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: Sarcopenia varies by ethnicity, and has a major impact on health in older adults. However, little is known about sarcopenia characteristics in African ancestry populations outside the United States. We examined sarcopenia characteristics in 2,142 African Caribbean men aged 59.0 ± 10.4 years (range: 40-92 years) in Tobago, and their association with incident mobility limitations in those aged 55+ (n = 738). METHODS: Body mass index (BMI), grip strength, dual-x-ray absorptiometry (DXA) appendicular lean mass (ALM), and self-reported mobility limitations were measured at baseline, and 6 years later. Change in sarcopenia characteristics, including grip strength, grip strength/BMI, ALMBMI, and ALM/ht2, were determined. Foundations for the National Institutes of Health Sarcopenia Project (FNIH) and European Working Group for Sarcopenia in Older People 2 (EWGSOP2) cut-points were also examined. Odds ratios (OR) and 95% confidence intervals (CI) for mobility limitation were calculated using multivariable linear regression models adjusted for covariates. RESULTS: Overall, sarcopenia prevalence was quite low using the FNIH (0.3%) and EWGSOP2 (0.6%) operational cut-points, but was higher in those aged 75+ (2.1% [FNIH] and 3.7% [EWGSOP2]). Prevalence was also higher when based on "weakness", versus "low ALM." When sarcopenia markers were examined separately, baseline levels, but not changes, were associated with incident mobility limitations. Baseline grip strength/BMI was a particularly strong risk factor for incident mobility limitations (OR per SD: 0.50; 95% CI: 0.37-0.68). CONCLUSIONS: Our findings suggest that grip strength normalized to body mass, measured at one time point, may be a particularly useful phenotype for identifying African Caribbean men at risk for future mobility limitations.
Assuntos
População Negra/estatística & dados numéricos , Limitação da Mobilidade , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Força da Mão , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição de Risco , Sarcopenia/complicações , Fatores Sexuais , Trinidad e TobagoRESUMO
BACKGROUND: Mobility limitations are common, with higher prevalence in African Americans compared with whites, and are associated with disability, institutionalization, and death. Aging is associated with losses of lean mass and a shift to central adiposity, which are more pronounced in African Americans. We aimed to examine the association of body composition remodeling with incident mobility limitations in older men of African ancestry. METHODS: Seven-year changes in body composition were measured using peripheral quantitative computed tomography (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African ancestry men aged ≥60 years and free of self-reported mobility limitations at baseline. Self-reported incident mobility limitations were assessed at 7-year follow-up. Odds of developing mobility limitations associated with baseline and change in body composition were quantified using separate logistic regression models. RESULTS: Seventy-five men (14.9%) developed incident mobility limitations over 6.2 ± 0.6 years. Baseline body composition was not associated with incident mobility limitations. After adjustment for covariates, gaining total and intermuscular fat were associated with incident mobility limitations (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.21-2.13; OR: 1.51; 95% CI: 1.18-1.94). Changes in DXA lean mass were not related to mobility limitations; however, maintaining pQCT calf muscle area was protective against mobility limitations (OR: 0.65; 95% CI: 0.48-0.87). CONCLUSIONS: Increases in body fat, and particularly intermuscular fat, and decreases in calf skeletal muscle area were associated with a higher risk of developing mobility limitations. Our findings emphasize the importance of body composition remodeling in the development of mobility limitations among African ancestry men.
