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1.
Diabetes Obes Metab ; 26(5): 1582-1592, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38246697

RESUMO

AIM: Chronotype reflects a circadian rhythmicity that regulates endothelial function. While the morning chronotype (MORN) usually has low cardiovascular disease risk, no study has examined insulin action on endothelial function between chronotypes. We hypothesized intermediate chronotypes (INT) would have lower vascular insulin sensitivity than morning chronotype (MORN). MATERIALS AND METHODS: Adults with obesity were classified per Morningness-Eveningness Questionnaire (MEQ) as either MORN (n = 27, 22 female, MEQ = 63.7 ± 4.7, 53.8 ± 6.7 years, 35.3 ± 4.9 kg/m2) or INT (n = 29, 23 female, MEQ = 48.8 ± 6.7, 56.6 ± 9.0 years, 35.7 ± 6.1 kg/m2). A 120 min euglycaemic-hyperinsulinaemic clamp (40 mU/m2/min, 90 mg/dl) was conducted to assess macrovascular insulin sensitivity via brachial artery flow-mediated dilation (%FMD; conduit artery), post-ischaemic flow velocity (resistance arteriole), as well as microvascular insulin sensitivity via contrast-enhanced ultrasound [e.g. microvascular blood volume (perfusion)]. Fasting plasma arginine and citrulline, as well as fasting and clamp-derived plasma endothelin-1 and nitrate/nitrite, were assessed as surrogates of vasoconstriction and nitric oxide-mediated vasodilation. Aerobic fitness (VO2max) and body composition (dual-energy X-ray absorptiometry) were also collected. RESULTS: MORN had a higher VO2max compared with INT (p < .01), although there was no difference in fat mass. While fasting FMD was similar between groups, insulin lowered FMD corrected to shear stress and microvascular blood volume in INT compared with MORN after co-varying for VO2max (both p ≤ .02). INT also had a lower fasting nitrate (p = .03) and arginine (p = .07). Higher MEQ correlated with elevated FMD (r = 0.33, p = .03) and lower post-ischaemic flow velocity (r = -0.33, p = .03) as well as shear rate (r = -0.36, p = .02) at 120 min. CONCLUSION: When measured during the morning, INT had a lower vascular insulin sensitivity than MORN. Additional work is needed to understand endothelial function differences among chronotypes to optimize cardiovascular disease risk reduction.


Assuntos
Doenças Cardiovasculares , Resistência à Insulina , Adulto , Humanos , Feminino , Cronotipo , Nitratos , Obesidade , Artéria Braquial/fisiologia , Insulina , Endotélio Vascular , Vasodilatação , Arginina
2.
Curr Cardiol Rep ; 26(3): 73-81, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38261251

RESUMO

PURPOSE OF REVIEW: In this narrative review, we discuss the current evidence related to the role of dietary interventions to prevent and treat type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). We also propose alternative therapeutic strategies other than weight loss in this population, namely, improvements in cardiorespiratory fitness and its determinants. RECENT FINDINGS: While weight loss has been consistently associated with the prevention of T2DM and improvements in glycemic control in those with established diseases, its role in preventing and treating CVD is less clear. In fact, in this setting, improvements in diet quality have provided greater benefits, suggesting that this might represent an alternative, or an even more effective strategy than energy-restriction. Improvements in diet quality, with and without caloric restriction have been shown to improve CVD risk and to prevent the development of T2DM in individuals at risk; however, with regard to glycemic control in patients with T2DM, any dietary intervention resulting in significant weight loss may produce clinically meaningful benefits. Finally, dietary interventions with and without energy restriction that can improve cardiorespiratory fitness, even in absence of weight loss in patients with obesity, should be encouraged.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/complicações , Obesidade/complicações , Obesidade/terapia , Dieta , Redução de Peso
3.
J Physiol ; 601(22): 5033-5050, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35081660

RESUMO

Extracellular vesicles (EVs) are often elevated in obesity and may modulate disease risk. Although acute exercise reduces fasting EVs in adults with obesity, no data exist on insulin-mediated EV responses. This study evaluated the effects of exercise on EV responses to insulin in relation to vascular function. Ten (5M/5F) sedentary adults with obesity (34.3 ± 3.7 kg/m2 ) completed an evening control and acute exercise condition (70% V ̇ O 2 max ${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ to expend 400 kcal). Following an overnight fast, participants underwent a 2 h euglycaemic-hyperinsulinaemic clamp (90 mg/dl; 40 mU/m2 /min) to determine metabolic insulin sensitivity (M-value), phenotypes of medium- to large-sized EVs, and aortic waveform measures. Endothelial (CD105+ , CD41- /CD31+ )-, leukocyte (CD45+ )-, platelet (CD41+ , CD41+ /31+ )- and tetraspanin (TX+ )-derived EVs, as well as platelet endothelial cell adhesion molecule (CD31+ ), were determined before and after the clamp using high resolution spectral flow cytometry. Although exercise did not alter fasting haemodynamics, it lowered the augmentation index (AIx75, P = 0.024) and increased the M-value (P = 0.042). Further, exercise decreased all fasting EVs (P < 0.01) and decreased insulin-stimulated TX+ (P = 0.060), CD31+ (P = 0.060) and CD41- /31+ (P = 0.045) compared to rest. Interestingly, greater insulin-stimulated decreases in CD41- /31+ were associated with reduced AIx75 during the clamp (r = 0.62, P = 0.059), while insulin-stimulated decreases in CD41+ (r = -0.68, P = 0.031), CD41+ /31+ (r = -0.69, P = 0.262), TX+ (r = -0.66, P = 0.037) and CD31+ (r = -0.69, P = 0.028) correlated with M-value following exercise. Thus, acute exercise may decrease fasting and insulin-stimulated medium- to large-size EVs in conjunction with improved M-value and AIx75. More research is needed to understand effects of exercise on EVs in the regulation of glucose homeostasis and vascular function. KEY POINTS: Extracellular vesicles (EVs) are increased in states of obesity and may play a role in altered insulin sensitivity and blood pressure; aerobic exercise decreases fasting EV concentrations the following day in adults with obesity. This study directly tested the effects of insulin on EVs and how a single bout of exercise impacts these responses. Together, these data highlight the positive effects of a single bout of exercise on fasting and insulin-stimulated EVs, with the latter relating to increased insulin sensitivity and decreased augmentation index. These results support future research identifying EVs as mechanistic factors in glucose regulation and vascular function as well as clinical use of exercise to reduce cardiovascular disease risk.


