RESUMO
Background: Adipose tissue (AT) around and within non-AT organs (i.e., ectopic adiposity) is emerging as a strong risk factor for type 2 diabetes (T2D). Not known is whether major ectopic adiposity depots, such as hepatic, skeletal muscle, and pericardial adiposity (PAT), are associated with T2D independent of visceral adiposity (VAT). More data are particularly needed among high-risk nonobese minority populations, as the race/ethnic gap in T2D risk is greatest among nonobese. Methods: Thus, we measured several ectopic adiposity depots by computed tomography in 718 (mean age = 64 years) African-Caribbean men on the Island of Tobago overall, and stratified by obesity (obese N = 187 and nonobese N = 532). Results: In age, lifestyle risk factors, health status, lipid-lowering medication intake, body mass index and all other adiposity-adjusted regression analyses, and hepatic and skeletal muscle adiposity were associated with T2D among nonobese men only (all P < 0.05), despite no association between VAT and PAT and T2D. Conclusions: Our results support the "ectopic fat syndrome" theory in the pathogenesis of T2D among nonobese African-Caribbean men. Longitudinal studies are needed to clarify the independent role of ectopic adiposity in T2D, and to identify possible biological mechanisms underlying this relationship, particularly in high-risk African ancestry and other nonwhite populations.
Assuntos
Adiposidade , Diabetes Mellitus Tipo 2/fisiopatologia , Gordura Intra-Abdominal/fisiopatologia , Fígado/fisiopatologia , Músculo Esquelético/fisiopatologia , Obesidade/fisiopatologia , Adiposidade/etnologia , Idoso , População Negra , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/etnologia , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Obesidade/diagnóstico por imagem , Obesidade/etnologia , Prevalência , Medição de Risco , Fatores de Risco , Tomografia Computadorizada por Raios X , Trinidad e Tobago/epidemiologiaRESUMO
Background Animal and in vitro experiments implicate the Wnt pathway in cardiac development, fibrosis, vascular calcification, and atherosclerosis, but research in humans is lacking. We examined peripheral blood Wnt pathway gene expression and arterial stiffness in 369 healthy African ancestry men (mean age, 64 years). Methods and Results Gene expression was assessed using a custom Nanostring nCounter gene expression panel (N=43 genes) and normalized to housekeeping genes and background signal. Arterial stiffness was assessed via brachial-ankle pulse-wave velocity. Fourteen Wnt genes showed detectable expression and were tested individually as predictors of pulse-wave velocity using linear regression, adjusting for age, height, weight, blood pressure, medication use, resting heart rate, current smoking, alcohol intake, and sedentary lifestyle. Adenomatous polyposis coli regulator of Wnt signaling pathway (APC), glycogen synthase kinase 3ß (GSK3B), and transcription factor 4 (TCF4) were significantly associated with arterial stiffness (P<0.05 for all). When entered into a single model, APC and TCF4 expression remained independently associated with arterial stiffness (P=0.04 and 0.003, respectively), and each explained ≈3% of the variance in pulse-wave velocity. Conclusions The current study establishes a novel association between in vivo expression of the Wnt pathway genes, APC and TCF4, with arterial stiffness in African ancestry men, a population at high risk of hypertensive vascular disease.
Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Fator de Transcrição 4/genética , Rigidez Vascular/genética , Via de Sinalização Wnt/genética , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , População Negra/genética , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso , Transcriptoma , Trinidad e TobagoRESUMO
OBJECTIVE: Decreased radiodensity of adipose tissue (AT) located in the visceral AT (VAT), subcutaneous AT (SAT), and intermuscular AT (IMAT) abdominal depots is associated with hyperglycemia, hyperinsulinemia, and insulin resistance independent of AT volumes. These associations were sought in African-ancestry men, who have higher risk for type 2 diabetes and have been underrepresented in previous studies. METHODS: This cross-sectional analysis included 505 nondiabetic men of African-Caribbean ancestry (median age: 61 years; median BMI: 26.8 kg/m2 ) from the Tobago Health Study. AT volumes and radiodensities were assessed using computed tomography, including abdominal (VAT and SAT) and thigh (IMAT) depots. Associations between AT radiodensities were assessed with fasting serum glucose and insulin and with insulin resistance (updated homeostatic model assessment of insulin resistance, HOMA2-IR). RESULTS: Higher radiodensity in any AT depot was associated with lower log-insulin and log-HOMA2-IR (ß range: -0.16 to -0.18 for each; all P < 0.0001). No AT radiodensity was associated with glucose. Thigh IMAT radiodensity associations were independent of, and similar in magnitude to, VAT radiodensities. Model fit statistics suggested that AT radiodensities were a better predictor for insulin and insulin resistance compared with AT volumes in individuals with overweight and obesity. CONCLUSIONS: AT radiodensities at multiple depots are significantly associated with insulin and insulin resistance in African-ancestry men.
