RESUMO
PURPOSE: Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (VÌO 2peak ) declines with aging and correlates with mortality and morbidity. Cardiopulmonary exercise testing (CPET) is the criterion method to assess CRF, but its feasibility, validity, and reliability in older adults are unclear. Our objective was to design and implement a dependable, safe, and reliable CPET protocol in older adults. METHODS: VÌO 2peak was measured by CPET, performed using treadmill exercise in 875 adults ≥70 yr in the Study of Muscle, Mobility and Aging (SOMMA). The protocol included a symptom-limited peak (maximal) exercise and two submaximal walking speeds. An adjudication process was in place to review tests for validity if they met any prespecified criteria (VÌO 2peak <12.0 mL·kg -1 ·min -1 ; maximum heart rate <100 bpm; respiratory exchange ratio <1.05 and a rating of perceived exertion <15). A subset ( N = 30) performed a repeat test to assess reproducibility. RESULTS: CPET was safe and well tolerated, with 95.8% of participants able to complete the VÌO 2peak phase of the protocol. Only 56 (6.4%) participants had a risk alert and only two adverse events occurred: a fall and atrial fibrillation. Mean ± SD VÌO 2peak was 20.2 ± 4.8 mL·kg -1 ·min -1 , peak heart rate 142 ± 18 bpm, and peak respiratory exchange ratio 1.14 ± 0.09. Adjudication was indicated in 47 tests; 20 were evaluated as valid and 27 as invalid (18 data collection errors, 9 did not reach VÌO 2peak ). Reproducibility of VÌO 2peak was high (intraclass correlation coefficient = 0.97). CONCLUSIONS: CPET was feasible, effective, and safe for older adults, including many with multimorbidity or frailty. These data support a broader implementation of CPET to provide insight into the role of CRF and its underlying determinants of aging and age-related conditions.
Assuntos
Aptidão Cardiorrespiratória , Teste de Esforço , Consumo de Oxigênio , Humanos , Idoso , Teste de Esforço/métodos , Aptidão Cardiorrespiratória/fisiologia , Consumo de Oxigênio/fisiologia , Masculino , Feminino , Estudos Prospectivos , Reprodutibilidade dos Testes , Frequência Cardíaca/fisiologia , Estudos de Viabilidade , Idoso de 80 Anos ou maisRESUMO
The nitrate-nitrite-NO pathway regulates NO synthase-independent vasodilation and NO signaling. Ingestion of inorganic nitrite has vasodilatory and blood pressure-lowering effects. Preclinical studies in rodent models suggest there may be a benefit of nitrite in lowering serum triglyceride levels and improving the metabolic syndrome. In a phase 2 study, we evaluated the safety and efficacy of chronic oral nitrite therapy in patients with hypertension and the metabolic syndrome. Twenty adult subjects with stage 1 or 2 hypertension and the metabolic syndrome were enrolled in an open-label safety and efficacy study. The primary efficacy end point was blood pressure reduction; secondary end points included insulin-dependent glucose disposal and endothelial function measured by flow-mediated dilation of the brachial artery and intima-media diameter of the carotid artery. Chronic oral nitrite therapy (40 mg/3× daily) was well tolerated. Oral nitrite significantly lowered systolic, diastolic, and mean arterial pressures, but tolerance was observed after 10 to 12 weeks of therapy. There was significant improvement in the intima-media thickness of the carotid artery and trends toward improvements in flow-mediated dilation of the brachial artery and insulin sensitivity. Chronic oral nitrite therapy is safe in patients with hypertension and the metabolic syndrome. Despite an apparent lack of enzymatic tolerance to nitrite, we observed tolerance after 10 weeks of chronic therapy, which requires additional mechanistic studies and possible therapeutic dose titration in clinical trials. Nitrite may be a safe therapy to concominantly improve multiple features of the metabolic syndrome including hypertension, insulin resistance, and endothelial dysfunction. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01681810.