Assuntos
Vesículas Extracelulares , Resistência à Insulina , Humanos , Adulto , Insulina/metabolismo , Resistência à Insulina/fisiologia , Obesidade/metabolismo , Exercício Físico/fisiologia , Glucose/metabolismo , Vesículas Extracelulares/metabolismo
4.
Am J Physiol Endocrinol Metab ; 323(4): E378-E388, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35858245

RESUMO

Elevated extracellular vesicles (EVs) are associated with glucose dysmetabolism. However, the effects of insulin on EVs and subsequent relationships with insulin sensitivity, substrate oxidation, and inflammation are unknown. We tested the hypothesis that insulin would lower EVs and relate to insulin action. Fifty-one sedentary adults (54.8 ± 1.0 yr; V̇o2peak : 22.1 ± 0.6 mL/kg/min) with metabolic syndrome (MetS) and obesity (36.4 ± 0.65 kg/m2) underwent a 2-h euglycemic-hyperinsulinemic clamp (5 mmol/L; 40 mU/m2/min). Count and size (medium: 200-624 nm; larger: 625-1,000 nm) for total particle count, endothelial- (CD105+), leukocyte- (CD45+), platelet- (CD41+), and tetraspanin- (TX+: CD9/CD81/CD63), as well as platelet endothelial cell adhesion molecule- (CD31+) derived EVs were determined before and following the clamp using Full Spectrum Profiling (FSPM). Size and MESF (molecules of equivalent soluble fluorochrome) data were generated using FCMPASS Software. Fat and carbohydrate oxidation, in addition to high-sensitivity c-reactive protein (hsCRP), were measured to understand insulin effects and associations between EVs, metabolic flexibility, and inflammation. Despite low metabolic insulin sensitivity (M-Value = 2.56 ± 0.17 mg/kg/min), insulin increased carbohydrate (P = 0.015) and decreased fat oxidation (P = 0.048) and hsCRP (P = 0.016) compared with fasting. Insulin also decreased total particle count (P < 0.001), attributable to decreased medium-sized CD105+ (P = 0.052) and CD45+ EVs (P < 0.001). Elevated fasting insulin was associated with reduced insulin-stimulated changes in all EVs phenotypes (P < 0.001). Interestingly, fasting EVs were associated with increased fasting carbohydrate oxidation (all P < 0.05). These findings suggest that insulin decreases medium-sized EVs in conjunction with metabolic flexibility under euglycemic conditions in adults with MetS. More research is needed to determine how therapies alter EV phenotype/size and consequent cardiometabolic risk.NEW & NOTEWORTHY This study is one of the first to investigate the effects of insulin on medium and larger extracellular vesicles (EVs) in relation to metabolic insulin sensitivity and fuel use in adults with metabolic syndrome. Our data suggest that insulin infusion decreases the concentration of total particle counts, mainly due to reductions in medium-sized EVs. Furthermore, EVs, predominantly medium-sized, are inversely associated with metabolic flexibility.


Assuntos
Vesículas Extracelulares , Resistência à Insulina , Síndrome Metabólica , Proteína C-Reativa , Moléculas de Adesão Celular/metabolismo , Vesículas Extracelulares/metabolismo , Corantes Fluorescentes/metabolismo , Glucose/metabolismo , Humanos , Inflamação/metabolismo , Insulina/metabolismo , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo
5.
J Vasc Res ; 59(3): 151-162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35272284

RESUMO

INTRODUCTION: Nocturnal systolic blood pressure (SBP) dipping is independently related to cardiovascular disease risk, but it is unclear if vascular insulin sensitivity associates with SBP dipping in patients with metabolic syndrome (MetS). METHODS: Eighteen adults with MetS (ATP III criteria 3.3 ± 0.6; 53.2 ± 6.5 years; body mass index 35.8 ± 4.5 kg/m2) were categorized as "dippers" (≥10% change in SBP; n = 4 F/3 M) or "non-dippers" (<10%; n = 9 F/2 M). Twenty-four-hour ambulatory blood pressure was recorded to assess SBP dipping. A euglycemic-hyperinsulinemic clamp (40 mU/m2/min, 90 mg/dL) with ultrasound (flow mediated dilation) was performed to test vascular insulin sensitivity. A graded, incremental exercise test was conducted to estimate sympathetic activity. Heart rate (HR) recovery after exercise was then used to determine parasympathetic activity. Metabolic panels and body composition (DXA) were also tested. RESULTS: Dippers had greater drops in SBP (16.63 ± 5.2 vs. 1.83 ± 5.6%, p < 0.01) and experienced an attenuated rise in both SBPslope (4.7 ± 2.3 vs. 7.2 ± 2.5 mm Hg/min, p = 0.05) and HRslope to the incremental exercise test compared to non-dippers (6.5 ± 0.9 vs. 8.2 ± 1.7 bpm/min, p = 0.03). SBP dipping correlated with higher insulin-stimulated flow-mediated dilation (r = 0.52, p = 0.03), although the relationship was no longer significant after covarying for HRslope (r = 0.42, p = 0.09). CONCLUSION: Attenuated rises in blood pressure and HR to exercise appear to play a larger role than vascular insulin sensitivity in SBP dipping in adults with MetS.