Assuntos
Adiposidade/fisiologia , População Negra/etnologia , Gordura Intra-Abdominal/metabolismo , Obesidade/etnologia , Sobrepeso/etnologia , Gordura Subcutânea/metabolismo , Tecido Adiposo/fisiopatologia , Adulto , Idoso , Glicemia/metabolismo , Composição Corporal/fisiologia , Estudos Transversais , Glucose/metabolismo , Humanos , Insulina/sangue , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/metabolismo , Sobrepeso/diagnóstico , Sobrepeso/metabolismo , Gordura Subcutânea/diagnóstico por imagem , Coxa da Perna/diagnóstico por imagem , Índias Ocidentais/etnologiaRESUMO
BACKGROUND AND AIMS: There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men. METHODS: Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height. RESULTS: All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p < 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p < 0.001) when entered in a single model. No ectopic fat measure was associated with CAC. CONCLUSIONS: Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body.
Assuntos
Adiposidade/etnologia , Aorta Abdominal , Doenças da Aorta/fisiopatologia , População Negra , Doença da Artéria Coronariana/fisiopatologia , Artéria Ilíaca , Gordura Intra-Abdominal/fisiopatologia , Fígado/fisiopatologia , Músculo Esquelético/fisiopatologia , Calcificação Vascular/fisiopatologia , Absorciometria de Fóton , Adulto , Idoso , Aorta Abdominal/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/etnologia , Aortografia/métodos , Distribuição de Qui-Quadrado , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etnologia , Humanos , Artéria Ilíaca/diagnóstico por imagem , Gordura Intra-Abdominal/diagnóstico por imagem , Fígado/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Trinidad e Tobago/epidemiologia , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etnologiaRESUMO
BACKGROUND: fat infiltration within and around skeletal muscle (i.e. myosteatosis) increases with ageing, is greater in African versus European ancestry men and is associated with poor health. Myosteatosis studies of mortality are lacking, particularly among African ancestry populations. METHODS: in the Tobago Health study, a prospective longitudinal study, we evaluated the association of all-cause mortality with quantitative computed tomography (QCT) measured lower leg myosteatosis (intermuscular fat (IM fat) and muscle density) in 1,652 African ancestry men using Cox proportional hazards models. Date of death was abstracted from death certificates and/or proxy. RESULTS: one hundred and twelve deaths occurred during follow-up (mean 5.9 years). In all men (age range 40-91 years), higher all-cause mortality was associated with greater IM fat (HR (95% CI) per SD: 1.29 (1.06-1.57)) and lower muscle density (HR (95% CI) per SD lower: 1.37 (1.08-1.75)) in fully adjusted models. Similar mortality hazard rates were seen in the subset of elderly men (aged ≥65 years) with greater IM fat (1.40 (1.11-1.78) or lower muscle density (1.66 (1.24-2.21)) in fully adjusted models. CONCLUSIONS: our study identified a novel, independent association between myosteatosis and all-cause mortality in African ancestry men. Further studies are needed to establish whether this association is independent of other ectopic fat depots and to identify possible biological mechanisms underlying this relationship.