Assuntos
Artéria Braquial , Endotélio Vascular , Hipertensão , Síndrome Metabólica , Nitrito de Sódio , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Espessura Intima-Media Carotídea , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Resistência à Insulina , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/fisiopatologia , Nitrito de Sódio/administração & dosagem , Nitrito de Sódio/efeitos adversos , Nitrito de Sódio/farmacologia , Resultado do Tratamento , Triglicerídeos/sangue , Vasodilatação/efeitos dos fármacosRESUMO
Accumulation of lipid in skeletal muscle is thought to be related to the development of insulin resistance and type 2 diabetes. Initial work in this area focused on accumulation of intramuscular triglyceride; however, bioactive lipids such as diacylglycerols and sphingolipids are now thought to play an important role. Specific species of these lipids appear to be more negative toward insulin sensitivity than others. Adding another layer of complexity, localization of lipids within the cell appears to influence the relationship between these lipids and insulin sensitivity. This article summarizes how accumulation of total lipids, specific lipid species, and localization of lipids influence insulin sensitivity in humans. We then focus on how these aspects of muscle lipids are impacted by acute and chronic aerobic and resistance exercise training. By understanding how exercise alters specific species and localization of lipids, it may be possible to uncover specific lipids that most heavily impact insulin sensitivity.
Assuntos
Exercício Físico/fisiologia , Resistência à Insulina/fisiologia , Lipídeos/química , Músculo Esquelético/efeitos dos fármacos , Composição Corporal , HumanosRESUMO
Dynamic positron emission tomography (PET) imaging was performed using sequential tracer injections ([(15)O]H2O, [(11)C]3-O-methylglucose [3-OMG], and [(18)F]fluorodeoxyglucose [FDG]) to quantify, respectively, skeletal muscle tissue perfusion (glucose delivery), kinetics of bidirectional glucose transport, and glucose phosphorylation to interrogate the individual contribution and interaction among these steps in muscle insulin resistance (IR) in type 2 diabetes (T2D). PET imaging was performed in normal weight nondiabetic subjects (NW) (n = 5), obese nondiabetic subjects (OB) (n = 6), and obese subjects with T2D (n = 7) during fasting conditions and separately during a 6-h euglycemic insulin infusion at 40 mU · m(-2) · min(-1). Tissue tracer activities were derived specifically within the soleus muscle with PET images and magnetic resonance imaging. During fasting, NW, OB, and T2D subjects had similar [(11)C]3-OMG and [(18)F]FDG uptake despite group differences for tissue perfusion. During insulin-stimulated conditions, IR was clearly evident in T2D (P < 0.01), and [(18)F]FDG uptake by muscle was inversely correlated with systemic IR (P < 0.001). The increase in insulin-stimulated glucose transport was less (P < 0.01) in T2D (twofold) than in NW (sevenfold) or OB (sixfold) subjects. The fractional phosphorylation of [(18)F]FDG during insulin infusion was also significantly lower in T2D (P < 0.01). Dynamic triple-tracer PET imaging indicates that skeletal muscle IR in T2D involves a severe impairment of glucose transport and additional impairment in the efficiency of glucose phosphorylation.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Resistência à Insulina , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Tomografia por Emissão de Pósitrons/métodos , 3-O-Metilglucose/farmacocinética , Adulto , Transporte Biológico , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , FosforilaçãoRESUMO
OBJECTIVE: To assess whether sensorimotor peripheral nerve function is associated with muscle power in community-dwelling older men. DESIGN: Longitudinal cohort study with 2.3±0.3 years of follow-up. SETTING: One clinical site. PARTICIPANTS: Participants (n=372; mean age ± SD, 77.2±5.1y; 99.5% white; body mass index, 27.9±3.7kg/m(2); power, 1.88±0.6W/kg) at 1 site of the Osteoporotic Fractures in Men Study (N=5994). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A nerve function ancillary study was performed 4.6±0.4 years after baseline. Muscle power was measured using a power rig. Peroneal motor nerve conduction amplitude, distal motor latency, and mean f-wave latency were measured. Sensory nerve function was assessed using 10-g and 1.4-g monofilaments and sural sensory nerve conduction amplitude and distal latency. Peripheral neuropathy symptoms at the leg and feet were assessed by self-report. RESULTS: After adjustments for age, height, and total body lean and fat mass, 1 SD lower motor (ß=-.07, P<.05) and sensory amplitude (ß=-.09, P<.05) and 1.4-g (ß=-.11, P<.05) and 10-g monofilament insensitivity (ß=-.17, P<.05) were associated with lower muscle power/kg. Compared with the effect of age on muscle power (ß per year, -.05; P<.001), this was equivalent to aging 1.4 years for motor amplitude, 1.8 years for sensory amplitude, 2.2 years for 1.4-g monofilament detection, and 3.4 years for 10-g detection. Baseline 1.4-g monofilament detection predicted a greater decline in muscle power/kg. Short-term change in nerve function was not associated with concurrent short-term change in muscle power/kg. CONCLUSIONS: Worse sensory and motor nerve function were associated with lower muscle power/kg and are likely important for impaired muscle function in older men. Monofilament sensitivity was associated with a greater decline in muscle power/kg, and screening may identify an early risk for muscle function decline in late life, which has implications for disability.