Assuntos
Pressão Sanguínea , Exercício Físico/fisiologia , Hipertensão , Resistência à Insulina/fisiologia , Síndrome Metabólica/fisiopatologia , Adulto , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano/fisiologia , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Síndrome Metabólica/diagnóstico
6.
Exp Physiol ; 107(11): 1255-1264, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36123314

RESUMO

NEW FINDINGS: What is the central question of this study? Chronotype reflects differences in circadian-mediated metabolic and hormonal profiles. But, does resting and/or exercise fuel use differ in early versus late chronotype as it relates to insulin sensitivity? What are the main finding and its importance? Early chronotypes with metabolic syndrome utilized more fat during rest and exercise independent of aerobic fitness when compared with late chronotypes. Early chronotypes were also more physically active throughout the day. Greater fat use was related to non-oxidative glucose disposal. These findings suggest that early chronotypes have differences in fuel selection that associate with type 2 diabetes risk. ABSTRACT: Early chronotypes (ECs) are often insulin-sensitive, in part, due to physical activity behaviour. It is unclear, however, if chronotypes differ in resting and/or exercise fuel oxidation in relation to insulin action. Using the Morningness-Eveningness Questionnaire (MEQ), adults with metabolic syndrome (ATP III criteria) were classified as EC (MEQ = 63.7 ± 0.9, n = 24 (19F), 54.2 ± 1.2 years) or late chronotype (LC; MEQ = 47.2 ± 1.4, n = 27 (23F), 55.3 ± 1.5 years). Carbohydrate (CHO) and fat oxidation (FOX, indirect calorimetry) were determined at rest, 55% and 85% V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ , along with heart rate and rating of perceived exertion. Physical activity patterns (accelerometers), body composition (DXA) and insulin sensitivity (clamp, 40 mU/m2 /min, 90 mg/dl) with an indirect calorimetry for non-oxidative glucose disposal (NOGD) were also determined. While demographics were similar, ECs had higher V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ (P = 0.02), NOGD (P < 0.001) and resting FOX (P = 0.02) than LCs. Both groups increased CHO reliance during exercise at 55% and 85% V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ (test effect, P < 0.01) from rest, although ECs used more fat (group effect, P < 0.01). ECs had lower sedentary behaviour and more physical activity during morning/midday (both, P < 0.05). FOX at 55% V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ correlated with V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ (r = 0.425, P = 0.004) whereas FOX at 85% V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ related to NOGD (r = 0.392, P = 0.022). ECs with metabolic syndrome used more fat in relation to insulin-stimulated NOGD.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Síndrome Metabólica , Adulto , Humanos , Insulina , Glucose/metabolismo , Glicemia/metabolismo , Exercício Físico/fisiologia
7.
Curr Oncol Rep ; 24(5): 555-561, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35199294

RESUMO

PURPOSE OF REVIEW: Although cancer treatments have increased overall survival rates, the cardiovascular consequences of cancer therapy place patients at an increased risk of adverse outcomes. This manuscript presents data accumulated to date regarding cardiovascular outcomes relating to the administration of 3-hydroxy-3-methylglutarylcoenzyme-A reductase inhibitor (or statin) therapy in individuals receiving potentially cardiotoxic cancer treatments. RECENT FINDINGS: Retrospective observational studies in humans and randomized controlled trials in animals suggest that statins may reduce cancer-specific and all-cause mortality. Further, statins may attenuate cancer therapy-induced declines in left ventricular ejection fraction (LVEF) and increases in blood pressure. Observational studies suggest a potential attenuation in LVEF decline in patients with cancer and primary or secondary indications to receive a statin for prevention of cardiovascular events. Large randomized clinical trials are warranted to understand the efficacy and potential impacts of statin class, dosage, and duration on cardiovascular outcomes in patients treated for cancer.


Assuntos
Insuficiência Cardíaca , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias , Animais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
8.
Am J Physiol Heart Circ Physiol ; 320(6): H2305-H2312, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33861146

