Identification of sarcopenic obesity in postmenopausal women: a cutoff proposal

Sarcopenic obesity is the combination of reduced fat-free mass (FFM) and increased fat mass (FM) with advancing age but there is lack of clear criteria for its identification. The purposes of the present investigation were: 1) to determine the prevalence of postmenopausal women with reduced FFM relative to their FM and height, and 2) to examine whether there are associations between the proposed classification and health-related variables. A total of 607 women were included in this cross-sectional study and were separated into two subsets: 258 older women with a mean age of 66.8 ± 5.6 years and 349 young women aged 18-40 years (mean age, 29.0 ± 7.5 years). All volunteers underwent body composition assessment by dual-energy X-ray absorptiometry. The FFM index relative to FM and height was calculated and the cutoff value corresponded to two standard deviations below the mean of the young reference group. To examine the clinical significance of the classification, all older participants underwent measurements of quadriceps strength and cardiorespiratory fitness. Values were compared between those who were classified as low FFM or not, using an independent samples t-test and correlations were examined. The cutoff corresponded to a residual of -3.4 and generated a sarcopenic obesity prevalence of 19.8% that was associated with reduced muscle strength and aerobic fitness among the older participants. Also, the index correlated significantly with the health-related fitness variables. The results demonstrated reduced functional capacity for those below the proposed cutoff and suggested applicability of the approach as a definition for sarcopenic obesity.

Higher levels of physical fitness are associated with a reduced risk of suffering sarcopenic obesity and better perceived health among elderly. The EXERNET multi-center study

Evaluar la asociación entre los niveles físicos de la aptitud, de calidad relacionada con la salud de la vida (CVRS) y la obesidad sarcopénica

Prevalence, pathophysiology, health consequences and treatment options of obesity in the elderly: a guideline.

The prevalence of obesity is rising progressively, even among older age groups. By the year 2030-2035 over 20% of the adult US population and over 25% of the Europeans will be aged 65 years and older. The predicted prevalence of obesity in Americans, 60 years and older was 37% in 2010. The predicted prevalence of obesity in Europe in 2015 varies between 20 and 30% dependent on the model used. This means 20.9 million obese 60+ people in the USA in 2010 and 32 million obese elders in 2015 in the EU. Although cut-off values of BMI, waist circumference and percentages of fat mass have not been defined for the elderly (nor for the elderly of different ethnicity), it is clear from several meta-analyses that mortality and morbidity associated with overweight and obesity only increases at a BMI above 30 kg/m(2). Thus, treatment should only be offered to patients who are obese rather than overweight and who also have functional impairments, metabolic complications or obesity-related diseases, that can benefit from weight loss. The weight loss therapy should aim to minimize muscle and bone loss but also vigilance as regards the development of sarcopenic obesity - a combination of an unhealthy excess of body fat with a detrimental loss of muscle and fat-free mass including bone - is important in the elderly, who are vulnerable to this outcome. Life-style intervention should be the first step and consists of a diet with a 500 kcal (2.1 MJ) energy deficit and an adequate intake of protein of high biological quality together with calcium and vitamin D, behavioural therapy and multi-component exercise. Multi-component exercise includes flexibility training, balance training, aerobic exercise and resistance training. The adherence rate in most studies is around 75%. Knowledge of constraints and modulators of physical inactivity should be of help to engage the elderly in physical activity. The role of pharmacotherapy and bariatric surgery in the elderly is largely unknown as in most studies people aged 65 years and older have been excluded.

Fat-free mass index and fat mass index percentiles in Caucasians aged 18-98 y.