Assuntos
Adiposidade/etnologia , População Negra , Causas de Morte , Músculo Esquelético/fisiopatologia , Doenças Musculares/etnologia , Idoso , Distribuição de Qui-Quadrado , Comorbidade , Nível de Saúde , Humanos , Estudos Longitudinais , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Músculo Esquelético/diagnóstico por imagem , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/mortalidade , Doenças Musculares/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Tomografia Computadorizada por Raios X , Trinidad e TobagoRESUMO
OBJECTIVE: Sclerostin, a Wingless (Wnt) pathway antagonist, is an established regulator of bone mineralization in humans but its potential importance in the regulation of vascular calcification is less clear. Therefore, our objective was to assess the relationship of serum sclerostin levels with coronary and aortic artery calcification (CAC and AAC, respectively) in Afro-Caribbean men on the island of Tobago. METHODS: Serum sclerostin levels and computed tomography of CAC and AAC were measured in 191 men (age mean(SD): 62.9(8.0)years) recruited without regard to health status. Multivariable logistic regression models were used to assess the cross-sectional association of sclerostin with prevalent arterial calcification. RESULTS: Mean(SD) sclerostin was 45.2 pmol/L (15.6 pmol/L). After adjusting for risk factors including age, physical and lifestyle characteristics, comorbidities, lipoproteins and kidney function, 1 SD greater sclerostin level was associated with a 1.61-times (95%CI 1.02-2.53) greater odds of having CAC. Sclerostin was not associated with AAC in any model. CONCLUSIONS: This is the first study to show that, among Afro-Caribbean men, greater serum sclerostin concentrations were associated with prevalence and extent of CAC. Further studies are needed to better define the role of the Wnt signaling pathway in arterial calcification in humans.
Assuntos
Proteínas Morfogenéticas Ósseas/sangue , Calcificação Vascular/sangue , Calcificação Vascular/etnologia , Doenças Vasculares/sangue , Doenças Vasculares/etnologia , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Aorta/patologia , População Negra , Glicemia/análise , Região do Caribe , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Tomografia Computadorizada por Raios X , Trinidad e Tobago , Calcificação Vascular/fisiopatologia , Via de Sinalização WntRESUMO
OBJECTIVE: Intima-media thickness, adventitial diameter and lumen diameter are indicators of cardiovascular disease risk. The influence of genetic factors on these measures in African ancestry populations is not well defined. Therefore, we estimated heritability and performed genome-wide linkage analysis of carotid ultrasound traits in 7 multigenerational families of African ancestry. METHODS: A total of 395 individuals (7 pedigrees; mean family size = 56; 2392 relative pairs) aged ≥18 years had a common carotid artery ultrasound scan. Statistical analyses were conducted using pedigree-based maximum likelihood methods. RESULTS: Significant covariates included age, sex, body mass index or height and waist, and systolic blood pressure. Residual heritabilities ranged from 0.35 ± 0.10 to 0.64 ± 0.12 (P < 0.0001). We identified a novel quantitative trait locus for adventitial and lumen diameters on chromosome 11 (max LOD = 4.09, 133 cm). CONCLUSION: Further fine mapping of this region may identify specific mutations predisposing to subclinical vascular disease among African ancestry individuals.
Assuntos
População Negra/genética , Doenças Cardiovasculares/epidemiologia , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Adulto , Túnica Adventícia/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/genética , Cromossomos Humanos Par 11/genética , Feminino , Ligação Genética , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Linhagem , Locos de Características Quantitativas , Trinidad e Tobago/epidemiologiaRESUMO
UNLABELLED: Abstract Background: Skeletal muscle adipose tissue (AT) infiltration, or myosteatosis, appears to be greater in African compared with European ancestry individuals and may play a role in type 2 diabetes mellitus (T2DM), a disease that disproportionally affects African ancestry populations. Inflammation is one mechanism that may link myosteatosis with increased T2DM risk, but studies examining the relationship between inflammation and myosteatosis are lacking. METHODS: To examine these associations, we measured skeletal muscle subcutaneous AT, intermuscular AT, and skeletal muscle density using quantitative computed tomography and serum markers of inflammation in 471 individuals from 8 Afro-Caribbean multigenerational families [mean family size 67; mean age 43 years; mean body mass index (BMI) 28 kg/m(2)]. RESULTS: After removing the variation attributable to significant covariates, heritabilities of inflammation markers [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)] ranged from 33% (TNFα) to 40% (CRP); all P<0.01. Higher CRP, IL-6, and TNF-α were associated with lower subcutaneous AT around skeletal muscle (r=-0.13 to -0.19, P<0.05). Higher CRP was additionally associated with lower skeletal muscle density, indicative of greater intramuscular AT (r=-0.10, P<0.05), hyperinsulinemia (r=0.12, P<0.05), and increased homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.17, P<0.01). CONCLUSIONS: Our findings suggest that heredity may play a significant role in the determination of several markers of inflammation in African ancestry individuals. Higher concentrations of CRP appear to be associated with greater skeletal muscle AT infiltration, lower subcutaneous AT, hyperinsulinemia, and insulin resistance. Longitudinal studies are needed to further evaluate the relationship between inflammation with changes in skeletal muscle AT distribution with aging and the incidence of T2DM.