RESUMO

Adults with metabolic syndrome (MetS) have increased fasting arterial stiffness and altered central hemodynamics that contribute, partly, to increased cardiovascular disease (CVD) risk. Although insulin affects aortic wave reflections in healthy adults, the effects in individuals with MetS are unclear. We hypothesized that insulin stimulation would reduce measures of pressure waveforms and hemodynamics in people with MetS. Thirty-five adults with obesity (27 women; 54.2 ± 6.0 yr; 37.1 ± 4.8 kg/m2) were selected for MetS (ATP III criteria) following an overnight fast. Pulse wave analysis was assessed using applanation tonometry before and after a 2-h euglycemic-hyperinsulinemic clamp (90 mg/dL, 40 mU/m2/min). Deconvolution analysis was used to decompose the aortic waveform [augmentation index corrected to heart rate of 75 beats/min (AIx@75); augmentation pressure (AP)] into backward and forward pressure components. Aerobic fitness (V̇o2max), body composition (DXA), and blood biochemistries were also assessed. Insulin significantly reduced augmentation index (AIx@75, 28.0 ± 9.6 vs. 23.0 ± 9.9%, P < 0.01), augmentation pressure (14.8 ± 6.4 vs. 12.0 ± 5.7 mmHg, P < 0.01), pulse pressure amplification (1.26 ± 0.01 vs. 0.03 ± 0.01, P = 0.01), and inflammation [high-sensitivity C-reactive protein (hsCRP): P = 0.02; matrix metallopeptidase 7 (MMP-7): P = 0.03] compared to fasting. In subgroup analyses to understand HTN influence, there were no insulin stimulation differences on any outcome. V̇o2max, visceral fat, and blood potassium correlated with fasting AIx@75 (r = -0.39, P = 0.02; r = 0.41, P = 0.03; r = -0.53, P = 0.002). Potassium levels were also associated with insulin-mediated reductions in AP (r = 0.52, P = 0.002). Our results suggest insulin stimulation improves indices of aortic reflection in adults with MetS.NEW & NOTEWORTHY This study is one of the first to investigate the effects of insulin on central and peripheral hemodynamics in adults with metabolic syndrome. We provide evidence that insulin infusion reduces aortic wave reflection, potentially through a reduction in inflammation and/or via a potassium-mediated vascular response.


Assuntos
Aorta/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Insulina/farmacologia , Síndrome Metabólica/fisiopatologia , Análise de Onda de Pulso , Rigidez Vascular/efeitos dos fármacos , Aorta/fisiopatologia , Composição Corporal , Aptidão Cardiorrespiratória , Feminino , Técnica Clamp de Glucose , Hemodinâmica/efeitos dos fármacos , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Consumo de Oxigênio , Rigidez Vascular/fisiologia
9.
Exp Physiol ; 105(4): 632-640, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020676

RESUMO

NEW FINDINGS: What is the central question of this study? What are the effects of work-matched continuous versus high-intensity interval training for 2 weeks on adiposopathy and cardiometabolic risk in obese adults with prediabetes? What is the main finding and its importance? Independent of intensity, short-term exercise improves adiposopathy and insulin sensitivity. While both exercise intensities reduced fasting leptin concentrations and metabolic syndrome severity, only interval training elevated total adiponectin. In contrast to previous work, neither condition altered high-molecular weight adiponectin. Collectively, these data suggest that short-term exercise can improve adipokine profiles, which may aid in reducing cardiometabolic risk prior to clinically meaningful weight loss in adults with prediabetes. ABSTRACT: Individuals with prediabetes who are overweight and obese are at an increased risk of developing endocrine disruption of fat tissue, known as adiposopathy. While short-term exercise improves adipokine profiles, the effects of exercise intensity when matched for energy expenditure on adiposopathy are unknown. We hypothesized that high-intensity exercise would elicit greater changes in adiposopathy compared to moderate exercise. Twenty-eight overweight and obese adults (age: 60.9 ± 8.4 years; BMI: 33.0 ± 5.4 kg m-2 ) with prediabetes were randomized to twelve 60-min sessions of either moderate-continuous (CONT; n = 14) or high-intensity interval (INT; n = 14) exercise training. Total and high molecular weight (HMW) adiponectin and leptin were collected to assess adiposopathy (ratio of total adiponectin to leptin; A/L). Insulin sensitivity (SIIS ) was determined using a 75 g oral glucose tolerance test before and after training. Cardiometabolic risk factors were measured and a z-score was calculated to determine metabolic syndrome (MetS) severity. CONT and INT increased A/L (P < 0.01) and decreased leptin (P < 0.01) and MetS severity (P = 0.04). Neither intervention altered circulating levels of HMW adiponectin (P = 0.76) and only INT increased total adiponectin levels (P = 0.02). Both intensities increased insulin sensitivity (P < 0.01), which was associated with improvements in A/L (r = 0.47, P = 0.01). Additionally, increases in A/L tended to relate to decreased MetS severity (r = -0.36, P = 0.09). Short-term exercise intensity, when matched for energy expenditure, does not differentially affect improvements in adiposopathy in overweight and obese adults with prediabetes. Further, 12 bouts of exercise improved insulin sensitivity and MetS severity, suggesting that improving adipokine profiles may aid in reducing cardiometabolic risk.


Assuntos
Tecido Adiposo/fisiopatologia , Exercício Físico/fisiologia , Resistência à Insulina/fisiologia , Síndrome Metabólica/fisiopatologia , Adiponectina/metabolismo , Índice de Massa Corporal , Metabolismo Energético/fisiologia , Jejum/fisiologia , Feminino , Teste de Tolerância a Glucose , Treinamento Intervalado de Alta Intensidade , Humanos , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Consumo de Oxigênio/fisiologia , Estado Pré-Diabético/fisiopatologia , Redução de Peso/fisiologia
10.
Adv Exp Med Biol ; 1134: 271-294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30919343

RESUMO

The development of obesity is cornerstone in the etiology of metabolic and vascular insulin resistance and consequently exacerbates glycemic control. Exercise is an efficacious first-line therapy for type 2 diabetes that improves insulin action through, in part, reducing hormone mediated inflammation. Together, improving the coordination of skeletal muscle metabolism with vascular delivery of glucose will be required for optimizing type 2 diabetes and cardiovascular disease treatment.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Exercício Físico , Mediadores da Inflamação/análise , Resistência à Insulina , Humanos
11.
J Sports Sci Med ; 18(4): 636-644, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31827347