OBJECTIVE: To determine reference values for fat-free mass index (FFMI) and fat mass index (FMI) in a large Caucasian group of apparently healthy subjects, as a function of age and gender and to develop percentile distribution for these two parameters. DESIGN: Cross-sectional study in which bioelectrical impedance analysis (50 kHz) was measured (using tetrapolar electrodes and cross-validated formulae by dual-energy X-ray absorptiometry in order to calculate FFMI (fat-free mass/height squared) and FMI (fat mass/height squared). SUBJECTS: A total of 5635 apparently healthy adults from a mixed non-randomly selected Caucasian population in Switzerland (2986 men and 2649 women), varying in age from 24 to 98 y. RESULTS: The median FFMI (18-34 y) were 18.9 kg/m(2) in young males and 15.4 kg/m(2) in young females. No difference with age in males and a modest increase in females were observed. The median FMI was 4.0 kg/m(2) in males and 5.5 kg/m(2) in females. From young to elderly age categories, FMI progressively rose by an average of 55% in males and 62% in females, compared to an increase in body mass index (BMI) of 9 and 19% respectively. CONCLUSIONS: Reference intervals for FFMI and FMI could be of practical value for the clinical evaluation of a deficit in fat-free mass with or without excess fat mass (sarcopenic obesity) for a given age category, complementing the classical concept of body mass index (BMI) in a more qualitative manner. In contrast to BMI, similar reference ranges seems to be utilizable for FFMI with advancing age, in particular in men.

Obesidade sarcopênica: diagnóstico, prevalência e associações com aptidão física, resistência insulínica, estresse inflamatório e oxidativo

Pós-graduação em Patologia - FMB

Effects of circuit-based exercise programs on the body composition of elderly obese women

Aim: The aim of this study was to investigate the impact of circuit-based exercise on the body composition in obese older women by focusing on physical exercise and body weight (BW) gain control in older people. Methods: Seventy older women (>60 years old) voluntarily took part in the study. Participants were randomized into six different groups according to body mass index (BMI): appropriate weight (AW) control (AWC) and trained (AWT) groups, overweight (OW) control (OWC) and trained (OWT) groups, and obesity (O) control (OC) and trained (OT) groups. The exercise program consisted of 50 minutes of exercise three times per week for 12 weeks. The exercises were alternated between upper and lower body using rest between sets for 40 seconds with intensity controlled by heart rate (70% of work). The contraction time established was 5 seconds to eccentric and concentric muscular action phase. The following anthropometric parameters were evaluated: height (m), body weight (BW, kg), body fat (BF, %), fat mass (FM, kg), lean mass (LM, kg), and BMI (kg/m(2)). Results: The values (mean +/- standard deviation [SD]) of relative changes to BW (-8.0% +/- 0.8%), BF (-21.4% +/- 2.1%), LM (3.0% +/- 0.3%), and FM (-31.2% +/- 3.0%) to the OT group were higher (P < .05) than in the AWT (BW: -2.0% +/- 1.1%; BF: -4.6% +/- 1.8%; FM: -7.0% +/- 2.8%; LM: 0.2% +/- 1.1%) and OWT (BW: -4.5% +/- 1.0%; BF: -11.0% +/- 2.2%; FM: -16.1% +/- 3.2%; LM: -0.2% +/- 1.0%) groups; additionally, no differences were found for C groups. While reduction (P < .03) in BMI according to absolute values was observed for all trained groups (AWT: 22 +/- 1 versus 21 +/- 1; OWT: 27 +/- 1 versus 25 +/- 1, OT: 34 +/- 1 versus 30 +/- 1) after training, no differences were found for C groups. Conclusion: In summary, circuit-based exercise is an effective method for promoting reduction in anthropometrics parameters in obese older women.

Effects of excess body mass on strength and fatigability of quadriceps in postmenopausal women

Objective: Obesity is a major public health problem leading to, among other things, reduced functional capacity. Moreover, obesity-related declines in functional capacity may be compounded by the detrimental consequences of menopause. The aim of this study was to understand the potential effects of excess body mass on measures of functional capacity in postmenopausal women. Methods: Forty-five postmenopausal women aged 50 to 60 years were divided into two groups according to body mass index (BMI): obese (BMI, >= 30 kg/m(2); n = 19) and nonobese (BMI, 18.5-29.9 kg/m(2); n = 26). To determine clinical characteristics, body composition, bone mineral density, and maximal exercise testing was performed, and a 3-day dietary record was estimated. To assess quadriceps function, isokinetic exercise testing at 60 degrees per second (quadriceps strength) and at 300 degrees per second (quadriceps fatigue) was performed. Results: The absolute value of the peak torque was not significantly different between the groups; however, when the data were normalized by body mass and lean mass, significantly lower values were observed for obese women compared with those in the nonobese group (128% +/- 25% vs 155% +/- 24% and 224% +/- 38% vs 257% +/- 47%, P < 0.05). The fatigue index did not show any significant difference for either group; however, when the data were normalized by the body mass and lean mass, significantly lower values were observed for obese women (69% +/- 16% vs 93% +/- 18% and 120% +/- 25% vs. 135% +/- 23%, P < 0.01). Conclusions: Our results show that despite reduced muscle force, the combination of obesity and postmenopause may be associated with greater resistance to muscle fatigue.