Assuntos
Extremidade Inferior/fisiologia , Força Muscular/fisiologia , Condução Nervosa/fisiologia , Nervo Fibular/fisiologia , Nervo Sural/fisiologia , Potenciais de Ação/fisiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Estudos de Coortes , Humanos , Modelos Lineares , Estudos Longitudinais , Extremidade Inferior/inervação , MasculinoRESUMO
Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T2DM in a black male population group at high risk of T2DM. Serum androgens, estrogens, and androgen precursors and metabolites were measured using mass spectrometry; and calf skeletal muscle fat distribution (subcutaneous and intermuscular fat; skeletal muscle density) was measured using quantitative computed tomography in 472 Afro-Caribbean men 65 years and older. Bioactive androgens, testosterone, free testosterone, and dihydrotestosterone were associated with less skeletal muscle fat infiltration (r = -0.14 to -0.18, P < .05) and increased skeletal muscle density (r = 0.10 to 0.14, P < .05), independent of total adiposity. In addition, glucuronidated androgen metabolites were associated with less subcutaneous fat (r = -0.11 to -0.15, P < .05). Multivariate logistic regression analysis identified an increased level of 3α-diol-3 glucuronide (odds ratio = 1.38, P < .01) and a decreased level of dihydrotestosterone (odds ratio = 0.66, P < .01) to be significantly associated with T2DM. Our findings suggest that, in elderly black men, independent of total adiposity, bioactive androgens and glucuronidated androgen metabolites may play previously unrecognized role in skeletal muscle fat distribution. Longitudinal studies are needed to further evaluate the relationship between androgens and androgen metabolites with changes in skeletal muscle fat distribution with aging and the incidence of T2DM.
Assuntos
Adiposidade/fisiologia , Envelhecimento/metabolismo , Androgênios/metabolismo , Músculo Esquelético/metabolismo , Idoso , Idoso de 80 Anos ou mais , População Negra , Composição Corporal/fisiologia , Índice de Massa Corporal , Humanos , Resistência à Insulina/fisiologia , Masculino , Sobrepeso/metabolismo , Trinidad e TobagoRESUMO
Skeletal muscle fat is greater in African ancestry individuals compared with whites, is associated with diabetes, and is a heritable polygenic trait. However, specific genetic factors contributing to skeletal muscle fat in humans remain to be defined. Muscle carnitine palmitoyltransferase-1B (CPT1B) is a key enzyme in the regulation of skeletal muscle mitochondrial beta-oxidation of long-chain fatty acids, and as such is a reasonable biological candidate gene for skeletal muscle fat accumulation. Therefore, we examined the association of three nonsynonymous coding variants in CPT1B (G531L, I66V, and S427C; a fourth, A320G, could not be genotyped) and quantitative computed tomography measured tibia skeletal muscle composition and BMI among 1,774 Afro-Caribbean men aged > or =40, participants of the population-based Tobago Health Study. For all variants, no significant differences were observed for BMI or total adipose tissue. Among individuals who were homozygous for the minor allele at G531L or I66V, intermuscular adipose tissue (IMAT) was 87% (P = 0.03) and 54% lower (P = 0.03), respectively. In contrast, subcutaneous adipose tissue (SAT) was 11% (P = 0.017) and 7% (P = 0.049) higher, respectively, than among individuals without these genotypes. These associations were independent of age, body size, and muscle area. Finally, no individuals with type 2 diabetes were found among those who were homozygous for the minor allele of either at G531L and I66V whereas 14-18% of men with the major alleles had type 2 diabetes (P = 0.03 and 0.007, respectively). Our results suggest a novel association between common nonsynonymous coding variants in CPT1B and ectopic skeletal muscle fat among middle-aged and older African ancestry men.