RESUMO

Prediabetes is associated with impaired oxidative capacity and altered substrate utilization during exercise. The effects of continuous (CONT) versus interval (INT) exercise training on fat oxidation during an acute exercise bout at the same absolute and relative intensities are unknown in this population. Obese females/males (n = 17, n = 5) with prediabetes (BMI 32.2 ± 1.2 kg·m-2; age 62.8 ± 1.6 y; fasting glucose 103.4 ± 1.6 mg·dL-1; 2-hour glucose 153.7 ± 7.1 mg·dL-1; VO2peak 19.9 ± 1.0 mL·kg-1·min-1) were screened with a 75g OGTT. Subjects completed a peak oxygen consumption test and a submaximal exercise substrate utilization test consisting of 5min stages at absolute (30W) and relative (70%HRpeak) intensities before and after randomization to 12 sessions (60min each) of CONT (70% HRpeak) or INT (alternating 3min 90% HRpeak, 3min 50% HRpeak) over a two-week period. Body mass decreased and VO2peak increased more after INT than CONT (INT: -0.6 ± 0.2 kg, CONT: -0.1 ± 0.2 kg; p = 0.04; INT: 1.9 ± 0.6 mL/kg/min, CONT: 0.1 ± 0.6 mL·kg-1·min-1; p = 0.04). Training increased fat oxidation by 0.7 ± 0.2 mL·kg-1·min-1 during the absolute intensity test (p < 0.001), independent of intensity. During the relative intensity test, fat oxidation increased more after INT than CONT (INT: 1.3 ± 0.4 mL·kg-1·min-1, CONT: 0.3 ± 0.3 mL·kg-1·min-1; p = 0.03), with no difference in exercise energy expenditure between groups. Enhanced fat oxidation during the relative test was correlated with increased VO2peak (r = 0.53 p = 0.01). High intensity INT training enhances fat oxidation during the same relative intensity exercise in people with prediabetes.


Assuntos
Tecido Adiposo/metabolismo , Treinamento Intervalado de Alta Intensidade , Obesidade/metabolismo , Estado Pré-Diabético/metabolismo , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Aptidão Cardiorrespiratória/fisiologia , Metabolismo Energético/fisiologia , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Oxirredução , Consumo de Oxigênio/fisiologia , Percepção/fisiologia , Esforço Físico/fisiologia , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações
12.
Chronobiol Int ; 41(3): 427-438, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38317499

RESUMO

Late chronotype (LC) is related to obesity and altered food intake throughout the day. But whether appetite perception and gut hormones differ among chronotypes is unclear. Thus, we examined if early chronotype (EC) have different appetite responses in relation to food intake than LC. Adults with obesity were categorized using the Morningness-Eveningness Questionnaire (MEQ) as either EC (n = 21, 18F, MEQ = 63.9 ± 1.0, 53.7 ± 1.2 yr, 36.2 ± 1.1 kg/m2) and LC (n = 28, 24F, MEQ = 47.2 ± 1.5, 55.7 ± 1.4 yr, 37.1 ± 1.0 kg/m2). Visual analog scales were used during a 120 min 75 g oral glucose tolerance test (OGTT) at 30 min intervals to assess appetite perception, as well as glucose, insulin, GLP-1 (glucagon-like polypeptide-1), GIP (glucose-dependent insulinotrophic peptide), PYY (protein tyrosine tyrosine), and acylated ghrelin. Dietary intake (food logs), resting metabolic rate (RMR; indirect calorimetry), aerobic fitness (maximal oxygen consumption (VO2max)), and body composition dual-energy X-ray absorptiometry (DXA) were also assessed. Age, body composition, RMR, and fasting appetite were similar between groups. However, EC had higher satisfaction and fullness as well as reduced desires for sweet, salty, savory, and fatty foods during the OGTT (P <0.05). Only GIP tAUC0-120 min was elevated in EC versus LC (p = 0.01). Daily dietary intake was similar between groups, but EC ate fewer carbohydrates (p = 0.05) and more protein (p = 0.01) at lunch. Further, EC had lower caloric (p = 0.03), protein (p = 0.03) and fat (p = 0.04) intake during afternoon snacking compared to LC. Dietary fat was lower, and carbohydrates was higher, in EC than LC (p = 0.05) at dinner. Low glucose and high insulin as well as GLP-1 tAUC60-120 min related to desires for sweet foods (p < 0.05). Taken together, EC had more favorable appetite and lower caloric intake later in the day compared with LC.


Assuntos
Apetite , Cronotipo , Adulto , Humanos , Apetite/fisiologia , Ritmo Circadiano , Obesidade/metabolismo , Insulina , Ingestão de Energia/fisiologia , Grelina , Peptídeo 1 Semelhante ao Glucagon , Glucose , Carboidratos , Tirosina , Glicemia/metabolismo
13.
Cardiooncology ; 10(1): 34, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845066

RESUMO

BACKGROUND: To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma. METHODS: Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change. RESULTS: Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047). CONCLUSIONS: These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet. TRIAL REGISTRATION: DETECTIV_NCT01719562, WF99112, & WF97415-NCT02791581.