El fitness como factor determinante en el riesgo de discapacidad, su relación con la composición corporal y el estado cognitivo en población mayor institucionalizada y de vida independiente = Fitness as a determinant factor in the risk of disability, and its relationship to body composition and cognitive status in institutionalized elderly population and independent living

La condición física, o como mejor se la conoce hoy en día el “fitness”, es una variable que está cobrando gran protagonismo, especialmente desde la perspectiva de la salud. La mejora de la calidad de vida que se ha experimentado en los últimos años en las sociedades desarrolladas, conlleva un aumento de la esperanza de vida, lo que hace que cada vez más personas vivan más años. Este rápido crecimiento de la población mayor de 60 años hace que, un grupo poblacional prácticamente olvidado desde el punto de vista de la investigación científica en el campo de la actividad física y del deporte, cobre gran relevancia, con el fin de poder ayudar a alcanzar el dicho “no se trata de aportar años a la vida sino vida a lo años”. La presente memoria de Tesis Doctoral tiene como principal objetivo valorar los niveles de fitness en población mayor española, además de analizar la relación existente entre el fitness, sus condicionantes y otros aspectos de la salud, tales como la composición corporal y el estado cognitivo. Entendemos que para poder establecer futuras políticas de salud pública en relación a la actividad física y el envejecimiento activo es necesario conocer cuáles son los niveles de partida de la población mayor en España y sus condicionantes. El trabajo está basado en los datos del estudio multicéntrico EXERNET (Estudio Multi-céntrico para la Evaluación de los Niveles de Condición Física y su relación con Estilos de Vida Saludables en población mayor española no institucionalizada), así como en los datos de dos estudios, llevados a cabo en población mayor institucionalizada. Se han analizado un total de 3136 mayores de vida independiente, procedentes de 6 comunidades autónomas, y 153 mayores institucionalizados en residencias de la Comunidad de Madrid. Los principales resultados de esta tesis son los siguientes: a) Fueron establecidos los valores de referencia, así como las curvas de percentiles, para cada uno de los test de fitness, de acuerdo a la edad y al sexo, en población mayor española de vida independiente y no institucionalizada. b) Los varones obtuvieron mejores niveles de fitness que las mujeres, excepto en los test de flexibilidad; existe una tendencia a disminuir la condición física en ambos sexos a medida que la edad aumenta. c) Niveles bajos de fitness funcional fueron asociados con un aumento en la percepción de problemas. d) El nivel mínimo de fitness funcional a partir del cual los mayores perciben problemas en sus actividades de la vida diaria (AVD) es similar en ambos sexos. e) Niveles elevados de fitness fueron asociados con un menor riesgo de sufrir obesidad sarcopénica y con una mejor salud percibida en los mayores. f) Las personas mayores con obesidad sarcopénica tienen menor capacidad funcional que las personas mayores sanas. g) Niveles elevados de fuerza fueron asociados con un mejor estado cognitivo siendo el estado cognitivo la variable que más influye en el deterioro de la fuerza, incluso más que el sexo y la edad. ABSTRACT Fitness is a variable that is gaining in prominence, especially from the health perspective. Improvement of life quality that has been experienced in the last few years in developed countries, leads to an expanded life expectancy, increasing the numbers of people living longer. This population consisting of people of over 60 years, an almost forgotten population group from the point of view of scientific research in the field of physical activity and sport, is becoming increasingly important, with the main aim of helping to achieve the saying “do not only add years to life, but also add life to years”. The principal aim of the current thesis was to assess physical fitness levels in Spanish elderly people, of over 65 years, analyzing relationship between physical fitness, its determinants, and other aspects of health such as body composition and cognitive status. In order to establish further public health policies in relation to physical activity and active ageing it is necessary to identify the starting physical fitness levels of the Spanish population and their determinants. The work is based on data from the EXERNET multi-center study ("Multi-center Study for the Evaluation of Fitness levels and their relationship to Healthy Lifestyles in noninstitutionalized Spanish elderly"), and on data from two studies conducted in institutionalized elderly people: a total of 3136 non-institutionalized elderly, from 6 Regions of Spain, and 153 institutionalized elderly in nursing homes of Madrid. The main outcomes of this thesis are: a) sex- and age-specific physical fitness normative values and percentile curves for independent and non-institutionalized Spanish elderly were established. b) Greater physical fitness was present in the elderly men than in women, except for the flexibility test, and a trend toward decreased physical fitness in both sexes as their age increased. c) Lower levels of functional fitness were associated with increased perceived problems. d) The minimum functional fitness level at which older adults perceive problems in their ADLs, is similar for both sexes e) Higher levels of physical fitness were associated with a reduced risk of suffering sarcopenic obesity and better perceived health among the elderly. f) The elderly with sarcopenic obesity have lower physical functioning than healthy counterparts. g) Higher strength values were associated with better cognitive status with cognitive status being the most influencing variable in strength deterioration even more than sex and age.