Assuntos
Adiposidade/genética , Adiposidade/fisiologia , População Negra/genética , Distribuição da Gordura Corporal , Carnitina O-Palmitoiltransferase/genética , Músculo Esquelético/fisiopatologia , Adiposidade/etnologia , Idoso , Alelos , População Negra/etnologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Gordura Subcutânea/fisiopatologia , Trinidad e TobagoRESUMO
BACKGROUND: Although obesity is strongly associated with diabetes, the greater prevalence of diabetes in persons of African ancestry than in those of other ancestries cannot be explained simply by differences in total or central adiposity. OBJECTIVE: We examined whether skeletal muscle composition is associated with diabetes in 1249 men of African ancestry aged >or=40 y. DESIGN: Anthropometry and fasting serum glucose were measured, and lower-leg skeletal muscle composition was assessed with peripheral quantitative computerized tomography (pQCT). RESULTS: The prevalence of diabetes in this population was high (21%). We observed an age-associated adipose tissue remodeling in skeletal muscle and greater intermuscular (IMAT) and lesser subcutaneous (SAT) adipose tissue area with advancing age (P < 0.0001). Multivariate stepwise logistic regression identified more IMAT and less SAT to be significantly associated with a greater prevalence of diabetes. Even among normal-weight men [body mass index (BMI; in kg/m(2)) < 25], diabetic men had significantly (P = 0.01) more IMAT than did those without diabetes. Greater IMAT was also associated with a greater prevalence of hyperglycemia in men with a family history of diabetes than in those without such history (P for interaction = 0.02). CONCLUSIONS: These findings underscore the independent associations of subcutaneous and intermuscular fat among men of African ancestry, an effect that may be modified by a family history of diabetes. Further studies are needed to identify the genetic and physiologic mechanisms that influence the distribution and remodeling of adipose tissue in skeletal muscle with aging.'
Assuntos
Tecido Adiposo/crescimento & desenvolvimento , Tecido Adiposo/fisiologia , Envelhecimento/fisiologia , População Negra , Diabetes Mellitus/epidemiologia , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/fisiologia , Adulto , Idoso , População Negra/estatística & dados numéricos , Glicemia/análise , Índice de Massa Corporal , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Trinidad e TobagoRESUMO
BACKGROUND: Although obesity is strongly associated with diabetes, the greater prevalence of diabetes in persons of African ancestry than in those of other ancestries cannot be explained simply by differences in total or central adiposity. OBJECTIVE: We examined whether skeletal muscle composition is associated with diabetes in 1249 men of African ancestry aged >or=40 y. DESIGN: Anthropometry and fasting serum glucose were measured, and lower-leg skeletal muscle composition was assessed with peripheral quantitative computerized tomography (pQCT). RESULTS: The prevalence of diabetes in this population was high (21%). We observed an age-associated adipose tissue remodeling in skeletal muscle and greater intermuscular (IMAT) and lesser subcutaneous (SAT) adipose tissue area with advancing age (P < 0.0001). Multivariate stepwise logistic regression identified more IMAT and less SAT to be significantly associated with a greater prevalence of diabetes. Even among normal-weight men [body mass index (BMI; in kg/m(2)) < 25], diabetic men had significantly (P = 0.01) more IMAT than did those without diabetes. Greater IMAT was also associated with a greater prevalence of hyperglycemia in men with a family history of diabetes than in those without such history (P for interaction = 0.02). CONCLUSIONS: These findings underscore the independent associations of subcutaneous and intermuscular fat among men of African ancestry, an effect that may be modified by a family history of diabetes. Further studies are needed to identify the genetic and physiologic mechanisms that influence the distribution and remodeling of adipose tissue in skeletal muscle with aging.'