Assuntos
População Negra , Composição Corporal , Limitação da Mobilidade , Absorciometria de Fóton , Adulto , Idoso , Estudos de Coortes , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Autorrelato , Trinidad e TobagoRESUMO
Although fracture rates are lower in individuals of African descent compared to individuals of European ancestry, morbidity and mortality following a fracture may be greater in individuals of African ancestry. However, fracture risk and associated clinical risk factors have not been well-defined among African ancestry populations, especially among men of African ancestry. We used data collected from the Tobago Bone Health Study to examine potential clinical risk factors for incident fractures, including demographic information, anthropometric measurements, medical history, lifestyle factors, bone mineral density (BMD), and hip structural geometry. Among 1933 Afro-Caribbean men aged ≥40 years at study entry (mean age: 57.2 ± 11.0 years), 65 reported at least one new fracture during 10 years of subsequent follow-up. Younger age, mixed Afro-Caribbean ancestry, prior fracture history, BMD, and hip structural geometry were statistically significant risk factors for incident fractures. A 1-SD change in several skeletal parameters (hip BMD, cross-sectional area, outer diameter, cortical thickness, and buckling ratio) were each associated with a 35% to 56% increase in incident fracture risk after adjusting for age. Men with a prior fracture history were three times more likely to experience a new fracture during follow-up, and the association remained strong after adjusting for age, mixed Afro-Caribbean ancestry, and skeletal parameters (hazard ratios ranged from 2.72 to 2.82). Our findings suggest that except for age, risk factors for fracture in men of African ancestry are similar to established risk factors in white populations. Prior fracture history is a powerful and independent risk factor for incident fractures among men of African ancestry and could easily be incorporated into clinical risk evaluation.
Assuntos
População Negra , Fraturas Ósseas/etiologia , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Fraturas Ósseas/epidemiologia , Quadril/diagnóstico por imagem , Fraturas do Quadril/etiologia , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trinidad e Tobago/epidemiologiaRESUMO
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
BACKGROUND: muscle strength is essential for physical functions and an indicator of morbidity and mortality in older adults. Among the factors associated with muscle strength loss with age, ethnicity has been shown to play an important role. OBJECTIVE: to examine the patterns and correlates of muscle strength change with age in a population-based cohort of middle-aged and older Afro-Caribbean men. METHODS: handgrip strength and body composition were measured in 1,710 Afro-Caribbean men. Data were also collected for demographic variables, medical history and lifestyle behaviours. RESULTS: the age range of the study population was 29-89 years. Grip strength increased below age 50 years, and decreased after age 50 years over 4.5-year follow-up. The average loss in grip strength was 2.2% (0.49% per year) for ages 50 years or older and 3.8% (0.64% per year) for ages 65 years or older. The significant independent predictors of grip strength loss included older age, a greater body mass index, lower initial arm lean mass and greater loss of arm lean mass. CONCLUSION: Afro-Caribbean men experience a significant decline in muscle strength with advanced age. The major independent factors associated with strength loss were similar to other ethnic groups, including age, body weight and lean mass.
Assuntos
Envelhecimento/etnologia , População Negra/estatística & dados numéricos , Força da Mão , Debilidade Muscular/etnologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Índice de Massa Corporal , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Debilidade Muscular/diagnóstico , Debilidade Muscular/fisiopatologia , Medição de Risco , Fatores de Risco , Fatores Sexuais , 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.
Assuntos
Adiposidade/genética , População Negra/genética , Mediadores da Inflamação/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Coristoma/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/anatomia & histologia , Fatores de Risco , Gordura Subcutânea/anatomia & histologia , Trinidad e Tobago , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
Vitamin D deficiency is highly prevalent worldwide, and is linked to several major chronic, inflammatory and autoimmune diseases. Vitamin D deficiency has not been evaluated in dark skinned individuals living in areas of high sun exposure utilizing more reliable mass spectrometry assay techniques. We determined the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency in Afro-Caribbean men on the tropical island of Tobago, where there is a high level of sunshine year round. Serum 25(OH)D2 and 25(OH)D3 metabolites were measured following extraction and purification using liquid chromatography and tandem mass spectrometry in 424 Afro-Caribbean men aged > 65 years from a larger population-based cohort study. The mean (+/- SD) serum total 25(OH)D concentration was 35.1 +/- 8.9 ng/mL. Deficiency (< 20 ng/mL) was present in only 2.8% and insufficiency (< 30 ng/mL) in 24% of the men. Multiple linear regression analysis identified age, BMI and daily vitamin D supplementation as the independent correlates of 25(OH)D. None of the men who consumed fish more than once per week had vitamin D deficiency, compared to 4% of the men who consumed fish once per week or less (P = .01, adjusted for age, BMI, and daily vitamin D supplementation). In conclusion, vitamin D deficiency is very uncommon in this Afro-Caribbean population. Longitudinal studies are needed to delineate the possible effects of high vitamin D levels in this population on major diseases hypothesized to be associated with vitamin D deficiency.