Prevalência e incidência de obesidade sarcopênica em coorte de idosos domiciliados no município de São Paulo

Introdução: Evidências epidemiológicas mostram que a obesidade sarcopênica (OS) em idosos está associada a um acelerado declínio funcional e alto risco de morbimortalidade, sendo que seu impacto tem se tornado grande preocupação dos profissionais de saúde. Objetivo: Estimar a prevalência e a incidência de obesidade sarcopênica, em coorte de idosos domiciliados no município de São Paulo/Brasil 2000 e 2010. Casuística e Métodos: Foram utilizados dados do Estudo SABE (Saúde, Bem-estar e Envelhecimento), realizado no município de São Paulo em 2000 (2.143 idosos), e em 2010 (795 idosos). A população deste estudo foi constituída por idosos ( 70 anos), de ambos os sexos, que apresentaram todos os dados necessários para este estudo e que concordaram em participar, totalizando 871 idosos analisados em 2000 e 656 idosos em 2010. As variáveis de estudo foram: 1. Dependente - obesidade sarcopênica, identificada segundo: obesidade, diagnosticada pelo valor da circunferência da cintura (CC 94 cm e CC 80 cm para homens e mulheres, respectivamente); sarcopenia, identificada por: 1- força muscular, pelo teste de preensão manual (FPM - kg) (baixa P25; normal > P25, da mesma população), 2- massa muscular (MM), obtida pelo índice de massa muscular (IMM=MM/altura²) (baixa P20; normal > P20, da mesma população) e 3- desempenho físico, identificado pelo teste (tempo dependente segundos) de sentar e levantar 5 vezes de uma cadeira (SeL) , com os braços cruzados sobre o peito (baixo P75; normal < P75); 2. Explanatórias - sexo e grupos etários (70 79 e 80). Foram classificados com OS idosos que apresentaram, simultaneamente, valores de CC adotados e baixo desempenho e baixa MM, ou então, desempenho normal, mas baixas FPM e MM. A prevalência de obesidade sarcopênica em 2000 e em 2010 foi estimada pelo número de casos de OS identificados nos dois momentos, onde foram realizadas comparações entre os intervalos de confiança, para verificar diferença estatística em idosos ( por cento ) com OS, segundo variáveis explanatórias, com nível de significância de 5 por cento . Para o cálculo do coeficiente de incidência de OS, em 2010, foi considerado o tempo de observação de cada indivíduo, determinado de maneira específica para cada caso. Para os cálculos foi utilizado o programa: Stata/SE ® 10.0 for Windows. Resultados: Dos 871 idosos analisados em 2000, 85 (7,4 por cento ) foram identificados com OS [6,5 por cento mulheres (IC 5,08,4) e 4,8 por cento 80 anos (IC 3,6-6,4)] (p 5 por cento ), e, em 2010, (n=656), 73 (9,2 por cento ) foram identificados com OS [7,2 por cento mulheres (IC 5,5-9,4) e 5,3 por cento 80 anos (IC 4,0-7,0)] (p 5 por cento ). Em 10 anos, foram identificados 43 novos casos de OS. O coeficiente de incidência foi 15,29/1000 pessoas/ano entre 2000 e 2010. Conclusões: A prevalência de OS em 2000 e 2010 foi maior nas mulheres e nos idosos mais longevos, sendo que, em ambos os casos, foi maior em 2010, quando comparada a 2000. Não houve diferença significativa entre os coeficientes de incidência, segundo as variáveis explanatórias.

