and 86,566 women), aged 50 to 71 years, were cancer free at baseline (1995 and 1996), and had valid anthropometric data. Cox proportional hazards regression was used to examine the associations between body size and HNCA, adjusted for current and past smoking habits, alcohol intake, education, race, and fruit and vegetable consumption, and reported as HR and 95% confidence intervals (CI). Results: Until December 31, 2006, 779 incident HNCAs occurred: 342 in the oral cavity, 120 in the oro- and hypopharynx, 265 in the larynx, 12 in the nasopharynx, and 40 at overlapping sites. There was an inverse association between HNCA and body mass index, which was almost exclusively among current smokers (HR = 0.76 per each 5 U increase; 95% CI, 0.63–0.93), and diminished as initial years of follow-up were excluded. We observed a direct association with waist-to-hip ratio (HR = 1.16 per 0.1 U increase; 95% CI, 1.03–1.31), particularly for cancers of the oral cavity (HR, 1.40; 95% CI, 1.17–1.67). Height was also directly associated with total HNCAs (P = 0.02), and oro- and hypopharyngeal cancers (P < 0.01). Conclusions: The risk of HNCAs was associated inversely with leanness among current smokers, and directly with abdominal obesity and height. Impact: Our study provides evidence that the association between leanness and risk of HNCAs may be due to effect modification by smoking. Cancer Epidemiol Biomarkers Prev; 23(11); 2422–9. ©2014 AACR.

Big and beautiful: attractiveness and health ratings of the female body by male "fat admirers"

This study examined the body weight and waist-to-hip ratio (WHR) preferences of “fat admirers” (FAs), that is, individuals who are sexually attracted to heavier partners. Fifty-six heterosexual men involved in the FA community rated a series of line drawings that varied in three levels of body weight and six of WHR for physical attractiveness and health. The results showed significant main effects of body weight and WHR, as well as a significant body weight × WHR interaction for both health ratings. In general, there was a preference for heavyweight figures and high WHRs for ratings of attractiveness and normal-weight figures and mid-ranging WHRs for ratings of health. Limitations of the study and explanations for fat admiration are discussed.

Circulating pancreatic polypeptide concentrations predict visceral and liver fat content

CONTEXT AND OBJECTIVE: No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in predicting visceral and liver fat. PATIENTS AND METHODS: Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy. RESULTS: Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01). CONCLUSIONS: Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.

Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Objective: Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with bodyfat mass and glucose intolerance in mice, but more evidence is needed in humans. The impact of diet and weight loss on this bacterial species is unknown. Our objective was to evaluate the association between fecal A. muciniphila abundance, fecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR). Design: The intervention consisted of a 6-week CR period followed by a 6-week weight stabilization (WS) diet in overweight and obese adults (N=49, including 41 women). Fecal A. muciniphila abundance, fecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and WS. Results: At baseline A. muciniphila was inversely related to fasting glucose, waist-to-hip ratio, and subcutaneous adipocyte diameter. Subjects with higher gene richness and A. muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline A. muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR. A. muciniphila was associated with microbial species known to be related to health. Conclusion: A. muciniphila is associated with a healthier metabolic status and better clinicaloutcomes after CR in overweight/obese adults, however the interaction between gut microbiota ecology and A. muciniphila has to be taken into account.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

The association between body composition and arterial stiffness in peri-pubescent children

The objective of this study was to examine the association between body composition and arterial stiffuess in peri-pubescent boys and girls. Differences in arterial distensibility were measured in 68 children (45 normal weight, 12 overweight, and 11 obese) between the ages of9 to 12 years. Weight classification was based on age and gender-specific body mass index cut-offs, while pubertal maturation was self-reported using Tanner staging. Distensibility was determined using two-dimensional, B-Mode echo Doppler ultrasound to measure changes at the right common carotid artery (CCA) diameter changes, while carotid pulse pressure (cPP) was measured at the left CCA by applanation tonometry. One-way ANOV A analysis revealed significant differences (p<0.001) in all anthropometric measures between the normal weight and overweight children, as well as the normal weight and obese children. Body stature was only higher in obese children compared to normal weight children (p<0.01). No significant differences were found between groups regarding age or Tanner stage. Common carotid artery distensibility showed a significant difference (p<0.01) between normal weight children (0.008 ± 0.002 mmHg-1 ) compared to obese children (0.005 ± 0.002 mmHg-1 ), with a borderline significant difference between the normal and overweight subjects (p=0.06). There was no significant effect for gender between males and females across all independent variables. The strongest determinants of distensibility in children were cPP (r= -0.52, pwaist-to-hip ratio explained 94% of the variance among peri-pubescent children. This study greatly underscores the need for weight management for long-term prevention of cardiovascular disease in overweight and obese children.