14.
J Diabetes Res ; 2023: 4618215, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780967

RESUMO

ß-Aminoisobutyric acid (BAIBA) is secreted by skeletal muscle and promotes insulin sensitivity, fat oxidation, and anti-inflammation. While BAIBA is purportedly lower in individuals with obesity, no work has examined if prediabetes (PD) differentially impacts BAIBA concentrations in people with obesity. Methods. Adults were classified as normal glucose tolerant (NGT; n = 22 (20F); 48.0 ± 2.4 yrs; 36.9 ± 1.2 kg/m2) or PD (n = 23 (18F); 54.2 ± 1.6 yrs; 38.4 ± 1.2 kg/m2) based on ADA criteria. A 180-minute 75 g OGTT was used to estimate fasting (HOMA-IR (liver)) and postprandial (Matsuda index (muscle)) insulin sensitivity as well as ß-cell function (disposition index (DI), glucose-stimulated insulin secretion adjusted for insulin sensitivity). Body composition and fasting measures of BAIBA, fat oxidation (indirect calorimetry), and adipokines were determined. Results. NGT and PD had similar BAIBA concentrations (1.4 ± 0.1 vs. 1.2 ± 0.1 µM, P = 0.23) and fat oxidation (P = 0.31), despite NGT having lower fasting (92.2 ± 1.2 vs. 104.1 ± 3.2 mg/dL, P = 0.002) and tAUC180min glucose (P < 0.001) compared to PD. Moreover, NGT had higher postprandial insulin sensitivity (P = 0.01) and higher total phase DIliver (P = 0.003) and DImuscle (P = 0.001). Increased BAIBA was associated with adiponectin (r = 0.37, P = 0.02), adiponectin/leptin ratio (r = 0.39, P = 0.01), and lower glucose and insulin at 180 minutes (r = -0.31, P = 0.03 and r = -0.39, P = 0.03, respectively). Adiponectin also correlated with lower glucose at 180 minutes (r = -0.45, P = 0.005), and mediation analysis showed that BAIBA was no longer a significant predictor of glucose at 180 minutes after controlling for adiponectin (P = 0.08). Conclusion. While BAIBA did not differ between NGT and PD, higher BAIBA is related to favorable glucose metabolism, possibly through an adiponectin-related mechanism. Additional work is required to understand how exercise and/or diet impact BAIBA in relation to type 2 diabetes risk.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Estado Pré-Diabético , Humanos , Adulto , Adiponectina , Resistência à Insulina/fisiologia , Diabetes Mellitus Tipo 2/complicações , Obesidade/complicações , Obesidade/metabolismo , Glucose/metabolismo , Insulina , Glicemia/metabolismo
15.
Physiol Rep ; 11(1): e15530, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36597186

RESUMO

Metabolic Syndrome (MetS) raises cardiovascular disease risk. Extracellular vesicles (EVs) have emerged as important mediators of insulin sensitivity, although few studies on vascular function exist in humans. We determined the effect of insulin on EVs in relation to vascular function. Adults with MetS (n = 51, n = 9 M, 54.8 ± 1.0 years, 36.4 ± 0.7 kg/m2 , ATPIII: 3.5 ± 0.1 a.u., VO2 max: 22.1 ± 0.6 ml/kg/min) were enrolled in this cross-sectional study. Peripheral insulin sensitivity (M-value) was determined during a euglycemic clamp (40 mU/m2 /min, 90 mg/dl), and blood was collected for EVs (CD105+, CD45+, CD41+, TX+, and CD31+; spectral flow cytometry), inflammation, insulin, and substrates. Central hemodynamics (applanation tonometry) was determined at 0 and 120 min via aortic waveforms. Pressure myography was used to assess insulin-induced arterial vasodilation from mouse 3rd order mesenteric arteries (100-200 µm in diameter) at 0.2, 2 and 20 nM of insulin with EVs from healthy and MetS adults. Adults with MetS had low peripheral insulin sensitivity (2.6 ± 0.2 mg/kg/min) and high HOMA-IR (4.7 ± 0.4 a.u.) plus Adipose-IR (13.0 ± 1.3 a.u.). Insulin decreased total/particle counts (p < 0.001), CD45+ EVs (p = 0.002), AIx75 (p = 0.005) and Pb (p = 0.04), FFA (p < 0.001), total adiponectin (p = 0.006), ICAM (p = 0.002), and VCAM (p = 0.03). Higher M-value related to lower fasted total EVs (r = -0.40, p = 0.004) while higher Adipose-IR associated with higher fasted EVs (r = 0.42, p = 0.004) independent of VAT. Fasting CD105+ and CD45+ derived total EVs correlated with fasting AIx75 (r = 0.29, p < 0.05) and Pb (r = 0.30, p < 0.05). EVs from MetS participants blunted insulin-induced vasodilation in mesenteric arteries compared with increases from healthy controls across insulin doses (all p < 0.005). These data highlight EVs as potentially novel mediators of vascular insulin sensitivity and disease risk.


Assuntos
Vesículas Extracelulares , Resistência à Insulina , Síndrome Metabólica , Adulto , Humanos , Animais , Camundongos , Insulina , Estudos Transversais , Chumbo/metabolismo , Obesidade/metabolismo , Vesículas Extracelulares/metabolismo
16.
JACC CardioOncol ; 5(5): 641-652, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37969655