Detection and quantification of protein oxidation in sarcopenic models:a mass spectrometry study

Oxidised biomolecules in aged tissue could potentially be used as biomarkers for age-related diseases; however, it is still unclear whether they causatively contribute to ageing or are consequences of the ageing process. To assess the potential of using protein oxidation as markers of ageing, mass spectrometry (MS) was employed for the identification and quantification of oxidative modifications in obese (ob/ob) mice. Lean muscle mass and strength is reduced in obesity, representing a sarcopenic model in which the levels of oxidation can be evaluated for different muscular systems including calcium homeostasis, metabolism and contractility. Several oxidised residues were identified by tandem MS (MS/MS) in both muscle homogenate and isolated sarcoplasmic reticulum (SR), an organelle that regulates intracellular calcium levels in muscle. These modifications include oxidation of methionine, cysteine, tyrosine, and tryptophan in several proteins such as sarcoplasmic reticulum calcium ATPase (SERCA), glycogen phosphorylase, and myosin. Once modifications had been identified, multiple reaction monitoring MS (MRM) was used to quantify the percentage modification of oxidised residues within the samples. Preliminary data suggests proteins in ob/ob mice are more oxidised than the controls. For example SERCA, which constitutes 60-70% of the SR, had approximately a 2-fold increase in cysteine trioxidation of Cys561 in the obese model when compared to the control. Other obese muscle proteins have also shown a similar increase in oxidation for various residues. Further analysis with complex protein mixtures will determine the potential diagnostic use of MRM experiments for analysing protein oxidation in small biological samples such as muscle needle biopsies.

Obesity And Inflammation And The Effect On The Hematopoietic System.

Bone marrow is organized in specialized microenvironments known as 'marrow niches'. These are important for the maintenance of stem cells and their hematopoietic progenitors whose homeostasis also depends on other cell types present in the tissue. Extrinsic factors, such as infection and inflammatory states, may affect this system by causing cytokine dysregulation (imbalance in cytokine production) and changes in cell proliferation and self-renewal rates, and may also induce changes in the metabolism and cell cycle. Known to relate to chronic inflammation, obesity is responsible for systemic changes that are best studied in the cardiovascular system. Little is known regarding the changes in the hematopoietic system induced by the inflammatory state carried by obesity or the cell and molecular mechanisms involved. The understanding of the biological behavior of hematopoietic stem cells under obesity-induced chronic inflammation could help elucidate the pathophysiological mechanisms involved in other inflammatory processes, such as neoplastic diseases and bone marrow failure syndromes.

Ikkε Is Key To Induction Of Insulin Resistance In The Hypothalamus, And Its Inhibition Reverses Obesity.

IKK epsilon (IKKε) is induced by the activation of nuclear factor-κB (NF-κB). Whole-body IKKε knockout mice on a high-fat diet (HFD) were protected from insulin resistance and showed altered energy balance. We demonstrate that IKKε is expressed in neurons and is upregulated in the hypothalamus of obese mice, contributing to insulin and leptin resistance. Blocking IKKε in the hypothalamus of obese mice with CAYMAN10576 or small interfering RNA decreased NF-κB activation in this tissue, relieving the inflammatory environment. Inhibition of IKKε activity, but not TBK1, reduced IRS-1(Ser307) phosphorylation and insulin and leptin resistance by an improvement of the IR/IRS-1/Akt and JAK2/STAT3 pathways in the hypothalamus. These improvements were independent of body weight and food intake. Increased insulin and leptin action/signaling in the hypothalamus may contribute to a decrease in adiposity and hypophagia and an enhancement of energy expenditure accompanied by lower NPY and increased POMC mRNA levels. Improvement of hypothalamic insulin action decreases fasting glycemia, glycemia after pyruvate injection, and PEPCK protein expression in the liver of HFD-fed and db/db mice, suggesting a reduction in hepatic glucose production. We suggest that IKKε may be a key inflammatory mediator in the hypothalamus of obese mice, and its hypothalamic inhibition improves energy and glucose metabolism.