RESUMO

Background: Cancer treatment increases cardiovascular disease risk, but physical activity (PA) may prevent cardiovascular disease. Objectives: This study examined whether greater PA was associated with better submaximal exercise capacity and cardiac function during cancer therapy. Methods: Participants included 223 women with stage I to III breast cancer (BC) before and 3 months after undergoing treatment and 126 control participants. Leisure-time PA (LTPA) was reported using the Godin-Shephard LTPA questionnaire. Cardiac function was assessed by cardiac magnetic resonance. Submaximal exercise capacity was determined by 6-minute walk distance. Results: BC participants reported similar baseline LTPA scores (24.7; 95% CI: 21.7-28.0) as control participants (29.4; 95% CI: 25.0-34.2). The BC group declined to 16.9 (95% CI: 14.4-19.6) at 3 months relative to 30.8 (95% CI: 26.2-35.8) in control participants. Among BC participants, more LTPA was related to better exercise capacity (ß ± SE: 7.1 ± 1.6; 95% CI: 4.0-10.1) and left ventricular (LV) circumferential strain (-0.16 ± 0.07; 95% CI: -0.29 to -0.02). Increased LTPA over the 3 months was associated with decreased likelihood of treatment-induced cardiac dysfunction according to LV circumferential strain classifications (OR: 0.98; 95% CI: 0.97-0.998). BC participants reporting insufficient LTPA according to PA guidelines exhibited deteriorations in exercise capacity (adjusted mean difference ± SE: -29 ± 10 m; P = 0.029), LV end-systolic volume (5.8 ± 1.3 mL; P < 0.001), LV ejection fraction (-3.2% ± 0.8%; P = 0.002), and LV circumferential strain (2.5% ± 0.5%; P < 0.001), but BC participants meeting LTPA guidelines did not exhibit these adverse changes. Conclusions: PA declined during BC therapy; however, PA participation was associated with attenuated declines in exercise capacity and cardiac function that are often observed in this population. (Understanding and Predicting Breast Cancer Events After Treatment [WF97415 UPBEAT]; NCT02791581).

17.
Physiol Rep ; 10(20): e15473, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36301720

RESUMO

Late chronotype (LC) correlates with reduced metabolic insulin sensitivity and cardiovascular disease. It is unclear if insulin action on aortic waveforms and inflammation is altered in LC versus early chronotype (EC). Adults with metabolic syndrome (n = 39, MetS) were classified as either EC (Morning-Eveningness Questionnaire [MEQ] = 63.5 ± 1.2) or LC (MEQ = 45.5 ± 1.3). A 120 min euglycemic clamp (40 mU/m2 /min, 90 mg/dL) with indirect calorimetry was used to determine metabolic insulin sensitivity (glucose infusion rate [GIR]) and nonoxidative glucose disposal (NOGD). Aortic waveforms via applanation tonometry and inflammation by blood biochemistries were assessed at 0 and 120 min of the clamp. LC had higher fat-free mass and lower VO2 max, GIR, and NOGD (between groups, all p ≤ 0.05) than EC. Despite no difference in 0 min waveforms, both groups had insulin-stimulated elevations in pulse pressure amplification with reduced AIx75 and augmentation pressure (AP; time effect, p ≤ 0.05). However, EC had decreased forward pressure (Pf; interaction effect, p = 0.007) with insulin versus rises in LC. Although LC had higher tumor necrosis factor-α (TNF-α; group effect, p ≤ 0.01) than EC, both LC and EC had insulin-stimulated increases in TNF-α and decreases in hs-CRP (time effect, both p ≤ 0.01). Higher MEQ scores related to greater insulin-stimulated reductions in AP (r = -0.42, p = 0.016) and Pf (r = -0.41, p = 0.02). VO2 max correlated with insulin-mediated reductions in AIx75 (r = -0.56, p < 0.01) and AP (r = -0.49, p < 0.01). NOGD related to decreased AP (r = -0.44, p = 0.03) and Pf (r = -0.43, p = 0.04) during insulin infusion. LC was depicted by blunted forward pressure waveform responses to insulin and higher TNF-α in MetS. More work is needed to assess endothelial function across chronotypes.


Assuntos
Hiperinsulinismo , Resistência à Insulina , Síndrome Metabólica , Adulto , Humanos , Insulina , Resistência à Insulina/fisiologia , Fator de Necrose Tumoral alfa , Glucose/metabolismo , Inflamação , Glicemia/metabolismo
18.
J Clin Endocrinol Metab ; 107(8): e3487-e3496, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35429387

RESUMO

CONTEXT: People characterized as late chronotype have elevated type 2 diabetes and cardiovascular disease risk compared to early chronotype. It is unclear how chronotype is associated with insulin sensitivity, metabolic flexibility, or plasma TCA cycle intermediates concentration, amino acids (AA), and/or beta-oxidation. OBJECTIVE: This study examined these metabolic associations with chronotype. METHODS: The Morningness-Eveningness Questionnaire (MEQ) was used to classify adults with metabolic syndrome (ATP III criteria) as either early (n = 15 [13F], MEQ = 64.7 ±â€…1.4) or late (n = 19 [16F], MEQ = 45.5 ±â€…1.3) chronotype. Fasting bloods determined hepatic (HOMA-IR) and adipose insulin resistance (Adipose-IR) while a 120-minute euglycemic clamp (40 mU/m2/min, 5 mmoL/L) was performed to test peripheral insulin sensitivity (glucose infusion rate). Carbohydrate (CHOOX) and fat oxidation (FOX), as well as nonoxidative glucose disposal (NOGD), were also estimated (indirect calorimetry). Plasma tricarboxylic acid cycle (TCA) intermediates, AA, and acyl-carnitines were measured along with VO2max and body composition (DXA). RESULTS: There were no statistical differences in age, BMI, fat-free mass, VO2max, or ATP III criteria between groups. Early chronotype, however, had higher peripheral insulin sensitivity (P = 0.009) and lower HOMA-IR (P = 0.02) and Adipose-IR (P = 0.05) compared with late chronotype. Further, early chronotype had higher NOGD (P = 0.008) and greater insulin-stimulated CHOOX (P = 0.02). While fasting lactate (P = 0.01), TCA intermediates (isocitrate, α-ketoglutarate, succinate, fumarate, malate; all P ≤ 0.04) and some AA (proline, isoleucine; P = 0.003-0.05) were lower in early chronotype, other AA (threonine, histidine, arginine; all P ≤ 0.05) and most acyl-carnitines were higher (P ≤ 0.05) compared with late chronotype. CONCLUSION: Greater insulin sensitivity and metabolic flexibility relates to plasma TCA concentration in early chronotype.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Síndrome Metabólica , Trifosfato de Adenosina/metabolismo , Adulto , Glicemia/metabolismo , Ciclo do Ácido Cítrico , Glucose/metabolismo , Técnica Clamp de Glucose , Humanos , Insulina/metabolismo
19.
Med Sci Sports Exerc ; 53(4): 796-803, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32925495