Fractalkine (cx3cl1) Is Involved In The Early Activation Of Hypothalamic Inflammation In Experimental Obesity.

Hypothalamic inflammation is a common feature of experimental obesity. Dietary fats are important triggers of this process, inducing the activation of toll-like receptor-4 (TLR4) signaling and endoplasmic reticulum stress. Microglia cells, which are the cellular components of the innate immune system in the brain, are expected to play a role in the early activation of diet-induced hypothalamic inflammation. Here, we use bone marrow transplants to generate mice chimeras that express a functional TLR4 in the entire body except in bone marrow-derived cells or only in bone marrow-derived cells. We show that a functional TLR4 in bone marrow-derived cells is required for the complete expression of the diet-induced obese phenotype and for the perpetuation of inflammation in the hypothalamus. In an obesity-prone mouse strain, the chemokine CX3CL1 (fractalkine) is rapidly induced in the neurons of the hypothalamus after the introduction of a high-fat diet. The inhibition of hypothalamic fractalkine reduces diet-induced hypothalamic inflammation and the recruitment of bone marrow-derived monocytic cells to the hypothalamus; in addition, this inhibition reduces obesity and protects against diet-induced glucose intolerance. Thus, fractalkine is an important player in the early induction of diet-induced hypothalamic inflammation, and its inhibition impairs the induction of the obese and glucose intolerance phenotypes.

Obesity Versus Osteoarthritis: Beyond The Mechanical Overload.

Obesity is currently considered a major public health problem in the world, already reaching epidemic characteristics, according to the World Health Organization. Excess weight is the major risk factor associated with various diseases, such as type 2 diabetes mellitus, hypertension, dyslipidemia and osteometabolic diseases, including osteoporosis and osteoarthritis. Osteoarthritis is the most prevalent rheumatic disease and the leading cause of physical disability and reduced quality of life of the population over 65 years. It mainly involves the joints that bear weight - knees and hips. However, along with the cases of obesity, its prevalence is increasing, and even in other joints, such as hands. Thus, it is assumed that the influence of obesity on the development of OA is beyond mechanical overload. The purpose of this review was to correlate the possible mechanisms underlying the genesis and development of these two diseases. Increased fat mass is directly proportional to excessive consumption of saturated fatty acids, responsible for systemic low-grade inflammation condition and insulin and leptin resistance. At high levels, leptin assumes inflammatory characteristics and acts in the articular cartilage, triggering the inflammatory process and changing homeostasis this tissue with consequent degeneration. We conclude that obesity is a risk factor for osteoarthritis and that physical activity and changes in diet composition can reverse the inflammatory and leptin resistance, reducing progression or preventing the onset of osteoarthritis.

Waist-to-height Ratio Percentiles And Cutoffs For Obesity: A Cross-sectional Study In Brazilian Adolescents.

This study aimed to describe the distribution of waist-to-height ratio (WHtR) percentiles and cutoffs for obesity in Brazilian adolescents. A cross-sectional study including adolescents aged 10 to 15 years was conducted in the city of São Paulo, Brazil; anthropometric measurements (weight, height, and waist-circumference) were taken, and WHtRs were calculated and then divided into percentiles derived by using Least Median of Squares (LMS) regression. The receiver operating characteristic (ROC) curve was used in determining cutoffs for obesity (BMI ≥ 97th percentile) and Mann-Whitney and Kruskal-Wallis tests were used for comparing variables. The study included 8,019 adolescents from 43 schools, of whom 54.5% were female, and 74.8% attended public schools. Boys had higher mean WHtR than girls (0.45 ± 0.06 vs 0.44 ± 0.05; p=0.002) and higher WHtR at the 95th percentile (0.56 vs 0.54; p<0.05). The WHtR cutoffs according to the WHO criteria ranged from 0.467 to 0.506 and 0.463 to 0.496 among girls and boys respectively, with high sensitivity (82.8-95%) and specificity (84-95.5%). The WHtR was significantly associated with body adiposity measured by BMI. Its age-specific percentiles and cutoffs may be used as additional surrogate markers of central obesity and its co-morbidities.