RESUMO

PURPOSE: Arterial stiffness is considered a predictor of cardiovascular disease. Females have higher values of arterial stiffness than males, suggesting a greater risk of heart-related complications. Although a low-calorie diet (LCD) reduces fasting arterial stiffness, in part through weight loss, it is unknown if interval exercise (INT) adds to the benefit of LCD on fasting and postprandial arterial stiffness in females with obesity. METHODS: Twenty-five females (47 ± 2.6 yr, 37.6 ± 1.3 kg·m-2) were randomized to 13 d of LCD (n = 12; mixed meals of ~1200 kcal·d-1) or LCD + INT (n = 13; 60 min·d-1 of supervised 3-min intervals at 90% HRpeak and 50% HRpeak). Arterial stiffness (augmentation index [AIx] and carotid-femoral pulse wave velocity [cfPWV]) and blood biochemistries were measured during a 75-g oral glucose tolerance test before and after the intervention to determine fasting and postprandial arterial stiffness as well as insulin sensitivity (simple index of insulin sensitivity [SIIS]) and inflammation (C-reactive protein, interleukin 8, and tumor necrosis factor alpha). RESULTS: Although LCD + INT increased V˙O2peak and HDL compared with LCD (P = 0.04 and P < 0.01, respectively), both interventions decreased body fat, LDL, total cholesterol, and triglycerides (all P < 0.01) and increased SIIS (P = 0.03). Despite no effect on fasting AIx (P = 0.27), LCD and LCD + INT decreased AIx60min (-7.4% ± 4.3% vs -7.0% ± 5.0%, P = 0.04) and tAUC120min (-663 ± 263 vs -457 ± 406, P = 0.03). There were no changes in fasting cfPWV (P = 0.91) or cfPWV120min (P = 0.62). Increased SIIS and decreased interleukin 8 were associated with reduced fasting AIx (r = -0.44, P = 0.03, and r = 0.40, P = 0.055), whereas decreased C-reactive protein correlated with reduced postprandial AIx60min (r = 0.43, P = 0.04). CONCLUSION: Independent of exercise, 13 d of LCD reduces postprandial AIx in females with obesity. Insulin sensitivity and inflammation correlated with improved arterial stiffness, suggesting unique mechanisms regulate fasted versus postprandial arterial stiffness.


Assuntos
Restrição Calórica , Exercício Físico/fisiologia , Jejum/fisiologia , Obesidade/fisiopatologia , Período Pós-Prandial/fisiologia , Rigidez Vascular/fisiologia , Aorta/fisiologia , Composição Corporal , Feminino , Teste de Tolerância a Glucose , Frequência Cardíaca/fisiologia , Humanos , Inflamação/sangue , Resistência à Insulina , Menopausa , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/dietoterapia , Aptidão Física , Análise de Onda de Pulso , Fatores de Tempo , Redução de Peso/fisiologia
20.
Obesity (Silver Spring) ; 29(9): 1487-1496, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34339111

RESUMO

OBJECTIVE: This crossover study explored the impact of a single bout of exercise on insulin-stimulated responses in conduit arteries and capillaries. METHODS: Twelve sedentary adults (49.5 [7.8] years; maximal oxygen consumption [VO2 max]: 23.7 [5.4] mL/kg/min) with obesity (BMI 34.5 [4.3] kg/m2 ) completed a control and exercise bout (70% VO2 max to expend 400 kcal). Sixteen hours later, participants underwent a 2-hour euglycemic-hyperinsulinemic clamp (90 mg/dL; 40 mU/m2 /min) to determine vascular and metabolic insulin sensitivity. Endothelial and capillary functions were assessed by brachial artery flow-mediated dilation and contrast-enhanced ultrasound, respectively. Metabolized glucose infusion rate, substrate oxidation (indirect calorimetry), nonoxidative glucose disposal (NOGD), and inflammation were also determined. RESULTS: Exercise increased insulin-stimulated preocclusion diameter (p = 0.01) and microvascular blood flow (condition effect: p = 0.04) compared with control. Furthermore, exercise improved metabolic insulin sensitivity by 21%, which paralleled rises in NOGD (p = 0.05) and decreases in soluble receptors for advanced glycation end products (condition effect: p = 0.01). Interestingly, changes in NOGD were related to increased insulin-stimulated microvascular blood flow (r = 0.57, p = 0.05). CONCLUSIONS: A single bout of exercise increases vascular insulin sensitivity in adults with obesity. Additional work is needed to determine vascular responses following different doses of exercise in order to design lifestyle prescriptions for reducing chronic disease risk.


Assuntos
Resistência à Insulina , Adulto , Glicemia , Estudos Cross-Over , Técnica Clamp de Glucose , Humanos , Insulina , Obesidade
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